title: Age-related increases in PGD(2) expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice.

text: The morbidity and mortality associated with respiratory virus infection is felt most keenly among the elderly. T cells are necessary for viral clearance, and many age-dependent intrinsic T cell defects have been documented. However, the development of robust T cell responses in the lung also requires respiratory DCs (rDCs), which must process antigen and migrate to draining LNs (DLNs), and little is known about age-related defects in these T cell-extrinsic functions. Here, we show that increases in prostaglandin D(2) (PGD(2)) expression in mouse lungs upon aging correlate with a progressive impairment in rDC migration to DLNs. Decreased rDC migration resulted in diminished T cell responses and more severe clinical disease in older mice infected with respiratory viruses. Diminished rDC migration associated with virus-specific defects in T cell responses and was not a result of cell-intrinsic defect, rather it reflected the observed age-dependent increases in PGD(2) expression. Blocking PGD(2) function with small-molecule antagonists enhanced rDC migration, T cell responses, and survival. This effect correlated with upregulation on rDCs of CCR7, a chemokine receptor involved in DC chemotaxis. Our results suggest that inhibiting PGD(2) function may be a useful approach to enhance T cell responses against respiratory viruses in older humans.


title: Challenges in the miRNA research.

text: While it is known that the human genes are regulated by microRNAs (miRNAs), recent links with cancer and other diseases have widely caught interest. With several bioinformatics platforms and approaches on rise that has led to discovery of human miRNAs, validation and need for understanding miRNAs from their progenitor messenger RNAs (mRNAs) have arisen. Furthermore, the miRNAs are known to have synergism involving regulation of their condition-specific target genes (mRNAs). In this review, we provide a bioinformatics approach of the miRNAs and their challenges with respect to annotation. With introduction of sequence-specific miRNA signatures recently found, we discussed myriad of dimensions where miRNAs are being associated with several putative functional and evolutionary events, and then we asked a question how far and relevant is the association of miRNAs with mRNAs?


Diagnosis of COVID-19 pneumonia in pregnant women: can we rely on lung ultrasound?


title: Cost-analysis and quality of life after laparoscopic and robotic ventral mesh rectopexy for posterior compartment prolapse: a randomized trial.

text: BACKGROUND The aim of this study was to assess, whether robotic-assistance in ventral mesh rectopexy adds benefit to laparoscopy in terms of health-related quality of life (HRQoL), cost-effectiveness and anatomical and functional outcome. METHODS A prospective randomized study was conducted on patients who underwent robot-assisted ventral mesh rectopexy (RVMR) or laparoscopic ventral mesh rectopexy (LVMR) for internal or external rectal prolapse at Oulu University Hospital, Finland, recruited in February-May 2012. The primary outcomes were health care costs from the hospital perspective and HRQoL measured by the 15D-instrument. Secondary outcomes included anatomical outcome assessed by pelvic organ prolapse quantification method and functional outcome by symptom questionnaires at 24 months follow-up. RESULTS There were 30 females (mean age 62.5 years, SD 11.2), 16 in the RVMR group and 14 in the LVMR group. The surgery-related costs of the RVMR were 1.5 times higher than the cost of the LVMR. At 3 months the changes in HRQoL were 'much better' (RVMR) and 'slightly better' (LVMR) but declined in both groups at 2 years (RVMR vs. LVMR, p > 0.05). The cost-effectiveness was poor at 2 years for both techniques, but if the outcomes were assumed to last for 5 years, it improved significantly. The incremental cost-effectiveness ratio for the RVMR compared to LVMR was €39,982/quality-adjusted life years (QALYs) at 2 years and improved to €16,707/QALYs at 5 years. Posterior wall anatomy was restored similarly in both groups. The subjective satisfaction rate was 87% in the RVMR group and 69% in the LVMR group (p = 0.83). CONCLUSIONS Although more expensive than LVMR in the short term, RVMR is cost-effective in long-term. The minimally invasive VMR improves pelvic floor function, sexual function and restores posterior compartment anatomy. The effect on HRQoL is minor, with no differences between techniques.


title: Open visiting in the NHS.

text: Sam Foster, Chief Nurse, Oxford University Hospitals, considers the balance of the benefits of enabling visiting with infection prevention and control practice during this pandemic.


title: Kawasaki disease in children.

text: Kawasaki disease (KD) is an acute self-limiting systemic vasculitis of unknown aetiology. It is the most common cause of acquired heart disease in young children. The intense inflammatory process has a predilection for the coronary arteries, resulting in the development of aneurysmal lesions, arterial thrombotic occlusion or, potentially, sudden death. There is no specific diagnostic test; however, treatment with immunoglobulin and aspirin effectively reduces cardiac complications from 25% to 4.7% in the UK. Inflammation of the myocardium, endocardium or pericardium can occur early in the disease and endothelial dysfunction along with abnormalities of myocardial blood flow may require continuing medication, interventional catheterisation or even cardiac surgery. Several new pharmacological treatments may have important roles to play in managing KD in children and adolescents. This review discusses the history of the disease, the diagnostic challenges, epidemiology, aetiology, pathology, immunopathogenesis, treatment, genetic influences and the long-term cardiovascular sequelae.


title: Meeting need vs. sharing the market: a systematic review of methods to measure the use of private sector family planning and childbirth services in sub-Saharan Africa.

text: BACKGROUND Ensuring universal access to maternal and reproductive health services is critical to the success of global efforts to reduce poverty and inequality. Engaging private providers has been proposed as a strategy for increasing access to healthcare in low- and middle-income countries; however, little consensus exists on how to estimate the extent of private sector use. Using research from sub-Saharan Africa, this study systematically compares and critiques quantitative measures of private sector family planning and childbirth service use and synthesizes evidence on the role of the private sector in the region. METHODS We conducted a systematic review of the Medline, Global Health, and Popline databases. All studies that estimated use of private sector of family planning or childbirth services in one or more sub-Saharan African countries were included in this review. For each study, we extracted data on the key study outcomes and information on the methods used to estimate private sector use. RESULTS Fifty-three papers met our inclusion criteria; 31 provided outcomes on family planning, and 26 provided childbirth service outcomes. We found substantial methodological variation between studies; for instance, while some reported on service use from any private sector source, others distinguished private sector providers either by their profit orientation or position within or outside the formal medical sector. Additionally, studies measured the use of private sector services differently, with some estimating the proportion of need met by the private sector and others examining the sector's share among the market of service users. Overall, the estimates suggest that the private sector makes up a considerable portion (> 20%) of the market for family planning and childbirth care, but its role in meeting women's need for these services is fairly low (< 10%). CONCLUSIONS Many studies have examined the extent of private sector family planning and childbirth service provision; however, inconsistent methodologies make it difficult to compare results across studies and contexts. Policymakers should consider the implications of both private market share and coverage estimates, and be cautious in interpreting data on the scale of private sector health service provision without a clear understanding of the methodology.


GP who was suspended for forging out-of-hours form can resume work to assist in pandemic.


title: Effect of feed deprivation on selected parameters of lipid mobilisation and hepatic function in healthy Akhal Teke horses.

text: BACKGROUND Gastrointestinal and other systemic diseases of Equidae are often characterised by partial or complete inappetence. The catabolic processes may lead to lipid mobilisation and other metabolic disturbances. Evidence from earlier studies has revealed that during feed deprivation/inappetence, the conjugation of bilirubin is reduced causing a substantial rise of the total bilirubin and its unconjugated fraction. OBJECTIVES We hypothesised that during feed deprivation, the serum concentration of free fatty acids (FFA), triglycerides (TG), blood urea nitrogen (BUN), total bilirubin (tBIL), total bile acids (tBA) and activity of GGT and GLDH increases, while the concentration of insulin and direct bilirubin (dBIL) decreases. STUDY DESIGN Observational experiment. METHODS Eleven horses were feed deprived for 96 h. Animals were closely monitored while blood samples were taken at the beginning, and then at 72, 84 and 96 h later. Variables of interest included serum FFA, TG, insulin, GGT, GLDH, total and direct BIL (t&dBIL), tBA and BUN. The data were analysed by descriptive statistics, paired t-test and one-way repeated measures ANOVA with post-hoc HSD test, and P≤0.05 was considered significant. RESULTS Horses tolerated feed restriction without complications. During this time, the concentration of TG, FFA, BUN, dBIL and insulin significantly increased (P≤0.05), as well as the activity of serum GGT, while the concentration of tBIL, tBA and the activity of GLDH did not change significantly (P>0.05). MAIN LIMITATIONS Sample size, lack of serum volatile fatty acid, cortisol and blood glucose measurements may have limited the value of the study. CONCLUSIONS Healthy Akhal Teke horses did not develop a catabolic crisis following 4 days of feed restriction and hyperlipaemia did not occur. Total BIL and tBA did not increase, thus were not useful indicators of inappetence in this group of horses.


Lessons in contact tracing from Germany.


title: The incidence of trocar-site hernia in minimally invasive bariatric surgery: a comparison of multi versus single-port laparoscopy.

text: INTRODUCTION Single-port laparoscopy (SPL) employs a 1.5- to 2.5-cm incision at the umbilicus for the placement of a single working port. We hypothesized that the longer incision created by SPL compared with multiport laparoscopy may increase the incidence of trocar-site hernias. We examined our experience with SPL in bariatric operations. METHODS There were 734 laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding procedures performed at our institution between 2001 and 2011. Fifty-eight patients were lost to follow-up or had a short duration of follow-up (<1 month). Of the remaining 676 cases, 163 were performed via SPL. All laparoscopic wounds created by trocar size greater than 12 mm were closed with absorbable suture. RESULTS Patient demographics of the SPL group and the multiport group were similar in terms of age, gender, and comorbidities. The average body mass index (BMI) of the SPL group was lower than the multiport group (43.5 ± 5.3 vs. 45.8 ± 7.7, p < 0.01). The mean follow-up for the SPL group was 11 months versus 24 months for the multiport group. There were three trocar-site hernias out of 513 cases in the multiport compared to one hernia out of 163 cases in the SPL group (0.6 vs. 0.6 %, p = 0.967). All trocar-site hernias occurred at the 15-mm port site. The median time to hernia occurrence for the multiport group was 13 months (range, 1-18). In the SPL group, the hernia occurred at 8 months. On multivariate analysis, age, BMI, SPL, procedure type, and the postoperative weight loss were not associated with the development of trocar-site hernias. CONCLUSIONS SPL did not increase the rate of trocar-site hernia in this series. A low rate of trocar-site hernia can be achieved with the use of SPL in bariatric surgery.


title: Nine-, but Not Four-Days Heat Acclimation Improves Self-Paced Endurance Performance in Females.

text: Although emerging as a cost and time efficient way to prepare for competition in the heat, recent evidence indicates that "short-term" heat acclimation (<7 days) may not be sufficient for females to adapt to repeated heat stress. Furthermore, self-paced performance following either short-term, or longer (>7 days) heat acclimation has not been examined in a female cohort. Therefore, the aim of this study was to investigate self-paced endurance performance in hot conditions following 4- and 9-days of a high-intensity isothermic heat acclimation protocol in a female cohort. Eight female endurance athletes (mean ± SD, age 27 ± 5 years, mass 61 ± 5 kg, VO2peak 47 ± 6 ml⋅kg⋅min-1) performed 15-min self-paced cycling time trials in hot conditions (35°C, 30%RH) before (HTT1), and after 4-days (HTT2), and 9-days (HTT3) isothermic heat acclimation (HA, with power output manipulated to increase and maintain rectal temperature (T rec) at ∼38.5°C for 90-min cycling in 40°C, 30%RH) with permissive dehydration. There were no significant changes in distance cycled (p = 0.47), mean power output (p = 0.55) or cycling speed (p = 0.44) following 4-days HA (i.e., from HTT1 to HTT2). Distance cycled (+3.2%, p = 0.01; +1.8%, p = 0.04), mean power output (+8.1%, p = 0.01; +4.8%, p = 0.05) and cycling speed (+3.0%, p = 0.01; +1.6%, p = 0.05) were significantly greater in HTT3 than in HTT1 and HTT2, respectively. There was an increase in the number of active sweat glands per cm2 in HTT3 as compared to HTT1 (+32%; p = 0.02) and HTT2 (+22%; p < 0.01), whereas thermal sensation immediately before HTT3 decreased ("Slightly Warm," p = 0.03) compared to ratings taken before HTT1 ("Warm") in 35°C, 30%RH. Four-days HA was insufficient to improve performance in the heat in females as observed following 9-days HA.


title: Modulation of ribosomal frameshifting frequency and its effect on the replication of Rous sarcoma virus.

text: Programmed -1 ribosomal frameshifting is widely used in the expression of RNA virus replicases and represents a potential target for antiviral intervention. There is interest in determining the extent to which frameshifting efficiency can be modulated before virus replication is compromised, and we have addressed this question using the alpharetrovirus Rous sarcoma virus (RSV) as a model system. In RSV, frameshifting is essential in the production of the Gag-Pol polyprotein from the overlapping gag and pol coding sequences. The frameshift signal is composed of two elements, a heptanucleotide slippery sequence and, just downstream, a stimulatory RNA structure that has been proposed to be an RNA pseudoknot. Point mutations were introduced into the frameshift signal of an infectious RSV clone, and virus replication was monitored following transfection and subsequent infection of susceptible cells. The introduced mutations were designed to generate a range of frameshifting efficiencies, yet with minimal impact on encoded amino acids. Our results reveal that point mutations leading to a 3-fold decrease in frameshifting efficiency noticeably reduce virus replication and that further reduction is severely inhibitory. In contrast, a 3-fold stimulation of frameshifting is well tolerated. These observations suggest that small-molecule inhibitors of frameshifting are likely to have potential as agents for antiviral intervention. During the course of this work, we were able to confirm, for the first time in vivo, that the RSV stimulatory RNA is indeed an RNA pseudoknot but that the pseudoknot per se is not absolutely required for virus viability.


title: [Analysis on the epidemic factors for the Corona Virus Disease].

text: Since December 2019, corona virus disease 2019 (COVID-19) , an emerging infection disease occurred in Wuhan, has spread in the mainland China. The epidemic factors on the basis of knowledge of SARS-CoV-2 were discussed in this paper. This puts a lot of pressure on clinical resources and care. SARS-CoV-2 is a novel corona virus, the onset of COVID-19 is slow, and the pathogenesis of SARS-CoV-2 remains unclear and may lead to multiple organ damage. These put a lot of pressure on clinical resources and care. Source of infection including the patients, asymptomatic carrier and patients in the incubation period are contagious. It is difficult to control source of infection. Routes of SARS-CoV-2 transmission are diversified and the main routes of transmission for COVID-19 are droplet transmission and close contact transmission. All population have susceptibility to SARS-CoV-2. Social factors such population movements and aggregation accelerated the spread of SARS-CoV-2. The Chinese government's adopted measures are positive and effective, and are accepted by the expert group from the World Health Organization. However, it will be a long-term hard work in the future to seriously summarize and think deeply to achieve public health security in China.


John Maddox 1925-2009.


title: Thiouracil cross-linking mass spectrometry: a cell-based method to identify host factors involved in viral amplification.

text: Eukaryotic RNA viruses are known to utilize host factors; however, the identity of these factors and their role in the virus life cycle remain largely undefined. Here, we report a method to identify proteins bound to the viral RNA during amplification in cell culture: thiouracil cross-linking mass spectrometry (TUX-MS). TUX-MS relies on incorporation of a zero-distance cross-linker into the viral RNA during infection. Proteins bound to viral RNA are cross-linked prior to cell lysis, purified, and identified using mass spectrometry. Using the TUX-MS method, an unbiased screen for poliovirus (PV) host factors was conducted. All host and viral proteins that are known to interact with the poliovirus RNA were identified. In addition, TUX-MS identified an additional 66 host proteins that have not been previously described in poliovirus amplification. From these candidates, eight were selected and validated. Furthermore, we demonstrate that small interfering RNA (siRNA)-mediated knockdown of two of these uncharacterized host factors results in either a decrease in copy number of positive-stranded RNA or a decrease in PV translation. These data demonstrate that TUX-MS is a robust, unbiased method to identify previously unknown host cell factors that influence virus growth. This method is broadly applicable to a range of RNA viruses, such as flaviviruses, alphaviruses, picornaviruses, bunyaviruses, and coronaviruses.


title: Hypochlorite killing of community-associated methicillin-resistant Staphylococcus aureus.

text: We tested in vitro hypochlorite (bleach) killing of community-associated methicillin-resistant Staphylococcus aureus isolates to determine optimal concentration and duration. For all isolates maximal killing, >3-log decrease in colony forming units (CFU), was found after 5 minutes in 2.5 microL/mL bleach. We estimate that 2.5 microL/mL bleach is approximately one-half cup of bleach in one-quarter tub of water.


title: Clipless versus conventional laparoscopic cholecystectomy.

text: Abstract Laparoscopic cholecystectomy has been the gold standard technique for cholecystectomy and has proven more effective than the conventional open technique. The laparoscopic technique utilizes surgical clips for cystic duct occlusion, which come with their own set of complications. With the advent of new vessel and duct sealing technology, alternative energy instruments have been explored for the occlusion of the cystic duct without the use of clips. The Harmonic(®) scalpel (Ethicon Endo-Surgery, Cincinnati, OH) has become one of the more widely used instruments. In this retrospective study, 208 patients received surgical clip placement or the Harmonic scalpel was used for cystic duct occlusion. The postoperative complications were documented, and rates were calculated for outpatient follow-up, for re-admission, and specifically for the complications of a bile leak. When adjusted for the cause of bile leak (cystic duct versus common bile duct versus accessory duct), the use of the Harmonic scalpel versus clip placement had comparable rates of bile leak at 1.75% and 0.66%, respectively. The use of the Harmonic scalpel is deemed safe and comparable to clip placement at the discretion of the surgeon for cystic duct ligation. Further research with larger homogeneous studies and assessments of cost-effectiveness would further enhance the increasing use of the Harmonic scalpel in laparoscopic cholecystectomy.


title: Robotic liver resection: initial experience with three-arm robotic and single-port robotic technique.

text: BACKGROUND AND OBJECTIVE Robotic-assisted surgery offers a solution to fundamental limitations of conventional laparoscopic surgery, and its use is gaining wide popularity. However, the application of this technology has yet to be established in hepatic surgery. METHODS A retrospective analysis of our prospectively collected liver surgery database was performed. Over a 6-month period, all consecutive patients who underwent robotic-assisted hepatic resection for a liver neoplasm were included. Demographics, operative time, and morbidity encountered were evaluated. RESULTS A total of 7 robotic-assisted liver resections were performed, including 2 robotic-assisted single-port access liver resections with the da Vinci-Si Surgical System (Intuitive Surgical Sunnyvalle, Calif.) USA. The mean age was 44.6 years (range, 21-68 years); there were 5 male and 2 female patients. The mean operative time (± SD) was 61.4 ± 26.7 minutes; the mean operative console time (± SD) was 38.2 ± 23 minutes. No conversions were required. The mean blood loss was 100.7 mL (range, 10-200 mL). The mean hospital stay (± SD) was 2 ± 0.4 days. No postoperative morbidity related to the procedure or death was encountered. CONCLUSION Our initial experience with robotic liver resection confirms that this technique is both feasible and safe. Robotic-assisted technology appears to improve the precision and ergonomics of single-access surgery while preserving the known benefits of laparoscopic surgery, including cosmesis, minimal morbidity, and faster recovery.


Coronavirus disease 19 (Covid-19) and non-steroidal anti-inflammatory drugs (NSAID).


title: Obstructive sleep apnea syndrome (OSAS) and swallowing function-a systematic review.

text: OBJECTIVES The purpose of this systematic review was to summarize and qualitatively analyze published evidence elucidating the prevalence of dysphagia and detail alterations in swallowing function in patients with OSAS. METHODS Computerized literature searches were performed from four search engines. The studies were selected based on the inclusion and exclusion criteria. The studies were screened using Covidence (Cochrane tool) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards (PRISMA-2009). A total 2645 studies were initially retrieved, of which a total of 17 studies met inclusion criteria. Two reviewers, blinded to each other, evaluated level and strength of evidence using the Oxford Centre for Evidence-based Medicine Levels of Evidence and QualSyst, respectively. RESULTS Dysphagia prevalence ranged from 16 to 78% among the eligible studies. Studies varied in operational definitions defining swallowing dysfunction (dysphagia) and method used to assess swallowing function. Approximately 70% of eligible studies demonstrated strong methodological quality. The majority of studies (n = 11; 65%) reported pharyngeal swallowing impairments in patients with OSAS, including delayed initiation of pharyngeal swallow and penetration/aspiration. CONCLUSION This systematic review describes swallowing function in patients with OSAS. However, due to the variability in defining OSAS and dysphagia, in the assessment method used to determine dysphagia, and heterogeneity of study designs, true prevalence is difficult to determine. Clinicians involved in the management of OSAS patients should employ validated assessment measures to determine if swallow dysfunction is present.


COVID-19 drives new threat to bats in China.


title: Predicting the risk of venous thromboembolism in patients hospitalized with heart failure.

text: BACKGROUND Whether heart failure (HF) increases the risk of venous thromboembolism (VTE) is not well established. In the phase III MAGELLAN (Multicenter, rAndomized, parallel Group Efficacy and safety study for the prevention of venous thromboembolism in hospitalized medically iLL patients comparing rivaroxabAN with enoxaparin) trial, extended-duration rivaroxaban was compared with standard-duration enoxaparin followed by placebo for VTE prevention in 8101 hospitalized acutely ill patients with or without HF. The aim of this analysis was to evaluate the relationship between HF severity and the risk of VTE in MAGELLAN patients. METHODS AND RESULTS Hospitalized patients diagnosed with HF were included according to New York Heart Association class III or IV at admission (n=2593). HF severity was determined by N-terminal probrain natriuretic peptide (NT-proBNP) plasma concentrations (median 1904 pg/mL). Baseline plasma D-dimer concentrations ranged from 0.6 to 1.7 μg/L for the less and more severe HF subgroups. Patients with more severe HF had a greater incidence of VTE versus patients with less severe HF, with a significant trend up to Day 10 (4.3% versus 2.2%; P=0.0108) and Day 35 (7.2% versus 4.1%; P=0.0150). Multivariable analysis confirmed that NT-proBNP concentration was associated with VTE risk up to Day 10 (P=0.017) and D-dimer concentration with VTE risk up to Day 35 (P=0.005). The association between VTE risk and HF severity that was observed in the enoxaparin/placebo group was not seen in the extended-duration rivaroxaban group. CONCLUSIONS Patients with more severe HF, as defined by high NT-proBNP plasma concentration, were at increased risk of VTE. NT-proBNP may be useful to identify high short-term risk, whereas elevated D-dimer may be suggestive of high midterm risk. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00571649.


title: Identification of the first synthetic inhibitors of the type II transmembrane serine protease TMPRSS2 suitable for inhibition of influenza virus activation.

text: TMPRSS2 (transmembrane serine proteinase 2) is a multidomain type II transmembrane serine protease that cleaves the surface glycoprotein HA (haemagglutinin) of influenza viruses with a monobasic cleavage site, which is a prerequisite for virus fusion and propagation. Furthermore, it activates the fusion protein F of the human metapneumovirus and the spike protein S of the SARS-CoV (severe acute respiratory syndrome coronavirus). Increased TMPRSS2 expression was also described in several tumour entities. Therefore TMPRSS2 emerged as a potential target for drug design. The catalytic domain of TMPRSS2 was expressed in Escherichia coli and used for an inhibitor screen with previously synthesized inhibitors of various trypsin-like serine proteases. Two inhibitor types were identified which inhibit TMPRSS2 in the nanomolar range. The first series comprises substrate analogue inhibitors containing a 4-amidinobenzylamide moiety at the P1 position, whereby some of these analogues possess inhibition constants of approximately 20 nM. An improved potency was found for a second type derived from sulfonylated 3-amindinophenylalanylamide derivatives. The most potent derivative of this series inhibits TMPRSS2 with a K(i) value of 0.9 nM and showed an efficient blockage of influenza virus propagation in human airway epithelial cells. On the basis of the inhibitor studies, a series of new fluorogenic substrates containing a D-arginine residue at the P3 position was synthesized, some of them were efficiently cleaved by TMPRSS2.


title: Interactions and oligomerization of hantavirus glycoproteins.

text: In this report the basis for the structural architecture of the envelope of hantaviruses, family Bunyaviridae, is systematically studied by the interactions of two glycoproteins N and C (Gn and Gc, respectively) and their respective disulfide bridge-mediated homo- and heteromeric oligomerizations. In virion extracts Gn and Gc associated in both homo- and hetero-oligomers which were, at least partially, thiol bridge mediated. Due to strong homo-oligomerization, the hetero-oligomers of Gn and Gc are likely to be mediated by homo-oligomeric subunits. A reversible pH-induced disappearance of a neutralizing epitope in Gc and dissociation of the Gn-Gc complex at pH values below 6.2 provide proteochemical evidence for the fusogenicity of Gc. Incomplete inactivation of virions at acidic pH indicates that additional factors are required for hantavirus fusion, as in the case of pestiviruses of the Flaviviridae. Based on similarities to class II fusion proteins, a structure model was created of hantavirus Gc using the Semliki Forest virus E1 protein as a template. In total, 10 binding regions for Gn were found by peptide scanning, of which five represent homotypic (Gn(I) to Gn(V)) and five represent heterotypic (Gc(I) to Gc(V)) interaction sites that we assign as intra- and interspike connections, respectively. In conclusion, the glycoprotein associations were compiled to a model wherein the surface of hantaviruses is formed of homotetrameric Gn complexes interconnected with Gc homodimers. This organization would create the grid-like surface pattern described earlier for hantaviruses in negatively stained electron microscopy specimens.


title: Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China.

text: Importance Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated. Objective To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died. Design, Setting, and Participants Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020. Exposures Confirmed COVID-19 pneumonia. Main Outcomes and Measures The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed. Results Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). Conclusions and Relevance Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.


title: A rapid and sensitive loop-mediated isothermal amplification procedure (LAMP) for Mycoplasma hyopneumoniae detection based on the p36 gene.

text: The aim of this study was to establish a method for sensitive and rapid diagnosis of Mycoplasma hyopneumoniae in clinical specimens. To this effect, we employed three sets of primers specifically designed for amplification of nucleic acids under isothermal conditions. After optimization of reaction conditions, M. hyopneumoniae could be successfully detected at 63°C in 45 min through use of the loop-mediated isothermal amplification (LAMP) assay. A positive reaction was identified visually as white precipitate and confirmed by gel electrophoresis. The detection limit for this assay was 10 copies/μL, as observed by electrophoretic analysis. The accuracy of the LAMP reaction was confirmed by restriction endonuclease digestion as well as by direct sequencing of the amplified product. This method can specifically detect M. hyopneumoniae; other species with high homology and other bacterial and virus strains gave negative results. To test the utility of this procedure, the LAMP assay was applied to 40 clinical samples collected from swine lung tissues experimentally challenged with M. hyopneumoniae isolates, and compared to the results from a real-time polymerase chain reaction (PCR) assay. A concordance of 100% was observed between the two assays. In conclusion, the results from our study demonstrated that the LAMP assay provided a rapid reaction and was inexpensive to perform, with no need of complex instruments or systems such as Geneamp PCR. The LAMP assay may therefore be applied in routine diagnosis in the clinical laboratory and for in-field detection of M. hyopneumoniae infection.


title: Special article: personal protective equipment for care of pandemic influenza patients: a training workshop for the powered air purifying respirator.

text: Virulent respiratory infectious diseases may present a life-threatening risk for health care professionals during aerosol-generating procedures, including endotracheal intubation. The 2009 Pandemic Influenza A (H1N1) brings this concern to the immediate forefront. The Centers for Disease Control and Prevention have stated that, when performing or participating in aerosol-generating procedures on patients with virulent contagious respiratory diseases, health care professionals must wear a minimum of the N95 respirator, and they may wish to consider using the powered air purifying respirator (PAPR). For influenza and other diseases transmitted by both respiratory and contact modes, protective respirators must be combined with contact precautions. The PAPR provides 2.5 to 100 times greater protection than the N95, when used within the context of an Occupational Safety and Health Administration-compliant respiratory protection program. The relative protective capability of a respirator is quantified using the assigned protection factor. The level of protection designated by the APF can only be achieved with appropriate training and correct use of the respirator. Face seal leakage limits the protective capability of the N95 respirator, and fit testing does not assure the ability to maintain a tight face seal. The protective capability of the PAPR will be defeated by improper handling of contaminated equipment, incorrect assembly and maintenance, and improper don (put on) and doff (take off) procedures. Stress, discomfort, and physical encumbrance may impair performance. Acclimatization through training will mitigate these effects. Training in the use of PAPRs in advance of their need is strongly advised. "Just in time" training is unlikely to provide adequate preparation for groups of practitioners requiring specialized personal protective equipment during a pandemic. Employee health departments in hospitals may not presently have a PAPR training program in place. Anesthesia and critical care providers would be well advised to take the lead in working with their hospitals' employee health departments to establish a PAPR training program where none exists. User instructions state that the PAPR should not be used during surgery because it generates positive outward airflow, and may increase the risk of wound infection. Clarification of this prohibition and acceptable solutions are currently lacking and need to be addressed. The surgical hood system is not an acceptable alternative. We provide on line a PAPR training workshop. Supporting information is presented here. Anesthesia and critical care providers may use this workshop to supplement, but not substitute for, the manufacturers' detailed use and maintenance instructions.


title: Robotically-assisted laparoscopic biliopancreatic diversion with duodenal switch: the utility of the robotic system in bariatric surgery.

text: Biliopancreatic diversion with duodenal switch (BPD/DS) is considered the most effective surgical option for morbidly obese patients. Several techniques have been described: open, laparoscopic, and the combination of open and laparoscopic. Only a few centers in the world perform robotically-assisted laparoscopic BPD/DS and the published literature is limited. We describe our experience using this technique as a safe alternative for treatment of morbid obesity. A review of a prospectively maintained database from 2008 to 2011 was conducted. A total of 107 consecutive patients (F:M = 83:24) were included in this series. Average age was 44.76 years (range 20-67), body mass index 49.97 kg/m(2) (range 37-70), and the number of preoperative comorbidities was 6.24 (range 3-11). The mean operative time for a typical BPD/DS with or without an appendectomy was 264 min (range 192-413), which increased to 298 min (range 210-463) when lysis of adhesion or additional procedures were performed. All study cases were completed using a minimally invasive approach. There were no intraoperative or 30-day major postoperative complications. Two patients returned to the operating room: one for endoscopic release of an inadvertently-sutured nasogastric tube during creation of the duodeno-ileal anastomosis and another patient for a port-site infection. Minor postoperative complications included carpal tunnel syndrome exacerbation (n = 1), which did not require surgical intervention. The median length of stay was 3.0 days (range 2-13). Two patients were readmitted within 30 day due to fluid retention and incarcerated umbilical hernia. The percentages of excess body weight loss (EBWL) at 1, 3, 6, 9, 12, and 18 months were 18.9, 36.4, 54.5, 67.4, 73.9, and 82.42 %, respectively. No mortality occurred in this study. Robotically-assisted laparoscopic technique for BPD/DS is a feasible, safe, and effective alternative for weight loss surgery with excellent outcomes.


title: Comparison of the Luminex xTAG respiratory viral panel with in-house nucleic acid amplification tests for diagnosis of respiratory virus infections.

text: Detection of respiratory viruses using sensitive real-time nucleic acid amplification tests (NATs) is invaluable for patient and outbreak management. However, the wide range of potential respiratory virus pathogens makes testing using individual real-time NATs expensive and laborious. The objective of this study was to compare the detection of respiratory virus targets using the Luminex xTAG respiratory viral panel (RVP) assay with individual real-time NATs used at the Provincial Laboratory of Public Health, Calgary, Alberta, Canada. The study included 1,530 specimens submitted for diagnosis of respiratory infections from December 2006 to May 2007. Direct-fluorescent-antigen-positive nasopharyngeal samples were excluded from this study. A total of 690 and 643 positives were detected by RVP and in-house NATs, respectively. Kappa correlation between in-house NATs and RVP for all targets ranged from 0.721 to 1.000. The majority of specimens missed by in-house NATs (96.7%) were positive for picornaviruses. Samples missed by RVP were mainly positive for adenovirus (51.7%) or respiratory syncytial virus (27.5%) by in-house NATs and in general had low viral loads. RVP allows for multiplex detection of 20 (and differentiation between 19) respiratory virus targets with considerable time and cost savings compared with alternative NATs. Although this first version of the RVP assay has lower sensitivity than in-house NATs for detection of adenovirus, it has good sensitivity for other targets. The identification of picornaviruses and coronaviruses and concurrent typing of influenza A virus by RVP, which are not currently included in our diagnostic testing algorithm, will improve our diagnosis of respiratory tract infections.


title: Patients' Experiences of Cardiovascular Health Education and Risk Communication: A Qualitative Synthesis.

text: Coronary heart disease (CHD) has no cure, and patients with myocardial infarction are at high risk for further cardiac events. Health education is a key driver for patients' understanding and motivation for lifestyle change, but little is known about patients' experience of such education. In this review, we aimed to explore how patients with CHD experience health education and in particular risk communication. A total of 2,221 articles were identified through a systematic search in five databases. 40 articles were included and synthesized using thematic analysis. Findings show that both "what" was communicated, and "the way" it was communicated, had the potential to influence patients' engagement with lifestyle changes. Communication about the potential of lifestyle change to reduce future risk was largely missing causing uncertainty, anxiety, and, for some, disengagement with lifestyle change. Recommendations for ways to improve health education and risk communication are discussed to inform international practice.


title: Metabolic profiling of endogenous bile acids: a novel method to assess hepatoprotective effect of Tanreqing capsule on carbon-tetrachloride-induced liver injury in rats.

text: Tanreqing (TRQ), a traditional Chinese medicine (TCM) formula, can alleviate liver injury and improve liver function. Its pharmacological mechanisms of actions are still unclear due to its complex components and multi-target natures. Metabolomic study is an effective approach to investigating drug pharmacological actions, new diagnostic markers, and potential mechanisms of actions. In the present study, a new strategy was used to evaluate the protective effect of TRQ capsule against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats, by analyzing metabolic profiling of endogenous bile acids (BAs) along with biochemical and histological analyses. BAs concentrations were determined by ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS). Principal component analysis and partial least squares discriminant analysis were then employed to analyze the UPLC-MS results and compare the hepatoprotective effect of TRQ capsule in different groups at the doses of 0.36, 1.44, and 2.88 g·kg-1 body weight, respectively. Moreover, our results suggested that taurocholic acid (TCA) and taurohyodesoxycholic acid (THDCA) were the most important biochemical markers, which were indicative of CCl4-induced acute hepatic damage and hepatoprotective effect of TRQ capsule. Therefore, this new strategy would be an excellent alternative method for evaluating hepatoprotective effect and proposing potential mechanisms of action for other drugs as well.


title: Translation of bone wax and its substitutes: History, clinical status and future directions.

text: Bone wax, primarily composed of beeswax and softening agent, is a century-old material used to control bleeding of disrupted bone surfaces by acting as a mechanical barrier to seal the wound. The current bone wax products are commonly packed in easy-to-open foil in the form of sterile sticks or plates, with excellent malleability and smooth consistency, enabling cost-effective and easy handling approach for bleeding control. It has also been reported that the inert nature of bone wax causes complications including foreign body reaction, infection promotion and bone healing inhibition. With the advances in biomaterials and the market boost of bone haemostatic materials, the arena of bone wax substitute research has expanded to a wide spectrum of material formulations and forms. However, the development of substitutes of bone wax for translation is a pivotal yet challenging topic because currently a potential candidate is recommended to be just as simple to use, effective and inexpensive to produce as traditional bone wax but also be absorbable and osteogenic. This review provides an overview of bone wax including its history, clinical applications and associated complication. In addition, emerging substitutes of bone wax and outlooks of future directions including the standardised evaluation methods are also discussed as an effort to catalyse the innovation and translation of bone haemostatic agents in the near future. The translational potential of this article: Occurrence of osseous haemorrhage is common in surgically incised or traumatically fractured bone. It is essential to stop bone bleeding to avoid further pathologic consequences such as tissue necrosis and eventually mortalities due to blood loss. Medical sterile bone wax is a classical material for haemostasis of bone during orthopaedic surgeries, thoracic surgeries, neurological surgeries and so on. Along with its widespread use, complications such as foreign body reaction, bone healing inhibition and infection promotion associated with bone wax are observed. With the growing knowledge in biomaterials and the boost of market of bone haemostatic materials, bone wax substitute research is thriving. An overview of bone and its substitutes together with evolution of their design criteria is carried out in this work, providing information for the innovation and translation of bone haemostatic agents in the near future.


title: Experiences of aging in place in the United States: protocol for a systematic review and meta-ethnography of qualitative studies.

text: BACKGROUND By 2035, older adults will outnumber children for the first time in the United States (US). In light of its aging population, the US has supported services focused on enabling older adults to continue living in their current homes, a model commonly described as "aging in place." The lived experience of aging in place is not well documented in existing systematic reviews. The aims of this systematic review are to synthesize and evaluate the existing qualitative evidence on experiences of aging in place in the US and identify knowledge gaps and directions for future studies. METHODS Six electronic bibliographic databases (PubMed, PsycINFO, CINAHL, Web of Science, EMBASE, and Sociological Abstracts) will be searched. Studies presenting qualitative data on the experiences of older adults currently aging in place in the US will be included. Covidence software will be used to screen studies and extract data. The Joanna Briggs Institute checklist for qualitative research will be used to assess quality and risk of bias of included studies. We will use meta-ethnography, following the method described by Noblit and Hare, to synthesize and evaluate the results of the included studies. DISCUSSION To the best of our knowledge, this is the first systematic review to integrate and synthesize the findings of qualitative studies of aging in place focusing on older adults in the US. The findings of this review will provide in-depth knowledge on lived experiences of aging in place and address important gaps in existing work. SYSTEMATIC REVIEW REGISTRATION International Prospective Register of Systematic Reviews (PROSPERO): CRD42018102847.


title: A comparison of leak compensation during pediatric noninvasive ventilation: a lung model study.

text: BACKGROUND Ventilators used for noninvasive ventilation (NIV) must be able to synchronize in the presence of system leaks. We compared the ability of 7 ICU ventilators and 3 dedicated NIV ventilators to compensate for leaks during pediatric NIV. METHODS Using a lung simulator, we compared the Maquet Servo-i, Dräger V500, Dräger Carina, Covidien PB840, Respironics V60, Respironics Vision, GE Healthcare/Engström Carestation, CareFusion Avea, Hamilton C3, and Hamilton G5 during increasing (n = 6) and decreasing leaks (n = 6). With a lung simulator we tested 4 leak levels (baseline [BL] 2-3 L/min, L1 5-6 L/min, L2 9-10 L/min, and L3 19-20 L/min); 3 patient weights (10, 20, and 30 kg); and 3 lung mechanics scenarios (normal, obstructive, and restrictive). The ventilator settings were NIV mode, pressure support of 10 cm H2O, and PEEP of 5 cm H2O. The synchronization rate (synchronized cycles/total simulated respirations) was recorded for each ventilator and each leak scenario. Synchronization was defined as triggering without auto-triggering, miss-triggering, delayed cycling, or premature cycling. RESULTS The mean synchronization rate across all ventilators was 68 ± 27% (range 23-96%) and marked differences existed between the ventilators (P < .001). Significant differences in synchronization rate were observed between the 10-kg model (mean 57 ± 30%, range 17-93%), the 20-kg model (69 ± 30%, 25-98%), and the 30-kg models (77 ± 22%, 28-97%) (P < .001). The synchronization rate for the obstructive model (60 ± 30%, 9-94%) was significantly different from the normal model (71 ± 29%, 18-98%) and the restrictive model (72 ± 28%, 23-98%) (P < .001). The PB840 and the C3 had synchronization rates over 90% overall across all body weights, all lung mechanic profiles, and all leak levels. CONCLUSIONS Leak compensation in NIV for pediatric use can partially compensate for leaks, but varies widely among ventilators, patient weights, and lung mechanics.


title: Residues of polybrominated diphenyl ethers in honeys from different geographic regions.

text: Polybrominated diphenyl ethers (PBDEs) are a class of widely used flame-retardants. Fifty honey samples labeled as being from different countries and regions were analyzed for 27 PBDE congeners. The concentrations of the 26 PBDEs, excluding BDE-209, ranged from 300 to 10,550 pg/g while the concentrations of BDE-209 ranged from nondetected to 9,260 pg/g. The honey samples labeled as originating in developed countries generally displayed higher concentrations of the total 27 PBDEs than those labeled as being from developing countries. Concentrations of 26 PBDEs ranged from 2,720 to 10,550 pg/g in honeys originating in developed countries and ranged from 1,030 to 3,470 pg/g in those from developing countries. BDE-209 was a dominant PBDE congener in all honey samples, on average accounting for 16% and 65% of the total 27 PBDEs in honeys from developed and developing countries, respectively. Honeys originating in developing countries, however, showed much higher BDE-209 levels and higher ratios of BDE-209 relative to the other PBDE congeners. In addition, some highly brominated PBDE congeners such as BDE-196, -197, -206, and -207 showed elevated concentrations in honeys from developing countries. The findings were in agreement with the long, heavy historical uses of PBDE products in developed countries and the current, heavy uses of BDE-209 in developing countries. When BDE-209 was fortified in honey and incubated in the dark for four weeks at 25 or 60 degrees C, BDE-153, -183, -206, and -207 were detected as debromination products of BDE-209. Less brominated congeners in honeys may primarily come from the environment. Debromination of BDE-209 is also a source of less brominated congeners in honeys. The detection of PBDEs in honeys suggests that human exposure to PBDEs occurs as a result of honey consumption.


title: Dysphagia Affecting Quality of Life in Cerebellar Ataxia-a Large Survey.

text: Dysphagia is a common symptom in neurodegenerative disorders and is generally associated with increased mortality. In the clinical care setting of ataxia patients, no systematical and standardized assessment of dysphagia is employed. Its impact on patients' health-related quality of life is not well understood. To assess the impact of dysphagia in ataxia patients on diet, body weight, and health-related quality of life. We conducted a large survey using self-reported questionnaires for swallowing-related quality of life (Swal-QOL) and a food frequency list in combination with retrospective clinical data of 119 patients with cerebellar ataxia treated in the neurological outpatient clinic of a large German university hospital. Seventeen percent of ataxia patients suffered from dysphagia based on the Swal-QOL score. Less than 1% of all patients reported dysphagia as one of their most disabling symptoms. Dysphagia was associated with unintentional weight loss (p = 0.02) and reduced health-related quality of life (p = 0.01) but did not affect individual nutritional habits (p > 0.05; Chi-squared test). Dysphagia is a relevant symptom in cerebellar ataxia. A systematic screening for dysphagia in patients with cerebellar ataxia would be desirable to enable early diagnosis and treatment.


title: Reference ranges and age-related changes of peripheral blood lymphocyte subsets in Chinese healthy adults.

text: This study was performed to build region-specific reference ranges of peripheral blood lymphocyte subsets for Chinese healthy adults from the young to the elderly and analyze the trends of changes in lymphocyte subsets for evaluating the impact of age on the values. 151 healthy adults aged 19-86 were recruited based on the SENIEUR protocol. Three sets of reference ranges were finally built applicable for the healthy young (19-44 years), middle-aged (45-64 years) and elder adults ([Symbol: see text]65). Comparisons in parameters among the three cohorts showed that a statistically significant increase in CD16CD56+ NK cell was observed between the middle-aged and elder cohorts, whereas for the majority of the parameters, a significant decline was observed between the young and the middle-aged cohorts. Further results showed that inverse correlations were observed between the age and CD19(+) B, CD3(+) T, CD3(+)CD4(+) T, CD4(+)CD45RA(+)CD62L(+) naïve T cell and CD4(+)CD28(+)/CD4(+), while the positive one was identified between the age and the NK cell. These significant changes of the most of immune parameters provided evidence for immunosenescence. Notably, T cell activation markers of CD8(+)CD38(+) and CD8(+)HLA-DR(+) showed reverse trends of association with age, which provides a clue for further researches on the mechanisms underlying the paradoxical clinical presentation of the elder patients.


title: Acute Respiratory Distress Syndrome Secondary to Radiotherapy for Breast Cancer: A Case Report.

text: BACKGROUND Radiotherapy is often used as an adjuvant therapy in breast cancer following surgical resection of the primary malignant tumor. It has multiple respiratory side effects, but acute respiratory distress syndrome (ARDS) is a rare complication. We describe here the case of a woman with breast cancer who developed ARDS 1 week after her final radiotherapy session. CASE REPORT A 69-year-old female with breast cancer presented 1 week after her final session of radiotherapy. She had developed a sudden onset of hypotension unresponsive to fluids, oxygen desaturation unresponsive to high flow oxygen, and new bilateral infiltrates had appeared on chest x-ray (CXR) predominant in the left upper lobe, which was interestingly the main area affected by the radiotherapy beams. A diagnosis of atypical ARDS secondary to radiotherapy was established. She was intubated and a low tidal volume/high positive end-expiratory pressure (PEEP) strategy was utilized to manage her condition. After 48 hours, the infiltrates diminished remarkably, and she was extubated the following day. On discharge, she had a completely normal CXR; a computed tomography (CT) chest performed 1 month later showed complete resolution of the alveolar opacities. CONCLUSIONS ARDS remains an extremely rare complication of thoracic radiotherapy. However, physicians must be wary of its development in order to diagnose it quickly and treat accordingly.


title: SARS-CoV-2 and COVID-19: between pathophysiology complexity and therapeutic uncertainty.

text: First isolated in China in early 2020, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for the ongoing pandemic of Coronavirus Disease 2019 (COVID-19). The disease has been spreading rapidly across the globe, with the largest burden falling on China, Europe and the United States. COVID-19 is a new clinical syndrome characterized by respiratory symptoms with variable degrees of severity, from mild upper respiratory illness to severe interstitial pneumonia and acute respiratory distress syndrome aggravated by thrombosis in pulmonary microcirculation. Three main phases of disease progression have been proposed for COVID-19: the early infection phase, the pulmonary phase and the hyperinflammation phase. Although current understanding of COVID-19 treatment mainly derives from small uncontrolled trials that are affected by a number of biases, strong background noise and a litany of confounding factors, emerging awareness suggests that drugs currently used to treat COVID-19 (antivirals, antimalarials, immunomodulators, anticoagulants, antibodies) should be evaluated in relation to the pathophysiology of disease progression. Drawing upon the international and Italian dramatic experiences, here we review the changing evolution of the disease and focus on current treatments uncertainties and new promising therapies.


Letter to the Editor.


The perpetual challenge of infectious diseases.


title: Strategic and Technical Considerations for the Endovascular Embolization of Intracranial Meningiomas.

text: Endovascular embolization is a frequently used adjunct to operative resection of meningiomas. Embolization may decrease intraoperative blood loss, operative time, and surgical difficulty associated with resection. The specific clinical applications of this treatment have not been defined clearly. Procedural indications, preferred embolic agent, and latency until tumor resection all differ across operators. It is clear that strategic patient selection, comprehensive anatomic understanding, and sound operative technique are critical to the success of the embolization procedure. This article reviews the management and technical considerations associated with preoperative meningioma embolization.


title: Periodontal tissue engineering by nano beta-tricalcium phosphate scaffold and fibroblast growth factor-2 in one-wall infrabony defects of dogs.

text: BACKGROUND AND OBJECTIVE Nanoparticle bioceramics are being investigated for biomedical applications. We fabricated a regenerative scaffold comprising type I collagen and beta-tricalcium phosphate (β-TCP) nanoparticles. Fibroblast growth factor-2 (FGF-2) is a bioeffective signaling molecule that stimulates cell proliferation and wound healing. This study examined the effects, on bioactivity, of a nano-β-TCP/collagen scaffold loaded with FGF-2, particularly on periodontal tissue wound healing. MATERIAL AND METHODS Beta-tricalcium phosphate was pulverized into nanosize particles (84 nm) and was then dispersed. A nano-β-TCP scaffold was prepared by coating the surface of a collagen scaffold with a nanosize β-TCP dispersion. Scaffolds were characterized using scanning electron microscopy, compressive testing, cell seeding and rat subcutaneous implant testing. Then, nano-β-TCP scaffold, nano-β-TCP scaffold loaded with FGF-2 and noncoated collagen scaffold were implanted into a dog one-wall infrabony defect model. Histological observations were made at 10 d and 4 wk postsurgery. RESULTS Scanning electron microscopy images show that TCP nanoparticles were attached to collagen fibers. The nano-β-TCP scaffold showed higher compressive strength and cytocompatibility compared with the noncoated collagen scaffold. Rat subcutaneous implant tests showed that the DNA contents of infiltrating cells in the nano-β-TCP scaffold and the FGF-2-loaded scaffold were approximately 2.8-fold and 3.7-fold greater, respectively, than in the collagen scaffold. Histological samples from the periodontal defect model showed about five-fold greater periodontal tissue repair following implantation of the nano-β-TCP scaffold loaded with FGF-2 compared with the collagen scaffold. CONCLUSION The β-TCP nanoparticle coating strongly improved the collagen scaffold bioactivity. Nano-β-TCP scaffolds containing FGF-2 are anticipated for use in periodontal tissue engineering.


title: Transcatheter CT arterial portography and CT hepatic arteriography for liver tumor visualization during percutaneous ablation.

text: PURPOSE To evaluate the feasibility of combining transcatheter computed tomography (CT) arterial portography or transcatheter CT hepatic arteriography with percutaneous liver ablation for optimized and repeated tumor exposure. MATERIALS AND METHODS Study participants were 20 patients (13 men and 7 women; mean age, 59.4 y; range, 40-76 y) with unresectable liver-only malignancies--14 with colorectal liver metastases (29 lesions), 5 with hepatocellular carcinoma (7 lesions), and 1 with intrahepatic cholangiocarcinoma (2 lesions)--that were obscure on nonenhanced CT. A catheter was placed within the superior mesenteric artery (CT arterial portography) or in the hepatic artery (CT hepatic arteriography). CT arterial portography or CT hepatic arteriography was repeatedly performed after injecting 30-60 mL 1:2 diluted contrast material to plan, guide, and evaluate ablation. The operator confidence levels and the liver-to-lesion attenuation differences were assessed as well as needle-to-target mismatch distance, technical success, and technique effectiveness after 3 months. RESULTS Technical success rate was 100%; there were no major complications. Compared with conventional unenhanced CT, operator confidence increased significantly for CT arterial portography or CT hepatic arteriography cases (P < .001). The liver-to-lesion attenuation differences between unenhanced CT, contrast-enhanced CT, and CT arterial portography or CT hepatic arteriography were statistically significant (mean attenuation difference, 5 HU vs 28 HU vs 70 HU; P < .001). Mean needle-to-target mismatch distance was 2.4 mm ± 1.2 (range, 0-12.0 mm). Primary technique effectiveness at 3 months was 87% (33 of 38 lesions). CONCLUSIONS In patients with technically unresectable liver-only malignancies, single-session CT arterial portography-guided or CT hepatic arteriography-guided percutaneous tumor ablation enables repeated contrast-enhanced imaging and real-time contrast-enhanced CT fluoroscopy and improves lesion conspicuity.


title: Outcomes of Laparoscopic Hiatal Hernia Repair in Nine Bariatric Patients with Prior Sleeve Gastrectomy.

text: BACKGROUND Laparoscopic sleeve gastrectomy (LSG) may exacerbate gastroesophageal reflux disease (GERD) in patients with a hiatal hernia (HH). Surgical repair may be needed, however prior LSG precludes standard HH repair with fundoplication. METHODS We retrospectively reviewed our experience with bariatric patients with prior LSG undergoing laparoscopic HH repair from August 2010 to July 2016. Patient demographics and outcomes including mortality, length of stay (LOS), readmission rates, reoperation, and complications were described. A validated 13-point questionnaire was used to determine symptomatic relief, weight loss, and overall satisfaction. RESULTS A total of nine consecutive patients with prior LSG underwent HH repair and were included in the analysis. Repair was performed using Bio-A Gore® mesh (W.L Gore Inc., Newark, DE) in six (66.7%) cases and posterior cruroplasty in three (33.3%) patients. Heartburn was significantly decreased at 1 year (1.4 ± 0.9 vs. 2.6 ± 0.9, p = 0.031), and 78% of patients reported some degree of symptomatic relief after HH repair. CONCLUSIONS Laparoscopic HH repair offers a safe and feasible approach in the management of persistent GERD after LSG in well-selected bariatric patients. Larger prospective studies are warranted to investigate the effectiveness of HH repair in this population as 22% of our patients did not demonstrate postoperative symptomatic improvement.


title: Prevalence of Covid-19 Infection and Subsequent Cohorting in a Residential Substance Use Treatment Program in Boston, MA.

text: OBJECTIVES The global pandemic of coronavirus disease 2019 (Covid-19) may disproportionately affect persons in congregate settings, including those in residential substance use treatment facilities. To limit the spread of SARS-CoV-2 through congregate settings, universal testing may be necessary. We aimed to determine the point prevalence of SARS-CoV-2 in a residential treatment program setting and to understand the unique challenges of Covid-19 transmission in this setting. METHODS We performed a case series of SARS-CoV-2 rT-PCR testing via nasopharyngeal in a residential substance use treatment program for women in Boston. Staff and residents of the treatment program were tested for SARS-CoV-2. The primary outcome was SARS-CoV-2 test result. RESULTS A total of 31 residents and staff were tested. Twenty-seven percent (6/22) of the residents and 44% (4/9) of staff tested positive for SARS-CoV-2. All of the SARS-CoV-2 positive residents resided in the same residential unit. Two positive cases resided together with two negative cases in a 4-person room. Two other positive cases resided together in a 2-person room. One positive case resided with two negative cases in a 3-person room. One positive case resided with a negative case in a 2-person room. Based on test results, residents were cohorted by infection status and continued to participate in addiction treatment on-site. CONCLUSIONS SARS-CoV-2 infection was common among staff and residents within a residential substance use treatment program for women in Boston. Universal SARS-CoV-2 testing in residential substance use programs can be instituted to reduce the risk of further transmission and continue addiction treatment programming when accompanied by adequate space, supplies, and staffing.


title: Mediastinoscopic extended thymectomy for pediatric patients with myasthenia gravis.

text: BACKGROUND Extended thymectomy is indicated for children with myasthenia gravis (MG) when drug-resistance or dependence is seen. We have employed a technique for mediastinoscopic extended thymectomy (MET) on children with MG. METHOD A total of 14 children underwent MET at Kanagawa Children's Medical Center between 2005 and 2013. A mediastinal operation field was made by a V-shaped hook infrasternally to extirpate the thymus with adipose tissue around the thymus. RESULTS The operation time and the amount of blood loss were 182±44 minutes and 34±43 ml, respectively. Postoperative complications, in the form of transient paralysis of the right recurrent nerve, occurred in 2 patients. The median length of postoperative hospital stay was 4.5 days. After MET, 6 patients achieved complete remission and 7 patients achieved steroid dose reduction, but no improvement was seen in 1 patient. CONCLUSIONS This procedure offers the advantage of good surgical access for dissection around the bilateral phrenic nerves in extended total thymectomy, while achieving good cosmetic results.


title: Clinical, angiographic and radiographic outcome differences among mechanical thrombectomy devices: initial experience of a large-volume center.

text: BACKGROUND AND PURPOSE Higher reperfusion rates have been established with endovascular treatment of acute ischemic stroke (AIS). There are limited data on the comparative performance of mechanical thrombectomy devices. METHODS A retrospective single-center analysis was undertaken of all consecutive patients who underwent thrombectomy using Merci, Penumbra or stent retrievers (SR) from September 2010 to November 2012. Baseline characteristics, rates of successful recanalization (modified Thrombolysis in Cerebral Infarction (mTICI) score 2b-3), symptomatic intracerebral hemorrhage (sICH), final infarct volume, 90-day mortality and independent functional outcomes at 90 days were compared across the three devices. RESULTS Our cohort included 287 patients. There were mild imbalances in baseline characteristics with trends towards higher National Institutes of Health Stroke Scale (NIHSS) score in patients in the Merci group (SR=18 vs Merci=21 vs Penumbra=19, p=0.06) and lower Alberta Stroke Program Early CT Score (ASPECTS) in patients in the SR group (>7: SR=51% vs Merci=61% vs Penumbra=62%, p=0.12). On univariate analysis there were no differences in the rate of sICH (SR=7% vs Merci=7% vs Penumbra=6%, p=0.921) and infarct volume (SR=61.5 mL vs Merci=69.5 mL vs Penumbra=59.2 mL, p=0.621). Trends towards better functional outcomes were found with Penumbra and SR vs Merci (41% vs 36% vs 25%, respectively, p=0.079). Complete or near complete reperfusion (mTICI 2b-3) was higher in the SR and Penumbra groups than in the Merci group (86% vs 78% vs 70%, respectively, p=0.027). Binary logistic regression showed that SR was an independent predictor of good functional outcome (OR 2.27, 95% CI 1.018 to 5.048; p=0.045). CONCLUSIONS Although our initial data confirm the superiority of SR technology over the Merci device, there was no significant difference in near complete/complete reperfusion, final infarct volumes or clinical outcomes between SR and Penumbra thromboaspiration.


title: The cysteine protease domain of porcine reproductive and respiratory syndrome virus non-structural protein 2 antagonizes interferon regulatory factor 3 activation.

text: There is growing evidence that porcine reproductive and respiratory syndrome virus (PRRSV) has developed mechanisms to subvert the host innate immune response. PRRSV non-structural protein 2 (Nsp2) was suggested previously as a potential interferon (IFN) antagonist. This study focused on Nsp2 to investigate its inhibitory mechanism of IFN induction. It was demonstrated that Nsp2 strongly inhibited IFN-β production by antagonizing activation of the IFN regulatory factor 3 (IRF-3) pathway induced by the Sendai virus (SeV). Further studies revealed that the cysteine protease domain (PL2) of Nsp2 was necessary for IFN antagonism. Additionally, both full-length Nsp2 and the PL2 protease domain of Nsp2 were found to inhibit SeV-induced phosphorylation and nuclear translocation of IRF-3. These findings suggest that Nsp2 is likely to play an important role in subversion of IRF-3-dependent innate antiviral defences, providing a basis for elucidating the mechanisms underlying PRRSV pathogenesis.


title: Preoxygenation with non-invasive ventilation versus high-flow nasal cannula oxygen therapy for intubation of patients with acute hypoxaemic respiratory failure in ICU: the prospective randomised controlled FLORALI-2 study protocol.

text: INTRODUCTION Endotracheal intubation in intensive care unit (ICU) is a procedure at high risk of life-threatening complications. Among them, severe oxygen desaturation, usually defined as a drop of pulse oxymetry (SpO2) below 80%, is the most common. Preoxygenation enables delaying oxygen desaturation occurring during apnea induced by anaesthetic drugs. Data suggest that non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) oxygen therapy could further increase PaO2 before intubation procedure and prevent oxygen desaturation episodes as compared with standard oxygen. However, no recommendation favours one technique rather than the other, since they have never been compared. Hence, whether a strategy of preoxygenation with NIV or HFNC is more effective than the other in patients with acute hypoxaemic respiratory failure remains to be established. METHODS AND ANALYSIS The FLORALI-2 study is a multicentre randomised controlled trial comparing a preoxygenation strategy with either NIV or HFNC in patients with acute hypoxaemic respiratory failure needing intubation in ICU. The 320 patients will be randomised with a ratio 1:1 in two groups according to the strategy of preoxygenation. The primary outcome is the occurrence of an episode of severe oxygen desaturation defined by a drop of SpO2 below 80% during the intubation procedure. Secondary outcomes include feasibility of the two strategies, immediate and late complications related to intubation. ETHICS AND DISSEMINATION The study has been approved by the central ethics committee (Ethics Committee Ouest-III, Poitiers, France) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER NCT02668458; Pre-results.


title: Identification and characterization of bocaviruses in cats and dogs reveals a novel feline bocavirus and a novel genetic group of canine bocavirus.

text: We report the identification and genome characterization of a novel bocavirus, feline bocavirus (FBoV), and novel bocaviruses closely related to canine bocavirus (CBoV) strain Con-161 in stray cats and dogs in Hong Kong, respectively. FBoV was detected by PCR in 7.2, 0.3, 1.6, 2.0 and 0.8% of faecal, nasal, urine, kidney and blood samples, respectively, from 364 cats, while CBoV was detected in 4.6, 5.1, 6.3 and 0.3% of faecal, nasal, urine and blood samples, respectively, from 351 dogs. Three FBoV genomes sequenced revealed the presence of three ORFs characteristic of bocaviruses. Phylogenetic analysis showed that FBoVs were related only distantly to other bocaviruses, forming a distinct cluster within the genus, with ≤ 5.7% nucleotide identities to the genome of minute virus of canines. The four CBoV genomes sequenced shared 87.4-89.2% nucleotide identities with that of CBoV strain Con-161. In addition to the three bocavirus ORFs, they encoded an additional ORF, ORF4, immediately downstream of the ORF for non-structural protein 1 (NS1), which was not found in other bocaviruses including CBoV strain Con-161. They also possessed a putative second exon encoding the C-terminal region of NS1 and conserved RNA-splicing signals, previously described in human bocaviruses. Partial VP1/VP2 sequence analysis of 23 FBoV and 25 CBoV strains demonstrated inter-host genetic diversity, with two potential genetic groups of FBoV and a novel CBoV group, CBoV-HK, distinct from the three groups, CBoV-A to -C, found in the USA. Although the pathogenicity of FBoV and CBoV remains to be determined, their presence in different host tissues suggested wide tissue tropism.


title: Interferon lambda genetic polymorphisms and viral infection: the tip of the iceberg?

text: Pathogen-host interaction studies have demonstrated the importance of host factors in the pathogenesis of infectious disease. An emerging theme is that polymorphisms in the genes encoding these factors can influence the host response to infection and the course of disease. Genetic variation affecting interferon lambda (IFN-λ) expression is now known to influence the outcome of both hepatitis C virus and herpes simplex virus type 1 infection in humans. IFN-λ is expressed at higher levels in organs with high epithelial cell content such as the respiratory and gastrointestinal tracts. Interestingly, data from animal models show that IFN-λ contributes to host control of viruses infecting these sites, including influenza A virus, severe acute respiratory syndrome coronavirus, and rotavirus. Furthermore, defective IFN-λ production by humans with asthma impairs the control of rhinovirus infection. We hypothesize that genetic variation of IFN-λ could potentially influence the course of disease during infection with many viruses that infect epithelial cells.


title: Laparoscopic adrenalectomy: An update.

text: OBJECTIVE To review the current role and outcome of laparoscopic adrenalectomy (LA) in the management of adrenal tumours. METHODS A Medline search using the keywords (adrenalectomy, laparoscopy, adrenal masses/tumours) was done for reports published between 1990 and 2011. Key articles were used to find more relevant references on the evaluation and laparoscopic management of adrenal masses. RESULTS The hormonal evaluation is not standardised, but initial screening tests are recommended and followed with confirmatory ones when positive, equivocal or the clinical presentation suggest adrenal hyperfunction. The imaging studies had, and continued to, advance, especially computed tomography (CT), magnetic resonance imaging and positron-emission tomography/CT. These advances have increased the accuracy of the diagnosis of adrenal masses, with a reported high sensitivity and specificity of 95-100%. The introduction of laparoscopy has resulted in more adrenal lesions being removed, especially incidental lesions smaller than the 5-6 cm that was previously the indication for surgical excision. The technique has developed and larger lesions of >6 cm are now considered for LA in the proper setting. The transperitoneal and retroperitoneal approaches are currently widely practised, with minor differences in the outcome. The reported outcome, although mostly retrospective, is excellent and with fewer complications. The role of LA for adrenal malignancy should be considered cautiously. Preoperative imaging signs of invasion into surrounding structures should be considered a contraindication for LA. CONCLUSION LA is the standard procedure for most adrenal lesions of appropriate size and no signs of surrounding tissue invasion, giving an excellent outcome.


title: Genetically modified live attenuated vaccine: a potential strategy to combat visceral leishmaniasis.

text: Visceral leishmaniasis (VL) is caused by a protozoan parasite Leishmania donovani mainly influencing the population of tropical and subtropical regions across the globe. The arsenal of drugs available is limited, and prolonged use of such drugs makes parasite to become resistant. Therefore, it is very imperative to develop a safe, cost-effective and inexpensive vaccine against VL. Although in recent years many strategies have been pursued by researchers, but so far only some of the vaccine candidates reached for clinical trial and more than half of them are still in pipeline. There is now a broad consent among Leishmania researchers that the perseverance of parasite is very essential for eliciting a protective immune response and may perhaps be attained by live attenuated parasite vaccination. For making a live attenuated parasite it is very essential to ensure that the parasite is deficient of virulence and should further study genetically modified parasites to perceive the mechanism of pathogenesis. So it is believed that in the near future, a complete understanding of the Leishmania genome will explore clear strategies to discover a novel vaccine. This review describes the need for a genetically modified live attenuated vaccine against VL, and obstacles associated with its development.


title: Feline gastrointestinal surgery: principles and essential techniques.

text: PRACTICAL RELEVANCE Gastrointestinal (GI) surgical procedures are performed commonly in cats in general practice for both diagnostic and treatment purposes. It is essential that the surgeon understands and adheres to the principles of GI surgery in order that postoperative morbidity and mortality are kept to a minimum. AUDIENCE This review is aimed at feline and general practitioners wanting to update their core skills in GI surgery. It discusses anatomical considerations and surgical principles, and aims to familiarise the surgeon with techniques (some well established, others newer) that will help to promote surgical success. EQUIPMENT Standard general surgical equipment is required, together with the facilities to provide adequate pre-, intra- and postoperative patient care. EVIDENCE BASE The author draws on clinical experience and evidence from the literature, where appropriate, in reviewing the guidance and techniques under discussion.


title: Uniportal and single-incision video-assisted thoracic surgery: the state of the art.

text: Over the past decade, uniportal video-assisted thoracic surgery (VATS) has evolved dramatically into a sophisticated technique capable of performing some of the most complex thoracic procedures. The idea of operating through fewer surgical incisions and, therefore, with potentially better cosmesis, less postoperative pain and paraesthesia, has led to uniportal VATS increasing in popularity worldwide. The uniportal approach demands instrument design to be better suited for operating with multiple instruments through a single small incision. Furthermore, the drive by surgeons and industry to develop novel, smaller, more specialized procedure-specific instruments for uniportal VATS to further allow reduction in incision size is relentless. Refinement of uniportal VATS instruments, angulated and narrower endostaplers, and improvements in video-camera systems, including 3D systems, and 120° articulating lens will make uniportal VATS major lung resection easier to perform and learn. In the future, we could see the development of subcostal or e-NOTES access, endorobotic arms that open and operate within the chest cavity, and cross-discipline imaging assistance for uniportal VATS procedures.


title: Jejunostomy-technique and controversies.

text: Malnutrition is quite common in patients with esophageal cancer, and can be secondary to tumor related dysphagia or treatment side effects. Traditionally, open feeding jejunostomy tube was performed in all patients undergoing surgical treatment of esophageal cancer. With the advent of minimally invasive approaches, placement of the jejunostomy tube can be currently accomplished with either robotic or laparoscopic assistance. Here, we discuss the technical aspects as well as the pros and cons of a minimally invasive jejunostomy feeding tube placement.


title: Recent advances in pulse oximetry.

text: Conventional pulse oximetry uses two wavelengths of light (red and infrared) transmitted through a finger and a photodetector to analyze arterial hemoglobin oxygen saturation and pulse rate. Recent advances in pulse oximetry include: extended analysis of the photo plethysmographic waveform; use of multiple wavelengths of light to quantify methemoglobin, carboxyhemoglobin and total hemoglobin content in blood; and use of electronic processes to improve pulse oximeter signal processing during conditions of low signal-to-noise ratio. These advances have opened new clinical applications for pulse oximeters that will have an impact on patient monitoring and management.


title: Oral Ribavirin for the Treatment of Noninfluenza Respiratory Viral Infections: A Systematic Review.

text: OBJECTIVE To review clinical outcomes data for patients treated with oral ribavirin for noninfluenza respiratory viral infections (NIRVIs). DATA SOURCES MEDLINE, EMBASE, and PubMed Central (1972 to June 1, 2015) were queried with the following search term combinations: "Oral" AND "ribavirin" AND ("respiratory syncytial virus" OR "metapneumovirus" OR "parainfluenza" OR "coronavirus" OR "rhinovirus" OR "enterovirus" OR "adenovirus"). STUDY SELECTION AND DATA EXTRACTION Included studies must have characterized the clinical outcomes of a cohort of patients treated with oral ribavirin for symptomatic NIRVIs. Case reports and series with <5 cases, conference abstracts, and articles written in languages other than English were excluded. DATA SYNTHESIS Of the 1256 unique reports, 15 met inclusion criteria: 12 retrospective, 3 prospective, and 3 comparative with untreated control groups. All studies except for 2 Middle East respiratory syndrome coronavirus (MERS-CoV) studies were in immunocompromised patients (9 malignancy/stem cell transplant, 4 lung transplant). The mortality rate ranged from 0% to 31% in malignancy/stem cell transplant recipients treated with oral ribavirin, and 1/108 (0.9%) ribavirin-treated lung transplant recipients died at 30 days. Three studies (one each for malignancy, lung transplant, and MERS-CoV) suggested a clinical outcomes benefit with oral ribavirin compared with supportive care alone; however, the nonrandomized design precludes efficacy determination. Hemolysis was the most common adverse reaction, occurring in 14% (54/375) of patients. Ribavirin was discontinued in 4% of patients secondary to adverse reactions. CONCLUSIONS Oral ribavirin should be considered for the treatment of NIRVI in immunocompromised adults (malignancy/stem cell transplant or lung transplant) or adults with MERS-CoV.


title: A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3).

text: Rationale Early reperfusion in patients experiencing acute ischemic stroke is effective in patients with large vessel occlusion. No randomized data are available regarding the safety and efficacy of endovascular therapy beyond 6 h from symptom onset. Aim The aim of the study is to demonstrate that, among patients with large vessel anterior circulation occlusion who have a favorable imaging profile on computed tomography perfusion or magnetic resonance imaging, endovascular therapy with a Food and Drug Administration 510 K-cleared mechanical thrombectomy device reduces the degree of disability three months post stroke. Design The study is a prospective, randomized, multicenter, phase III, adaptive, blinded endpoint, controlled trial. A maximum of 476 patients will be randomized and treated between 6 and 16 h of symptom onset. Procedures Patients undergo imaging with computed tomography perfusion or magnetic resonance diffusion/perfusion, and automated software (RAPID) determines if the Target Mismatch Profile is present. Patients who meet both clinical and imaging selection criteria are randomized 1:1 to endovascular therapy plus medical management or medical management alone. The individual endovascular therapist chooses the specific device (or devices) employed. Study outcomes The primary endpoint is the distribution of scores on the modified Rankin Scale at day 90. The secondary endpoint is the proportion of patients with modified Rankin Scale 0-2 at day 90 (indicating functional independence). Analysis Statistical analysis for the primary endpoint will be conducted using a normal approximation of the Wilcoxon-Mann-Whitney test (the generalized likelihood ratio test).


The COVID-19 pand-ECMO-ic.


MITS: an interim step towards improved cause of death data.


title: Gamma Knife surgical treatment for partially embolized cerebral arteriovenous malformations.

text: OBJECTIVE A combination of embolization and radiosurgery is used as a common strategy for the treatment of large and complex cerebral arteriovenous malformations (AVMs). This study presents the experiences of partially embolized cerebral AVMs followed by Gamma Knife surgery (GKS) and assesses predictive factors for AVM obliteration and hemorrhage. METHODS The interventional neuroradiology database that was reviewed included 404 patients who underwent AVM embolization. Using this database, the authors retrospectively analyzed all partially embolized AVM cases followed by GKS for a residual nidus. Except for cases of complete AVM obliteration, the authors excluded all patients with radiological follow-up of less than 2 years. Logistic regression analysis was used to analyze the predictive factors related to AVM obliteration and hemorrhage following GKS. Kaplan-Meier analysis was used to evaluate the obliteration with a cutoff AVM nidus volume of 3 cm(3) and 10 cm(3). RESULTS One hundred sixty-two patients qualified for the study. The median patient age was 26 years and 48.8% were female. Hemorrhage presented as the most common symptom (48.1%). The median preembolization volume of an AVM was 14.3 cm(3). The median volume and margin dose for GKS were 10.92 cm(3) and 16.0 Gy, respectively. The median radiological and clinical follow-up intervals were 47 and 79 months, respectively. The annual hemorrhage rate was 1.71% and total obliteration rate was 56.8%. Noneloquent area (p = 0.004), superficial location (p < 0.001), decreased volume (p < 0.001), lower Spetzler-Martin grade (p < 0.001), lower Virginia Radiosurgery AVM Scale (RAS; p < 0.001), lower Pollock-Flickinger score (p < 0.001), lower modified Pollock-Flickinger score (p < 0.001), increased maximum dose (p < 0.001), and increased margin dose (p < 0.001) were found to be statistically significant in predicting the probability of AVM obliteration in the univariate analysis. In the multivariate analysis, only volume (p = 0.016) was found to be an independent prognostic factor for AVM obliteration. The log-rank (Mantel-Cox) test of the Kaplan-Meier analysis (chi-square = 54.402, p < 0.001) showed a significantly decreased obliteration rate of different cutoff AVM volume groups of less than 3 cm(3), 3-10 cm(3), and more than 10 cm(3). No independent prognostic factor was found for AVM hemorrhage in multivariate analysis. CONCLUSIONS Partially embolized AVMs are amenable to successful treatment with GKS. The volume of the nidus significantly influences the outcome of radiosurgical treatment. The Virginia RAS and Pollock-Flickinger score were found to be reliable scoring systems for selection of patient candidates and prediction of partially embolized AVM closure and complications for GKS.


title: Long-term Effects of Pyrethrin and Cyfluthrin, a Type II Synthetic Pyrethroid, Insecticide Applications on Bull Reproductive Parameters.

text: The objectives of this study were to determine effects of cyfluthrin and pyrethrin spray products, used in combination with cyfluthrin topical and ear tag applications, on bull reproductive parameters over 18 weeks. Angus or Angus x Simmental bulls were randomly assigned to one of three treatment groups: (i) no exposure to pyrethrins/cyfluthrin (CONT; n = 10), (ii) cyfluthrin ear tag and topical applications (ET; n = 10), or (iii) cyfluthrin ear tag, topical, premise spray and pyrethrin fog spray applications (ET+S; n = 8). Bull body weight was measured every 3 week, and body condition score and scrotal circumference were recorded on weeks 0, 9 and 18. Semen and serum were collected every 3 weeks for sperm evaluation and testosterone measurement, respectively. There was a treatment × week interaction (p < 0.01) for sperm with primary defects; bulls in CONT group had a greater (p = 0.01) percentage of sperm with primary defects than bulls treated with insecticides at week 18. Overall and progressive sperm motility, normal sperm morphology, secondary sperm defects and serum testosterone concentrations changed (p < 0.01) over time in all bulls; however, treatment did not affect (p ≥ 0.13) any of these parameters. There were also no treatment effects (p ≥ 0.08) on bull body weight, body condition score or scrotal circumference. The use of pyrethrin- and cyfluthrin-based insecticides, regardless of application, did not negatively affect reproductive parameters in beef bulls when administered over 18 weeks.


Earth Day at 50.


title: Genetically diverse coronaviruses in captive bird populations in a Brazilian zoological park.

text: This study aimed to investigate the occurrence of coronaviruses (CoVs) in captive birds placed inside a zoological park in Brazil. The role of captive birds in the epidemiology of CoVs in the tropics is poorly understood. A total of 25 (n=25) different species were tested for viral RNA using individual fecal samples collected from healthy birds. Reverse transcription-polymerase chain reaction targeting the 3' untranslated region was used to detect CoV RNA, and positive samples were submitted for sequence analysis. The phylogenetic search revealed nine mutations in the black shouldered peafowl (Pavus cristatus) CoV sequence, which clustered separately from samples previously described in England. This is the first report on the detection of the CoV genome in captive birds in Brazil.


title: Delineating antibody recognition against Zika virus during natural infection.

text: Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that shares a considerable degree of homology with dengue virus (DENV). Here, we examined longitudinal antibody response against ZIKV during natural infection in 2 convalescent individuals. By decomposing the antibody recognition into DI/DII and DIII of the E glycoprotein, we showed their development in humans followed a spatiotemporal hierarchy. Plasma binding to DI/DII appeared to peak and wane during early infection with extensive cross-reactivity with DI/DII of DENV. Binding to DIII, however, peaked early but persisted months into the infection without detectable cross-reactivity with DIII of DENV. A clear trend of increase in DIII-specific neutralizing activity was observed over the course of infection. mAbs isolated during early infection are largely DI/DII specific, weakly neutralizing, and highly cross-reactive with DENV, while those from later infection are more diverse in recognition, potently neutralizing, and ZIKV specific. The most potent neutralizing mAb targeting the DIII provided 100% protection in mice from lethal ZIKV infection and could therefore serve as a promising candidate for antibody-based therapy and prevention. The dynamic features unveiled here will assist us to better understand the pathogenesis of ZIKV infection and inform rational design of vaccines.


title: A brief report of toxicity end points of HER2 vaccines for the treatment of patients with HER2+ breast cancer.

text: Human epidermal growth factor receptor 2 (HER2)-targeted vaccines are under development, but have so far demonstrated only modest clinical efficacy. Additionally, there has been a lack of adequate safety assessment in large-scale prospective clinical trials. Therefore, we performed a meta-analysis of available clinical trial data to summarize the toxicity profiles of these treatments. Literature search was conducted in February 2018. The trials analyzed had at least one study arm consisting of HER2 vaccine monotherapy. Heterogeneity across studies was analyzed using I 2 statistics. Data were analyzed using random-effects meta-analysis for absolute risk (AR). Eight trials and 248 patients were included. There was no evidence of heterogeneity between studies for grades 3/4 adverse events (AEs) or for death. The AR for treatment-related serious AEs was 5% with no treatment-related deaths. The AR of all-grade fatigue, injection site reaction, and fever/chills/rigors was 33%, 23%, and 31%, respectively. Asymptomatic drop in left ventricle ejection fraction was rare (8%). HER2 vaccines are well tolerated with increased AR of fatigue, injection site reactions, and fever/chills/rigors.


title: Symptomatic SARS-CoV-2 infections display specific IgG Fc structures.

text: The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a public health crisis that is exacerbated by our poor understanding of correlates of immunity. SARS-CoV-2 infection can cause Coronavirus Disease 2019 (COVID-19), with a spectrum of symptoms ranging from asymptomatic carriage to life threatening pneumonia and cytokine dysregulation [1-3]. Although antibodies have been shown in a variety of in vitro assays to promote coronavirus infections through mechanisms requiring interactions between IgG antibodies and Fc gamma receptors (FcγRs), the relevance of these observations to coronavirus infections in humans is not known [4-7]. In light of ongoing clinical trials examining convalescent serum therapy for COVID-19 patients and expedited SARS-CoV-2 vaccine testing in humans, it is essential to clarify the role of antibodies in the pathogenesis of COVID-19. Here we show that adults with PCR-diagnosed COVID-19 produce IgG antibodies with a specific Fc domain repertoire that is characterized by reduced fucosylation, a modification that enhances interactions with the activating FcγR, FcγRIIIa. Fc fucosylation was reduced when compared with SARS-CoV-2-seropositive children and relative to adults with symptomatic influenza virus infections. These results demonstrate an antibody correlate of symptomatic SARS-CoV-2 infections in adults and have implications for novel therapeutic strategies targeting FcγRIIIa pathways.


title: NS-based live attenuated H1N1 pandemic vaccines protect mice and ferrets.

text: Although vaccines against influenza A virus are the most effective method to combat infection, it is clear that their production needs to be accelerated and their efficacy improved. We generated live attenuated human influenza A vaccines (LAIVs) by rationally engineering mutations directly into the genome of a pandemic-H1N1 virus. Two LAIVs (NS1-73 and NS1-126) were based on the success of LAIVs for animal influenza A viruses. A third candidate (NSΔ5) is a unique NS-mutant that has never been used as a LAIV. The vaccine potential of each LAIV was determined through analysis of attenuation, interferon production, immunogenicity, and their ability to protect mice and ferrets. This study demonstrates that NSΔ5 is an ideal LAIV candidate, provides important information on the effects that different NS mutations have on the pandemic-H1N1 virus and shows that LAIVs can be engineered directly from the genomes of emerging/circulating influenza A viruses.