title: Impact of the COVID-19 pandemic on orthopedic trauma workload in a London level 1 trauma center: the "golden month".

text: Background and purpose - The COVID-19 pandemic has been recognized as an unprecedented global health crisis. This is the first observational study to evaluate its impact on the orthopedic workload in a London level 1 trauma center (i.e., a major trauma center [MTC]) before (2019) and during (2020) the "golden month" post-COVID-19 lockdown.Patients and methods - We performed a longitudinal observational prevalence study of both acute orthopedic trauma referrals, operative and anesthetic casemix for the first "golden" month from March 17, 2020. We compared the data with the same period in 2019. Statistical analyses included median (median absolute deviation), risk and odds ratios, as well as Fisher's exact test to calculate the statistical significance, set at p ≤ 0.05.Results - Acute trauma referrals in the post-COVID period were almost halved compared with 2019, with similar distribution between pediatric and adult patients, requiring a significant 19% more admissions (RR 1.3, OR 2.6, p = 0.003). Hip fractures and polytrauma cases accounted for an additional 11% of the modal number of injuries in 2020, but with 19% reduction in isolated limb injuries that were modal in 2019. Total operative cases fell by a third during the COVID-19 outbreak. There was a decrease of 14% (RR 0.85, OR 0.20, p = 0.006) in aerosol-generating anesthetic techniques used.Interpretation - The impact of the COVID-19 pandemic has led to a decline in the number of acute trauma referrals, admissions (but increased risk and odds ratio), operations, and aerosolizing anesthetic procedures since implementing social distancing and lockdown measures during the "golden month."


Healing the suffering of the lonely heart.


title: Closed-loop mechanical ventilation for lung injury: a novel physiological-feedback mode following the principles of the open lung concept.

text: Adherence to low tidal volume (VT) ventilation and selected positive end-expiratory pressures are low during mechanical ventilation for treatment of the acute respiratory distress syndrome. Using a pig model of severe lung injury, we tested the feasibility and physiological responses to a novel fully closed-loop mechanical ventilation algorithm based on the "open lung" concept. Lung injury was induced by surfactant washout in pigs (n = 8). Animals were ventilated following the principles of the "open lung approach" (OLA) using a fully closed-loop physiological feedback algorithm for mechanical ventilation. Standard gas exchange, respiratory- and hemodynamic parameters were measured. Electrical impedance tomography was used to quantify regional ventilation distribution during mechanical ventilation. Automatized mechanical ventilation provided strict adherence to low VT-ventilation for 6 h in severely lung injured pigs. Using the "open lung" approach, tidal volume delivery required low lung distending pressures, increased recruitment and ventilation of dorsal lung regions and improved arterial blood oxygenation. Physiological feedback closed-loop mechanical ventilation according to the principles of the open lung concept is feasible and provides low tidal volume ventilation without human intervention. Of importance, the "open lung approach"-ventilation improved gas exchange and reduced lung driving pressures by opening atelectasis and shifting of ventilation to dorsal lung regions.


title: Identify, isolate, inform: a 3-pronged approach to management of public health emergencies.

text: During an evolving public health emergency, a simple algorithm for initial patient identification and management is essential for providers on the front lines. This article recommends a 3-pronged system of Identify, Isolate, Inform to describe the actions necessary in the first few minutes of encountering a potential Ebola patient. Application of the "vital sign zero" triage concept of early recognition of potential threats coupled with this novel algorithm will optimize protection of health care workers and the public health while concurrently providing a safe method for individual patient care.


title: Imaging of EGFR expression in murine xenografts using site-specifically labelled anti-EGFR 111In-DOTA-Z EGFR:2377 Affibody molecule: aspect of the injected tracer amount.

text: INTRODUCTION Overexpression of epidermal growth factor receptor (EGFR) is a prognostic and predictive biomarker in a number of malignant tumours. Radionuclide molecular imaging of EGFR expression in cancer could influence patient management. However, EGFR expression in normal tissues might complicate in vivo imaging. The aim of this study was to evaluate if optimization of the injected protein dose might improve imaging of EGFR expression in tumours using a novel EGFR-targeting protein, the DOTA-Z(EGFR:2377) Affibody molecule. METHODS An anti-EGFR Affibody molecule, Z(EGFR:2377), was labelled with (111)In via the DOTA chelator site-specifically conjugated to a C-terminal cysteine. The affinity of DOTA-Z(EGFR:2377) for murine and human EGFR was measured by surface plasmon resonance. The cellular processing of (111)In-DOTA-Z(EGFR:2377) was evaluated in vitro. The biodistribution of radiolabelled Affibody molecules injected in a broad range of injected Affibody protein doses was evaluated in mice bearing EGFR-expressing A431 xenografts. RESULTS Site-specific coupling of DOTA provided a uniform conjugate possessing equal affinity for human and murine EGFR. The internalization of (111)In-DOTA-Z(EGFR:2377) by A431 cells was slow. In vivo, the conjugate accumulated specifically in xenografts and in EGFR-expressing tissues. The curve representing the dependence of tumour uptake on the injected Affibody protein dose was bell-shaped. The highest specific radioactivity (lowest injected protein dose) provided a suboptimal tumour-to-blood ratio. The results of the biodistribution study were confirmed by gamma-camera imaging. CONCLUSION The (111)In-DOTA-Z(EGFR:2377) Affibody molecule is a promising tracer for radionuclide molecular imaging of EGFR expression in malignant tumours. Careful optimization of protein dose is required for high-contrast imaging of EGFR expression in vivo.


title: Rationale for prescription, and effectiveness of, upper limb orthotic intervention for children with cerebral palsy: a systematic review.

text: PURPOSE To explore (i) reasons for upper limb orthosis prescription for children with cerebral palsy (CP), (ii) the link between reason and effect according to intended outcome and outcome measure utilized and (iii) to classify the prescribed orthoses using standard terminology. METHOD A prospectively registered (center for reviews and dissemination: 42015022067) systematic review searched for experimental and observational studies investigating rigid/thermoplastic upper limb orthotic intervention for children aged 0-18 with CP. The Cochrane central register, MEDLINE, CINAHL, Embase, SCOPUS and Web of Science databases were searched. Included studies were assessed for risk of bias. RESULTS Sixteen studies met selection criteria. Two studies described a specific reason for orthosis prescription, six prescribed orthoses to manage a clinical symptom and eight did not describe a reason. Eight studies were analyzed for effect according to intended outcome with no clear connection found between reasons for prescription, outcome measures utilized and effect reported. INTERPRETATION The lack of evidence for upper limb orthotic intervention for children with CP leads to uncertainty when considering this treatment modality. Future research is needed to evaluate the effect of orthosis wear in relation to intended outcome utilizing robust methods and valid and reliable outcome measures. Implications for rehabilitation: Insufficient evidence exists about the reason for prescription of upper limb orthoses. The connection between reason for orthosis prescription, intended outcome, outcome measure utilized and observed effect is unclear. Recommend orthosis prescription to be accompanied by clear documentation of the aim of the orthosis and description using orthosis classification system terminology. Outcome measures consistent with the reason for orthosis prescription and intended outcome of the intervention are essential to measure effectiveness of the intervention.


title: Pronounced inflammatory response to endotoxaemia during nighttime: a randomised cross-over trial.

text: BACKGROUND Circadian variation in bodily functions has been shown to impact health in acute and chronic medical conditions. Little is known about the relationship between circadian rhythm and sepsis in humans. We aimed to investigate circadian variations in the host response in a human endotoxaemia model. DESIGN AND METHODS A cross-over study, where 12 healthy young men received E. coli endotoxin (lipopolysaccharide, LPS) 0.3 ng/kg at 12 noon and, on another day, at 12 midnight. Blood samples were analysed for pro- and anti-inflammatory cytokines: tumour-necrosis factor (TNF)-alpha, soluble TNF receptors (sTNF-R)-1 and -2, interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, and IL-10 as well as YKL-40 and the oxidative stress markers malondialdehyde (MDA), ascorbic acid (AA) and dehydroascorbic acid (DHA) before and at 2, 4, 6 and 8 hours after LPS administration. RESULTS The levels of MDA and IL-10 where significantly higher during the day time (P<0.05) whereas levels of TNF-alpha, sTNF-RI, sTNF-RII, IL-1Ra, IL-6, and YKL-40 were higher (P<0.01 for all comparisons) during the night time. No significant differences were seen in the levels of AA and DHA. CONCLUSION A day-night difference in the acute phase response to endotoxaemia exists in healthy volunteers with a more pronounced inflammatory response during the night time. This circadian difference in the response to endotoxaemia may play an important role in the clinical setting and should be investigated further.


title: Effect of alteplase on the CT hyperdense artery sign and outcome after ischemic stroke.

text: OBJECTIVE To investigate whether the location and extent of the CT hyperdense artery sign (HAS) at presentation affects response to IV alteplase in the randomized controlled Third International Stroke Trial (IST-3). METHODS All prerandomization and follow-up (24-48 hours) CT brain scans in IST-3 were assessed for HAS presence, location, and extent by masked raters. We assessed whether HAS grew, persisted, shrank, or disappeared at follow-up, the association with 6-month functional outcome, and effect of alteplase. IST-3 is registered (ISRCTN25765518). RESULTS HAS presence (vs absence) independently predicted poor 6-month outcome (increased Oxford Handicap Scale [OHS]) on adjusted ordinal regression analysis (odds ratio [OR] 0.66, p < 0.001). Outcome was worse in patients with more (vs less) extensive HAS (OR 0.61, p = 0.027) but not in proximal (vs distal) HAS (p = 0.420). Increasing age was associated with more HAS growth at follow-up (OR 1.01, p = 0.013). Treatment with alteplase increased HAS shrinkage/disappearance at follow-up (OR 0.77, p = 0.006). There was no significant difference in HAS shrinkage with alteplase in proximal (vs distal) or more (vs less) extensive HAS (p = 0.516 and p = 0.580, respectively). There was no interaction between presence vs absence of HAS and benefit of alteplase on 6-month OHS (p = 0.167). CONCLUSIONS IV alteplase promotes measurable reduction in HAS regardless of HAS location or extent. Alteplase increased independence at 6 months in patients with and without HAS. CLASSIFICATION OF EVIDENCE This study provides Class I evidence that for patients within 6 hours of ischemic stroke with a CT hyperdense artery sign, IV alteplase reduced intra-arterial hyperdense thrombus.


title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of Adjunctive Pimavanserin in Patients With Major Depressive Disorder and an Inadequate Response to Therapy (CLARITY).

text: OBJECTIVE Pimavanserin is a 5-hydroxytryptamine-2A antagonist and inverse receptor agonist. This phase 2 study examined the efficacy and safety of pimavanserin as adjunctive therapy in patients with major depressive disorder (MDD). METHODS This was a multicenter, randomized, double-blind, placebo-controlled study in patients with DSM-5-defined MDD and an inadequate response to a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). Using a 2-stage sequential parallel-comparison design, patients were initially randomized in a 3:1 ratio to placebo or pimavanserin added to ongoing SSRI or SNRI therapy; at 5 weeks, placebo nonresponders were re-randomized to placebo or pimavanserin for an additional 5 weeks. Key endpoints were change from baseline to the end of each stage in 17-item Hamilton Depression Rating Scale (HDRS-17) total score and Sheehan Disability Scale (SDS) score. RESULTS Between December 2016 and October 2018, 207 patients were randomized. For the prespecified pooled Sequential Parallel Comparison Design analyses of Stages 1 and 2, the least squares (LS) mean (SE) difference for the HDRS-17 total score was -1.7 (0.85) (P = .039) and for the SDS score was -0.8 (0.29) (P = .004). At week 5 of Stage 1, LS mean (SE) difference for pimavanserin versus placebo was significant for changes on the HDRS-17 (-4.0 [1.09], P = .0003) and SDS (-1.2 [0.40], P = .0036) with effect sizes of 0.626 and 0.498, respectively. Early and sustained separation of pimavanserin from placebo (P < .05) occurred at 1 week. The most common adverse events with pimavanserin were dry mouth, nausea, and headache. CONCLUSIONS Pimavanserin demonstrated robust efficacy in patients with MDD and an inadequate response to an SSRI or SNRI. Tolerability was consistent with previous experience. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03018340.


Two for one with split- or co-ventilation at the peak of the Covid-19 tsunami: is there any role for communal care when the resources for personalised medicine are exhausted?


title: Apical loop-internal loop RNA pseudoknots: a new type of stimulator of -1 translational frameshifting in bacteria.

text: Nearly all members of a widespread family of bacterial transposable elements related to insertion sequence 3 (IS3), therefore called the IS3 family, very likely use programmed -1 ribosomal frameshifting to produce their transposase, a protein required for mobility. Comparative analysis of the potential frameshift signals in this family suggested that most of the insertion sequences from the IS51 group contain in their mRNA an elaborate pseudoknot that could act as a recoding stimulator. It results from a specific intramolecular interaction between an apical loop and an internal loop from two stem-loop structures. Directed mutagenesis, chemical probing, and gel mobility assays of the frameshift region of one element from the IS51 group, IS3411, provided clear evidences of the existence of the predicted structure. Modeling was used to generate a three-dimensional molecular representation of the apical loop-internal loop complex. We could demonstrate that mutations affecting the stability of the structure reduce both frameshifting and transposition, thus establishing the biological importance of this new type of RNA structure for the control of transposition level.


title: Comparative study of safety and outcomes of single-port access versus conventional laparoscopic colorectal surgery.

text: BACKGROUND Single-port access (SPA) offers cosmetic advantages in addition to the well-recognised benefits of conventional multi-port laparoscopic (CL) surgery, and can be carried out using standard straight instruments. We report the outcomes of our early experience with SPA colorectal resections in comparison with CL surgery. METHODS We compared the following data, patient characteristics, operating time, morbidity, operative mortality, length of hospital stay and tumour variables, of patients who underwent SPA right, left, sigmoid and total colon resections, as well as high anterior resections and panproctocolectomies, with that of patients who underwent equivalent conventional laparoscopic (CL) operations. The 40 SPA and 78 CL patients studied underwent surgery between February 2008 and September 2011. RESULTS There was no difference between the SPA and CL operations, as regards the patient's sex (55.0 vs. 62.8% males, p = 0.411), comorbidity (ASA I 10.0 vs. 12.8%; ASA II 57.5 vs. 59.0%; ASA III 32.5 vs. 25.6%; ASA IV 0 vs. 2.6%, p = 0.722) and body mass index (26.2 vs. 28.0 kg/m(2), p = 0.073). However, SPA patients were younger (mean age 54.1 vs. 64.8 years, p = 0.001), and malignancy was a less common indication for surgery (25.0 vs. 71.8%, p < 0.001). There were no conversions to open surgery, and one death occurred in the CL group (1.3%). Mean operating time (162 vs. 170 min, p = 0.547), median post-operative hospital stay (4 vs. 4 days, p = 0.255) and morbidity (7.5 vs. 12.8%, p = 0.538) were comparable. CONCLUSIONS SPA laparoscopic surgery appears safe in the hands of experienced laparoscopic surgeons, with no increase in operating time, length of stay, morbidity and mortality. Selection of patients with indications for surgery for benign disease may be of importance to ensure an oncologically safe initial uptake of SPA colorectal practice.


title: Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial.

text: BACKGROUND Present mechanical devices are unable to achieve recanalisation in up to 20-40% of large vessel occlusion strokes. We compared efficacy and safety of the Trevo Retriever, a new stent-like device, with its US Food and Drug Administration-cleared predecessor, the Merci Retriever. METHODS In this open-label randomised controlled trial, we recruited patients at 26 sites in the USA and one in Spain. We included adults aged 18-85 years with angiographically confirmed large vessel occlusion strokes and US National Institutes of Health Stroke Scale (NIHSS) scores of 8-29 within 8 h of symptom onset. We randomly assigned patients (1:1) with sequentially numbered sealed envelopes to thrombectomy with Trevo or Merci devices. Randomisation was stratified by age (≤68 years vs 69-85 years) and NIHSS scores (≤18 vs 19-29) with alternating blocks of various sizes. The primary efficacy endpoint, assessed by an unmasked core laboratory, was thrombolysis in cerebral infarction (TICI) scores of 2 or greater reperfusion with the assigned device alone. The primary safety endpoint was a composite of procedure-related adverse events. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01270867. FINDINGS Between Feb 3, 2011, and Dec 1, 2011, we randomly assigned 88 patients to the Trevo Retriever group and 90 patients to Merci Retriever group. 76 (86%) patients in the Trevo group and 54 (60%) in the Merci group met the primary endpoint after the assigned device was used (odds ratio 4·22, 95% CI 1·92-9·69; p(superiority)<0·0001). Incidence of the primary safety endpoint did not differ between groups (13 [15%] patients in the Trevo group vs 21 [23%] in the Merci group; p=0·1826). INTERPRETATION Patients who have had large vessel occlusion strokes but are ineligible for (or refractory to) intravenous tissue plasminogen activator should be treated with the Trevo Retriever in preference to the Merci Retriever. FUNDING Stryker Neurovascular.


title: Assessment of immunodeficiency scoring index performance in enterovirus/rhinovirus respiratory infection after allogeneic hematopoietic stem cell transplantation.

text: BACKGROUND Enterovirus/rhinoviruses (EvRh) are the most common cause of respiratory virus infections in recipients of allogeneic stem cell transplantation (allo-HSCT). OBJECTIVE We sought to analyze the value of the immunodeficiency scoring index (ISI) in predicting lower respiratory tract disease (LRTD) progression and mortality in a prospective cohort of consecutive adult (> 16 years) allo-HSCT recipients with EvRh infection from December 1 2013 to December 1 2019 at two Spanish transplant centers. RESULTS We included 234 allo-HSCT recipients with 383 EvRh episodes. Out of 383 EvRh episodes, 98 (25%) had LRTD. Multivariate logistic regression analysis identified three independent factors associated with LRTD progression: Ig G <400 mg/dl, community-acquired respiratory virus (CARV) co-infection and high-risk ISI. Inclusion of Ig G levels and CARV co-infection in the ISI improved its performance by significantly increasing the area under the receiver operator characteristic curve (AUROC) from 0.643 to 0.734 (p= 0.03). Likewise, the two conditions identified by multivariate analyses as associated with higher probability of mortality were high-risk ISI and EvRh infection within 6 months after transplant. CONCLUSIONS Our findings confirm the value of high-risk ISI in predicting both probability of EvRh LRTD and 3-month overall mortality. We also demonstrate that the original ISI could be adapted to other CARV types by including additional variables to improve its performance.


title: High hematocrit resulting from administration of erythropoiesis-stimulating agents is not fully predictive of mortality or toxicities in preclinical species.

text: We conducted a retrospective analysis of publicly available preclinical toxicology studies with erythropoiesis-stimulating agents (ESAs) to examine common adverse events in rats, Beagle dogs, and cynomolgus monkeys. Mortality and/or thrombotic events were reported sporadically in a subset of studies and attributed to the high hematocrit (HCT) achieved in the animals. However, similarly high HCT was achieved in both high-dose and low-dose groups, but there were no reported adverse events in the low-dose group suggesting HCT was not the sole contributing factor leading to toxicity. Our analysis indicated that increased dose, dose frequency, and dosing duration in addition to high HCT contributed to mortality and thrombosis. To further evaluate this relationship, the incidence of toxicities was compared in rats administered an experimental hyperglycosylated analog of recombinant human erythropoietin (AMG 114) at varying dosing schedules in 1-month toxicity studies. The incidence of mortality and thrombotic events increased in higher dose groups and when dosed more frequently, despite a similarly high HCT in all animals. The results from the investigative study and retrospective analysis demonstrate that ESA-related toxicities in preclinical species are associated with dose level, dose frequency, and dosing duration, and not solely dependent upon a high HCT.


Much on early intervention, some thoughts on COVID-19 and a paradox to ponder on.


An immunopathogenic perspective of interleukin-1 signaling.


title: Surgical technique for allogeneic uterus transplantation in macaques.

text: No study has reported an animal model of uterus transplantation (UTx) using cynomolgus macaques. We aimed to establish a surgical technique of allogeneic UTx assuming the recovery of a uterus from a deceased donor in cynomolgus macaques. Four allogeneic UTxs were performed in female cynomolgus macaques. Donor surgeries comprised en bloc recovery of organs with iliac vessels on both sides, and/or abdominal aorta/vena cava after sufficient perfusion from one femoral artery or external iliac artery. Before perfusion, 150 mL of whole blood was obtained from the donor for subsequent blood transfusion to the recipient. Four uterine grafts were orthotopically transplanted to recipients. End-to-side anastomosis was performed to the iliac vessels on one side in case 1 and iliac vessels on both sides in case 2; aorto-aorto/cavo-caval anastomosis was performed in cases 3 and 4. Arterial blood flow of the uterine grafts was determined by intraoperative indocyanine green (ICG) angiography. ICG angiography results showed sufficient blood flow to all uterine grafts, and anaemia did not progress. Under appropriate immune suppression, all recipients survived for more than 90 days post-transplantation, without any surgical complications. We describe a surgical technique for allogeneic UTx in cynomolgus macaques.


title: Lack of effect of continuous glycyrrhizin administration on the pharmacokinetics of the P-glycoprotein substrate talinolol in healthy volunteers.

text: PURPOSE To investigate the effects of repeated glycyrrhizin ingestion on the oral pharmacokinetics of talinolol, a probe drug for P-glycoprotein (P-gp) activity in humans. METHODS Fourteen healthy adult male subjects were enrolled in a two-phase randomized crossover-design study. In each phase the volunteers received placebo or compound glycyrrhizin tablets (75 mg glycyrrhizin three times daily) for 6 days. On the seventh day, a single oral dose of 100 mg talinolol was administered, and blood samples were obtained to determine plasma talinolol concentrations, measured in plasma by high-performance liquid chromatography with an ultraviolet detector. Non-compartmental analysis was used to characterize talinolol plasma concentration-time profiles. All pharmacokinetics parameters were calculated using DAS ver. 2.1 software, and statistical analyses were performed with SPSS ver. 13.0 software. Analysis of variance was used to check the difference of the means of the pharmacokinetic parameters between the two treatments at a significance level of 0.05. RESULTS All treatments were well tolerated during the study period. The geometric mean ± standard deviation of the AUC(0-∞) for talinolol treated by glycyrrhizin and talinolol treated by placebo was 2,218.3 ± 724.3 and 1,988.2 ± 649.2 ng·h/mL, respectively. The 90 % confidence intervals for the ratio of adjusted geometric means (glycyrrhizin:placebo) for AUC(0-∞) and C (max) fell wholly within the interval [80, 125]. Six days of glycyrrhizin treatment resulted in no significant alterations in the pharmacokinetic parameters (AUC(0-∞), AUC(0-24), C (max), t (max), t (½)) for talinolol. CONCLUSIONS Continuous glycyrrhizin administration had no induction effect on the expression of P-gp in our trial. Further research is needed to study the direct inhibition effect of glycyrrhizin on the function of P-gp with the simultaneous administration of both glycyrrhizin and P-gp substrate.


title: What use are words at a time like this?

text: What use are words at a time like this? I am writing this on 27th March as the world is plunging further into the coronavirus crisis. Like many worldwide, I am in virtual 'lockdown' in Australia while the exponential spread of the virus continues. At a follow-up tele-consult with my medical consultant recently, he said that he was apprehensive about the 'calm before the storm' that our health services face. He was deadly serious.


title: Functional properties and genetic relatedness of the fusion and hemagglutinin-neuraminidase proteins of a mumps virus-like bat virus.

text: UNLABELLED A bat virus with high phylogenetic relatedness to human mumps virus (MuV) was identified recently at the nucleic acid level. We analyzed the functional activities of the hemagglutinin-neuraminidase (HN) and the fusion (F) proteins of the bat virus (batMuV) and compared them to the respective proteins of a human isolate. Transfected cells expressing the F and HN proteins of batMuV were recognized by antibodies directed against these proteins of human MuV, indicating that both viruses are serologically related. Fusion, hemadsorption, and neuraminidase activities were demonstrated for batMuV, and either bat-derived protein could substitute for its human MuV counterpart in inducing syncytium formation when coexpressed in different mammalian cell lines, including chiropteran cells. Cells expressing batMuV glycoproteins were shown to have lower neuraminidase activity. The syncytia were smaller, and they were present in lower numbers than those observed after coexpression of the corresponding glycoproteins of a clinical isolate of MuV (hMuV). The phenotypic differences in the neuraminidase and fusion activity between the glycoproteins of batMuV and hMuV are explained by differences in the expression level of the HN and F proteins of the two viruses. In the case of the F protein, analysis of chimeric proteins revealed that the signal peptide of the bat MuV fusion protein is responsible for the lower surface expression. These results indicate that the surface glycoproteins of batMuV are serologically and functionally related to those of hMuV, raising the possibility of bats as a reservoir for interspecies transmission. IMPORTANCE The recently described MuV-like bat virus is unique among other recently identified human-like bat-associated viruses because of its high sequence homology (approximately 90% in most genes) to its human counterpart. Although it is not known if humans can be infected by batMuV, the antigenic relatedness between the bat and human forms of the virus suggests that humans carrying neutralizing antibodies against MuV are protected from infection by batMuV. The close functional relationship between MuV and batMuV is demonstrated by cooperation of the respective HN and F proteins to induce syncytium formation in heterologous expression studies. An interesting feature of the glycoproteins of batMuV is the downregulation of the fusion activity by the signal peptide of F, which has not been reported for other paramyxoviruses. These results are important contributions for risk assessment and for a better understanding of the replication strategy of batMuV.


title: Tibialis anterior muscle fascicle dynamics adequately represent postural sway during standing balance.

text: To maintain a stable, upright posture, the central nervous system (CNS) must integrate sensory information from multiple sources and subsequently generate corrective torque about the ankle joint. Although proprioceptive information from the muscles that cross this joint has been shown to be vital in this process, the specific source of this information remains questionable. Recent research has been focused on the potential role of tibialis anterior (TA) muscle during standing, largely due to the lack of modulation of its activity throughout the sway cycle. Ten young, healthy subjects were asked to stand normally under varying conditions, for periods of 60 s. During these trials, intramuscular electromyographic (EMG) activity and the fascicle length of three distinct anatomical regions of TA were sampled synchronously with kinematic data regarding sway position. In the quiet standing conditions, TA muscle activity was unmodulated and fascicle length changes in each region were tightly coupled with changes in sway position. In the active sway condition, more EMG activity was observed in TA and the fascicle length changes were decoupled from sway position. No regional specific differences in correlation values were observed, contrasting previous observations. The ability of the fascicles to follow sway position builds upon the suggestion that TA is well placed to provide accurate, straightforward sensory information to the CNS. As previously suggested, through reciprocal inhibition, afferent information from TA could help to regulate plantar flexor torque at relevant phases of the sway cycle. The proprioceptive role of TA appears to become complicated during more challenging conditions.


title: Impact of renal impairment on long-term retention of gadolinium in the rodent skin following the administration of gadolinium-based contrast agents.

text: OBJECTIVE Several publications have suggested a possible association between Gd-based contrast agents (GBCAs) and the development of nephrogenic systemic fibrosis, a rare but serious disease. To date, nephrogenic systemic fibrosis has been observed only in patients with severe renal insufficiency.The aim of this study was to determine the impact of a prolonged circulation time of GBCAs caused by reduced renal clearance on the long-term retention of Gd in the skin of rats after administration of different GBCAs. MATERIAL AND METHODS Renally impaired Han Wistar Rats (5/6-nephrectomized rats) were injected with Omniscan, OptiMARK, Magnevist, or Gadovist. The contrast agents were administered once daily for 5 consecutive days into the tail vein at a dose of 2.5 mmol Gd/kg b.w. Skin biopsies were taken at various time points, and the gadolinium (Gd) concentration was determined by inductive coupled plasma mass spectrometry (ICP-MS) over an observation period of 168 days post injection (p.i.). RESULTS Differences in the skin Gd concentrations were observed between the 4 investigated GBCAs. For the nonionic linear compounds, Omniscan and OptiMARK, high Gd concentrations were maintained in the skin over the observation period of up to 168 days p.i. For the ionic linear compound, Magnevist, comparatively lower Gd retention in the skin was observed over time. For the macrocyclic compound, Gadovist, the Gd values in the skin were even lower, and significantly lower than Gd values in the skin in Omniscan and OptiMARK treated animals. CONCLUSION The results of this preclinical study support the use of 5/6-nephrectomized rats as a model for prolonged circulation time of GBCAs as seen in patients with severe renal impairment. Surgically induced severe renal impairment resulted in delayed clearance of the administered GBCAs in the study animals. The highest amount of Gd was observed in the skin after treatment with the nonionic linear GBCAs, whereas the lowest Gd values were observed after treatment with the macrocyclic agent. This suggests that the difference in the Gd values observed in rat skin tissue after treatment with the different GBCAs is caused of a different propensity of the different GBCAs to release Gd in vivo. However, the analytical method used does not distinguish between chelated and unchelated Gd.


title: Comparison of long-term survival and immediate postoperative liver function after laparoscopic and open distal gastrectomy for early gastric cancer patients with liver cirrhosis.

text: BACKGROUND Several studies have suggested no difference in the liver function of early gastric cancer (EGC) patients with liver cirrhosis (LC) between laparoscopic and open distal gastrectomy. However, the number of patients and comparison of long-term survival rates between the two groups are limited. The purpose of this study was to compare the long-term survival and immediate postoperative liver function of EGC patients with LC after laparoscopic and open distal gastrectomy. MATERIALS AND METHODS The clinical data of EGC patients with LC who had no other malignancy and underwent distal gastrectomy at Asan Medical Center between January 2005 and April 2013 were investigated retrospectively. All patients were divided into two groups: the open group (OG) and laparoscopic group (LG). The clinicopathologic data of the two groups were compared. RESULTS The number of patients in each group was 48 and 27 in the OG and LG, respectively. There were no significant differences in the age, sex ratio, ASA score, cause of liver cirrhosis, preoperative Child-Pugh classification, tumor location, TNM stage, total postoperative drain amount, albumin, total bilirubin, alkaline phosphatase, alanine aminotransferase, prothrombin time, morbidity and recurrence rate. Shorter hospital stay, longer operative time and more retrieved lymph nodes were observed in LG. The long-term overall survival rate was not different between the two groups (P = 0.356). CONCLUSIONS For EGC patients with liver cirrhosis, especially Child A cirrhosis, laparoscopic or laparoscopy-assisted distal gastrectomy can be a safe surgical procedure in comparison to open distal gastrectomy in terms of the long-term survival rate and immediate postoperative liver function.


title: Membrane fusion-mediated autophagy induction enhances morbillivirus cell-to-cell spread.

text: In the context of viral infections, autophagy induction can be beneficial or inhibitory. Within the Paramyxoviridae family, only morbilliviruses have been investigated and are reported to induce autophagy. Here we show that morbilliviruses rapidly induce autophagy and require this induction for efficient cell-to-cell spread. Coexpression of both glycoproteins in cells expressing one of the cellular receptors was required for autophagy induction, and LC3 punctum formation, indicative of autophagy, was mainly observed in syncytia. A similar correlation between syncytium formation and autophagy induction was also observed for other paramyxovirus glycoproteins, suggesting that membrane fusion-mediated autophagy may be common among paramyxoviruses and possibly other enveloped viruses.


title: Hepatocellular carcinoma tumor thrombus entering the inferior vena cava treated with percutaneous RF ablation: a case report.

text: PURPOSE Hepatocellular carcinoma (HCC) is the most common form of liver cancer. In advanced cancer stages (metastatic disease and/or vascular invasion), the generally accepted standard of care is systemic therapy using sorafenib as first-line treatment and, recently, regorafenib and nivolumab as second-line treatment, but the quality of life and the prognosis of patients remain very poor. Our paper reports a case of US-guided radiofrequency ablation (RFA) of both intraparenchymal HCC and inferior vena cava tumor thrombus. METHODS We treated a patient with HCC associated with tumor thrombus extending into vena cava after failure of sorafenib therapy using US-guided radiofrequency ablation (RFA). RESULTS A good radiological and clinical response was observed in association with excellent tolerability. The patient has been followed up for 15 months from the ablation, is alive, and is in a good clinical condition without evidence of tumor recurrence. CONCLUSION This is the first case in which this minimally invasive percutaneous procedure has been successfully used to treat an HCC thrombus entering the vena cava.


title: Reproductive outcomes following robotic-assisted laparoscopic myomectomy (RALM).

text: Uterine myomas are the most common type of benign tumor in women of reproductive age and are commonly associated with menorrhagia, dysmenorrhea, dyspareunia, and urinary symptoms. Uterine fibroids have been also linked to infertility and pregnancy loss. Women wishing to preserve or restore their fertility are best treated by myomectomy. Robotic-assisted laparoscopic myomectomy is one of the latest technological applications of minimally invasive surgery. Limited data exist regarding the feasibility of robotic-assisted laparoscopic myomectomy (RALM) in terms of pregnancy and surgical outcomes, and more studies are needed. The goal of this study is to assess reproductive outcomes following RALM in a private practice setting. The study was performed in the form of a retrospective chart review. Female patients 22-44 years old diagnosed with intramural myoma were eligible for inclusion. Presence of a myoma was a necessary but not necessarily the presenting symptom. All patients underwent RALM between January 2006 and May 2009 under the care of one surgeon at two clinical sites. Patients were selected postsurgically via chart review based on inclusion parameters outlined above. Median values for pregnancy rate, number of myomas, diameter of largest myoma, surgery duration, and blood loss were calculated and used for subsequent statistical analysis. Clinically useful markers for pregnancy outcomes evaluation following RALM were identified. Thirty patients were enrolled, of whom 16 were interested in conception due to infertility. A pregnancy rate of 75 % was recorded. Among those who conceived, eight patients (67 %) reported natural conception within 6 months of unprotected intercourse, while four patients (33 %) utilized assisted reproductive technologies to conceive. One patient (8 %) miscarried. Two patients (17 %) experienced premature delivery, at 28 and 32 weeks, respectively. All deliveries were performed via Cesarean section. No surgical complications were reported following RALM. There were no cases of scar dehiscence or rupture. The median number of myomas in those who delivered was estimated at 1.0 compared with 3.5 in those unable to conceive (p < 0.05). In addition, median age was 34 compared with 42.5 years, respectively (p < 0.05). This retrospective study assessed pregnancy outcomes following RALM. Our pregnancy rate of 75 % combined with a low incidence of complications contributes to the limited pool of data available on this topic, and supports the need for a multicenter trial to further evaluate effectiveness and safety of RALM in terms of pregnancy outcomes.


title: Examination of Hospital Workers' Emotional Responses to an Infectious Disease Outbreak: Lessons From the 2015 MERS Co-V Outbreak in South Korea.

text: ABSTRACTHospital workers are critical for a successful response to an infectious disease outbreak and for preventing disease transmission to the community. Therefore, hospital crisis management should implement efforts to improve hospital workers' preparedness in responding to public health emergencies caused by infectious diseases. Traditionally, preparedness and skill of hospital workers have been emphasized, but awareness of the importance of the emotional mindset of hospital workers in dealing with disease outbreaks has only recently increased; therefore, empirical approaches to examining emotional responses of hospital workers has been limited. This study analyzed qualitative data of the 2015 Middle East Respiratory Syndrome outbreak in South Korea. In particular, negative emotions and stress experienced by hospital workers who treated patients were characterized, as were the events that triggered such experiences. These events were categorized into four themes (eg, Mistake, Missing, Delay Due to Communication Failure). Identifying events that trigger negative emotions in hospital workers has important implications for hospitals' management guidance in relation to an infectious disease outbreak. (Disaster Med Public Health Preparedness. 2018;page 1 of 7).


title: Leg hammock for closed reduction of tibial shaft fractures.

text: Tibial shaft fractures are common injuries in emergency departments (EDs). Although many of these fractures require surgery, nearly all are stabilized in the ED with a long leg splint or bivalved cast. Long leg splinting is often challenging for a single health care provider. Further, even with assistance or previously described techniques for fracture reduction and stabilization, fracture angulation may occur, potentially leading to pain for the patient, fracture displacement, or further soft tissue injury. The authors propose a method for splinting tibial fractures that avoids fracture angulation, is cost-effective and quick, and can be easily performed by a single health care provider.


title: Relationship between the magnetic resonance imaging appearance of adenomyosis and endometriosis phenotypes.

text: STUDY QUESTION What is the relationship between endometriosis phenotypes superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), deep infiltrating endometriosis (DIE) and the adenomyosis appearance by magnetic resonance imaging (MRI)? SUMMARY ANSWER Focal adenomyosis located in the outer myometrium (FAOM) was observed more frequently in women with endometriosis, and was significantly associated with the DIE phenotype. WHAT IS KNOWN ALREADY An association between endometriosis and adenomyosis has been reported previously, although data regarding the association between MRI appearance of adenomyosis and the endometriosis phenotype are currently still lacking. STUDY DESIGN, SIZE, DURATION This was an observational, cross-sectional study using data prospectively collected from non-pregnant patients who were between 18 and 42 years of age, and who underwent surgery for symptomatic benign gynecological conditions between January 2011 and December 2014. For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding the surgery. Only women with preoperative standardized uterine MRIs were retained for this study. PARTICIPANTS/MATERIALS, SETTING, METHODS Surgery was performed on 292 patients with signed consent and available preoperative MRIs. After a thorough surgical examination of the abdomino-pelvic cavity, 237 women with histologically proven endometriosis were allocated to the endometriosis group and 55 symptomatic women without evidence of endometriosis to the endometriosis free group. The existence of diffuse or FAOM was studied in both groups and according to surgical endometriosis phenotypes (SUP, OMA and DIE). MAIN RESULTS AND THE ROLE OF CHANCE Adenomyosis was observed in 59.9% (n = 175) of the total sample population (n = 292). Based on MRI, the distribution of adenomyosis was as follows: isolated diffuse adenomyosis (53 patients; 18.2%), isolated FAOM (74 patients; 25.3%), associated diffuse and FAOM (48 patients; 16.4%). Diffuse adenomyosis (isolated and associated to FAOM) was observed in one-third of the patients regardless of whether they were endometriotic patients or endometriosis free women taken as controls (34.2% (81 cases) versus 36.4% (20 cases)); P = 0.764. Among endometriotic women, diffuse adenomyosis (isolated and associated to FAOM) failed to reach significant correlation with the endometriosis phenotypes (SUP, 20.0% (8 cases); OMA, 45.2% (14 cases) and DIE, 35.5% (59 cases); P = 0.068). In striking contrast, there was a significant increase in the frequency of FAOM in endometriosis-affected women than in controls (119 cases (50.2%) versus 5.4% (3 cases); P < 0.001). FAOM correlated with the endometriosis phenotypes, significantly with DIE (SUP, 7.5% (3 cases); OMA, 19.3% (6 cases) and DIE, 66.3% (110 cases); P < 0.001). LIMITATIONS, REASONS FOR CAUTION There was a possible selection bias due to the specificity of the study design, as it only included surgical patients in a referral center that specializes in endometriosis surgery. Therefore, women referred to our center may have suffered from particularly severe forms of endometriosis. This could explain the high number of women with DIE (166/237-70%) in our study group. This referral bias for women with severe lesions may have amplified the difference in association of FAOM with the endometriosis-affected patients compared to women without endometriosis. Furthermore, according to inclusion criteria, women in the endometriosis free group were symptomatic women. This may introduce some bias as symptomatic women may be more prone to have associated adenomyosis that in turn could have been overrepresented in the endometriosis free group. Whether this selection could have introduced a bias in the relationship between endometriosis and adenomyosis remains unknown. WIDER IMPLICATIONS OF THE FINDINGS This study opens the door to future epidemiological, clinical and mechanistic studies aimed at better characterizing diffuse and focal adenomyosis. Further studies are necessary to adequately determine if diffuse and focal adenomyosis are two separate entities that differ in terms of pathogenesis. STUDY FUNDING/COMPETING INTEREST(S) No funding supported this study. The authors have no conflict of interest to declare.


title: The pain quality response profile of a corticosteroid injections and heated lidocaine/tetracaine patch in the treatment of shoulder impingement syndrome.

text: OBJECTIVES To describe the effects of 2 pain treatments for shoulder impingement syndrome (SIS), and illustrate how investigators can use pain quality information to understand treatment response differences. MATERIALS AND METHODS This study presents pain quality data from a randomized open-label study comparing the effects of an injection of triamcinolone and up to twice daily application of a heated lidocaine/tetracaine (Trilexis) patch in individuals with SIS. Study participants completed a measure of pain quality at baseline and again on study days 14, 28, and 42 following initiation of 2 treatments for SIS. Baseline and posttreatment pain quality scores were graphed to provide a visual representation of treatment-associated changes. Analyses of variance were used to examine the differences between treatment conditions in changes in pain quality with treatment. RESULTS Both treatments resulted in substantial (and similar) pretreatment to posttreatment improvements in many pain qualities. However, differences in the time course of treatment effects were observed for itchy and heavy qualities. DISCUSSION Although 2 different pain treatments appear to have the same effects when only pretreatment to posttreatment changes are examined, treatment differences emerged when the time course of treatment is examined. The findings support the importance of assessing both pain qualities and time course of treatment as outcome domains. The results illustrate how investigators can use data from clinical trials to provide a more fine-tuned description of treatment effects, providing knowledge that could be helpful in selecting treatment options at the individual patient level. SUMMARY Examination of the effects of pain treatments on pain qualities over time will help researchers and clinicians understand if certain pain quality domains respond faster to one treatment versus another, and may identify differences between treatments that would not be observed by measures of global pain intensity alone.


title: Percutaneous CT-guided thermal ablation as salvage therapy for recurrent non-small cell lung cancer after external beam radiotherapy: A retrospective study.

text: PURPOSE The aim of this study was to evaluate radiofrequency ablation (RFA) and microwave ablation (MWA) as a viable salvage option for patients with locally recurrent non-small cell lung cancer (NSCLC) after radiotherapy. MATERIALS AND METHODS This retrospective study was conducted on patients who had received thermal ablation for recurrent NSCLC post-curative radiotherapy. Medical records and follow-up imaging with computed tomography (CT) and PET-CT were analysed to determine time to local progression (TTLP) and overall survival (OS). TTLP was determined according to the modified RECIST criteria. RESULTS Twelve patients, mean age 71 ± 7 years, received 17 thermal ablation sessions, with RFA performed for four lesions and MWA for 13. Nine tumours were squamous cell cancers (SCC) and eight were adenocarcinomas. Eleven tumours had recurred post-external beam radiation and one post-stereotactic body radiation therapy. Mean tumour size was 34.2 ± 12.8 mm, tumour stages prior to radiotherapy were Ia (2), Ib (3), IIa (4), IIb (1) and III (2). Follow-up period was 19 ± 11 months. Overall median TTLP was 14 months (95% CI: 8, 19), and median OS was 35 months (95% CI: 12, 58). Mean TTLP for tumours <30 mm was 23 months and for tumours >30 mm 14 months (p = 0.20). Recurrence rates reduced from 50% after initial ablation to 20% with a second ablation. Complication rate for pneumothorax requiring intervention was 17%. CONCLUSION Both RFA and MWA ablation prolonged local tumour control with minimal morbidity in this study group of recurrent NSCLC after radiotherapy.


title: Assessing groundwater quality for drinking water supply using hybrid fuzzy-GIS-based water quality index.

text: Groundwater is a vital source of freshwater in both urban and rural regions of the world. However, its injudicious abstraction and rapidly increasing contamination are posing a severe threat for sustainable water supply worldwide. Geographical Information System (GIS)-based groundwater quality evaluation using Groundwater Quality Index (GQI) has been proved to be a cost-effective tool for assessing groundwater quality and its variability at a larger scale. However, the conventional GQI approach is unable to deal with uncertainties involved in the assessment of environmental problems. To overcome this limitation, a novel hybrid framework integrating Fuzzy Logic with the GIS-based GQI is proposed in this study for assessing groundwater quality and its spatial variability. The proposed hybrid framework is demonstrated through a case study in a hard-rock terrain of Southern India using ten prominent groundwater-quality parameters measured during pre-monsoon and post-monsoon seasons. Two conventional GIS-based GQI models GQI-10 (using all the ten groundwater-quality parameters) and GQI-7 (using seven 'concerned/critical' groundwater-quality parameters) as well as hybrid Fuzzy-GIS-based GQI (FGQI) models (using seven critical parameters) were developed for the two seasons and the results were compared. The Trapezoidal membership functions classified the model input parameters into 'desirable', 'acceptable' and 'unacceptable' classes based on the experts' knowledge and water quality standards for drinking purposes. The concentrations of Ca2+, Mg2+, and SO42- in groundwater were found within the WHO desirable limits for drinking water throughout the year, while the concentrations of seven parameters (TDS, NO3--N, Na+, Cl-, K+, F- and Hardness) exceed their permissible limits during pre-monsoon and post-monsoon seasons. A comparative evaluation of GQI models revealed that the FGQI model predicts groundwater quality better than the conventional GQI-10 and GQI-7 models. GQI modeling results suggest that the groundwater of most of eastern and southern parts (∼60% in pre-monsoon season; ∼90% in post-monsoon season) of the study area is unsuitable for drinking. Further, the groundwater quality deteriorates during post-monsoon seasons compared to pre-monsoon seasons, which indicates an increased influx of contaminants from different industries, mining areas, waste disposal sites and agricultural fields during monsoon seasons. This finding calls for the strict enforcement of regulations for proper handling of effluents from various contamination sources in the study area. It is concluded that the fuzzy logic-based decision-making approach (FGQI) is more reliable and pragmatic for groundwater-quality assessment and analysis at a larger scale. It can serve as a useful tool for the water planners and decision makers in efficiently monitoring and managing groundwater quality at watershed or basin scales.


The Italian dermatologic community facing COVID-19 pandemic: recommendation from the Italian society of dermatology and venereology.


title: Thiazolides: a new class of antiviral drugs.

text: BACKGROUND Thiazolides have emerged as a new class of broad-spectrum antiviral drugs, and the first thiazolide, nitazoxanide, is in late-stage clinical trials for treating chronic hepatitis C. OBJECTIVE To review the chemistry, pharmacology, toxicology and efficacy of thiazolides as antiviral agents with emphasis on clinical development of nitazoxanide in treating chronic hepatitis C. METHODS Literature search, information from Romark Laboratories and my personal experience with the discovery and development of thiazolides serve as the sources for this review. CONCLUSIONS Thiazolides are metabolically stable, highly bound to plasma proteins and are associated with a favorable toxicology profile. Phase II clinical trials have demonstrated efficacy and safety of nitazoxanide added to peginterferon with or without ribavirin in treating patients with chronic hepatitis C. More limited clinical data indicated potential in treating chronic hepatitis B, and three randomized controlled trials have demonstrated efficacy in reducing the duration of viral gastroenteritis. New generation thiazolides with the nitro group of nitazoxanide replaced by a non-reducible group are not active against anaerobes but retain broad-spectrum activity against viruses. Further studies are needed. Research indicates that these drugs may play an important and complementary role in combination with other classes of antiviral drugs.


Combined Use of Intra-aortic Balloon Pump and Venoarterial Extracorporeal Membrane Oxygenation Support With Femoral Arterial Cannulation Impairs Cerebral Microcirculation: Evaluation With Laser Speckle Flowgraphy.


title: Tracheal Microbiota in Patients With a Tracheostomy Before, During and After an Acute Respiratory Infection.

text: Examining tracheal microbiota before, during and after acute respiratory infection in patients with a tracheostomy demonstrated large baseline intrapatient microbiota variability and a significant bloom of Haemophilus and Moraxella on day 1 of acute respiratory infection symptoms. The tracheal microbiota community composition changed significantly from baseline to 1 month after acute respiratory infection.


title: Discovery of swine as a host for the Reston ebolavirus.

text: Since the discovery of the Marburg and Ebola species of filovirus, seemingly random, sporadic fatal outbreaks of disease in humans and nonhuman primates have given impetus to identification of host tropisms and potential reservoirs. Domestic swine in the Philippines, experiencing unusually severe outbreaks of porcine reproductive and respiratory disease syndrome, have now been discovered to host Reston ebolavirus (REBOV). Although REBOV is the only member of Filoviridae that has not been associated with disease in humans, its emergence in the human food chain is of concern. REBOV isolates were found to be more divergent from each other than from the original virus isolated in 1989, indicating polyphyletic origins and that REBOV has been circulating since, and possibly before, the initial discovery of REBOV in monkeys.


title: Modified thresholds for fibrosis risk scores in nonalcoholic fatty liver disease are necessary in the obese.

text: BACKGROUND Obesity and its related comorbidities are significant risk factors for nonalcoholic fatty liver disease (NAFLD). Liver fibrosis is the major determinant of long-term outcomes in NAFLD. A non-invasive tool that accurately identifies obese patients at elevated risk of liver fibrosis would be of significant value. Fibrosis risk scores in patients with NAFLD have been proposed but have not been validated in obese populations. We aimed to validate established simple fibrosis scores in bariatric surgical patients. METHODS We conducted a prospective study of 107 consecutive high-risk obese patients undergoing primary bariatric surgery. Proposed fibrosis scores (NAFLD fibrosis score; body mass index (BMI), aspartate aminotransferase (AST)/alanine aminotransferase ratio (ALT), and diabetes (BARD); Fibrosis-4 (FIB-4); Forn; and AST to platelet ratio index) were calculated and compared hepatic fibrosis determined by histology of intraoperative liver biopsies. Accuracy was determined, and fibrosis score thresholds were optimized. These modified thresholds were then validated in an independent bariatric surgical population. RESULTS Liver biopsies were available in 101 patients. Sixty-eight patients had some degree of fibrosis, with 23 patients (23 %) having significant fibrosis (F2-4). The Forn score best predicted significant fibrosis (area under the receiver operator characteristic curve (AUROC) 0.724, p = 0.001). With standard thresholds, the sensitivity for the Forn score for identification of significant fibrosis (F2-4) was 0 %. Using modified thresholds of 3.5, the sensitivity and negative predictive value increased to 85.7 and 94.7 %. This threshold was applied to an independent validation cohort with good accuracy. CONCLUSIONS Fibrosis risk scores using simple markers have moderate success at delineating obese patients with significant NAFLD-related fibrosis. Thresholds, however, need to be lowered to maximize diagnostic accuracy in this cohort.


title: The laboratory tests and host immunity of COVID-19 patients with different severity of illness.

text: BACKGROUND The Coronavirus Disease-2019 (COVID-19), infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a severe outbreak in China. The host immunity of COVID-19 patients is unknown. METHODS The routine laboratory tests and host immunity in COVID-19 patients with different severity of illness were compared after patient admission. RESULTS A total of 65 SARS-CoV-2-positive patients were classified as mild (n=30), severe (n=20), and extremely severe (n=15) illness. Many routine laboratory tests such as ferritin, lactate dehydrogenase and D-dimer were increased in severe and extremely severe patients. The absolute numbers of CD4+ T cells, CD8+ T cells and B cells were all gradually decreased with increased severity of illness. The activation markers such as HLA-DR and CD45RO expressed on CD4+ and CD8+ T cells were increased in severe and extremely severe patients compared with mild patients. The co-stimulatory molecule CD28 had opposite results. The percentage of natural regulatory T cells was decreased in extremely severe patients. The percentage of IFN-γ producing CD8+ T cells was increased in both severe and extremely severe patients compared with mild patients. The percentage of IFN-γ producing CD4+ T cells was increased in extremely severe patients. The IL-2R, IL-6, and IL-10 were all increased in extremely severe patients. The activation of DC and B cells was decreased in extremely severe patients. CONCLUSIONS The number and function of T cells are inconsistent in COVID-19 patients. The hyperfunction of CD4+ and CD8+ T cells is associated with the pathogenesis of extremely severe SARS-CoV-2 infection.


SARS-CoV-2 Does Not Spread Through ECMO or Dialysis Membranes.


title: Prevalence of Cerebral Palsy in Indian Children: A Systematic Review and Meta-Analysis.

text: OBJECTIVE To determine the pooled-prevalence of cerebral palsy in Indian children. METHODS The authors searched the published literature from different databases (PubMed, Ovid SP and EMBASE) and also tried to acquire information from the unpublished literature about the prevalence of cerebral palsy. They screened prospective/retrospective, cross-sectional, and cohort studies of children with cerebral palsy in the Indian population. Data were extracted from the included studies, and quality assessment was performed. Data were analysed using STATA MP12 (Texas, College Station). RESULTS Of the 862 publications searched, eight studies were qualified and included for quantitative analysis. The overall pooled prevalence of cerebral palsy per 1000 children surveyed was 2.95 (95% CI 2.03-3.88). Sub-group analysis for rural, urban and mixed rural-urban study population demonstrated the pooled prevalence as 1.83 (95% CI 0.41-3.25), 2.29 (95% CI 1.43-3.16) and 4.37 (95% CI 2.24-6.51) respectively. CONCLUSIONS This systematic review observed a paucity of high-quality, prevalence studies of cerebral palsy in India, which is a limitation to estimate the inferences for a national estimate. The observed prevalence of cerebral palsy in India is near similar to global estimates. There is a need to re-allocate resources and revisit the implementation of the existing policies for the prevention and management of cerebral palsy, taking into account the current disease burden.


Animal source of the coronavirus continues to elude scientists.


title: TLR4-mediated activation of macrophages by the polysaccharide fraction from Polyporus umbellatus(pers.) Fries.

text: AIM OF THE STUDY Zhu Ling (Polyporus umbellatus) is well-known to reduce the risk of a variety of diseases. In this study, we explored the molecular mechanism of its immunostimulatory potency in immune responses of macrophages, using polysaccharides prepared from Polyporus umbellatus (PPS). MATERIALS AND METHODS Splenocyte proliferation was analyzed with (3)H-TdR incorporation method. Nitric oxide (NO) was measured by Griess method and cytokines of culture supernatants was detected by enzyme linked immunosorbent assay (ELISA). The fluoresceinamine-labeled PPS (Flu-PPS) and dextran (Flu-dextran) were prepared by the cyanogen bromide activation method. The cell-binding activity of Flu-PPS was analyzed with FACS and confocal microscopy. NF-κB activity was measured by ELISA assay. RESULTS We found that PPS is able to strongly upregulate the functions of macrophages such as Nitric oxide (NO) production and cytokine expression. Compared with C3H/HeJ group, PPS significantly stimulated the proliferation of splenocytes and the production of TNF-α, IL-1β and NO of peritoneal macrophages from C3H/HeN mice. The function blocking antibodies to TLR-4, but not TLR-2 and CR3, markedly suppressed PPS-mediated TNF-α and IL-1β production. Flow cytometric and confocal laser-scanning microscopy analysis shown that fluorescence-labeled PPS (f-PPS) can bind specifically to the target cells, and the binding can blocked by unlabeled PPS and anti-TLR4, but not anti-TLR2 and CR3 monoclonal antibodies. Nuclear translocation and DNA binding activity of NF-κB was significantly induced by PPS. CONCLUSIONS Therefore, our data suggest that PPS may exert its immunostimulating potency via TLR-4 activation of signaling pathway.


title: Lack of Diversity in Personal Health Record Evaluations with Older Adult Participants: A Systematic Review of Literature.

text: BACKGROUND Older adults are not adopting personal health records (PHRs) at the same rates as other adult populations. Disparities in adoption rates are also reported in older adult subgroups. The variability in adoption may be because PHRs are not designed to meet older adult users. OBJECTIVE We analyzed PHR evaluation studies to examine the characteristics and perspectives of older adult study participants to identify their self-reported needs. METHOD We searched Medline, CINAHL, PsycINFO, and Embase for PHR evaluation studies that involved older adult participants. RESULTS 1017 abstracts were identified, and 179 publications went through full text review. 10 publications met inclusion criteria. These publications described studies conducted in 3 countries, and evaluated 7 PHRs. Homogeneity was found in the study populations and participant opinions of the systems. DISCUSSION Many PHR evaluations do not include diverse older adult participants. This may lead to consistency in outcomes, but it also may create gaps in identifying user needs. Additional studies, specifically targeting diverse older adult participants, are needed to gain a more comprehensive understanding of the opinions of older adults on PHRs and how these systems could benefit older adult healthcare consumers. CONCLUSION The body of research shows that older adults are highly satisfied using PHRs. These outcomes may be generalizable because most PHR evaluation studies do not include diverse older adult participants. This lack of participant diversity may be contributing to the disparities observed in PHR adoption rates.


title: Quantification of M13 and T7 bacteriophages by TaqMan and SYBR green qPCR.

text: TaqMan and SYBR Green quantitative PCR (qPCR) methods were developed as DNA-based approaches to reproducibly enumerate M13 and T7 phages from phage display selection experiments individually and simultaneously. The genome copies of M13 and T7 phages were quantified by TaqMan or SYBR Green qPCR referenced against M13 and T7 DNA standard curves of known concentrations. TaqMan qPCR was capable of quantifying M13 and T7 phage DNA simultaneously with a detection range of 2.75*101-2.75*108genome copies(gc)/μL and 2.66*101-2.66*108 genome copies(gc)/μL respectively. TaqMan qPCR demonstrated an efficient amplification efficiency (Es) of 0.97 and 0.90 for M13 and T7 phage DNA, respectively. SYBR Green qPCR was ten-fold more sensitive than TaqMan qPCR, able to quantify 2.75-2.75*107gc/μL and 2.66*101-2.66*107gc/μL of M13 and T7 phage DNA, with an amplification efficiency Es of 1.06 and 0.78, respectively. Due to its superior sensitivity, SYBR Green qPCR was used to enumerate M13 and T7 phage display clones selected against a cell line, and quantified titers demonstrated accuracy comparable to titers from traditional double-layer plaque assay. Compared to enzyme linked immunosorbent assay, both qPCR methods exhibited increased detection sensitivity and reproducibility. These qPCR methods are reproducible, sensitive, and time-saving to determine their titers and to quantify a large number of phage samples individually or simultaneously, thus avoiding the need for time-intensive double-layer plaque assay. These findings highlight the attractiveness of qPCR for phage enumeration for applications ranging from selection to next-generation sequencing (NGS).


title: Increasing signal processing sophistication in the calculation of the respiratory modulation of the photoplethysmogram (DPOP).

text: DPOP (∆POP or Delta-POP) is a non-invasive parameter which measures the strength of respiratory modulations present in the pulse oximetry photoplethysmogram (pleth) waveform. It has been proposed as a non-invasive surrogate parameter for pulse pressure variation (PPV) used in the prediction of the response to volume expansion in hypovolemic patients. Many groups have reported on the DPOP parameter and its correlation with PPV using various semi-automated algorithmic implementations. The study reported here demonstrates the performance gains made by adding increasingly sophisticated signal processing components to a fully automated DPOP algorithm. A DPOP algorithm was coded and its performance systematically enhanced through a series of code module alterations and additions. Each algorithm iteration was tested on data from 20 mechanically ventilated OR patients. Correlation coefficients and ROC curve statistics were computed at each stage. For the purposes of the analysis we split the data into a manually selected 'stable' region subset of the data containing relatively noise free segments and a 'global' set incorporating the whole data record. Performance gains were measured in terms of correlation against PPV measurements in OR patients undergoing controlled mechanical ventilation. Through increasingly advanced pre-processing and post-processing enhancements to the algorithm, the correlation coefficient between DPOP and PPV improved from a baseline value of R = 0.347 to R = 0.852 for the stable data set, and, correspondingly, R = 0.225 to R = 0.728 for the more challenging global data set. Marked gains in algorithm performance are achievable for manually selected stable regions of the signals using relatively simple algorithm enhancements. Significant additional algorithm enhancements, including a correction for low perfusion values, were required before similar gains were realised for the more challenging global data set.


title: A review of evolving dialysis catheter technologies.

text: Dialysis catheters continue to play a vital role in the delivery of hemodialysis to patients for both temporary vascular access, serving as a bridge to permanent access, and for long-term access for patients with end-stage renal disease (ESRD). During the past decade, there has been an emergence of technological advancements in the design of dialysis catheters in an attempt to reduce catheter malfunction, decrease infection rates, and improve their long-term efficiency. New improvements in catheter design are aimed at translating into improved catheter performance. This review article summarizes some of the novel catheter designs developed within the last decade.


title: Rescue of Recombinant Zika Virus from a Bacterial Artificial Chromosome cDNA Clone.

text: The association of Zika virus (ZIKV) infection with neurological complications during the recent worldwide outbreak and the lack of approved vaccines and/or antivirals have underscored the urgent need to develop ZIKV reverse genetic systems to facilitate the study of ZIKV biology and the development of therapeutic and/or prophylactic approaches. However, like with other flaviviruses, the generation of ZIKV full-length infectious cDNA clones has been hampered due to the toxicity of viral sequences during its amplification in bacteria. To overcome this problem, we have developed a nontraditional approach based on the use of bacterial artificial chromosomes (BACs). Using this approach, the full-length cDNA copy of the ZIKV strain Rio Grande do Norte Natal (ZIKV-RGN) is generated from four synthetic DNA fragments and assembled into the single-copy pBeloBAC11 plasmid under the control of the human cytomegalovirus (CMV) immediate-early promoter. The assembled BAC cDNA clone is stable during propagation in bacteria, and infectious recombinant (r)ZIKV is recovered in Vero cells after transfection of the BAC cDNA clone. The protocol described here provides a powerful technique for the generation of infectious clones of flaviviruses, including ZIKV, and other positive-strand RNA viruses, particularly those with large genomes that have stability problems during bacterial propagation.


title: Clinical characteristics of 82 cases of death from COVID-19.

text: A recently developed pneumonia caused by SARS-CoV-2 bursting in Wuhan, China, has quickly spread across the world. We report the clinical characteristics of 82 cases of death from COVID-19 in a single center. Clinical data on 82 death cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospital's electronic medical records according to previously designed standardized data collection forms. All patients were local residents of Wuhan, and a large proportion of them were diagnosed with severe illness when admitted. Due to the overwhelming of our system, a total of 14 patients (17.1%) were treated in the ICU, 83% of deaths never received Critical Care Support, only 40% had mechanical ventilation support despite 100% needing oxygen and the leading cause of death being pulmonary. Most of the patients who died were male (65.9%). More than half of the patients who died were older than 60 years (80.5%), and the median age was 72.5 years. The bulk of the patients who died had comorbidities (76.8%), including hypertension (56.1%), heart disease (20.7%), diabetes (18.3%), cerebrovascular disease (12.2%), and cancer (7.3%). Respiratory failure remained the leading cause of death (69.5%), followed by sepsis/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhagic, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On admission, lymphopenia (89.2%), neutrophilia (74.3%), and thrombocytopenia (24.3%) were usually observed. Most patients had a high neutrophil-to-lymphocyte ratio of >5 (94.5%), high systemic immune-inflammation index of >500 (89.2%), and increased C-reactive protein (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%) levels. A high level of IL-6 (>10 pg/ml) was observed in all detected patients. The median time from initial symptoms to death was 15 days (IQR 11-20), and a significant association between aspartate aminotransferase (p = 0.002), alanine aminotransferase (p = 0.037) and time from initial symptoms to death was remarkably observed. Older males with comorbidities are more likely to develop severe disease and even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but the virus itself and cytokine release syndrome-mediated damage to other organs, including cardiac, renal, hepatic, and hemorrhagic damage, should be taken seriously as well.


title: An adipogenic gel for surgical reconstruction of the subcutaneous fat layer in a rat model.

text: 'Off-the-shelf' tissue-engineered skin alternatives for epidermal and dermal skin layers are available; however, no such alternative for the subdermal fat layer exists. Without this well-vascularized layer, skin graft take is variable and grafts may have reduced mobility, contracture and contour defects. In this study a novel adipose-derived acellular matrix (Adipogel) was investigated for its properties to generate subdermal fat in a rat model. In a dorsal thoracic site, a 1 × 1 cm Adipogel implant was inserted within a subdermal fat layer defect. In a dorsal lumbar site, an Adipogel implant was inserted in a subfascial pocket. Contralateral control defects remained empty. At 8 weeks wound/implant sites were evaluated histologically, immunohistochemically and morphometrically. Identifiable thoracic Adipogel implants lost volume in vivo over 8 weeks. Neovascularization and adipogenesis were evident within implants and adipocyte percentage volume was 33.07 ± 6.55% (mean ± SEM). A comparison of entire cross-sections of thoracic wounds demonstrated a significant increase in total wound fat in Adipogel-implanted wounds (37.19 ± 4.48%, mean ± SEM) compared to control (16.53 ± 4.60%; p = 0.0092), indicating that some Adipogel had been completely converted to normal fat. At the lumbar site, Adipogel also lost volume, appearing flattened, although fat generation and angiogenesis occurred. At both sites macrophage infiltration was mild, whilst many infiltrating cells were PDGFRβ-positive mesenchymal cells. Adipogel is adipogenic and angiogenic and is a promising candidate for subcutaneous fat regeneration; it has the potential to be a valuable adjunct to wound-healing therapy and reconstructive surgery practice. Copyright © 2015 John Wiley & Sons, Ltd.


title: Stress management interventions for multiple sclerosis: A meta-analysis of randomized controlled trials.

text: Stress management interventions can help to improve mental health for adults living with multiple sclerosis. However, uncontrolled study designs may overestimate intervention effects. A systematic search of the Embase, PsycINFO, PubMed, and Scopus databases identified eight randomized controlled trials evaluating cognitive behavioral approaches for a pooled sample of 568 adults with multiple sclerosis. Both group and individual-based stress management interventions appear to be effective in promoting self-management of stress. Further research is needed to confirm the optimal timing of stress management interventions across the MS spectrum and strategies to maintain intervention effects.


Thanks to Reviewers.


title: Real-time sonographically guided percutaneous dilatational tracheostomy using a long-axis approach compared to the landmark technique.

text: OBJECTIVES Sonographic evaluation of neck anatomy before performing percutaneous dilatational tracheostomy (PDT) has been shown to predict PDT success. In this study, we compared the real-time, long-axis, in-plane approach to the traditional bronchoscopically guided landmark technique. METHODS Data were analyzed from a prospectively maintained PDT database at a university tertiary care medical intensive care unit. A convenience sample of adult patients requiring PDT for prolonged mechanical ventilation dependence was enrolled. Critical care fellows, under direct supervision of an attending intensivist, performed all PDTs. Tracheostomy performance from the sonographically guided and landmark techniques was compared. RESULTS Twenty-three patients were enrolled: 11 in the sonography group and 12 in the landmark group. Initial midline introducer needle puncture was achieved in 72.7% in the sonography group compared to 8.3% in the landmark group (P< .001). The mean number of introducer needle punctures ± SD was significantly lower in the sonography group compared to the landmark group (1.4 ± 0.7 versus 2.6 ± 0.9; P < .001). The total tracheostomy time was 11.4 ± 4.2 minutes in the sonography group versus 15.3 ± 6.8 minutes in the landmark group (P = .12). Sonography accurately predicted tracheal ring space insertion in 90.9% of patients. Procedural complications did not differ significantly between the groups. CONCLUSIONS Percutaneous dilatational tracheostomy under real-time sonographic guidance using a long-axis approach may increase the rate of midline punctures and decrease the number of needle punctures when compared to the landmark technique. Sonographic guidance can also help guide accurate and efficient placement of a tracheostomy tube into the desired tracheal ring space.


title: Advances in plant virus evolution: translating evolutionary insights into better disease management.

text: Recent studies in plant virus evolution are revealing that genetic structure and behavior of virus and viroid populations can explain important pathogenic properties of these agents, such as host resistance breakdown, disease severity, and host shifting, among others. Genetic variation is essential for the survival of organisms. The exploration of how these subcellular parasites generate and maintain a certain frequency of mutations at the intra- and inter-host levels is revealing novel molecular virus-plant interactions. They emphasize the role of host environment in the dynamic genetic composition of virus populations. Functional genomics has identified host factors that are transcriptionally altered after virus infections. The analyses of these data by means of systems biology approaches are uncovering critical plant genes specifically targeted by viruses during host adaptation. Also, a next-generation resequencing approach of a whole virus genome is opening new avenues to study virus recombination and the relationships between intra-host virus composition and pathogenesis. Altogether, the analyzed data indicate that systematic disruption of some specific parameters of evolving virus populations could lead to more efficient ways of disease prevention, eradication, or tolerable virus-plant coexistence.


title: Structure-function analysis of severe acute respiratory syndrome coronavirus RNA cap guanine-N7-methyltransferase.

text: Coronaviruses possess a cap structure at the 5' ends of viral genomic RNA and subgenomic RNAs, which is generated through consecutive methylations by virally encoded guanine-N7-methyltransferase (N7-MTase) and 2'-O-methyltransferase (2'-O-MTase). The coronaviral N7-MTase is unique for its physical linkage with an exoribonuclease (ExoN) harbored in nonstructural protein 14 (nsp14) of coronaviruses. In this study, the structure-function relationships of the N7-MTase were analyzed by deletion and site-directed mutagenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) nsp14. The results showed that the ExoN domain is closely involved in the activity of the N7-MTase, suggesting that coronavirus N7-MTase is different from all other viral N7-MTases, which are separable from other structural domains located in the same polypeptide. Two of the 12 critical residues identified to be essential for the N7-MTase were located at the N terminus of the core ExoN domain, reinforcing a role of the ExoN domain in the N7-MTase activity of nsp14. The other 10 critical residues were distributed throughout the N7-MTase domain but localized mainly in the S-adenosyl-l-methionine (SAM)-binding pocket and key structural elements of the MTase fold of nsp14. The sequence motif DxGxPxA (amino acids [aa] 331 to 338) was identified as the key part of the SAM-binding site. These results provide insights into the structure and functional mechanisms of coronaviral nsp14 N7-MTase.


title: Short- and Mid-Term Outcomes after Endoscopic Transanal or Laparoscopic Transabdominal Total Mesorectal Excision for Low Rectal Cancer: A Single Institutional Case-Control Study.

text: BACKGROUND Transabdominal laparoscopic proctectomy (LAP) for rectal cancer was associated with postoperative recovery improvement. Early studies showed favorable short-term results of endoscopic transanal proctectomy (ETAP), with low conversion rates to open procedures. We aimed to compare efficacy, morbidity, and functional outcomes of ETAP to standard LAP for low rectal cancer. STUDY DESIGN From 2008 to 2013, 72 consecutive patients received proctectomy and coloanal manual anastomosis for low rectal adenocarcinoma. Thirty-four patients had transanal endoscopic proctectomy, and 38 patients underwent the standard laparoscopic procedure. RESULTS When compared with the LAP group, the ETAP group demonstrated a lower conversion rate to open procedures (23.7% vs 2.9%, respectively; p = 0.015), shorter in-hospital stays (9 vs 8 days, respectively; p = 0.04), and a lower readmission rate (13.2% vs 0%; p = 0.03). Overall postoperative morbidity rates for the LAP and the ETAP groups (36.8% vs 32.4%, respectively; p = 0.69) and functional results (Kirwan score 1/2, 73.7% vs 73.5%, respectively; p = 0.85) were comparable; additionally, we found similar oncologic quality criteria (R1 resection 10.5% vs 5.9%, respectively; p = 0.68; grade 3 mesorectal integrity 52.6% vs 55.9%, respectively; p = 0.66). Disease-free survival of 24 months (Kaplan-Meier estimation) was comparable in the 2 groups: 86% in the ETAP group vs 88% in the LAP group; p = 0.91. At the date of last follow-up, 91.2% of ETAP patients and 92.1% of LAP patients were free of stoma. CONCLUSIONS The endoscopic transanal approach could facilitate mesorectal excision and improve short-term outcomes without impairing the oncologic quality of the resection or mid-term functional and oncologic results.


title: Sildenafil Exposure in the Neonatal Intensive Care Unit.

text: OBJECTIVE Pulmonary hypertension causes substantial morbidity and mortality in infants. Although Food and Drug Administration approved to treat pulmonary arterial hypertension in adults, sildenafil is not approved for infants. We sought to describe sildenafil exposure and associated diagnoses and outcomes in infants. STUDY DESIGN Retrospective cohort of neonates discharged from more than 300 neonatal intensive care units from 2001 to 2016. RESULTS Sildenafil was administered to 1,336/1,161,808 infants (0.11%; 1.1 per 1,000 infants); 0/35,977 received sildenafil in 2001 versus 151/90,544 (0.17%; 1.7 per 1,000 infants) in 2016. Among infants <32 weeks' gestational age (GA) with enough data to determine respiratory outcome, 666/704 (95%) had bronchopulmonary dysplasia (BPD). Among infants ≥32 weeks GA, 248/455 (55%) had BPD and 76/552 (14%) were diagnosed with meconium aspiration. Overall, 209/921 (23%) died prior to discharge. CONCLUSION The use of sildenafil has increased since 2001. Exposed infants were commonly diagnosed with BPD. Further studies evaluating dosing, safety, and efficacy of sildenafil are needed.


Data Error in Viewpoint on COVID-19 in Italy.


Blood sampling after COVID-19 - How to organize large scale phlebotomy services in the post SARS CoV-2 era.


Involvement of Cisgender and Transgender Individuals in Studies on the Impact of Hormonal Therapy on COVID-19.


Pandemic publishing poses a new COVID-19 challenge.


title: A DGKζ-FoxO-ubiquitin proteolytic axis controls fiber size during skeletal muscle remodeling.

text: Skeletal muscle rapidly remodels in response to various stresses, and the resulting changes in muscle mass profoundly influence our health and quality of life. We identified a diacylglycerol kinase ζ (DGKζ)-mediated pathway that regulated muscle mass during remodeling. During mechanical overload, DGKζ abundance was increased and required for effective hypertrophy. DGKζ not only augmented anabolic responses but also suppressed ubiquitin-proteasome system (UPS)-dependent proteolysis. We found that DGKζ inhibited the transcription factor FoxO that promotes the induction of the UPS. This function was mediated through a mechanism that was independent of kinase activity but dependent on the nuclear localization of DGKζ. During denervation, DGKζ abundance was also increased and was required for mitigating the activation of FoxO-UPS and the induction of atrophy. Conversely, overexpression of DGKζ prevented fasting-induced atrophy. Therefore, DGKζ is an inhibitor of the FoxO-UPS pathway, and interventions that increase its abundance could prevent muscle wasting.


title: Canadian Cardiovascular Society and Canadian Pediatric Cardiology Association Position Statement on the Approach to Syncope in the Pediatric Patient.

text: Pediatric syncope is a common problem that peaks in adolescence, for which there are few data or evidence-based consensus on investigation and management. This document offers guidance for practical evaluation/management of pediatric patients (age < 19 years) with syncope encountered in the acute or primary care setting. The writing committee used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Most syncope is vasovagal, which is benign and does not require extensive investigation. This Position Statement presents recommendations to encourage an efficient and cost-effective disposition for the many patients with a benign cause of syncope, and highlights atypical or concerning clinical findings associated with other causes of transient loss of consciousness. The prodrome and the circumstances around which the event occurred are the most important aspects of the history. Syncope occurring midexertion suggests a cardiac etiology. A family history, which includes sudden death in the young or from unknown causes or causes that might be suspected to be other than natural can be a red flag. The electrocardiogram is the most frequently ordered test, but the yield is low and the test is not cost-effective when applied broadly to a population of patients with syncope. We recommend an electrocardiogram when the history is not suggestive of vasovagal syncope and there are features suggestive of a cardiac cause like absence of a prodrome, midexertional event, family history of early-life sudden death or heart disease, abnormal physical examination, or new medication with potential cardiotoxicity. For most patients with syncope, medical testing is not required and lifestyle modifications without medications suffice to prevent recurrences.


title: Caloric restriction reverses left ventricular hypertrophy through the regulation of cardiac iron homeostasis in impaired leptin signaling mice.

text: Leptin-deficient and leptin-resistant mice manifest obesity, insulin resistance, and left ventricular hypertrophy (LVH); however, LVH's mechanisms are not fully understood. Cardiac iron dysregulation has been recently implicated in cardiomyopathy. Here we investigated the protective effects of caloric restriction on cardiac remodeling in impaired leptin signaling obese mice. RNA-seq analysis was performed to assess the differential gene expressions in the heart of wild-type and ob/ob mice. In particular, to investigate the roles of caloric restriction on iron homeostasis-related gene expressions, 10-week-old ob/ob and db/db mice were assigned to ad libitum or calorie-restricted diets for 12 weeks. Male ob/ob mice exhibited LVH, cardiac inflammation, and oxidative stress. Using RNA-seq analysis, we identified that an iron uptake-associated gene, transferrin receptor, was upregulated in obese ob/ob mice with LVH. Caloric restriction attenuated myocyte hypertrophy, cardiac inflammation, fibrosis, and oxidative stress in ob/ob and db/db mice. Furthermore, we found that caloric restriction reversed iron homeostasis-related lipocalin 2, divalent metal transporter 1, transferrin receptor, ferritin, ferroportin, and hepcidin expressions in the heart of ob/ob and db/db mice. These findings demonstrate that the cardioprotective effects of caloric restriction result from the cellular regulation of iron homeostasis, thereby decreasing oxidative stress, inflammation, and cardiac remodeling. We suggest that decreasing iron-mediated oxidative stress and inflammation offers new therapeutic approaches for obesity-induced cardiomyopathy.


title: Multifunctional photopolymerized semiinterpenetrating network (sIPN) system containing bupivacaine and silver sulfadiazine is an effective donor site treatment in a swine model.

text: Previously, we have shown in a cross-comparison study that multifunctional photopolymerized semiinterpenetrating network (sIPN) system is an effective donor site treatment in a swine model. The advantages of sIPN include spray-on application, in situ photopolymerization, and ability to cover large contoured areas. sIPN has also been shown to be an effective delivery vehicle for keratinocyte growth factor, dexamethasone, bupivacaine, and silver sulfadiazine in vitro. Our aim for this study was to show that these products delivered to the wound bed with sIPN would not change the wound healing characteristics compared with the control site through qualitative clinical evaluation and to compare the rate and quality of donor site healing through histologic evaluation. Eight Yucatan swine of 40 lbs each were randomly divided into four groups of two pigs before surgery. Each animal had 5.6% TBSA of skin harvested from two different dorsal regions, with one at 22/1000th-inch and the other at 30/1000th-inch setting on the dermatome. Each test site on each animal was then sequentially dressed with 50 cm(2) of Xeroform gauze, sIPN, sIPN loaded with 0.5% bupivacaine, or sIPN loaded with 1% silver sulfadiazine. sIPN with or without soluble drugs were applied as liquid, then photopolymerized in situ to form an elastic covering. Each of the test areas was separated by 50 cm(2) of autograft, which was used to divide the test areas. Wound assessment and killing occurred at days 7, 9, 14, and 21. A full-thickness biopsy was taken from each of the study areas for histological analysis. By 14 days, all areas showed complete epidermal coverage histologically. The 30/1000th-inch site revealed a thicker, more irregular dermis compared with the 22/1000th-site. Evaluation of the day-21 sites revealed equal thinning and flattening of the new epidermis. No site showed full restoration of the rete ridges. No signs of infection were seen in clinical or histological evaluations of any treatment. The addition of bupivacaine and silver sulfadiazine to sIPN does not show any alterations in wound healing of a donor site in a swine model when compared with sIPN without loaded drugs and a standard control dressing. This efficacy may be coupled with established localized sIPN drug delivery profiles and allow further studies to evaluate the efficacy of these drugs to promote healing, eradicate and prevent infection, and manage pain.


title: Robotic versus laparoscopic resection for sigmoid diverticulitis with fistula.

text: Robotic abdominal surgery is growing despite a paucity of clinical reports to evaluate its impact on patient outcomes. In this retrospective case series, we aim to analyze our early experience with robotic resection in 11 consecutive patients with chronic colonic diverticulitis complicated by fistula to bladder, vagina, or skin and to compare the results of the robotic approach to 20 patients undergoing laparoscopic resection for the same indication. Our main outcome measures include operative time, blood loss, conversion rate, transfusion rate, hospital length of stay, complications, readmission, and fistula healing rate. In our study, we found robotic resection for colonic diverticulitis with fistula was technically feasible and yielded 100% fistula healing rate. The operative time, complication and readmission rates were similar to laparoscopy. A higher conversion rate, diverting stoma need, and longer hospital length of stay were noted in the robotic group; however, these findings could have been attributed to a higher number of cases involving rectal excision in the robotic group. Larger studies are needed to further examine the impact of robotic surgery on the outcome of patients with complicated chronic sigmoid diverticulitis.


title: Respiratory syncytial virus and other respiratory viruses in the setting of bone marrow transplantation.

text: PURPOSE OF REVIEW Several epidemiologic studies have enhanced our understanding of the impact of respiratory viruses on bone marrow transplant recipients. RECENT FINDINGS Respiratory viral infections occur frequently following stem cell transplantation but present atypically. Many patients have asymptomatic infections. There is a growing armamentarium of antiviral agents currently under development, although prospective studies in transplant patients are needed. SUMMARY Respiratory viral infections occur frequently after hematopoietic stem cell transplant. Newer agents may prove useful in the prevention and treatment of respiratory viral infections in this population.


Iran's experience in establishing convalescent care facilities for patients with Covid-19.


title: Laparoscopy-assisted transvaginal resection of sigmoid cancer.

text: OBJECTIVE To investigate the feasibility and safety of laparoscopy-assisted transvaginal resection of sigmoid cancer. METHODS From 2009 to 2011 we performed 21 laparoscopy-assisted transvaginal resections of sigmoid cancers. RESULTS The resected tumours were T1(6), T2(7) and T3(8). The median number of resected lymph nodes was 15. Median operative time was 150 min and no conversion to open technique was necessary. A total of eighteen patients tolerated a liquid diet 24 h after surgery. The average VAS pain score (0 = no pain, 10 = unbearable pain) was 1.8 after 24 h and 1.1 after 48 h. One patient experienced a postoperative ileus, two patients had vaginal spotting with serous flow and three patients suffered urinary tract infections. One patient developed a hernia at the umbilical trocar site that was operated on. None of the sexually active patients reported any differences in sexual activity pre-op and postop on a postoperative questionnaire. After a median of 25 (10-41) months of follow-up, all patients are alive and well, with no evidence of recurrent disease. CONCLUSION Laparoscopy-assisted transvaginal resection of sigmoid cancer is feasible and safe in a selected group of patients.


title: [Research progress of the impact of COVID-19 outbreak on people living with HIV].

text: The rapid spread of COVID-19 global outbreak will inevitably pose great challenges for public health and medical care, especially for major concerns of public health such as HIV. In the light of the COVID-19 pandemic, UNAIDS is urging countries to remain steadfast in their HIV prevention efforts. Few studies of COVID-19 have been focused on marginalized populations, especially those with HIV infection. This study aims to review the studies and researches of COVID-19 among people living with HIV, covering the impacts of COVID-19 on their disease progression, HIV-related medical services, HIV epidemics, and measures on relieving the above-mentioned impacts, which might provide references for targeted scientific research and prevention practice of COVID-19 in HIV population, and optimizing prevention and treatment services in the context of this pandemic.