title: Detection of antigenic heterogeneity in feline coronavirus nucleocapsid in feline pyogranulomatous meningoencephalitis.

text: A new monoclonal antibody (mAb), CCV2-2, was compared with the widely used FIPV3-70 mAb, both directed against canine coronavirus (CCoV), as a diagnostic and research tool. Western blot showed that both anti-CCoV mAbs only reacted with a protein of 50 kD, a weight consistent with the feline coronavirus (FCoV) viral nucleocapsid. A competitive inhibition enzyme-linked immunosorbent assay showed that the 2 recognized epitopes are distinct. Preincubation of CCV2-2 mAb with FCoV antigen suppressed the immunostaining. Formalin-fixed, paraffin-embedded sections from brains of 15 cats with the dry form of feline infectious peritonitis (FIP) were examined by immunohistochemistry. Immunohistochemistry was performed with both anti-CCoV mAbs, either on consecutive or on the same sections. A myeloid-histiocytic marker, MAC 387, was also used to identify FIP virus-infected cells. In all regions where MAC 387-positive cells were present, positive staining with the CCV2-2 mAb was systematically detected, except at some levels in 1 cat. In contrast, none or only a few cells were positive for the FIPV3-70 mAb. Double immunostaining showed macrophages that were immunopositive for either CCV2-2 alone or alternatively for CCV2-2 and FIPV3-70 mAbs. This reveals the coexistence of 2 cohorts of phagocytes whose FIP viral contents differed by the presence or absence of the FIPV3-70-recognized epitope. These findings provide evidence for antigenic heterogeneity in coronavirus nucleocapsid protein in FIP lesions, a result that is in line with molecular observations. In addition, we provide for the first time morphologic depiction of viral variants distribution in these lesions.


Pediatric airway scope is available for gastric tube insertion in adult patients.


title: Role of Fixation and Postoperative Regimens in the Long-Term Outcomes of Distal Chevron Osteotomy: A Randomized Controlled Two-by-Two Factorial Trial of 100 Patients.

text: The necessity of chevron osteotomy fixation is controversial and evidence for the effectiveness of postoperative regimens is limited. In a prospective, randomized study, we compared the long-term results of 2 operative techniques (osteotomy fixation versus no fixation) and 2 postoperative regimens (a soft cast versus an elastic bandage) in 100 patients who underwent surgery for hallux valgus. Clinical evaluations with the American Orthopaedic Foot and Ankle Society (AOFAS) scale scoring were performed at baseline and 6 weeks, 6 months, 1 year, and a mean of 7.9 years postoperatively. The mean AOFAS function score were better in the group treated without osteotomy fixation and with an elastic bandage at 6 weeks postoperatively, but the differences then disappeared. The total AOFAS scores improved significantly in all 4 subgroups during the first 12 months; however, in the long term, some deterioration occurred. In the AOFAS scores, the average function, alignment, and total points were significantly worse when the preoperative hallux valgus angles exceeded 30°. The incidence of complication was low (1%); there was 1 superficial wound infection. The AOFAS score did not differ statistically among the groups in our population. An elastic bandage for postoperative treatment is recommended. The risk of recurrence is greater and functional result worse if the preoperative hallux valgus angle exceeds 30°.


title: Long-term response of Dictyota dichotoma var. intricata (C. Agardh) Greville (Phaeophyceae) to ocean acidification: Insights from high pCO2 vents.

text: The ocean acidification may severely affect macroalgal communities of the shallowest coastal habitats where they play relevant structural and functional roles. In this paper were investigated the physiological traits of two populations of Dictyota dichotoma var. intricata, living at two different pH for several generations to assess the reasons of the algae reduced abundance at current (8.1) compared to low pH (6.7). Besides, through transplant experiments, the two populations were analysed for the stress response and reversibility of physiological performance at different pH. The long-term acclimation to high pCO2/low pH favours an ecotype characterised by low energetic costs, higher photochemical efficiency and more resistance to the oxidative stress, compared to individuals living at current pH. These traits promoted the growth and reproduction of the community living at pH 6.7, favouring a lower macroalgal diversity, but a higher ecological success under ocean acidification. The similar behaviour observed between Dictyota living at pH 6.7 and transplanted thalli from pH 6.7 to 8.1, suggested a high tolerance to pH changes in the short-term. On the contrary, adaptive responses may have favoured molecular adjustments on the long-term, as showed by the significant differences between the wild populations at pH 8.1 and 6.7. The overall data indicate that both plasticity and adaptive mechanisms may be the reasons for the success of the brown seaweeds under future high pCO2/low pH. The plasticity due to photochemistry adjustments is likely involved in the early response to environmental changes. Conversely, modifications in the photosynthetic biochemical machinery suggest that more complex adaptive mechanisms occurred in the current population of Dictyota living at pH 6.7. Further studies on population genetics will reveal if any differentiation is taking place at the population level or a local adaptation has already occurred in Dictyota and other brown algae under chronic low pH.


Mesoscale coordination constructs.


Effect of Coronavirus Disease 2019 and Pandemics on Global Surgical Outreach.


title: A left-to-right shunt via the ductus arteriosus is associated with increased regional cerebral oxygen saturation during neonatal transition.

text: BACKGROUND Oxygen delivery to the brain is dependent on cardiac output and arterial oxygen content. OBJECTIVES The study was designed to investigate the influence of a left-to-right shunt via the ductus arteriosus (DA) on regional oxygen saturation (rSO2) of the brain and peripheral tissue during postnatal transition. METHODS Nested case-control study. In term neonates after elective cesarian section, rSO2 of the brain and pre- and postductal peripheral tissue were measured 15 min after uncomplicated postnatal transition. Two groups were formed according to shunt flow characteristics via the DA: shunt group (with a left-to-right shunt), and nonshunt group (no shunt). RESULTS Of 80 infants, in 58 (72%) a left-to-right shunt was identified, and in 22 (28%) no flow was seen via the DA. The 22 infants formed the nonshunt group. They were matched with 22 newborn infants with a left-to-right shunt via the DA (shunt group). Infants in the nonshunt group had significantly lower cerebral rSO2 values and higher fractional tissue oxygen extraction and heart rate values. There were no significant differences in regard to peripheral rSO2 values. CONCLUSION During postnatal transition, term infants with a left-to-right shunt via the DA have significantly higher cerebral rSO2 values compared to infants without shunt flow.


title: Comparative biodistribution of 12 ¹¹¹In-labelled gastrin/CCK2 receptor-targeting peptides.

text: PURPOSE Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in various tumours such as medullary thyroid carcinomas and small-cell lung cancers. Due to this high expression, CCK-2 receptors might be suitable targets for radionuclide imaging and/or radionuclide therapy. Several CCK-2 receptor-binding radiopeptides have been developed and some have been tested in patients. Here we aimed to compare the in vivo tumour targeting properties of 12 (111)In-labelled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated gastrin/CCK2 receptor-binding peptides. METHODS Two CCK8-based peptides and ten gastrin-based peptide analogues were tested. All peptides were conjugated with DOTA and labelled with (111)In. Biodistribution studies were performed in mice with subcutaneous CCK2/gastrin receptor-expressing tumours and with receptor-negative tumours contralaterally. Biodistribution was studied by counting dissected tissues at 1 and 4 h after injection. RESULTS Both the CCK analogues displayed relatively low tumour uptake (approximately 2.5%ID/g) as compared to minigastrin analogues. Two linear minigastrin peptides (MG0 and sargastrin) displayed moderate tumour uptake at both 1 and 4 h after injection, but also very high kidney uptake (both higher than 48%ID/g). The linear MG11, lacking the penta-Glu sequence, showed lower tumour uptake and also low kidney uptake. Varying the N-terminal Glu residues in the minigastrin analogues led to improved tumour targeting properties, with PP-F11 displaying the optimal biodistribution. Besides the monomeric linear peptides, a cyclized peptide and a divalent peptide were tested. CONCLUSION Based on these studies, optimal peptides for peptide receptor radionuclide targeting of CCK2/gastrin receptor-expressing tumours were the linear minigastrin analogue with six D-Glu residues (PP-F11), the divalent analogue MGD5 and the cyclic peptide cyclo-MG1. These peptides combined high tumour uptake with low kidney retention, and may therefore be good candidates for future clinical studies.


title: GapMind: Automated Annotation of Amino Acid Biosynthesis.

text: GapMind is a Web-based tool for annotating amino acid biosynthesis in bacteria and archaea (http://papers.genomics.lbl.gov/gaps). GapMind incorporates many variant pathways and 130 different reactions, and it analyzes a genome in just 15 s. To avoid error-prone transitive annotations, GapMind relies primarily on a database of experimentally characterized proteins. GapMind correctly handles fusion proteins and split proteins, which often cause errors for best-hit approaches. To improve GapMind's coverage, we examined genetic data from 35 bacteria that grow in defined media without amino acids, and we filled many gaps in amino acid biosynthesis pathways. For example, we identified additional genes for arginine synthesis with succinylated intermediates in Bacteroides thetaiotaomicron, and we propose that Dyella japonica synthesizes tyrosine from phenylalanine. Nevertheless, for many bacteria and archaea that grow in minimal media, genes for some steps still cannot be identified. To help interpret potential gaps, GapMind checks if they match known gaps in related microbes that can grow in minimal media. GapMind should aid the identification of microbial growth requirements.IMPORTANCE Many microbes can make all of the amino acids (the building blocks of proteins). In principle, we should be able to predict which amino acids a microbe can make, and which it requires as nutrients, by checking its genome sequence for all of the necessary genes. However, in practice, it is difficult to check for all of the alternative pathways. Furthermore, new pathways and enzymes are still being discovered. We built an automated tool, GapMind, to annotate amino acid biosynthesis in bacterial and archaeal genomes. We used GapMind to list gaps: cases where a microbe makes an amino acid but a complete pathway cannot be identified in its genome. We used these gaps, together with data from mutants, to identify new pathways and enzymes. However, for most bacteria and archaea, we still do not know how they can make all of the amino acids.


title: Conservative management of pelvic abscess following sacrocolpopexy: a report of three cases and review of the literature.

text: INTRODUCTION AND HYPOTHESIS After sacrocolpopexy, intra-abdominal pelvic abscesses are often managed with intravenous antibiotics, excision of the mesh involved, and debridement of compromised tissue. METHODS AND RESULTS Three cases of successful management of pelvic abscesses after sacrocolpopexy using long-term antibiotics and percutaneous drainage of intra-abdominal abscesses without removing the mesh are presented. CONCLUSIONS In selected patients who have undergone sacrocolpopexy, with careful counseling, conservative management of pelvic abscesses with percutaneous drainage and long-term antibiotic treatment without the surgical excision of the mesh may play a role.


title: Recent advances in understanding the pathogenesis of Lawsonia intracellularis infections.

text: Proliferative enteropathy is an infectious disease caused by an obligate intracellular bacterium, Lawsonia intracellularis, and characterized by thickening of the intestinal epithelium due to enterocyte proliferation. The disease is endemic in swine herds and has been occasionally reported in various other species. Furthermore, outbreaks among foals began to be reported on breeding farms worldwide within the past 5 years. Cell proliferation is directly associated with bacterial infection and replication in the intestinal epithelium. As a result, mild to severe diarrhea is the major clinical sign described in infected animals. The dynamics of L. intracellularis infection in vitro and in vivo have been well characterized, but little is known about the genetic basis for the pathogenesis or ecology of this organism. The present review focuses on the recent advances regarding the pathogenesis and host-pathogen interaction of L. intracellularis infections.


title: Glutathione and multidrug resistance protein transporter mediate a self-propelled disposal of bismuth in human cells.

text: Glutathione and multidrug resistance protein (MRP) play an important role on the metabolism of a variety of drugs. Bismuth drugs have been used to treat gastrointestinal disorder and Helicobacter pylori infection for decades without exerting acute toxicity. They were found to interact with a wide variety of biomolecules, but the major metabolic pathway remains unknown. For the first time (to our knowledge), we systematically and quantitatively studied the metabolism of bismuth in human cells. Our data demonstrated that over 90% of bismuth was passively absorbed, conjugated to glutathione, and transported into vesicles by MRP transporter. Mathematical modeling of the system reveals an interesting phenomenon. Passively absorbed bismuth consumes intracellular glutathione, which therefore activates de novo biosynthesis of glutathione. Reciprocally, sequestration by glutathione facilitates the passive uptake of bismuth and thus completes a self-sustaining positive feedback circle. This mechanism robustly removes bismuth from both intra- and extracellular space, protecting critical systems of human body from acute toxicity. It elucidates the selectivity of bismuth drugs between human and pathogens that lack of glutathione, such as Helicobacter pylori, opening new horizons for further drug development.


B-cell chronic lymphocytic leukaemia presenting as lower motor neuron disease and SS.


Provision of e-learning programmes to replace undergraduate medical students' clinical general practice attachments during COVID-19 stand-down: a student perspective.


A map and new directions for the (pro)renin receptor in the brain: focus on "A role of the (pro)renin receptor in neuronal cell differentiation".


title: Alert for non-respiratory symptoms of Coronavirus Disease 2019 (COVID-19) patients in epidemic period: A case report of familial cluster with three asymptomatic COVID-19 patients.

text: At present, Coronavirus Disease 2019 (COVID-19) is rampaging around the world. However, asymptomatic carriers intensified the difficulty of prevention and management. Here we reported the screening, clinical feathers, and treatment process of a family cluster involving three COVID-19 patients. The discovery of the first asymptomatic carrier in this family cluster depends on the repeated and comprehensive epidemiological investigation by disease control experts. In addition, the combination of multiple detection methods can help clinicians find asymptomatic carriers as early as possible. In conclusion, the prevention and control experience of this family cluster showed that comprehensive rigorous epidemiological investigation and combination of multiple detection methods were of great value for the detection of hidden asymptomatic carriers. This article is protected by copyright. All rights reserved.


title: [Recommendations for general surgery clinical practice in 2019 coronavirus disease situation].

text: The 2019 coronavirus disease(COVID-19) is a highly infectious disease, has a long incubation period and a variety of clinical manifestations, which has a significant impact on public health and life. Afterwards, scientific and standardized work processing during the epidemic is of great significance for prevention and control. In order to implement the central government's decision-making deployment and defeat the COVID-19 as soon as possible, we had focused on the key points in the clinical work of general surgery according to latest relevant guidelines, literature and experience in epidemic prevention. Finally, we drafted the prevention and control strategies and recommendations to make a reference for medical staff of general surgery to fight against COVID-19.


Diaphragm electrical activity monitoring as a breakpoint in the management of a tetraplegic child.


Risk factors for anticoagulant thromboprophylaxis failure in critically ill patients.


Intensive care medicine: new insights to improve care.


title: Genetic predisposition to respiratory infection and sepsis.

text: Genetic variations, in part, determine individual susceptibility to sepsis and pneumonia. Advances in genetic sequence analysis as well as high throughput platform analysis of gene expression has allowed for a better understanding of immunopathogenesis during sepsis. Differences in genes can also modulate immune and inflammatory response during sepsis thereby translating to differences in clinical outcomes. An increasing number of candidate genes have been implicated to play a role in sepsis susceptibility, most of which are controversial with few exceptions. This does not refute the significance of genetic polymorphisms in sepsis, but rather highlights the difficulties and pitfalls related to genetic association studies. These difficulties include differences in study design such as heterogeneous patient cohorts and differences in pathogenic organisms, linkage disequilibrium, and lack of power for detailed haplotype analysis or examination of gene-gene interactions. There is extensive diversity in the pathways of inflammation and immune response during sepsis making it even harder to prove the functional and clinical significance of one single genetic polymorphism which could be easily masqueraded or compensated by other upstream or downstream events of the pathway involved. The majority of studies have analysed candidate genes in isolation from other possible polymorphisms. It is likely that susceptibility to sepsis is the result of polymorphisms from multiple genes rather than one single mutation. Future studies should aim for multi-centered collaborative approach looking at genome wide association or gene profiling to provide a more complete appraisal of the key genetic players in determining genetic susceptibility to sepsis. This review paper will summarise the prominent candidate gene polymorphisms with known functional changes or those with haplotype data. In addition, a summary of the expanding research in the field of epigenetics and post-sepsis immunosuppression will be discussed.


title: Closure of a direct inguinal hernia defect in laparoscopic repair with barbed suture: a simple method to prevent seroma formation?

text: PURPOSE Seroma is a frequent postoperative complication after laparoscopic direct inguinal hernia repair (both in TAPP and TEP). There are several methods to address this problem; however, these techniques are not without problems. The purpose of this study was to introduce and evaluate a new technique to address this problem. METHODS This is a prospective study of consecutive patients. All patients diagnosed with direct inguinal hernias eligible for laparoscopic repair were included. A single surgeon performed all the included operations. During laparoscopic inguinal hernia repair (TAPP or TEP), we closed the direct hernia defect with barbed sutures around the transversalis fascia, inverted the apex of the attenuated transversalis fascia, and sutured it at the base to completely eradicate the defect cavity. Prosthetic mesh was not additionally fixed in all patients. The primary postoperative outcome parameter was seroma formation, and secondary outcome parameters included groin pain, surgical complications, and hernia recurrence. RESULTS Twenty-five male patients with 36 sides of direct hernias were included in this study, and all procedures were carried out laparoscopically and successfully. Only one patient developed significant seroma, which resolved 1 month later. The early postoperative pain was minimal, and no recurrence and chronic pain occurred during the follow-up period (4-13 months). CONCLUSIONS The present direct inguinal hernia defect closing technique with barbed suture is a simple, easily reproducible, and effective method for the prevention of seroma formation.


title: Sarcomatoid Squamous Cell Carcinoma of the Renal Pelvis Masquerading as Emphysematous Pyelonephritis with Staghorn Calculus.

text: BACKGROUND Staghorn calculi are well-established risk factors for recurrent urinary tract infections (UTIs) and subsequent renal deterioration. Less commonly, long-term urothelial irritation from a calculus may also pose a risk of malignant transformation. CASE PRESENTATION A 77-year-old male with multiple medical comorbidities presented with a chronic right renal pelvic staghorn calculus and findings concerning for emphysematous pyelonephritis. He was subsequently taken to the operating room for a planned laparoscopic right nephrectomy. Final pathology analysis revealed sarcomatoid squamous cell carcinoma (SCC) of the renal pelvis with superimposed pyelonephritis and renal abscesses. Preoperative imaging was not suggestive of malignancy. CONCLUSION Although SCC of the urothelium can be caused by chronic irritation, its presentation is usually isolated to the lower urinary tract and is rarely encountered in the renal pelvis. Our patient's presentation with sarcomatoid SCC is an even rarer entity. Chronic staghorn calculi must be considered as a potential risk factor for the development of both UTI and malignant urothelial transformation.


title: Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff.

text: BACKGROUND In epidemics of highly infectious diseases, such as Ebola Virus Disease (EVD) or Severe Acute Respiratory Syndrome (SARS), healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Contact precautions by means of personal protective equipment (PPE) can reduce the risk. It is unclear which type of PPE protects best, what is the best way to remove PPE, and how to make sure HCW use PPE as instructed. OBJECTIVES To evaluate which type of full body PPE and which method of donning or doffing PPE have the least risk of self-contamination or infection for HCW, and which training methods increase compliance with PPE protocols. SEARCH METHODS We searched MEDLINE (PubMed up to 15 July 2018), Cochrane Central Register of Trials (CENTRAL up to 18 June 2019), Scopus (Scopus 18 June 2019), CINAHL (EBSCOhost 31 July 2018), and OSH-Update (up to 31 December 2018). We also screened reference lists of included trials and relevant reviews, and contacted NGOs and manufacturers of PPE. SELECTION CRITERIA We included all controlled studies that compared the effects of PPE used by HCW exposed to highly infectious diseases with serious consequences, such as Ebola or SARS, on the risk of infection, contamination, or noncompliance with protocols. This included studies that used simulated contamination with fluorescent markers or a non-pathogenic virus.We also included studies that compared the effect of various ways of donning or doffing PPE, and the effects of training in PPE use on the same outcomes. DATA COLLECTION AND ANALYSIS Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We planned to perform meta-analyses but did not find sufficiently similar studies to combine their results. MAIN RESULTS We included 17 studies with 1950 participants evaluating 21 interventions. Ten studies are Randomised Controlled Trials (RCTs), one is a quasi RCT and six have a non-randomised controlled design. Two studies are awaiting assessment.Ten studies compared types of PPE but only six of these reported sufficient data. Six studies compared different types of donning and doffing and three studies evaluated different types of training. Fifteen studies used simulated exposure with fluorescent markers or harmless viruses. In simulation studies, contamination rates varied from 10% to 100% of participants for all types of PPE. In one study HCW were exposed to Ebola and in another to SARS.Evidence for all outcomes is based on single studies and is very low quality.Different types of PPEPPE made of more breathable material may not lead to more contamination spots on the trunk (Mean Difference (MD) 1.60 (95% Confidence Interval (CI) -0.15 to 3.35) than more water repellent material but may have greater user satisfaction (MD -0.46; 95% CI -0.84 to -0.08, scale of 1 to 5).Gowns may protect better against contamination than aprons (MD large patches -1.36 95% CI -1.78 to -0.94).The use of a powered air-purifying respirator may protect better than a simple ensemble of PPE without such respirator (Relative Risk (RR) 0.27; 95% CI 0.17 to 0.43).Five different PPE ensembles (such as gown vs. coverall, boots with or without covers, hood vs. cap, length and number of gloves) were evaluated in one study, but there were no event data available for compared groups.Alterations to PPE design may lead to less contamination such as added tabs to grab masks (RR 0.33; 95% CI 0.14 to 0.80) or gloves (RR 0.22 95% CI 0.15 to 0.31), a sealed gown and glove combination (RR 0.27; 95% CI 0.09 to 0.78), or a better fitting gown around the neck, wrists and hands (RR 0.08; 95% CI 0.01 to 0.55) compared to standard PPE.Different methods of donning and doffing proceduresDouble gloving may lead to less contamination compared to single gloving (RR 0.36; 95% CI 0.16 to 0.78).Following CDC recommendations for doffing may lead to less contamination compared to no guidance (MD small patches -5.44; 95% CI -7.43 to -3.45).Alcohol-based hand rub used during the doffing process may not lead to less contamination than the use of a hypochlorite based solution (MD 4.00; 95% CI 0.47 to 34.24).Additional spoken instruction may lead to fewer errors in doffing (MD -0.9, 95% CI -1.4 to -0.4).Different types of trainingThe use of additional computer simulation may lead to fewer errors in doffing (MD -1.2, 95% CI -1.6 to -0.7).A video lecture on donning PPE may lead to better skills scores (MD 30.70; 95% CI 20.14,41.26) than a traditional lecture.Face to face instruction may reduce noncompliance with doffing guidance more (OR 0.45; 95% CI 0.21 to 0.98) than providing folders or videos only.There were no studies on effects of training in the long term or on resource use.The quality of the evidence is very low for all comparisons because of high risk of bias in all studies, indirectness of evidence, and small numbers of participants. AUTHORS' CONCLUSIONS We found very low quality evidence that more breathable types of PPE may not lead to more contamination, but may have greater user satisfaction. Alterations to PPE, such as tabs to grab may decrease contamination. Double gloving, following CDC doffing guidance, and spoken instructions during doffing may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than video or folder based training. Because data come from single small studies with high risk of bias, we are uncertain about the estimates of effects.We still need randomised controlled trials to find out which training works best in the long term. We need better simulation studies conducted with several dozen participants to find out which PPE protects best, and what is the safest way to remove PPE. Consensus on the best way to conduct simulation of exposure and assessment of outcome is urgently needed. HCW exposed to highly infectious diseases should have their use of PPE registered and should be prospectively followed for their risk of infection in the field.


title: Gastric bypass leads to improvement of diabetic neuropathy independent of glucose normalization--results of a prospective cohort study (DiaSurg 1 study).

text: OBJECTIVE Surprisingly, 40% to 95% of patients with type 2 diabetes mellitus (T2DM) show early remission of hyperglycemia after obesity surgery. It is unknown to what extent other diabetes-associated comorbidities such as distal peripheral neuropathy (DPN) might be influenced by obesity surgery. This pilot study aimed at providing further evidence for the impact of Roux-en-Y gastric bypass (RYGB) on both glycemic control and DPN in non-severely obese patients with insulin-dependent T2DM. METHODS In the present prospective cohort study, 20 patients with long-standing, insulin-dependent T2DM and a body mass index (BMI) between 25 and 35 kg/m underwent laparoscopic RYGB. Body mass index, glycosylated hemoglobin (HbA1c), and DPN [quantified by the Neuropathy Symptom Score (NSS) and the Neuropathy Deficit Score (NDS)] were investigated. RESULTS Six months after surgery, the preoperative BMI of 32.8 ± 2.1 kg/m (mean ± standard deviation) dropped to 25.6 ± 2.5 kg/m (P < 0.001). Preoperative HbA1c levels decreased from 8.5 ± 1.2% to 7.1 ± 1.2% (P < 0.001), with 15% of patients having a normalized HbA1c level lower than 6.2%. Of 12 patients with documented DPN, the median NSS was 8 (range, 0-10) preoperatively and 0 (range, 0-9) postoperatively (P = 0.004), with 8 patients scoring an NSS of 0. The median NDS was 6 (range, 2-8) preoperatively and 4 (range, 0-8) postoperatively (P = 0.027), with 1 patient scoring an NDS of 0. All patients had an improvement or normalization in either 1 or both scores. CONCLUSIONS As expected, BMI and HbA1c levels improved significantly after RYGB. More interestingly, neuropathy scores, such as NSS and NDS, improved significantly early after surgery. Symptomatic neuropathy was completely reversible in 67% of the patients. These findings add further evidence to the fact that RYGB might be a valuable treatment option not only for improving glycemic control but also for reducing diabetes-associated comorbidities, such as DPN. This points to a complex metabolic effect of RYGB that exceeds glucose normalization. However, the results still need to be confirmed in controlled trials.


title: Spinal/epidural block as an alternative to general anesthesia for laparoscopic appendectomy: a prospective randomized clinical study.

text: Introduction Laparoscopic appendectomy (LA) has been generally performed under general anesthesia. Laparoscopic appendectomy is rarely performed under regional anesthesia because of pneumoperitoneum-related problems. Aim To compare spinal/epidural anesthesia (SEA) and general anesthesia (GA) during LA with respect to perioperative and postoperative adverse events and postoperative pain. Material and methods Fifty patients, aged 18-65, who underwent LA, were randomly allocated to two groups: the GA (n = 25) and SEA (n = 25) groups. Perioperative and postoperative adverse events, postoperative pain level, and patient satisfaction were compared between the groups. Results None of the patients needed conversion to an open procedure or conversion from SEA to GA. In the SEA group we encountered shoulder pain in 6 (24%) patients, abdominal discomfort/pain in 4 (16%) patients, anxiety in 4 (16%) patients, and hypotension in 2 (8%) patients intraoperatively. Also, post-spinal headache was observed in 5 (20%) patients in the SEA group. Postoperative right shoulder pain was significantly higher in the GA group compared to the SEA group (32% vs. 8%; p = 0.037). In the SEA group the incidence of urinary retention and in the GA group the incidence of postoperative nausea and vomiting (PONV) were higher, but these differences were not statistically significant. The postoperative surgical pain level was significantly lower in the SEA group (p < 0.001). Conclusions Spinal/epidural anesthesia is effective and safe in ASA I healthy patients undergoing LA. Less postoperative pain, PONV and shoulder pain are the advantages of SEA compared to GA.


title: Knowledge about bacterial and viral pathogens present in wild mammals in Chile: a systematic review.

text: This study organizes all available information about viral and bacterial pathogens of wild mammals in Chile. This was done in order to identify pathogens that have been well-documented and recognize those that have not been properly studied, determine the number of articles that have been published annually about this topic and identify regions in Chile that concentrate the highest and lowest number of studies concerning viral and bacterial pathogens. A total of 67 scientific articles published in peer-reviewed journals from 1951 to 2018 were selected for revision. Results indicate that the number of publications has increased per decade but there are years in which no articles were published. Most studies addressed Leptospira, rabies, hantavirus, Mycobacterium avium paratuberculosis (MAP) and distemper. Rodentia, Carnivora, Chiroptera and Cetartiodactyla were the most studied mammal orders. Information about presence/absence of pathogens was found for 44 wild mammal species. Research was mainly carried out in central and southern Chile and the most commonly employed methods for pathogen diagnosis were serology and molecular techniques. Overall, research in wild mammals has been directed towards the evaluation of zoonotic diseases, while vector-borne and non-zoonotic diseases have been mostly neglected by the scientific community over the years.


Providing surgery for cancer during the COVID-19 pandemic: experience of a northern Italian referral centre.


title: Gastroesophageal reflux in laparoscopic sleeve gastrectomy: hiatal findings and their management influence outcome.

text: BACKGROUND Sleeve gastrectomy (SG) has become a definitive treatment for morbid obesity. There is conflicting evidence on the effects of SG on gastroesophageal reflux disease (GERD). OBJECTIVE The objective of this study was to assess whether taking an aggressive approach to managing hiatal weakness in patients undergoing SG results in an alteration in GERD symptoms. SETTING Tertiary public hospital and private hospital, Sydney, Australia. METHODS Patients undergoing laparoscopic extended (beginning within 2 cm from pylorus) SG were included. If evidence of weakness was present, an anterior hiatal dissection and tight suture repair was performed. If a hiatus hernia was present, formal repair was undertaken. Patients were questioned and scored on preoperative and postoperative reflux symptom frequency and severity, proton pump inhibitor (PPI) usage, current weight, and satisfaction. RESULTS A continuous cohort of 262 patients experienced a significant reduction in heartburn frequency (P = .035) and severity (P = .017). Moderate/severe preoperative reflux (Visick score 3 and 4) often improved whether there was a defect requiring repair or not (no repair P = .02, hiatal suture P = .001, hiatus hernia repair P<.001). The severity of symptoms also improved (no repair P = 0.005, hiatal suture P<.001, hiatus hernia repair P< .001). CONCLUSION Moderate or severe preexisting gastroesophageal reflux improved for most of our obese patients undergoing an extended SG when hiatal defects were routinely repaired. Moderate to severe preoperative reflux also improved in the average obese patient when there was no hiatal defect to repair.


title: The effect of blinding on estimates of mortality in randomised clinical trials of intensive care interventions: protocol for a systematic review and meta-analysis.

text: INTRODUCTION Evidence exists that unblinded randomised clinical trials (RCTs) overestimate intervention effects compared with blinded RCTs. It has been suggested that this is less pronounced for objective (ie, not subject to interpretation) outcome measures, including mortality. This may not apply in the intensive care unit (ICU), as most deaths are preceded by decisions to withhold or withdraw treatments. Lack of blinding of physicians in RCTs of ICU interventions may potentially influence the decision towards a higher threshold for discontinuing treatment in patients who receive the investigational treatment and/or a lower threshold for discontinuing treatment in patients who receive the comparator (control). This may have important implications for patients, caregivers, researchers and society. Accordingly, we aim to assess whether lack of blinding affects mortality effect estimates in RCTs of ICU interventions. METHODS AND ANALYSIS We will conduct a systematic review with meta-analyses and assess the effect of blinding versus no blinding on mortality effect estimates in RCTs of interventions used in adult ICU patients.We will systematically search the Cochrane Library for systematic reviews reporting mortality effect estimates of any intervention used in adult ICU patients which includes at least one RCT with 'low risk of bias' in the bias domains 'blinding of participants and personnel' and/or 'blinding of outcome assessment' and one RCT with 'unclear' or 'high risk of bias' in the same bias domain(s). For each intervention, we will compare summary mortality effect estimates in blinded versus unblinded trials. ETHICS AND DISSEMINATION This research does not require ethical approval as we will use summary data from trials already approved by relevant ethical institutions. We will report the results in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and submit the final paper to an international peer-reviewed journal. TRIAL REGISTRATION NUMBER PROSPERO, registration number: CRD42017056212.


title: Frailty measurement and outcomes in interventional studies: protocol for a systematic review of randomised control trials.

text: INTRODUCTION Frailty is associated with reduced functional capacity, decreased resistance to stressors and is predictive of a range of adverse health outcomes, including dependency, hospitalisation and mortality. Early identification of frailty may prevent, reduce and postpone adverse health outcomes. However, there is a need for additional evidence to guide decision-making for the care of frail patients since frail persons are frequently excluded from studies, the differential impact of frailty is often not examined in clinical trials and few large-scale clinical trials examining frail cohorts have been conducted. Randomised control trials (RCTs) published to date have used a diverse range of definitions of frailty, as well as a variety of outcome measures. The objective of this systematic review is to comprehensively characterise the frail populations enrolled and the end points reported in frailty RCTs. METHODS AND ANALYSIS We will identify all RCTs reporting on the outcome of interventions in adult (age ≥18 years) frail populations as defined by authors, in all settings of care. Databases will include MEDLINE, CINAHL, EMBASE, PsycInfo, Global Health, the Joanna Briggs database and Cochrane Library. Two reviewers will independently determine trial eligibility. For each included trial, we will conduct duplicate independent data extraction, inter-rater reliability, risk of bias assessment and evaluation of the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. ETHICS AND DISSEMINATION This systematic review will comprehensively identify RCTs including frail patients to identify how frailty is measured and which outcomes are reported. The results of this systematic review may inform clinicians caring for persons with frailty, facilitate conduct of future RCTs and inform future efforts to develop common data elements and core outcomes for frailty studies. Our findings will be disseminated through conference presentation and publication in peer-reviewed journals. PROSPERO REGISTRATION NUMBER CRD42017065233.


title: In vitro and in vivo evaluation of an innocuous drug cocktail to improve the quality of folic acid targeted nuclear imaging in preclinical research.

text: Folate receptor (FR) targeting is an attractive strategy for nuclear imaging of cancer and activated macrophages through application of folic acid radioconjugates. However, significant renal accumulation of folate radioconjugates and hence exceedingly high emission of radiation from the kidneys may mask uptake of radioactivity at sites of interest such as small metastases in the abdominal region of animal models of ovarian cancer. Recently it was observed that the antifolate pemetrexed (PMX) reduces undesired renal uptake of radiofolates. A disadvantage of this strategy is the fact that pemetrexed is a chemotherapeutic agent which may have toxic side effects. The aims of this study were therefore to investigate whether the desired effect of PMX to reduce renal accumulation of folate radioconjugates would be maintained if it was applied as a cocktail together with its antidote, thymidine, and to explore whether thymidine was an effective rescue agent against PMX's related toxicity in vitro and in vivo. In vitro internalization of (67)Ga-EC0800 was investigated using FR-positive KB tumor cells and embryonic monkey MA104 kidney cells in the absence and presence of PMX alone and in combination with thymidine. Uptake of (67)Ga-EC0800 into KB cells was increased by coincubation of the cells with PMX. In contrast uptake of (67)Ga-EC0800 into MA104 cells was reduced under the same conditions. In both cell lines coincubation of thymidine did not change the results obtained with PMX. Biodistribution and SPECT/CT imaging studies of (67)Ga-EC0800 were performed with KB tumor bearing mice injected with PMX alone or with a cocktail of PMX and thymidine. The radiofolate's kidney uptake reducing effect of PMX in mice was maintained also if PMX was employed together with its antidote thymidine. The tumor uptake of (67)Ga-EC0800 remained unchanged independent of the administration of PMX or a combination of PMX and thymidine. The effect of thymidine to abrogate PMX-induced cytotoxicity was demonstrated in vitro with an MTT assay using KB and MA104 cells. Cell viability was reduced to 50% (KB cells) and 70% (MA104 cells) of untreated controls if PMX (5 μM and 15 μM, respectively) was coincubated. Addition of thymidine (10 μM or 100 μM) compensated PMX's toxic effects in a dose-dependent manner. The effect of thymidine was also investigated in non-tumor bearing mice treated with high-dosed PMX. Rescue of mice with side effects after the third and fourth cycles of PMX application (1 mg/mouse) was achieved by application of thymidine (20 mg/mouse) at five consecutive days starting the day of PMX injection. Application of PMX together with thymidine as a cocktail is effective to improve the tissue distribution of radiofolates while preventing pharmacological and potentially toxic side effects of the chemotherapeutic agent PMX. These findings open new perspectives for folate-based nuclear imaging in preclinical research potentially allowing longitudinal investigations and monitoring therapies in animal models of cancer and inflammatory diseases.


title: Antimycobacterial and antioxidant activities of reserpine and its derivatives.

text: In view of the attributed medicinal properties of reserpine, a number of acyl reserpine derivatives were prepared and tested for antimycobacterial activity against Mycobacterium tuberculosis, strain H(37)Rv and antioxidant activities. The results indicated that in the case of antimycobacterial activity, 10 out of 18 derivatives caused more inhibition than that caused by reserpine itself. The results of antioxidant activity revealed that acylation in benzene ring of reserpine decreases the percentage inhibition of DPPH in all the derivatives compared to the parent compound.


Covid-19: a digital epidemic.


title: Evaluation of fibrin sealant for biologic mesh fixation at the hiatus in a porcine model.

text: BACKGROUND The ideal method to secure biologic mesh during laparoscopic hiatal hernia repair remains uncertain. Suture or tack fixation can be technically difficult, and serious cardiovascular complications have been reported. Fibrin sealant (FS) offers a potential solution to this problem. We hypothesized that FS provides comparable mesh fixation to suture repair during laparoscopic mesh hiatoplasty. STUDY DESIGN Using a porcine model, laparoscopic hiatal hernia repair was performed with suture reapproximation of the crura and reinforcement with an acellular porcine dermal matrix. Prior to repair, animals were randomized to mesh fixation with sutures (S) or FS. After 30-day survival, an esophagram was performed, the diaphragm harvested, and mesh position, fixation, and incorporation were evaluated histologically and biomechanically using a T-peel test. RESULTS Twenty (10 S and 10 FS) laparoscopic hiatal hernia repairs were performed. Total operative time was significantly less in the FS group (74.7 versus 127.0 min, p < 0.01). There were no instances of mesh migration in any animal. Mean peel force did not differ significantly between the S and FS groups (0.21 vs. 0.18 N/mm, respectively; p = 0.49). There was no significant difference in cellular repopularization or inflammatory changes around the mesh. CONCLUSIONS Fibrin sealant offers a reasonable alternative to suturing biologic mesh during laparoscopic hiatal hernia repair with equivalent mesh fixation. At 30 days it provides adhesive strength similar to suture fixation, while significantly reducing operative time.


title: Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19.

text: OBJECTIVE To test the hypothesis that COVID-19 has an impact on the CNS by measuring plasma biomarkers of CNS injury. METHODS We recruited 47 patients with mild (n=20), moderate (n=9) or severe (n=18) COVID-19 and measured two plasma biomarkers of CNS injury by Single molecule array (Simoa): neurofilament light chain protein (NfL) (a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp) (a marker of astrocytic activation/injury) in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with 33 age-matched controls derived from an independent cohort. RESULTS The patients with severe COVID-19 had higher plasma concentrations of GFAp (p=0.001) and NfL (p<0.001) than controls, while GFAp was also increased in patients with moderate disease (p=0.03). In severe patients an early peak in plasma GFAp decreased upon follow-up (p<0.01) while NfL showed a sustained increase from first to last follow-up (p<0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury. CONCLUSION We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19-related CNS damage, and its relation to both clinically-defined CNS events such as hypoxic and ischemic events and to mechanisms more closely linked to systemic SARS-CoV-2 infection and consequent immune activation, and also to evaluate the clinical utility of monitoring plasma NfL and GFAp in management of this group of patients.


title: Ethnic variations in morbidity and mortality from lower respiratory tract infections: a retrospective cohort study.

text: OBJECTIVE There is evidence of substantial ethnic variations in asthma morbidity and the risk of hospitalisation, but the picture in relation to lower respiratory tract infections is unclear. We carried out an observational study to identify ethnic group differences for lower respiratory tract infections. DESIGN A retrospective, cohort study. SETTING Scotland. PARTICIPANTS 4.65 million people on whom information was available from the 2001 census, followed from May 2001 to April 2010. MAIN OUTCOME MEASURES Hospitalisations and deaths (any time following first hospitalisation) from lower respiratory tract infections, adjusted risk ratios and hazard ratios by ethnicity and sex were calculated. We multiplied ratios and confidence intervals by 100, so the reference Scottish White population's risk ratio and hazard ratio was 100. RESULTS Among men, adjusted risk ratios for lower respiratory tract infection hospitalisation were lower in Other White British (80, 95% confidence interval 73-86) and Chinese (69, 95% confidence interval 56-84) populations and higher in Pakistani groups (152, 95% confidence interval 136-169). In women, results were mostly similar to those in men (e.g. Chinese 68, 95% confidence interval 56-82), although higher adjusted risk ratios were found among women of the Other South Asians group (145, 95% confidence interval 120-175). Survival (adjusted hazard ratio) following lower respiratory tract infection for Pakistani men (54, 95% confidence interval 39-74) and women (31, 95% confidence interval 18-53) was better than the reference population. CONCLUSIONS Substantial differences in the rates of lower respiratory tract infections amongst different ethnic groups in Scotland were found. Pakistani men and women had particularly high rates of lower respiratory tract infection hospitalisation. The reasons behind the high rates of lower respiratory tract infection in the Pakistani community are now required.


title: Prophylactic mesh vs suture in the closure of the umbilical trocar site after laparoscopic cholecystectomy in high-risk patients for incisional hernia. A randomized clinical trial.

text: BACKGROUND Prosthetic repair has become the standard method for hernia repair. Mesh placement for the prevention of trocar site incisional hernia (TSIH) is still a controversial issue. We tested the hypothesis that closure with an intraperitoneal prophylactic mesh of the umbilical trocar after a laparoscopic cholecystectomy can reduce the incidence of a TSIH in high-risk patients. STUDY DESIGN A randomized clinical trial was conducted among patients undergoing elective laparoscopic cholecystectomy who presented the following high-risk factors for incisional hernia, according to the literature: age 65 years and older, diabetes mellitus, chronic pulmonary disease, and obesity (ie, body mass index ≥30 kg/m(2)). Patients were assigned to have closure of the umbilical trocar site with either nonabsorbable sutures (group A) or intraperitoneal polypropylene omega-3 mesh (group B). Trocar site incisional hernia, pain, and surgical complications were evaluated at the early postoperative course and at 1, 6, and 12 months after surgery. RESULTS A total of 106 patients were randomized into the study and 92 patients were finally analyzed, including 47 in group A and 45 in group B. The TSIH rate was higher in group A (31.9%) than in group B (4.4%) (odds ratio = 10.1; 95% CI, 2.15-47.6; p < 0.001)). The wound infection rate was 4.3%; 8.5% in group A and 0% in group B (odds ratio = 2.04; 95% CI, 1.7-2.5; p = 0.045). Median postoperative pain evaluated by a visual analogue scale was 3 in group A and 2 in group B (p = 0.05). No differences were observed in complication rate, operative time, or hospital stay between the groups. CONCLUSIONS Prosthetic closure of the umbilical trocar site after laparoscopic surgery could become the standard method for preventing TSIH in high-risk patients.


title: Metformin exposure is associated with improved progression-free survival in diabetic patients after resection for early-stage non-small cell lung cancer.

text: OBJECTIVE There are little clinical data assessing the antineoplastic effect of metformin in patients with non-small cell lung cancer. We hypothesized that in diabetic patients undergoing pulmonary resection for early-stage non-small cell lung cancer, metformin exposure is associated with improved survival. METHODS An institutional database was used to identify patients with stage I or II non-small cell lung cancer who underwent pulmonary resection between 2004 and 2013. Patients were divided into 3 cohorts: type II diabetic patients with metformin exposure (cohort A, n = 81), type II diabetic patients without metformin exposure (cohort B, n = 57), and nondiabetic individuals (cohort C, n = 77). Univariate, multivariate, and propensity-matched analyses were performed to assess progression-free and overall survivals between groups. RESULTS A total of 215 patients with stage I and II non-small cell lung cancer treated with surgical resection were identified for analysis with a median follow-up of 19.5 months. Patients in cohort A had lower T- and N-stage tumors than those in cohorts B or C. However, on multivariate analysis adjusting for age, gender, and T and N stage, progression-free survival was greater for cohort A than cohort B (hazard ratio [HR], 0.410; 95% confidence interval, 0.199-0.874; P = .022) or cohort C (HR, 0.415; 95% confidence interval, 0.201-0.887; P = .017). Likewise, when propensity-matched analyses were performed, cohort A demonstrated a trend toward improved progression-free survival compared with cohort B (P = .057; HR, 0.44; c-statistic = 0.832) and improved progression-free survival compared with cohort C (P = .02; HR, 0.41; c-statistic = 0.843). No differences were observed in overall survival. CONCLUSIONS Metformin exposure in diabetic patients with early-stage non-small cell lung cancer may be associated with improved progression-free survival, but no effect was seen on overall survival. Further studies are warranted to evaluate if there is a therapeutic role for metformin in the treatment of non-small cell lung cancer.


title: Novel Alphacoronaviruses and Paramyxoviruses Cocirculate with Type 1 and Severe Acute Respiratory System (SARS)-Related Betacoronaviruses in Synanthropic Bats of Luxembourg.

text: Several infectious disease outbreaks with high mortality in humans have been attributed to viruses that are thought to have evolved from bat viruses. In this study from Luxembourg, the genetic diversity and epidemiology of paramyxoviruses and coronaviruses shed by the bat species Rhinolophus ferrumequinum and Myotis emarginatus were evaluated. Feces collection (n = 624) was performed longitudinally in a mixed-species colony in 2015 and 2016. In addition, feces (n = 254) were collected cross-sectionally from six Myotis emarginatus colonies in 2016. By use of degenerate primers in a nested format, overall prevalences of 1.1% (10/878) and 4.9% (43/878) were determined for paramyxoviruses and coronaviruses. Sequences of the partial RNA-dependent RNA polymerase and spike glycoprotein genes of coronaviruses, as well as sequences of the partial L gene of paramyxoviruses, were obtained. Novel paramyxovirus and Alphacoronavirus strains were identified in different Myotis emarginatus colonies, and severe acute respiratory syndrome (SARS)-related Betacoronavirus strains were shed by Rhinolophus ferrumequinum Logistic regression revealed that the level of Alphacoronavirus shedding was highest in July (odds ratio, 2.8; P < 0.01), probably due to periparturient stress. Phylogenetic analyses point to close virus-host coevolution, and the high genetic similarity of the study strains suggests that the Myotis emarginatus colonies in Luxembourg are socially connected. Most interestingly, we show that bats also host Betacoronavirus1 strains. The high similarity of the spike gene sequences of these viruses with mammalian Betacoronavirus 1 strains may be of concern. Both the SARS-related and Betacoronavirus 1 strains detected in bats in Luxembourg may cross the species barrier after a host adaptation process.IMPORTANCE Bats are a natural reservoir of a number of zoonotic pathogens. Several severe outbreaks in humans (e.g., a Nipah virus outbreak in Malaysia in 1998, and the almost global spread of severe acute respiratory syndrome in 2003) have been caused by bat-borne viruses that were transmitted to humans mostly after virus adaptation (e.g., in intermediate animal hosts). Despite the indigenousness of bat species that host viruses with suspected zoonotic potential and despite the zoonotic transmission of European bat 1 lyssavirus in Luxembourg, knowledge about the diversity and epidemiology of bat viruses remains limited in this country. Moreover, in contrast to other European countries, bat viruses are currently not included in the national surveillance activities of this land-locked country. We suggest that this gap in disease surveillance should be addressed, since we show here that synanthropic bats host viruses that may be able to cross the species barrier.


title: The functional study of human umbilical cord mesenchymal stem cells harbouring angiotensin-converting enzyme 2 in rat acute lung ischemia-reperfusion injury model.

text: Acute lung ischemia-reperfusion injury (ALIRI) is featured as non-specific alveolar damage, lung edema and hypoxemia, often occurring within 72 h after surgery. It is the leading cause for primary graft failure and mortality after lung surgery and transplantation. Here we aimed to find a more effective therapeutic approach to treat ALIRI. We evaluated the combinational effects of human umbilical cord mesenchymal stem cells (HUMSCs) and angiotensin-converting enzyme 2 (ACE2) in the rat ALIRI model. HUMSCs were isolated for lentiviral-ACE2 transfection. Fifty rats were randomly divided into five groups: sham surgery, physiological saline (PS), ACE2, HUMSCs and HUMSCs-ACE2 group. Several physiological, biochemical and histological indicators were examined and compared among the five groups, such as blood oxygen saturation (Sat O2 %) and right ventricular systolic blood pressure (RVSBP), pulmonary morphology observations, several kinds of cell markers and the abundance of glutathione reductase (GR), glutathione peroxidase (GPX) and NAD(P)H quinone oxidoreductase (NQO1). Compared with HUMSCs and ACE2 groups, HUMSCs-ACE2 group showed lighter lung injuries, higher CD31 and vWF expression (endothelial cell surface markers), lower γ-H2AX (DNA damage marker) and CD68 (inflammatory cell marker) and higher anti-oxidants expression (GR, GPX and NQO1). The results indicated that HUMSCs harbouring ACE2 were more effective than either HUMSCs or ACE2 alone in alleviating the ALIRI damages. The synergistic effects of HUMSCs and ACE2 provide informative clues for mechanism study and therapeutic method development of ALIRI.


title: Robotic-assisted intracorporeal anastomosis versus extracorporeal anastomosis in laparoscopic right hemicolectomy for cancer: a case control study.

text: INTRODUCTION Extracorporeal ileocolic anastomosis in laparoscopic right hemicolectomy for cancer has a significant risk of complications. The aim of this study is to evaluate the operative and postoperative results of hybrid right hemicolectomy with intracorporeal robotic-assisted anastomosis for adenocarcinoma of the ascending colon compared with the standard extracorporeal anastomosis in a case control study. PATIENTS AND METHODS Forty-eight right hemicolectomies for cancer (2009-2012) with laparoscopic medial to lateral dissection, vascular ligation, bowel transection, and robotic-assisted intracorporeal anastomosis with specimen extraction through a Pfannestiel incision (robotic group [RG]) were compared with 48 laparoscopic hemicolectomies (2009-2011) with extracorporeal anastomosis (laparoscopic group [LG]). RESULTS The two groups were comparable with respect to age, gender, stage of cancer, and body mass index. Surgery time was significantly longer in RG patients (RG, 266±41 minutes; LG, 223±51 minutes; P<.05). Operative results were similar in the two groups. Recovery of bowel function (day of first bowel movement: RG, 3.0±1.0 days; LG, 4.0±1.2 days; P<.05) and hospital stay (RG, 7.5±2.0 days; LG, 9.0±3.2 days; P<.05) were quicker and shorter, respectively, in RG. There were four anastomotic complications and four incisional hernias in LG and none in RG (P<.05). CONCLUSIONS There are fewer anastomotic and wound complications in RG patients. Intracorporeal robotic-assisted ileocolic anastomosis allows a faster recovery compared with extracorporeal anastomosis.


title: Real-world effectiveness and safety of tolvaptan in liver cirrhosis patients with hepatic edema: results from a post-marketing surveillance study (START study).

text: BACKGROUND This large-scale post-marketing surveillance study (START study) evaluated the effectiveness and safety of tolvaptan in Japanese liver cirrhosis patients with hepatic edema in real-world clinical settings. Here, we present the final analysis outcomes. METHODS A prospective, multicenter, non-interventional study involving patients who received tolvaptan for the treatment of liver cirrhosis with hepatic edema with an insufficient response to conventional diuretics. The observation period was up to 6 months. Effectiveness evaluation included changes in body weight and clinical symptoms. Safety analysis included evaluation of adverse drug reactions (ADRs). RESULTS Case reports of 1111 patients were collected. Of these, 1109 were included in the safety analysis and 1098 in the effectiveness analysis. The mean age was 69.4 ± 11.5 years and 695 (62.7%) patients were male. After tolvaptan treatment, a decrease in body weight from baseline was - 2.6 ± 2.7 kg on day 7 and - 3.8 ± 4.1 kg on day 14. Moreover, clinical symptoms significantly improved over the 14-day treatment. Frequently reported ADRs were thirst (6.6%), hepatic encephalopathy (2.3%), dehydration (1.5%), and hypernatremia (1.2%). A serum sodium level of ≥ 150 mEq/L was reported in five patients (0.5%). Multivariate analyses showed that the baseline blood urea nitrogen (BUN) level (cut-off value: 22.4 mg/dL) was the predictive factor for tolvaptan treatment response. CONCLUSIONS The results suggest that tolvaptan was effective and well-tolerated in liver cirrhosis patients with hepatic edema. In the real-world clinical setting, tolvaptan provides a useful option for the treatment of hepatic edema.


title: [Structure and Function of a Novel Class of High Mannose-binding Proteins with Anti-viral or Anti-tumor Activity].

text: The recently discovered high mannose (HM)-binding lectin family in lower organisms such as bacteria, cyanobacteria, and marine algae represents a novel class of anti-viral or anti-tumor compounds. This lectin family shows unique carbohydrate binding properties with exclusive high specificity for HM glycans with core trisaccharide comprising Manα(1-3)Manα(1-6)Man at the D2 arm. At low nanomolar levels, these lectins exhibit potent antiviral activity against HIV and influenza viruses through the recognition of HM glycans on virus spike glycoproteins. In addition, some of these lectins, such as bacterial PFL, show cytotoxicity for various cancer cells at low micromolar levels. Cell surface molecules to which PFL bound were identified as integrin alpha 2 and epidermal growth factor receptor (EGFR) by peptide mass finger printing with MALDI-TOF MS. Upon PFL binding, these molecules were rapidly internalized to cytoplasm. EGFR was time dependently degraded in the presence of PFL, and this process was largely responsible for autophagy. Furthermore, PFL sensitizes cancer cells to the EGFR kinase inhibitor, gefitinib. In vivo experiments showed that intratumoral injection of PFL significantly inhibited the growth of tumors in nude mice. PFL-mediated down regulation of integrin/EGFR ultimately contributed to the inhibition of tumor growth both in vitro and in vivo. Thus, the novel anti-cancer mechanism of PFL suggests that this lectin is potentially useful as an anti-cancer drug or as an adjuvant for other drugs. This class of proteins will likely have beneficial impact as a tool for biochemical and biomedical research because of its unique carbohydrate specificity and various biological activities.


title: Single-incision laparoscopic surgery for cholecystectomy: an evolving technique.

text: BACKGROUND Laparoscopic techniques have allowed surgeons to perform complicated intraabdominal surgery with minimal trauma. Recent innovators have pioneered the use of single-incision laparoscopic surgery (SILS), which has the potential of further reducing the trauma of surgical access. This may lead to reduced postoperative pain and improved patient cosmesis. METHODS This article reports the authors' method of performing SILS cholecystectomy, with carefully placed sutures used to puppeteer the gallbladder and thus aid retraction. RESULTS The authors have performed SILS cholecystectomy for 23 patients with good results. CONCLUSIONS Single-incision laparoscopic surgery is a feasible way to perform cholecystectomy. Further work in the form of randomized controlled trials is needed to investigate the advantages of this new technique.


title: A pilot study on vaginally assisted laparoscopic sacrocolpopexy for patients with uterovaginal prolapse.

text: OBJECTIVES : The primary objective of this pilot study was to compare the short-term anatomic outcomes and complication rates of vaginally assisted laparoscopic sacrocolpopexy (VALS) with those of conventional laparoscopic sacrocolpopexy (LS) in patients undergoing concurrent hysterectomy. The secondary objective was to compare operative times of the 2 different techniques. METHODS : This is a retrospective pilot study comparing VALS-a method using transvaginal mesh attachment to the vaginal apex-to conventional LS in patients undergoing concurrent hysterectomy. RESULTS : Forty-four women underwent VALS, and 26 women underwent LS. There was no significant difference in intraoperative complication rates (2.3% vs 3.8%, not statistically significant), postoperative complication rates (4.5% vs 0.0%, P = 0.526), mesh extrusion rates (2.3% vs 0%, not statistically significant), or postoperative pelvic organ prolapse quantification scores. The mean total operative time was 55 minutes shorter for the VALS group (215.2 [SD, 41.0] minutes) than the LS group (269.7 [SD, 55.6] minutes; P < 0.001). CONCLUSIONS : There was no significant difference in short-term anatomic outcomes or complication rates between groups. Vaginally assisted LS was associated with significantly shorter operative times than conventional LS.


UK response to covid-19: obfuscation, misrepresentation, and ignoring advice.


Notions of "Corona" from the perspective of a clinical immunologist and medical historian.


title: [Epidemiological characteristics of novel coronavirus pneumonia in Henan].

text: Objective: To study the epidemiological characteristics of COVID-19 in Henan Province. Methods: An epidemiological study was conducted based on the latest epidemic information of 1,265 confirmed cases (including regional distribution, severe illness, and deaths) announced by Health Commission of Henan Province, as well as the details of 1,079 COVID-19 officially released by Health Commission of municipalities in Henan Province collected as of 24:00 on February 19, 2020. Results: Among 1 079 patients diagnosed with COVID-19, there were 573 male (53.2%) and 505 female (46.8%) , with the ratio of male to female of 1.14:1; The majority of patients were 36-59 years old (553 cases, 51.3%) , and the mean age was 46 (interquartile range is 24) years old; 515 cases (47.7%) had a history of living, traveling, doing business in Wuhan or a brief stopover at Wuhan train stop, and 382 (35.4%) had a history of close contact with confirmed patients; There were 72 severe cases (5.7%) in 1 265 patients, and the fatality rate was 1.5%. A high number of cases were reported in Xinyang (269 cases, 21.26%) , Zhengzhou (156 cases, 12.33%) , Nanyang (155 cases, 12.25%) , Zhumadian (139 cases, 10.99%) , followed by Shangqiu (91 cases, 7.19%) , Zhoukou (76 cases, 6.01%) . Among 605 patients, the symptoms were fever (553 cases, 91.4%) , debilitation (44 cases, 7.3%) , cough (110 cases, 18.2%) , expectoration (19 cases, 3.1%) , chills (6 cases, 1.0%) , shiver (7 cases, 1.2%) , running nose (21 cases, 3.5%) , stuffy noses (8 cases, 1.3%) , throat dryness and sore (24 cases, 4.0%) , headache (21 cases, 3.5%) , chest pain (6 cases, 1.0%) , anhelation (18 cases, 3.0%) , and gastrointestinal symptom (21 cases, 3.5%) . The age of deaths ranged from 33 to 86 years old, with an average age of 72 (interquartile range of 17) years old; there be 7 males (63.6%) and 4 females (36.4%) . Conclusion: The cases in Henan Province were mainly imported cases and had certain geographical location relevance; meanwhile, there was a family-focused incidence. The overall trend of new cases was wave-like decline, and the number of deaths was high among elderly men with underlying diseases.


title: Escitalopram but not placebo modulates brain rhythmic oscillatory activity in the first week of treatment of Major Depressive Disorder.

text: Serotonin modulates brain oscillatory activity, and serotonergic projections to the thalamus and cortex modulate the frequency of prefrontal rhythmic oscillations. Changes in serotonergic tone have been reported to shift oscillations between the combined delta-theta (2.5-8 Hz) and the alpha (8-12 Hz) frequency ranges. Such frequency shifts may constitute a useful biomarker for the effects of selective serotonin reuptake inhibitor (SSRI) medications in Major Depressive Disorder (MDD). We utilized quantitative electroencephalography (qEEG) to measure shifts in prefrontal rhythmic oscillations early in treatment with either the SSRI escitalopram or placebo, and examined the relationship between these changes and remission of depressive symptoms. Prefrontal delta-theta and alpha power were calculated for 194 subjects with moderate MDD prior to and one week after start of treatment. Changes at one week in delta-theta and alpha power, as well as the delta-theta/alpha ratio, were examined in three cohorts: initial (N = 70) and replication (N = 76) cohorts treated with escitalopram, and a cohort treated with placebo (N = 48). Mean delta-theta power significantly increased and alpha power decreased after one week of escitalopram treatment, but did not significantly change with placebo treatment. The delta-theta/alpha ratio change was a specific predictor of the likelihood of remission after seven weeks of medication treatment: a large increase in this ratio was associated with non-remission in escitalopram-treated subjects, but not placebo-treated subjects. Escitalopram and placebo treatment have differential effects on delta-theta and alpha frequency oscillations. Early increase in delta-theta/alpha may constitute a replicable biomarker for non-remission during SSRI treatment of MDD.


title: A systemic neutrophil response precedes robust CD8(+) T-cell activation during natural respiratory syncytial virus infection in infants.

text: Severe primary respiratory syncytial virus (RSV) infections are characterized by bronchiolitis accompanied by wheezing. Controversy exists as to whether infants suffer from virus-induced lung pathology or from excessive immune responses. Furthermore, detailed knowledge about the development of primary T-cell responses to viral infections in infants is lacking. We studied the dynamics of innate neutrophil and adaptive T-cell responses in peripheral blood in relation to the viral load and parameters of disease in infants admitted to the intensive care unit with severe RSV infection. Analysis of primary T-cell responses showed substantial CD8(+) T-cell activation, which peaked during convalescence. A strong neutrophil response, characterized by mobilization of bone marrow-derived neutrophil precursors, preceded the peak in T-cell activation. The kinetics of this neutrophil response followed the peak of clinical symptoms and the viral load with a 2- to 3-day delay. From the sequence of events, we conclude that CD8(+) T-cell responses, initiated during primary RSV infections, are unlikely to contribute to disease when it is most severe. The mobilization of precursor neutrophils might reflect the strong neutrophil influx into the airways, which is a characteristic feature during RSV infections and might be an integral pathogenic process in the disease.


title: Single-site surgery for simultaneous totally extraperitoneal bilateral herniorrhaphy and transperitoneal radical nephrectomy in one patient.

text: AIM This study reports a case undergoing laparoendoscopic totally extraperitoneal herniorrhpahy and transperitoneal laparoscopic radical nephrectomy through transumbilical single-site incisions. METHOD A 56-year-old man presented with incidental left renal tumor and bilateral inguinal hernia. Accordingly, a homemade single-port in subumbilicus was applied for totally extraperitoneal herniorrhpahy, following which the incisional wound was extended upward for transperitoneal radical nephrectomy as well. RESULTS No extraumbilical port was required. Pathology confirmed the diagnosis of renal cell carcinoma. The peri- and postoperative course was quite smooth with rapid recovery, and the patient was discharged home on the fifth postoperative day. DISCUSSION The laparoendoscopic single-site surgery with homemade single-port allowed extraperitoneal and transperitoneal procedures to be carried out at the same time, which was feasible and safe with negligible complications. CONCLUSIONS Performing 2 procedures with single-site incision greatly diminished the number of port site incisions and offered obvious cosmetic advantage.


Pneumoperitoneum after Percutaneous Endoscopic Gastrostomy.


title: Neighbourhood socioeconomic indicators and depressive symptoms in the Czech Republic: a population based study.

text: OBJECTIVES Previous research shows only limited evidence on the contextual (neighbourhood-based) socioeconomic influences on mental health and depression. We investigated the association between individual and neighbourhood socioeconomic characteristics and depressive symptoms in the Czech Republic. METHODS Dichotomized CESD score of depressive symptoms was used as the outcome in a random sample of 3534 men and 4082 women aged 45-69 years in the Czech HAPIEE Study. 220 small areas were characterized by the proportion of university educated persons and the proportion of unemployed from the economically active population in the 2001 Census. Multilevel logistic regression was used for the analysis. RESULTS After controlling for individual-level variables, the effects of area-based characteristics were largely eliminated. The strongest area-based effect was that of the proportion of university educated persons; the ORs for 2(nd), 3(rd) and 4(th) quartile, compared with the 1(st) quartile, were 1.02, 0.93, and 0.82, respectively (p-value for trend 0.06). There were no cross-level interactions between socioeconomic variables. CONCLUSIONS The effects of neighbourhood characteristics in this study were largely explained by individual socioeconomic variables.


title: Laparoscopic colostomy reversal after a Hartmann procedure: a prospective series, literature review and an argument against laparotomy as the primary approach.

text: BACKGROUND Open restoration of bowel continuity after a Hartmann procedure has been associated with significant morbidity, including anastomotic leak, incisional hernia, wound infections and inability to re-establish intestinal continuity. Few studies have examined the role of laparoscopy in performing a Hartmann reversal. The aim of this study was to review our laparoscopic Hartmann reversal (LHR) experience with an emphasis on intra- and postoperative adverse events. METHODS A prospectively collected laparoscopic colorectal database involving 3 surgeons in 4 academic centres between 1991 and 2008 was reviewed. Factors evaluated were patient demographics, diagnosis, duration of surgery, intra- and postoperative complications, recovery of bowel function and length of stay in hospital. RESULTS Twenty-eight consecutive patients (13 men, 15 women) with a mean age of 61.1 (standard deviation [SD] 15.3) years and a mean weight of 72.3 (SD 20.1) kg underwent LHR. The diagnosis at initial surgery was complicated diverticulitis in 19 patients (67.9%), cancer in 6 patients (21.4%) and "other" in 3 patients (10.7%). The median duration of surgery was 166.2 (SD 74.4) minutes. There were no conversions. There was 1 major intraoperative complication (bleeding; 3.6%). There were 3 postoperative complications (10.7%): 1 abscess, 1 prolonged ileus and 1 wound hematoma. Only 1 patient with an abscess required readmission. There were no observed clinical anastomotic leaks. All patients underwent successful reanastomosis. The median time to return of bowel function was 4 (interquartile range [IQR] 3-4) days. The median length of stay in hospital was 5 (IQR 3-6) days. There was no mortality. CONCLUSION Laparoscopic colostomy reversal after a Hartmann procedure is safe and feasible in experienced hands. It is associated with low morbidity, quick return of bowel function and short stay in hospital.


title: The efficacy of smoking cessation interventions in low- and middle-income countries: a systematic review and meta-analysis.

text: AIMS To summarize evidence for the efficacy of smoking cessation interventions in low- and middle-income countries (LMICs). DESIGN Systematic review and meta-analysis of randomized controlled trials. SETTING LMICs as defined by the World Bank. PARTICIPANTS Adult current cigarette smokers residing in LMICs. INTERVENTIONS Behavioral and/or pharmacotherapy smoking cessation interventions. MEASUREMENTS PubMed MEDLINE, EMBASE (embase.com), Cochrane Central Register of Controlled Trials (Wiley), PsycINFO (Ebsco), SciELO, WHO Global Index Medicus and Scopus were searched from inception to 4 April 2018. Only studies with at least 6 months of follow-up were included. We used the most rigorous assessment of abstinence reported by each study. Effect sizes were computed from abstracted data. Where possible, a meta-analysis was performed using Mantel-Haenzel random-effect models reporting odds ratios (OR) and 95% confidence intervals (CI). FINDINGS Twenty-four randomized controlled trials were included. Six investigated the efficacy of pharmacological agents. Four trials that compared nicotine replacement therapy (NRT) to placebo found NRT improved cessation rates (n : NRT 546, control 684, OR = 1.76, 95% CI = 1.30-2.77, P < 0.001, I2 = 13%). Eight trials found that behavioral counseling was more effective than minimal interventions (e.g. brief advice); n : Counseling 2941, control 2794, OR = 6.87, 95% CI = 4.18-11.29, P < 0.001, I2 = 67%). There was also evidence of the benefit of brief advice over usual care (n : Brief advice 373, control 355, OR = 2.46, 95% CI = 1.56-3.88, P < 0.001, I2 = 0%). CONCLUSION Nicotine replacement therapy, behavioral counseling and brief advice appear to be effective in aiding smoking cessation in low- and middle-income countries. There is limited rigorous research on other smoking cessation interventions in these regions.


title: A highly sensitive europium nanoparticle-based immunoassay for detection of influenza A/B virus antigen in clinical specimens.

text: We report the development of a novel europium nanoparticle-based immunoassay (ENIA) for rapid detection of influenza A and influenza B viruses. The ENIA demonstrated sensitivities of 90.7% (147/162) for influenza A viruses and 81.80% (9/11) for influenza B viruses compared to those for an in-house reverse transcription (RT)-PCR assay in testing of influenza-positive clinical samples.


title: Hydroxychloroquine use in the COVID-19 patient.

text: Hydroxychloroquine (HCQ) has multiple potential antiviral mechanisms of action that differ according to the pathogen studied (eg, Chikungunya, Dengue virus, human immunodeficiency virus, poliovirus, Zika virus). Data on HCQ for treatment of coronavirus disease 2019 (COVID-19) are rapidly evolving. To date there is no evidence from randomized controlled trials that any single therapy improves outcomes in patients infected with COVID-19. There are also no clinical trial data supporting prophylactic HCQ therapy in COVID-19. Hydroxychloroquine (HCQ) use in patients with COVID-19 is being investigated examining prophylaxis, postexposure prophylaxis, and treatment regimens.


title: Improved microtitre plate production of single chain Fv fragments in Escherichia coli.

text: The new era of functional genomics demands several antibodies as specific detection reagents for proteins, their complexes and post-translational modifications. Only in vitro antibody selection technologies are able to provide the required throughput to generate these large numbers. Phage display is the most widely used technology for in vitro selection of antibodies. The major bottleneck of a phage display selection pipeline is the production of monoclonal antibody fragments for screening and further analysis. In this study, we describe the development of improved protocols for the production of single chain Fv (scFv) antibody fragments in 96-well microtitre plates (MTPs) in Escherichia coli. Four scFvs were expressed using the antibody expression vector pOPE101-XP to analyse the influence of a set of different parameters on their production. Further, six scFvs were expressed using the phage display vector pHAL14 to investigate the effect on the production of functional scFvs using those parameters that improved production from pOPE101-XP. Yield in MTPs was influenced by a variety of conditions and was also strongly dependent on the individual scFv clone. Although it was not possible to deduce a single set of optimal parameters applicable to all the tested scFvs, a combined protocol was developed which improved the expression of scFv fragments over standard methods.


Using guidance from disaster psychiatry to frame psychiatric support for cancer patients during the COVID-19 lockdown.


title: Efficacy and safety of rescue stenting following failed mechanical thrombectomy for anterior circulation large vessel occlusion: propensity score analysis.

text: PURPOSE To evaluate the effectiveness and safety of rescue stenting (RS) after failed mechanical thrombectomy (MT) for patients with large artery occlusion in the anterior circulation. METHODS Consecutive patients who experienced failed reperfusion and subsequently did or did not undergo RS at 16 comprehensive stroke centers were enrolled from January 2015 to June 2018. Propensity score matching was used to achieve baseline balance between the patient groups. Symptomatic intracranial hemorrhage (sICH) at 48 hours and the modified Rankin Scale scores and mortality at 3 months in the two groups were compared. RESULTS A total of 90 patients with RS and 117 patients without RS after failed MT were enrolled. Propensity score matching analysis selected 132 matched patients. The good outcome rate was significantly higher in matched patients with RS than in those without RS (36.4% vs 19.7%, p=0.033), whereas the sICH (13.6% vs 21.2%, p=0.251) and mortality (31.9% vs 43.9%, p=0.151) were not significantly different between the groups. CONCLUSIONS RS seems to be an effective safe choice for patients with large vessel occlusion of the anterior circulation who underwent failed MT.


title: Predictive factors of outcome and hemorrhage after acute ischemic stroke treated by mechanical thrombectomy with a stent-retriever.

text: INTRODUCTION The study attempts to identify notable factors predicting poor outcome, death, and intracranial hemorrhage in patients with acute ischemic stroke undergoing mechanical thrombectomy with stent retriever. These data could be useful to improve the selection of patients for thrombectomy. METHODS Patients with acute ischemic stroke treated with the Solitaire FR device were retrospectively analyzed from a prospectively collected database. We assessed the effect of selected demographic characteristics, clinical and imaging factors on poor outcome at 3 months (modified Rankin score 3-6), mortality at 3 months, and hemorrhage at day 1 (symptomatic and asymptomatic). RESULTS From May 2010 to April 2012, 59 consecutive patients with an acute ischemic stroke underwent mechanical thrombectomy. At 3 months, 57.6% of the patients were functionally independent (modified Rankin Scale 0-2) and mortality was 20.4%. Multivariate analyses revealed that a thrombus length > 14 mm (p = 0.02; OR 7.55; 95% CI 1.35-42.31) and longer endovascular procedure duration (p = 0.01; OR 1.04; 95% CI 1.01-1.07) were independently associated with poor outcome. A higher baseline Alberta Stroke Program Early CT (ASPECT) score (p = 0.04; OR 0.79 per point; 95% CI 0.63-0.99) and successful recanalization (p = 0.02; OR 0.07; 95% CI 0.01-0.72) were independent predictors of good functional outcome. Baseline ASPECT score (p < 0.01; OR 0.65; 95% CI 0.54-0.78) independently predicted symptomatic intracranial hemorrhage at day 1. CONCLUSION Absolute baseline ASPECT score reflects early symptomatic hemorrhage risk and functional outcome at 3 months. Thrombus length measured on MRI play an important role on functional outcome at 3 months after thrombectomy. Further analyses are needed to determine its importance in the selection of patients for mechanical thrombectomy.


title: Epidemiological Analysis of the Covid-19 Epidemic in Greece.

text: During the last months the Coronavirus disease 2019 (COVID-2019) has been recognized as a global threat. Transmission of the infection has rapidly increased in Europe as well as in Greece, living behind a huge number of deaths. During this situation an analysis of the spread of the disease must be undertaken and characteristics of the virus must be recognized. For the analysis of the impact of the disease in the population during this time period, epidemiological indexes have been introduced.


title: Influence of temperature and CO2 on plasma-membrane permeability to CO2 and HCO3 - in the marine haptophytes Emiliania huxleyi and Calcidiscus leptoporus (Prymnesiophyceae).

text: Membrane permeabilities to CO2 and HCO3 - constrain the function of CO2 concentrating mechanisms that algae use to supply inorganic carbon for photosynthesis. In diatoms and green algae, plasma-membranes are moderately to highly permeable to CO2 but effectively impermeable to HCO3 - . Here, CO2 and HCO3 - membrane permeabilities were measured using an 18 O-exchange technique on two species of haptophyte algae, Emiliania huxleyi and Calcidiscus leptoporus, which showed that the plasma membranes of these species are also highly permeable to CO2 (0.006 to 0.02 cm · s-1 ) but minimally permeable to HCO3 - . Increased temperature and CO2 generally increased CO2 membrane permeabilities in both species, possibly due to changes in lipid composition or CO2 channel proteins. Changes in CO2 membrane permeabilities showed no association with the density of calcium carbonate coccoliths surrounding the cell, which could potentially impede passage of compounds. Haptophyte plasma membrane permeabilities to CO2 were somewhat lower than those of diatoms but generally higher than membrane permeabilities of green algae. One caveat of these measurements is that the model used to interpret 18 O-exchange data assumes that carbonic anhydrase, which catalyzes 18 O-exchange, is homogeneously distributed in the cell. The implications of this assumption were tested by using a two-compartment model with an inhomogeneous distribution of carbonic anhydrase to simulate 18 O-exchange data and then inferring plasma-membrane CO2 permeabilities from the simulated data. This analysis showed that the inferred plasma-membrane CO2 permeabilities are minimal estimates but should be quite accurate under most conditions.


Analysis of Dual Antiplatelet Therapy.


title: Radiological role in the detection, diagnosis and monitoring for the coronavirus disease 2019 (COVID-19).

text: OBJECTIVE Coronavirus disease 2019 (COVID-19) has officially been declared a pandemic by the World Health Organization (WHO). Radiological examinations, especially computed tomography (CT), play an important role in the fight against COVID-19. A comprehensive and timely review of radiological role in the fight against COVID-19 remains urgent and mandatory. Hence, the aim of this review is to summarize the radiological role in the fight against COVID-19. This review of current studies on COVID-19 provides insight into the radiological role in the detection, diagnosis, and monitoring for COVID-19. The typical radiological features of COVID-19 include bilateral, multifocal, and multilobar ground glass opacification with patchy consolidation, a peripheral/subpleural or posterior distribution (or both), mainly in the lower lobes. A combination of chest CT and repeat Reverse Transcription-Polymerase Chain Reaction (RT-PCR) testing may be beneficial for the diagnosis of COVID-19 in the setting of strongly clinical suspicion. Chest CT may improve the sensitivity for COVID-19 diagnosis, but patients' exposure to radiation should be kept as low as possible especially for children and pregnant women patients.


title: Strength of a bifurcated H bond.

text: Macromolecules are characterized by their particular arrangement of H bonds. Many of these interactions involve a single donor and acceptor pair, such as the regular H-bonding pattern between carbonyl oxygens and amide H(+)s four residues apart in α-helices. The H-bonding potential of some acceptors, however, leads to the phenomenon of overcoordination between two donors and one acceptor. Herein, using isotope-edited Fourier transform infrared measurements and density functional theory (DFT) calculations, we measured the strength of such bifurcated H bonds in a transmembrane α-helix. Frequency shifts of the (13)C=(18)O amide I mode were used as a reporter of the strength of the bifurcated H bond from a thiol and hydroxyl H(+) at residue i + 4. DFT calculations yielded very similar frequency shifts and an energy of -2.6 and -3.4 kcal/mol for the thiol and hydroxyl bifurcated H bonds, respectively. The strength of the intrahelical bifurcated H bond is consistent with its prevalence in hydrophobic environments and is shown to significantly impact side-chain rotamer distribution.


title: Acetaminophen (paracetamol) oral absorption and clinical influences.

text: Acetaminophen (paracetamol) is a widely used nonopioid, non-NSAID analgesic that is effective against a variety of pain types, but the consequences of overdose can be severe. Because acetaminophen is so widely available as a single agent and is increasingly being formulated in fixed-ratio combination analgesic products for the potential additive or synergistic analgesic effect and/or reduced adverse effects, accidental cumulative overdose is an emergent concern. This has rekindled interest in the sites, processes, and pharmacokinetics of acetaminophen oral absorption and the clinical factors that can influence these. The absorption of oral acetaminophen occurs primarily along the small intestine by passive diffusion. Therefore, the rate-limiting step is the rate of gastric emptying into the intestines. Several clinical factors can affect absorption per se or the rate of gastric emptying, such as diet, concomitant medication, surgery, pregnancy, and others. Although acetaminophen does not have the abuse potential of opioids or the gastrointestinal bleeding or organ adverse effects of NSAIDs, excess amounts can produce serious hepatic injury. Thus, an understanding of the sites and features of acetaminophen absorption--and how they might be influenced by factors encountered in clinical practice--is important for pain management using this agent. It can also provide insight for design of formulations that would be less susceptible to clinical variables.


Electronic health record: what do you expect from them?


Letter by Heldner et al Regarding Article, "Prehospital Acute Stroke Severity Scale to Predict Large Artery Occlusion: Design and Comparison With Other Scales".


title: Imaging selection for acute stroke intervention.

text: This review summarizes the current state of knowledge regarding the use of imaging to guide stroke treatment. Brain imaging plays a central role in the diagnosis of stroke and identification of the mechanism of stroke, which is relevant to acute treatment, prognosis, and secondary prevention. The chief potential modalities are computed tomography (CT) and magnetic resonance imaging (MRI). Currently, most imaging occurs in hospital but mobile stroke units have expanded CT brain imaging into the prehospital field. The proven therapies for ischemic stroke are based on achieving reperfusion and the DAWN and DEFUSE 3 trials have now firmly established a need for imaging selection based on estimated ischemic core volume to guide reperfusion decisions in patients beyond 6 h of stroke onset. However, data also indicate that estimated ischemic core volume, in conjunction with patient factors and expected time delay to reperfusion, forms one of the most useful prognostic assessments that could alter decision-making for patients within 6 h. Current trials are also investigating agents that aim to achieve neuroprotection, reduction in edema or prevention of hemorrhagic transformation. Imaging may play a role in identifying patients likely to benefit from this next generation of interventions for stroke patients.


Radiofrequency ablation for Barrett esophagus with confirmed low-grade dysplasia.


title: Assessment of cognitive instrumental activities of daily living: a systematic review.

text: Purpose: Cognitive instrumental activities of daily living are particularly related to executive functions, such as scheduling appointments, monthly payments, managing the household economy, shopping or taking the bus. The aim of this systematic review was to determine the available tests for the assessment of executive functions with ecological validity to predict individuals' functioning. Materials and methods: An electronic search was conducted in MEDLINE, Cochrane Central, PsyCInfo and IEEE Xplore until May 2019, in addition to a manual search. The PRISMA criteria and the Covidence platform were used to select articles and extract data. Results: After applying the search selection criteria, 76 studies were identified. They referred to 110 tools to assess instrumental activities of daily living. Those that have received most attention are related to menu preparation and shopping. Performance-based measures are the most widely used traditional methods. Most tests were aimed at the adult population with acquired brain damage, cognitive impairment or dementia. There was a predominance of tests based on the Multiple Errands Test paradigm. Conclusions: In recent years, it has increased the number of tools that assess the instrumental activities of daily living based on technologies such as personal or environmental sensors and serious games. IMPLICATIONS FOR REHABILITATION Assessment of Instrumental Activities of Daily Living through performance-based measures is especially useful for the early detection of dysfunctions or preclinical disability. Difficulties in performing instrumental activities of daily living are closely associated with deficits in executive functions and prospective memory. Activities of Daily Living can be understood as multitasks. The use of virtual reality-based tests was shown to be sensitive to the detection of cognitive deficits in Activities of Daily Living. An advantage of using virtual reality in assessments is that it can help to predict the level of personal autonomy in patients who are in an institutional environment and could be a first approximation to the real environment.


title: Should this event be notified to the World Health Organization? Reliability of the international health regulations notification assessment process.

text: OBJECTIVE To investigate the reliability of the public health event notification assessment process under the International Health Regulations (2005) (IHR). METHODS In 2009, 193 National IHR Focal Points (NFPs) were invited to use the decision instrument in Annex 2 of the IHR to determine whether 10 fictitious public health events should be notified to WHO. Each event's notifiability was assessed independently by an expert panel. The degree of consensus among NFPs and of concordance between NFPs and the expert panel was considered high when more than 70% agreed on a response. FINDINGS Overall, 74% of NFPs responded. The median degree of consensus among NFPs on notification decisions was 78%. It was high for the six events considered notifiable by the majority (median: 80%; range: 76-91) but low for the remaining four (median: 55%; range: 54-60). The degree of concordance between NFPs and the expert panel was high for the five events deemed notifiable by the panel (median: 82%; range: 76-91) but low (median: 51%; range: 42-60) for those not considered notifiable. The NFPs identified notifiable events with greater sensitivity than specificity (P < 0.001). CONCLUSION When used by NFPs, the notification assessment process in Annex 2 of the IHR was sensitive in identifying public health events that were considered notifiable by an expert panel, but only moderately specific. The reliability of the assessments could be increased by expanding guidance on the use of the decision instrument and by including more specific criteria for assessing events and clearer definitions of terms.