title: Genome engineering.

text: For more than 50 years, those engineering genetic material have pursued increasingly challenging targets. During that time, the tools and resources available to the genetic engineer have grown to encompass new extremes of both scale and precision, opening up new opportunities in genome engineering. Today, our capacity to generate larger de novo assemblies of DNA is increasing at a rapid pace (with concomitant decreases in manufacturing cost). We are also witnessing potent demonstrations of the power of merging randomness and selection with engineering approaches targeting large numbers of specific sites within genomes. These developments promise genetic engineering with unprecedented levels of design originality and offer new avenues to expand both our understanding of the biological world and the diversity of applications for societal benefit.


title: Olfactory Dysfunction in COVID-19 Patients: Prevalence and Prognosis for Recovering Sense of Smell.

text: While olfactory dysfunction associated with coronavirus disease 2019 (COVID-19) has attracted considerable interest, few studies have tracked outcomes at serial time points or beyond 2 weeks. Furthermore, data are conflicting regarding whether COVID-19 severity correlates with degree of olfactory dysfunction. This prospective case-control study analyzed prevalence and severity of subjective loss of smell in outpatients (n = 23) and inpatients (n = 20) with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vs healthy controls (n = 25). Olfactory dysfunction was reported more commonly in COVID-19 patients than in healthy controls (P < .001), and outpatients paradoxically reported loss of smell more commonly than inpatients (P = .02). Headaches were present in 52% of patients with olfactory dysfunction. Anosmia or hyposmia persisted beyond 5 days but most of the patients recovered by 30 days, suggesting favorable prognosis for olfaction. Differences between inpatients and outpatients are potentially reflective of timeline of olfactory symptoms and contextual factors, underscoring the importance of corroborative objective testing, coupled with careful tracking of temporal relationships.


docid: dffztnhu

title: Chronic rhinosinusitis: pathogenesis, therapy options, and more.

text: INTRODUCTION When rhinosinusitis - the inflammation of the nasal cavity and paranasal sinuses - persists for over 12 weeks, it is termed 'chronic rhinosinusitis' (CRS). Both innate and adaptive immunity contribute to the heterogeneous inflammatory pathogenesis of CRS, which is driven by genetic and environmental factors and the microbiome. CRS is classified by the presence of polyps. Molecular mechanisms in CRS with nasal polyps are similar to those in atopic diseases. AREAS COVERED This review focuses on the immune pathogenesis of CRS, differences between the two CRS subtypes, and latest treatments that may aid in the provision of personalized medicine. EXPERT OPINION Basic research in the last decade has helped significantly in enhancing our knowledge of the pathophysiologic processes of CRS, due to which there is now a better understanding of the associated natural history, physiopathology, novel treatments, and prevention strategies. Treatment success depends on the clarification of the underlying pathogenesis and disease-contributing factors. The exploration of disease endotypes and introduction of novel agents are important advancements. Prior studies performed without disease-endotyping resulted in the inefficiency of certain drugs and insignificant results. The identification of biomarkers, development of personalized approaches, and utilization of disease algorithms are required for CRS therapy success.


title: Persistent Smell Loss Following Undetectable SARS-CoV-2.

text: The association of smell and taste loss with COVID-19 has been well demonstrated with high prevalence rates. In certain cases, chemosensory loss may be the only symptom of COVID-19 and may linger while other symptoms have resolved. The significance of persistent smell and taste loss and its relationship to ongoing viral shedding has yet to be investigated. In this cross-sectional study, of the 316 laboratory test-confirmed COVID-19 cases at our institution, 46 had subsequent test-based confirmation of viral clearance with 2 consecutive negative RT-PCR test results (reverse transcriptase polymerase chain reaction). Olfactory dysfunction was reported by 50% of the patients (23 of 46), with 78% (18 of 23) having subjective persistent smell loss despite negative RT-PCR test results. These preliminary data demonstrate the persistence of self-reported smell loss despite otherwise clinical resolution and undetectable nasal viral RNA.


title: The Trevo XP 3×20 mm retriever ('Baby Trevo') for the treatment of distal intracranial occlusions.

text: OBJECTIVE To report our single-center initial experience using the Trevo XP ProVue Retriever 3×20 mm ('Baby Trevo') for distal intracranial occlusions. METHODS We performed a retrospective review of our interventional database for consecutive patients who underwent treatment for acute ischemic stroke with the Baby Trevo device between February and December 2014. RESULTS Of 134 patients treated during the study period, 8 underwent treatment with the Baby Trevo for distal occlusions. Their mean age was 51±20 years, 5 (62.5%) were male, mean baseline National Institutes of Health Stroke Scale was 19±5. The mean interval between the time the patient was last-known normal to groin puncture was 527±285 min, and the overall procedural length was 110±26 min. Intra-arterial tissue plasminogen activator was used in 5 (62.5%) cases. The device was used for a total of 10 branches: five middle cerebral artery (four superior M3 and one inferior M3), three anterior cerebral arteries (two pericallosal and one callosomarginal), and two posterior cerebral arteries (one P2 and one P3) occlusions. All patients achieved complete recanalization of the artery targeted by the Baby Trevo (arterial occlusive lesion 3). Good capillary reperfusion (TICI 2b-3) was noted in 6 (75%) cases. One pass was performed in 7 vessels and 2 passes in three branches. Vasospasm was noted in 5 (62.5%) of the vessels and fully responded to intra-arterial vasodilator infusion. Follow-up MRI revealed no infarct within the territory vascularized by the artery targeted by the Baby Trevo in 4 cases, partial infarct in 5, and complete infarct in 1. Two patients had parenchymal hematomas (one PH1 and one PH2). No vessel perforations, dissections, or subarachnoid hemorrhage were noted. CONCLUSIONS Our initial data suggest that treatment of distal cerebrovascular occlusions with the Trevo XP 3×20 mm Retriever is feasible. Although this device emerges as a promising technology for small and tortuous distal intracranial vessels, larger studies are still necessary to establish its safety and clinical benefit.


Tuberculosis: progress and challenges in product development and delivery.


Is extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest superior compared with conventional resuscitation?


title: Exploitation of reverse vaccinology and immunoinformatics as promising platform for genome-wide screening of new effective vaccine candidates against Plasmodium falciparum.

text: BACKGROUND In the current scenario, designing of world-wide effective malaria vaccine against Plasmodium falciparum remain challenging despite the significant progress has been made in last few decades. Conventional vaccinology (isolate, inactivate and inject) approaches are time consuming, laborious and expensive; therefore, the use of computational vaccinology tools are imperative, which can facilitate the design of new and promising vaccine candidates. RESULTS In current investigation, initially 5548 proteins of P. falciparum genome were carefully chosen for the incidence of signal peptide/ anchor using SignalP4.0 tool that resulted into 640 surface linked proteins (SLP). Out of these SLP, only 17 were predicted to contain GPI-anchors using PredGPI tool in which further 5 proteins were considered as malarial antigenic adhesins by MAAP and VaxiJen programs, respectively. In the subsequent step, T cell epitopes of 5 genome derived predicted antigenic adhesins (GDPAA) and 5 randomly selected known malarial adhesins (RSKMA) were analysed employing MHC class I and II tools of IEDB analysis resource. Finally, VaxiJen scored T cell epitopes from each antigen were considered for prediction of population coverage (PPC) analysis in the world-wide population including malaria endemic regions. The validation of the present in silico strategy was carried out by comparing the PPC of combined (MHC class I and II) predicted epitope ensemble among GDPAA (99.97%), RSKMA (99.90%) and experimentally known epitopes (EKE) of P. falciparum (97.72%) pertaining to world-wide human population. CONCLUSIONS The present study systematically screened 5 potential protective antigens from P. falciparum genome using bioinformatics tools. Interestingly, these GDPAA, RSKMA and EKE of P. falciparum epitope ensembles forecasted to contain highly promiscuous T cell epitopes, which are potentially effective for most of the world-wide human population with malaria endemic regions. Therefore, these epitope ensembles could be considered in near future for novel and significantly effective vaccine candidate against malaria.


title: Porcine Deltacoronavirus Accessory Protein NS6 Antagonizes Interferon Beta Production by Interfering with the Binding of RIG-I/MDA5 to Double-Stranded RNA.

text: Porcine deltacoronavirus (PDCoV) has recently emerged as an enteric pathogen that can cause serious vomiting and diarrhea in suckling piglets. The first outbreak of PDCoV occurred in the United States in 2014 and was followed by reports of PDCoV in South Korea, China, Thailand, Lao People's Democratic Republic, and Vietnam, leading to economic losses for pig farms and posing a considerable threat to the swine industry worldwide. Our previous studies have shown that PDCoV encodes three accessory proteins, NS6, NS7, and NS7a, but the functions of these proteins in viral replication, pathogenesis, and immune regulation remain unclear. Here, we found that ectopic expression of accessory protein NS6 significantly inhibits Sendai virus-induced interferon beta (IFN-β) production as well as the activation of transcription factors IRF3 and NF-κB. Interestingly, NS6 does not impede the IFN-β promoter activation mediated via key molecules in the RIG-I-like receptor (RLR) signaling pathway, specifically RIG-I, MDA5, and their downstream molecules MAVS, TBK1, IKKε, and IRF3. Further analyses revealed that NS6 is not an RNA-binding protein; however, it interacts with RIG-I/MDA5. This interaction attenuates the binding of double-stranded RNA by RIG-I/MDA5, resulting in the reduction of RLR-mediated IFN-β production. Taken together, our results demonstrate that ectopic expression of NS6 antagonizes IFN-β production by interfering with the binding of RIG-I/MDA5 to double-stranded RNA, revealing a new strategy employed by PDCoV accessory proteins to counteract the host innate antiviral immune response.IMPORTANCE Coronavirus accessory proteins are species specific, and they perform multiple functions in viral pathogenicity and immunity, such as acting as IFN antagonists and cell death inducers. Our previous studies have shown that PDCoV encodes three accessory proteins. Here, we demonstrated for the first time that PDCoV accessory protein NS6 antagonizes IFN-β production by interacting with RIG-I and MDA5 to impede their association with double-stranded RNA. This is an efficient strategy of antagonizing type I IFN production by disrupting the binding of host pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs). These findings deepen our understanding of the function of accessory protein NS6, and they may direct us toward novel therapeutic targets and lead to the development of more effective vaccines against PDCoV infection.


title: Oral care and pulmonary infection - the importance of plaque scoring.

text: Improving the quality of oral hygiene is recognised as an important counter measure for reducing the incidence of ventilator-associated pneumonia amongst critically ill patients. Toothbrushing physically disrupts the dental plaque that acts as a reservoir for pulmonary infection and therefore has the potential to reduce the incidence of ventilator-associated pneumonia. Gu and colleagues performed a systematic review and meta-analysis of oral hygiene with and without a toothbrush and found no difference in the incidence of pneumonia in mechanically ventilated patients. The diagnosis of ventilator-associated pneumonia is prone to bias and future studies of oral care interventions should focus on measures of oral cleanliness such as plaque and gingival scores. Once the optimal strategy for oral hygiene is defined in the critically ill, larger studies focussing on ventilator-associated pneumonia or mortality can be conducted.


title: The host immune dynamics of pneumococcal colonization: implications for novel vaccine development.

text: The human nasopharynx (NP) microbiota is complex and diverse and Streptococcus pneumoniae (pneumococcus) is a frequent member. In the first few years of life, children experience maturation of their immune system thereby conferring homeostatic balance in which pneumococci are typically rendered as harmless colonizers in the upper respiratory environment. Pneumococcal carriage declines in many children before they acquire capsular-specific antibodies, suggesting a capsule antibody-independent mechanism of natural protection against pneumococcal carriage in early childhood. A child's immune system in the first few years of life is Th2-skewed so as to avoid inflammation-induced immunopathology. Understanding Th1/Th2 and Th17 ontogeny in early life and how adjuvant vaccine formulations shift the balance of T helper-cell differentiation, may facilitate the development of new protein-based pneumococcal vaccines. This article will discuss the immune dynamics of pneumococcal colonization in infants. The discussion aims to benefit the design and improvement of protein subunit-based next-generation pneumococcal vaccines.


title: Impact of the defect size, the mesh overlap and the fixation depth on ventral hernia repairs: a combined experimental and numerical approach.

text: BACKGROUND Ventral hernia repairs (VHRs) still exhibit clinical complications in terms of recurrence, pain, and discomfort. Factors such as surgical technique or mesh features are thought to be highly influent. The aim was to evaluate the impact of the defect size, the mesh overlap and the fixation depth on VHR using both physical and numerical models. METHODS The physical model was developed to mimic a passive abdominal wall. Healthy, damaged, and repaired configurations were evaluated using a spherical plunger. The associated numerical (Finite Elements) model was first loaded by a plunger for validation. A parametric study was then conducted with the numerical model loaded by a uniform pressure. Two defect sizes (3.5 × 5 cm and 8.25 × 12 cm elliptic shape), two overlaps (2 and 5 cm), and two fixation depths (peritoneum or muscle) were investigated for both passive and active abdominal walls. RESULTS With the physical model, the repaired configuration was 22 % stiffer than the damaged configuration. The statistical analysis of the parametric study showed that the defect size was the most influential parameter regarding the stress in the mesh, the bulging and the pull-out force at the fixation points. The overlap was influential in terms of stress in the mesh. The fixation depth was not influential. These trends increased with the abdominal wall activity. CONCLUSION Increase of the defect size and decrease of the overlap affected significantly the VHR mechanical performances. Such numerical models could help to better understand the behavior of the repaired abdominal wall and finally to reduce the clinical complications.


title: Coronavirus Disease 2019 and Transplantation: a view from the inside.

text: Since December 2019, world healthcare community faced with Coronavirus Disease 2019 (COVID-19) outbreak caused by SARS-CoV-2. Due to the high viral contagiousness and the possible transmission during the pre-symptomatic phase, COVID-19 progressively spread to several countries. Currently, Italy is the third Country for number of confirmed cases after mainland China and South Chorea, and the first western nation with a well-established deceased transplant program to tackle a COVID-19 outbreak1 .


Corrigendum: Myeloid-derived growth factor (C19orf10) mediates cardiac repair following myocardial infarction.


Intraoperative airway obstruction from a whole dissection of the inner wall of a reinforced endotracheal tube.


title: The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities.

text: The pulmonary endothelium is a dynamic, metabolically active layer of squamous endothelial cells ideally placed to mediate key processes involved in lung homoeostasis. Many of these are disrupted in acute respiratory distress syndrome (ARDS), a syndrome with appreciable mortality and no effective pharmacotherapy. In this review, we consider the role of the pulmonary endothelium as a key modulator and orchestrator of ARDS, highlighting advances in our understanding of endothelial pathobiology and their implications for the development of endothelial-targeted therapeutics including cell-based therapies. We also discuss mechanisms to facilitate the translation of preclinical data into effective therapies including the application of biomarkers to phenotype patients with ARDS with a predominance of endothelial injury and emerging biotechnologies that could enhance delivery, discovery and testing of lung endothelial-specific therapeutics.


title: Gasless robotic perineal radical prostatectomy: An initial experience.

text: Radical prostatectomy (RP) is the gold standard treatment method of localized prostate cancer. Today, this surgery is performed with open or minimally invasive methods. The history of open perineal RP (RPP) is very old, but it is not often preferred by urologists. The use of robot-assisted laparoscopic RP (RALP) is very frequently applied today. Robotic perineal RP (r-RPP) by using a Gel-Point and insufflating CO2 into the perineal region was first described in 2014. In this case report, we report a 68-year-old patient with localized prostate cancer in whom we successfully performed gasless r-RPP, and according to our knowledge, this is the first case of gasless r-RPP to be reported.


title: [Noninvasive Respiratory Support for Novel Coronavirus Pneumonia: Enough is Enough].

text: 新型冠状病毒易导致急性呼吸窘迫综合征(ARDS)，已对生命安全构成极大的威胁。无创呼吸辅助治疗是新型冠状病毒肺炎引起ARDS的常规治疗手段，但在新型冠状病毒肺炎治疗中，往往存在过度使用无创呼吸功能支持治疗而导致气管插管延迟进而影响患者的临床预后，因此，了解无创通气使用的指征和禁忌，早期识别无创通气治疗失败的危险因素，适时终止无创通气转为有创通气是目前临床医师治疗新型冠状病毒肺炎亟需关注的问题。.


title: Virus infection cycle events coupled to RNA replication.

text: Replication, the process by which the genetic material of a virus is copied to generate multiple progeny genomes, is the central part of the virus infection cycle. For an infection to be productive, it is essential that this process is coordinated with other aspects of the cycle, such as translation of the viral genome, encapsidation, and movement of the genome between cells. In the case of positive-strand RNA viruses, this represents a particular challenge, as the infecting genome must not only be replicated but also serve as an mRNA for the production of the replication-associated proteins. In recent years, it has become apparent that in positive-strand RNA plant viruses all the aspects of the infection cycle are intertwined. This article reviews the current state of knowledge regarding replication-associated events in such viruses.


Is Sensitivity the Key Measure to Predict Acute Liver Failure in Drug-Induced Liver Injury Patients?


Isolationist Policies Threaten Public Health.


title: Nonneoplastic and neoplastic Barrett's esophagus: the European perspective.

text: The cancer risk of nondysplastic Barrett's esophagus is very low (0.33-0.5 per year). Therefore, any endoscopic ablation technique is an overtreatment. Patients with low-grade intraepithelial neoplasia confirmed by a specialized GI pathologist seem to have a significant risk for developing high-grade intraepithelial neoplasia (HGIN) or cancer. Therefore, endoscopic treatment in this case seems to be justified. However, up to now there has been no prospective study supporting this. In recent years, endoscopic treatment of HGIN and mucosal Barrett's cancer has become a widely accepted treatment approach and even the therapy of choice in many countries. Endoscopic resection (ER) is the best validated treatment method in patients with HGIN and mucosal Barrett's cancer, and is widely used all over the world. In contrast to ablative treatment methods like argon plasma coagulation and radiofrequency ablation, ER allows histological assessment of the resected specimen in order to assess the depth of infiltration of the tumor. However, ER of the neoplastic lesions should always be followed by ablation of the nondysplastic remaining Barrett's esophagus in order to reduce the risk of recurrence or metachronous neoplasia. The long-time complete remission rate with this two-step strategy is ≥95%. A matter of continuing debate is whether patients with Barrett's cancer infiltrating the upper third of the mucosal layer (pT1sm1) can be treated by ER. Data from our and other centers indicate that a subgroup of patients with pT1sm1 adenocarcinomas without the presence of risk factors (poor differentiation grade, lymph or blood vessel infiltration, size >20 mm, ulcerated lesion) have a very low risk for lymph node metastasis (<2%) and endoscopic therapy can be an alternative to radical surgery.


title: Fingolimod treatment abrogates chikungunya virus-induced arthralgia.

text: Chikungunya virus (CHIKV) is one of the many rheumatic arthropod-borne alphaviruses responsible for debilitating joint inflammation in humans. Despite the severity in many endemic regions, clinically approved intervention targeting the virus remains unavailable. CD4+ T cells have been shown to mediate CHIKV-induced joint inflammation in mice. We demonstrate here that transfer of splenic CD4+ T cells from virus-infected C57BL/6 mice into virus-infected T cell receptor-deficient (TCR-/-) mice recapitulated severe joint pathology including inflammation, vascular leakages, subcutaneous edema, and skeletal muscle necrosis. Proteome-wide screening identified dominant CD4+ T cell epitopes in nsP1 and E2 viral antigens. Transfer of nsP1- or E2-specific primary CD4+ T cell lines into CHIKV-infected TCR-/- recipients led to severe joint inflammation and vascular leakage. This pathogenic role of virus-specific CD4+ T cells in CHIKV infections led to the assessment of clinically approved T cell-suppressive drugs for disease intervention. Although drugs targeting interleukin-2 pathway were ineffective, treatment with fingolimod, an agonist of sphingosine 1-phosphate receptor, successfully abrogated joint pathology in CHIKV-infected animals by blocking the migration of CD4+ T cells into the joints without any effect on viral replication. These results set the stage for further clinical evaluation of fingolimod in the treatment of CHIKV-induced joint pathologies.


Techniques used in lung metastasectomy.


title: Measles vaccination: Threat from related veterinary viruses and need for continued vaccination post measles eradication.

text: Measles virus (MV) is the only human virus within the morbillivirus genus of the Paramyxoviridae. The veterinary members are canine distemper virus (CDV), peste des petits ruminants virus (PPRV), Rinderpest Virus (RPV) as well as the marine morbilliviruses phocine distemper virus (PDV), dolphin morbillivirus (DMV) and porpoise morbillivirus (PMV). Morbilliviruses have a severe impact on humans and animal species. They confer diseases which have contributed to morbidity and mortality of the population on a global scale. There is substantial evidence from both natural and experimental infections that morbilliviruses can readily cross species barriers. Of most concern with regard to zoonosis is the more recently reported fatal infection of primates in Japan and China with strains of CDV which have adapted to this host. The close genetic relationship, shared cell entry receptors and similar pathogenesis between the morbilliviruses highlights the potential consequences of complete withdrawal of MV vaccination after eradication. Therefore, it would be prudent to continue the current MV vaccination. Ultimately development of novel, safe vaccines which have higher efficacy against the veterinary morbilliviruses is a priority. These would to protect the human population long term against the threat of zoonosis by these veterinary viruses.


title: Long-term recurrence and complication rates after incisional hernia repair with the open onlay technique.

text: BACKGROUND Incisional hernia after abdominal surgery is a well-known complication. Controversy still exists with respect to the choice of hernia repair technique. The objective of this study was to evaluate the long-term recurrence rate as well as surgical complications in a consecutive group of patients undergoing open repair using an onlay mesh technique. METHODS Consecutive patients undergoing open incisional hernia repair with onlay-technique between 01/05/1995 and 01/09/2007 at a single institution were included in the study. For follow-up patients were contacted by telephone, and answered a questionnaire containing questions related to the primary operation, the hernia and general risk factors. Patients were examined by a consultant surgeon in the outpatient clinic or in the patient's home if there was suspicion of an incisional hernia recurrence. RESULTS The study included 56 patients with 100% follow-up. The median follow-up was 35 months (range 4-151). Recurrent incisional hernia was found in 8 of 56 patients (15%, 95% CI: 6-24). The overall complication rate was 13% (95% CI, 4-22). All complications were minor and needed no hospital admission. CONCLUSION This study with a long follow-up showed low recurrence and complication rates in patients undergoing incisional hernia repair with the open onlay technique.


title: Comparison of simultaneous dual-isotope multipinhole SPECT with rotational SPECT in a group of patients with coronary artery disease.

text: UNLABELLED A triple-detector, multipinhole SPECT system was optimally configured to perform simultaneous (201)Tl (stress)/(99m)Tc (rest) myocardial perfusion imaging (MPI) using a protocol that permitted direct diagnostic comparison of this multipinhole SPECT system with conventional rotational SPECT. METHODS Both the rotational and the multipinhole SPECT systems used the same model gamma-detectors. The 2 systems were applied in tandem to study 26 patients with documented coronary status. Visual image evaluation of the MPI together with quantitative analysis using circumferential profile curves (CPC) were used for interpretation of stress/rest myocardial flow differences. A dual-peak attenuation compensation (DPAC) technique was applied to the stress (201)Tl multipinhole SPECT images by weighted combination of the images from the upper and lower peaks. RESULTS Detection of myocardial infarction by location and extent correlated closely, and correlation of differential flow changes between stress and rest indicated similar accuracy in terms of location and extent of myocardial blood flow differences as well. In addition, the application of DPAC clarified the multipinhole stress (201)Tl images through reduced background and increased statistics and also improved the relative superposition of the normalized CPC, especially for the inferior and more basal reconstructed regions. CONCLUSION The prototype 3-detector multipinhole SPECT system achieved diagnostic results comparable to those for rotational SPECT and required only a single image-acquisition session to generate stress/rest MPI and 16-segment poststress gated studies. This reduction in acquisition time significantly improves productivity without compromising diagnostic accuracy. In addition, DPAC is a useful adjunct to the multipinhole SPECT modality because it improves both the visual clarity of the stress images and the stress/rest quantitative comparability.


title: Progression of kidney injury and cardiac remodeling in obese spontaneously hypertensive rats: the role of renal sympathetic innervation.

text: BACKGROUND Hypertension and metabolic syndrome (MetS) are associated with increased sympathetic activation possibly contributing to the progression of renal damage and cardiac remodeling. Renal sympathetic denervation (RDN) decreases sympathetic renal efferent and afferent nerve activity. METHODS Obese spontaneously hypertensive rats (SHRs-ob) were subjected to RDN at the age of 34 weeks (SHRs-ob + RDN) and were compared with sham-operated SHRs-ob and their normotensive lean controls (Ctrs). Blood pressure was measured by telemetry. Kidney and heart function were determined by magnetic resonance imaging (MRI). Renal and cardiac remodeling were characterized by immunohistochemical analyses. Animals were killed at the age of 48 weeks. RESULTS In SHRs-ob, RDN attenuated the progressive increase in blood pressure and preserved a mean blood pressure of 156±7mm Hg compared with 220±8mm Hg in sham-operated SHRs-ob at 100 days after RDN, whereas heart rate, body weight, and metabolic parameters remained unchanged. Renal catecholamine and tyrosine hydroxylase levels were significantly reduced after RDN, suggesting effective renal denervation. Progression of renal dysfunction as characterized by increased urinary albumin/creatinine ratio and reduced glomerular filtration rate were attenuated by RDN. In SHRs-ob, renal perfusion was significantly reduced and normalized by RDN. Cardiac fibrosis and cardiac diastolic dysfunction measured by MRI and invasive pressure measurements were significantly attenuated by RDN. CONCLUSIONS In SHRs-ob, progressive increase in blood pressure and progression of renal injury and cardiac remodelling are mediated by renal sympathetic activation as they were attenuated by RDN.


title: Stereotactic radiosurgery for central nervous system hemangioblastoma: systematic review and meta-analysis.

text: Hemangioblastomas are rare, benign, vascular tumors of the central nervous system (CNS), often associated with von-hippel lindau (VHL) disease. Current therapeutic options include microsurgical resection or stereotactic radiosurgery (SRS). With no randomized controlled studies and minimal data beyond single-institution reviews, the optimal management approach for patients with CNS hemangioblastomas is unclear. We completed a Pubmed/SCOPUS literature search from January 1990 to January 2017 for eligible studies on SRS for CNS hemangioblastomas. Relevant articles were identified and reviewed in accordance to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. 26 studies met eligibility criteria for qualitative synthesis, representing 596 subjects and 1535 tumors. The Gamma Knife was the most published SRS method for CNS hemangioblastomas. After critical study appraisal for intra-study bias, 14 studies were used for quantitative meta-analysis of 5-year progression free survival (PFS). The pooled 5-year PFS across all eligible studies was 88.4%. No difference was observed between spine versus intracranial studies. Individual patient data (IPD) was extracted from 14 studies, representing 322 tumors. Univariate analysis of IPD revealed that VHL patients were younger, and had smaller tumors compared to those with sporadic disease. Adverse events were associated with increasing marginal dose, independent of tumor volume. VHL status, sex, radiosurgical method, tumor location, and tumor volume were not found to be significantly associated with tumor progression. Multiple studies show excellent tumor control at 5-year follow up, however, the long-term efficacy of SRS for CNS hemangioblastomas still needs to be investigated, and the studies exploring the role of SRS for early treatment of asymptomatic lesions is wanting.


title: First documentation of persistent SARS-CoV-2 infection presenting with late acute severe myocarditis.

text: A 64 year-old man presented with severe myocarditis 6 weeks after an initial almost asymptomatic SARS-CoV2 infection. He was found to have a persistent positive swab. Mechanisms explaining myocardial injury in patients with COVID-19 remains unclear, but this case suggests that severe acute myocarditis can develop in the late phase of COVID-19 infection, even after a symptom-free interval.


title: Response to Covid-19: An ethical imperative to build a resilient health system in India.

text: China reported cases of a severe form of pneumonia in December 2019 from Wuhan city, Hubei province. The virus causing this illness was identified as the novel Coronavirus 2019, which has now been christened Covid-19. The illness is characterised by fever, cough, body pain and in a few cases, progression to acute respiratory distress syndrome (ARDS) which marks very serious damage to the lungs (1-4). Apart from Wuhan, China, the virus has spread to 26 other countries as on February 18, 2020. Of these 26 countries, the cases of Covid-19 have been exported directly from China in 23 of them. As on February 23, 2020, a total of 78,811 confirmed cases, 2445 deaths have been reported globally. The World Health Organization declared this as a Public Health Emergency of International Concern (PHEIC) on January 30, 2020 (5).


title: Gaussian position weighted center of gravity algorithm for multiplexed readout.

text: Readout signal multiplexing is a commonly used method to reduce the electronics cost in PET systems, and calculation of the scintillation coordinates typically is done by using a Center of Gravity (CoG) technique due to its simplicity and ease of implementation. This comes with a drawback, since CoG has a non-linear response at the periphery of the detector due to the lack of weights beyond the detector. Detectors with multiplexed readout that are based on finely segmented scintillators and coarsely segmented photosensors are known to suffer from the so called edge effect where a pile-up of the reconstructed coordinates from the edge crystals is observed. This may lead to incorrect assignment of the events to crystal pixels and result in formation of erroneous lines of response causing a degradation of spatial resolution and reduction of image contrast. To overcome abovementioned limitations in gamma ray detectors with multiplexed photosensor readout, we propose to use modified Gaussian Position Weighted Center of Gravity technique for calculation of gamma ray interaction position. Here the proposed method is applied to PET detectors with 24×24 LYSO crystals read out by 8 × 8 SiPM array with 64:16 row/column multiplexing. Furthermore, we compared the modified Gaussian Position Weighted Center of Gravity (PW-CoG) and Truncated Center of Gravity (TCoG) coordinate reconstruction methods. It was observed that both algorithms resolve peaks corresponding to events registered in the crystal pixels on the periphery of the crystal array, however peak-to-valley ratios and crystal resolvability metrics for PW-CoG algorithm are generally greater.


title: Crohn's disease-associated ATG16L1 polymorphism modulates pro-inflammatory cytokine responses selectively upon activation of NOD2.

text: OBJECTIVE Autophagy has recently been shown to modulate the production of pro-inflammatory cytokine production and to contribute to antigen processing and presentation through the major histocompatibility complex. Genetic variation in the autophagy gene ATG16L1 has been recently implicated in Crohn's disease pathogenesis. The mechanisms underlying this association are not yet known, although experimental models suggest an inhibitory effect of autophagy on interleukin 1β (IL-1β) responses. Here, the effect of ATG16L1 genetic variation on cytokine responses has been assessed in humans. DESIGN AND SETTING Peripheral blood mononuclear cells from healthy individuals and patients with Crohn's disease with different ATG16L1 genotypes were stimulated with ligands for Toll-like receptor 2 (TLR2), TLR4 and nucleotide-binding oligomerisation domain 2 (NOD2), with or without the autophagy inhibitor 3-methyladenine. Induction of cytokine production and related factors were measured at the mRNA and protein level. Furthermore, protein levels of ATG16L1 were assessed by western blot. RESULTS The present study demonstrates that cells isolated from individuals bearing the ATG16L1 Thr300Ala risk variant, which is shown to affect ATG16L1 protein expression upon NOD2 stimulation, display increased production of the pro-inflammatory cytokines IL-1β and IL-6, specifically after stimulation with NOD2 ligands. In contrast, no differences were found when cells were stimulated with TLR2 or TLR4 agonists. These findings were confirmed in two independent cohorts of volunteers and in a group of patients with Crohn's disease. The increased production could be ascribed to increased mRNA expression, while processing of pro-IL-1β by caspase-1 activation was not affected. The effect of the ATG16L1 polymorphism was abrogated when autophagy was blocked. CONCLUSIONS The present study is the first to link the ATG16L1 polymorphism with an excessive production of IL-1β and IL-6 in humans, which may explain the effects of this polymorphism on the inflammatory process in Crohn's disease.


Preparing for the Sickest Patients With 2009 Influenza A(H1N1).


Legal and Policy Interventions to Address Social Isolation.


title: Anesthesia for liver transplantation.

text: Orthotopic liver transplantation is the only definitive treatment for end-stage liver disease. More than 6000 procedures are performed in the United States annually with excellent survival rates. The shortage of donor organs leads to continued interest in techniques to enlarge the potential donor pool. Patients presenting for liver transplant suffer from important cardiovascular, respiratory, renal, neurological, and gastroenterological comorbidity. In the Western world, liver failure is increasingly caused by steatohepatitis, and transplant candidates are thus becoming older and more comorbid. The role of the transplant anesthesiologist is highly important in the preoperative assessment, intraoperative management, and postoperative care of these complex and sick patients. Appropriate investigation and management of comorbidities such as coronary artery disease and portopulmonary hypertension is controversial and differs between programs. The transplant procedure is a major surgery, and although massive transfusion is no longer commonplace, there is potential for significant hemodynamic instability, coagulopathy, and metabolic disturbance. Liver transplant surgery can be divided into the preanhepatic phase, the anhepatic phase, and the reperfusion phase, with important anesthetic considerations at each point. An understanding of the surgical techniques used for vascular exclusion of the liver and the role of venovenous bypass is crucial for the anesthesiologist. Recent trends in perioperative care include the use of antifibrinolytic drugs and point-of-care coagulation tests, intraoperative renal replacement therapy, and "fast-track" extubation and postoperative care. Care of patients with fulminant hepatic failure or those receiving split-liver grafts requires special consideration.


title: Modifications of Surgical Suction Tip Geometry for Flow Optimisation: Influence on Suction-Induced Noise Pollution.

text: Introduction Suction devices for clearing the surgical field are among the most commonly used tools of every surgeon because a better view of the surgical field is essential. Forced suction may produce disturbingly loud noise, which acts as a nonnegligible stressor. Especially, in emergency situations with heavy bleeding, this loud noise has been described as an impeding factor in the medical decision-making process. In addition, there are reports of inner ear damage in patients due to suction noises during operations in the head area. These problems have not been solved yet. The purpose of this study was to analyse flow-dependent suction noise effects of different surgical suction tips. Furthermore, we developed design improvements to these devices. Methods We compared five different geometries of suction tips using an in vitro standardised setup. Two commercially available standard suction tips were compared to three adapted new devices regarding their flow-dependent (10-2000 mL/min) noise emission (dB, weighting filter (A), distance 10 cm) and acoustic quality of resulting noises (Hamilton fast Fourier analysis) during active suction at the liquid-air boundary. Noise maps at different flow rates were created for all five suction devices, and the proportion of extracted air was measured. The geometries of the three custom-made suction tips (new models 1, 2, and 3) were designed considering the insights after determining the key characteristics of the two standard suction models. Results The geometry of a suction device tip has significant impact on its noise emission. For the standard models, the frequency spectrum at higher flow rates significantly changes to high-frequency noise patterns (>3 kHz). A number of small side holes designed to prevent tissue adhesion lead to increased levels of high-frequency noise. Due to modifications of the tip geometry in our new models, we are able to achieve a highly significant reduction of noise level at low flow rates (new model 2 vs. standard models p < 0.001) and also the acoustic quality improved. Additionally, we attain a highly significant reduction of secondary air intake (new model 2 vs. the other models p < 0.001). Conclusion Improving flow-relevant features of the geometry of suction heads is a suitable way to reduce noise emissions. Optimized suction tips are significantly quieter. This may help us to reduce noise-induced hearing damage in patients as well as stress of medical staff during surgery and should lead to quieter operation theatres overall. Furthermore, the turbulence reduction and reduced secondary air intake during the suction process are expected to result in protective effects on the collected blood and thus could improve the quality of autologous blood retransfusions. We are on the way to evaluate potential benefits.


title: A Pre-Hospital Patient Education Program Improves Outcomes of Bariatric Surgery.

text: BACKGROUND We designed an assessment and education program which was delivered to patients prior to first outpatient appointment for bariatric surgery. We hypothesised that this program would streamline care and would lead to improved weight loss following bariatric surgery. METHODS The program incorporates a structured general practitioners (GP) review, a patient information evening and an on-line learning package. It was introduced in September 2012. Patient flow through the program was recorded. Outcomes of the new program were compared with contemporaneously treated patients who did not undertake the pre-hospital program. RESULTS All 636 patients on the waiting list for first appointment at the Alfred Health bariatric surgery clinic were invited to participate. There were 400 patients ultimately removed from the waiting list for first appointment. Of the remaining 236 patients, 229 consented to participate in the new program. The mean BMI was 47.8 ± 9.2. The fail to attend first appointment rate dropped from 12 to 2.1 %. At 12 months post-bariatric surgery, patients who undertook the new program (n = 82) had a mean excess weight loss (EWL) of 41.1 ± 20.3 % where as those treated on the standard pathway (n = 61) had a mean EWL 32 ± 18.0 % (p = 0.012). CONCLUSIONS The introduction of a pre-hospital education program has led to an improvement in attendance rates and early weight loss post-bariatric surgery.


Covid-19 ray of hope as vets lend a hand.


title: Medina® Embolization Device for the Treatment of Intracranial Aneurysms: Safety and Angiographic Effectiveness at 6 Months.

text: BACKGROUND The Medina Embolization Device (MED) is a new concept device that combines the design of a detachable coil and the one of an intrasaccular flow disruption device. OBJECTIVE To evaluate the feasibility, safety, and 6- to 9-mo effectiveness of this new device for the treatment of intracranial wide-necked aneurysms. METHODS Twelve patients (10 females, mean age = 56 yr) with 13 wide-necked intracranial aneurysms (3 ruptured; 10 unruptured) were treated by means of the MED from January 2015 to October 2015. In 15% of the cases, MEDs were used in a standalone fashion; in 85% of the cases, additional regular coils were used. Adjunctive compliant balloon was used in 4 of 13 cases (31%). Procedure-related complications were systematically recorded; discharge and 6- to 9-mo follow-up modified Rankin Scale was assessed. Angiographic follow-up was performed with a mean delay of 5.5 ± 1.7 mo. Occlusion rate was evaluated in postprocedure and at midterm follow-up using the Roy-Raymond scale. RESULTS The deployment of the MED was feasible in all cases. No perforation was recorded. One case of thromboembolic complication was observed in a ruptured anterior communicating artery aneurysm, without any clinical consequence at follow-up. Grade A occlusion rate was 61.5% in postprocedure and 83% at 6-mo follow-up. Two cases (17%) of recanalization were documented angiographically. CONCLUSION The MED is a new generation device combining the design of a detachable coil and an intrasaccular flow disruption device. According to our early experience, this device is safe and provides a satisfactory occlusion rate at angiographic follow-up of 6 mo.


A Message from the Guest Editor.


Critical Organizational Issues for Cardiologists in the COVID-19 Outbreak: A Frontline Experience From Milan, Italy.


title: Diagnostic Yield of Colon Capsule Endoscopy in Detection of Superficial Colorectal Lesions.

text: BACKGROUND The efficacy of second-generation PillCam -COLON2 capsule endoscopy (CCE2) in detecting colorectal superficial lesions remains unclear. OBJECTIVE We sought to determine the diagnostic yield of CCE2 in the detection of colorectal superficial lesions. METHODS We performed CCE2 in 60 consecutive patients between April 2011 and -December 2017. Lesions ≥6 mm in size were detected in 34 patients (25 males, average age: 60.5 years). We performed endoscopic resection and histopathological analysis of all resected lesions within 3 months after CCE2. We considered the optical colonoscopy (OC) findings as the gold standard and evaluated CCE2 sensitivity. RESULTS Sixty-seven lesions (≥6 mm) were detected via OC, with 27 colorectal superficial lesions and 40 protruded lesions. CCE2 sensitivity for ≥6-mm-sized, superficial, and protruded lesions was 84, 78, and 88%, respectively. No significant intergroup differences were observed. CCE2 false-negative colorectal superficial lesions accounted for 31% of right-sided colon lesions and 50% of sessile serrated adenomas/polyps (SSA/Ps). The CCE2 false-negative protruded lesions accounted for 17% of right-sided colon lesions. CONCLUSION CCE2 sensitivities for colorectal superficial and protruded lesions were not significantly different. However, flat-type SSA/Ps in the right colon, especially when the transit time is fast, have a risk of demonstrating CCE2 false-negative results.


title: [Investigation and analysis on characteristics of a cluster of COVID-19 associated with exposure in a department store in Tianjin].

text: Objective: To describe the epidemiological characteristics of a cluster of COVID-19 cases reported in Baodi district of Tianjin as of 18 February, 2020, which might be associated with the exposure in a local department store, and provide suggestions for prevention and control strategy development. Methods: The basic characteristics, time and area distributions, clinical manifestations, epidemiological history and transmission mode of the COVID-19 cases associated with the department store exposure were analyzed. Results: A total of 40 COVID-19 cases were associated with the department store exposure, accounting for 75.47% of the total confirmed cases (53 cases) reported in Baodi district. The cases were mainly at the age of 60 years or older (35.00%) and farmers (40.00%). The main clinical manifestations included fever (95.00%), cough (35.00%), and diarrhea (15.00%). The proportion of confirmed severe cases was 32.50%. The incidence curve showed that the incidence peak occurred on 31 January, 2020. Among the 40 cases, 6(15.00%) were department store employees, 19(47.50%) were customers and 15(37.50%) were close contacts (secondary cases). The first case occurred on 21 January, 2020, this case was a department store employee who had a purchasing history at whole sale markets in other provinces and cities before the onset, and 3 employees were still on duty after symptom onsets. The median of the incubation period of customer cases was 6 days, and the median of the interval between onset and medical treatment of customer cases was 7 days. Conclusion: This was a cluster epidemic of COVID-19, which might be associated with the exposure in the department store. By now, the current prevention and control measures have achieved satisfied effects.


Annals On Call - Understanding the Spread of COVID-19.


COVID-19 Research in Brief: 20 March to 27 March, 2020.


title: Swelling after laparoscopic total extraperitoneal repair of inguinal hernias: review of one surgeon's experience in 1,065 cases.

text: BACKGROUND It is often difficult to assess the clinical significance of scrotal or operative site swelling after a laparoscopic total extraperitoneal (TEP) repair of an inguinal hernia. Specifically, surgeons are often faced with the dilemma of determining whether such a swelling is a recurrent hernia or just a swelling only. MATERIALS AND METHODS A total of 1,065 laparoscopic TEP inguinal hernia repairs were performed on 944 patients by a single surgeon between December 2000 and December 2008, and we reviewed these data. RESULTS The overall incidence of swelling formation was 6.5% (70 of 1,065 cases). Swellings were more frequent in males, and in association with the following diagnoses: indirect inguinal hernias, larger hernia defects, scrotal hernias, omental incarcerations, and the presence of residual distal sacs. Fifty-eight (83%) of 70 patients who had swelling after laparoscopic TEP did not need any intervention for swelling and the swelling resolved spontaneously. CONCLUSIONS Although postoperative swellings are a common complication after laparoscopic TEP repairs of inguinal hernias, swellings are minor complications, are not associated with hernia recurrence, and generally subside spontaneously.


[Cholecystectomy using single-incision laparoscopic surgery (SILS)].


title: Oral diosmectite reduces stool output and diarrhea duration in children with acute watery diarrhea.

text: BACKGROUND & AIMS Diosmectite is a clay used to treat children with acute watery diarrhea. However, its effects on stool output reduction, the key outcome for pediatric antidiarrheal drugs, have not been shown. METHODS Two parallel, double-blind studies of diosmectite efficacy on stool reduction were conducted in children 1 to 36 months old in Peru (n = 300) and Malaysia (n = 302). Inclusion criteria included 3 or more watery stools per day for less than 72 hours and weight/height ratios of 0.8 or greater. Exclusion criteria were the need for intravenous rehydration, gross blood in stools, fever higher than 39 degrees C, or current treatment with antidiarrheal or antibiotic medications. Rotavirus status was determined. Diosmectite dosage was 6 g/day (children 1-12 months old) or 12 g/day (children 13-36 months old), given for at least 3 days, followed by half doses until complete recovery. Patients were assigned randomly to groups given diosmectite or placebo, in addition to oral rehydration solution (World Health Organization). RESULTS Children in each study had comparable average ages and weights. The frequencies of rotavirus infection were 22% in Peru and 12% in Malaysia. Similar amounts of oral rehydration solution were given to children in the diosmectite and placebo groups. Stool output was decreased significantly by diosmectite in both studies, especially among rotavirus-positive children. In pooled data, children had a mean stool output of 94.5 +/- 74.4 g/kg of body weight in the diosmectite group versus 104.1 +/- 94.2 g/kg in the placebo group (P = .002). Diarrhea duration was reduced by diosmectite, which was well tolerated. CONCLUSIONS These results show that diosmectite significantly decreased stool output in children with acute watery diarrhea, especially those who were rotavirus-positive.


COVID-19: new challenges, risks, and the future provision of care in spinal services.


[SARS-CoV-2 infection and its relation with the nutritional status].


title: Companion diagnostics: emerging strategies and issues in pharmaceutical development.

text: This article summarizes the broad messages from pharmaceutical and diagnostic companies on the collaborations required to support companion diagnostics. Since the groundbreaking herceptin HER2 diagnostic model in 1998, it has taken until 2011 for the US FDA to issue a draft guidance document, which was then immediately followed with approvals for two new drugs and their companion diagnostics. This conference summarized the current state of thinking in new projects and innovative technologies in pharmaceutical and diagnostic codevelopment. Attitudes are slowly changing and collaborations are rapidly ensuing, although the alignment between pharmaceutical and diagnostic understanding of value, timelines, outcomes and impact is difficult and remains a contentious area. The value of this conference has been to address these issues.


title: Containing the first outbreak of COVID-19 in a healthcare setting in India: The sree chitra experience.

text: The response to the first health worker case in India and novel strategies adopted in the context of evolving pandemic of COVID-19 is presented here. On the same day of confirmation, institutional COVID cell was established, and contact tracing was started. A total of 184 contacts were identified and quarantined. Hospital services were scaled down, and responsibilities were reassigned. In-house digital platforms were used for daily meetings, contact tracing, line listing, risk stratification, and research. Reverse transcription polymerase chain reaction-based severe acute respiratory syndrome-CoV2 testing facility was established in the institute. All high-risk contacts were given hydroxychloroquine prophylaxis. No secondary cases were found. Hospital preparedness, participatory decision-making through institutional COVID cell, optimal use of in-house digital platforms, and coordination with the state health department and national bodies, including Indian Council of Medical Research, were the supporting factors. Rapidly evolving guidelines, trepidation about the disease, logistic delays, and lack of support systems for people under quarantine were the challenges in the containment exercise.


title: An investigation of the questions posted on medical consultation websites.

text: BACKGROUND Online medical consultation has recently become a more and more popular alternative venue for healthcare. It allows patients and caregivers to discuss their health problems and symptoms with qualified medical health professionals via the Internet. OBJECTIVE This study investigates the questions posted on an asynchronous online medical consultation website, Taiwan eDoctor. Five research themes are explored: (1) length of questions, (2) moment of seeking consultation, (3) strategies of communicating chief complaints, (4) purpose of seeking consultation and (5) identity disclosure. METHODS Data collection was conducted by randomly selecting 50 resolved consultation Q&As for each of 24 medical specialties, resulting in a total of 1200 entries in the primary data set. Data analysis was conducted qualitatively and quantitatively. RESULTS Average length of questions was 161.21 words. Online medical consultation was sought when healthy, healthy but not robust, when suspicious of illness, when diagnosed as ill and during treatment/recovery. In communicating chief complaints, consultation seekers were engaged in contextual, focal or emotional communication styles. Nine distinct purposes to seek online consultation were identified and can be broadly interpreted as intellectual, social and emotional. The finding also suggests that more than two-third of questions were asked for by the patients themselves. CONCLUSION Through content analysis of questions posted on an online medical consultation website, this study characterises communication patterns during the health information seeking process. These findings can help guide the design of more effective patient-centred online medical consultation services.


title: Design and synthesis of MMP inhibitors with appended fluorescent tags for imaging and visualization of matrix metalloproteinase enzymes.

text: We describe the synthesis, MMP-2 and 9 potency, and in vitro evaluation of a series of α-sulfone hydroxmate MMP inhibitors conjugated to a series of dyes with different absorption/emission lamina maxima's that can be used to visualize tumors.


title: The Mark Coventry Award: diagnosis of early postoperative TKA infection using synovial fluid analysis.

text: BACKGROUND Synovial fluid white blood cell count is useful for diagnosing periprosthetic infections but the utility of this test in the early postoperative period remains unknown as hemarthrosis and postoperative inflammation may render standard cutoff values inaccurate. QUESTIONS/PURPOSES We evaluated the diagnostic performance of four common laboratory tests, the synovial white blood cell count, differential, C-reactive protein, and erythrocyte sedimentation rate to detect infection in the first 6 weeks after primary TKA. METHODS We reviewed 11,964 primary TKAs and identified 146 that had a knee aspiration within 6 weeks of surgery. Infection was diagnosed in 19 of the 146 knees by positive cultures or gross purulence. We compared demographic information, time from surgery, and the laboratory test values between infected and noninfected knees to determine if any could identify infection early postoperatively. Receiver operating characteristic curves were constructed to determine optimal cutoff values for each of the test parameters. RESULTS Synovial white blood cell count (92,600 versus 4200 cells/μL), percentage of polymorphonuclear cells (89.6% versus 76.9%), and C-reactive protein (171 versus 88 mg/L) were higher in the infected group. The optimal synovial white blood cell cutoff was 27,800 cells/μL (sensitivity, 84%; specificity, 99%; positive predictive value, 94%; negative predictive value, 98%) for diagnosing infection. The optimal cutoff for the differential was 89% polymorphonuclear cells and for C-reactive protein 95 mg/L. CONCLUSIONS With a cutoff of 27,800 cells/μL, synovial white blood cell count predicted infection within 6 weeks after primary TKA with a positive predicted value of 94% and a negative predictive value of 98%. The use of standard cutoff values for this parameter (~ 3000 cells/μL) would have led to unnecessary reoperations. LEVEL OF EVIDENCE Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.


title: Detection of SARS-CoV-2 antibodies using commercial assays and seroconversion patterns in hospitalized patients.

text: OBJECTIVES SARS-CoV-2 antibody assays are needed for serological surveys and as a complement to molecular tests to confirm COVID-19. However, the kinetics of the humoral response against SARS-CoV-2 remains poorly described and relies on the performance of the different serological tests. METHODS In this study, we evaluated the performance of six CE-marked point-of-care tests (POC) and three ELISA assays for the diagnosis of COVID-19 by exploring seroconversions in hospitalized patients who tested positive for SARS-CoV-2 RNA. RESULTS Both the ELISA and POC tests were able to detect SARS-CoV-2 antibodies in at least half of the samples collected seven days or more after the onset of symptoms. After 15 days, the rate of detection rose to over 80% but without reaching 100%, irrespective of the test used. More than 90% of the samples collected after 15 days tested positive using the iSIA and Accu-Tell® POC tests and the ID.Vet IgG ELISA assay. Seroconversion was observed 5 to 12 days after the onset of symptoms. Three assays suffer from a specificity below 90% (EUROIMMUN IgG and IgA, UNscience, Zhuhai Livzon). CONCLUSIONS The second week of COVID-19 seems to be the best period for assessing the sensitivity of commercial serological assays. To achieve an early diagnosis of COVID-19 based on antibody detection, a dual challenge must be met: the immunodiagnostic window period must be shortened and an optimal specificity must be conserved.


docid: tnrinhwk

title: Surgical Training With Live Animal Models for Laparoscopic Gastrectomy.


Is BCG vaccination effecting the spread and severity of COVID-19?


title: Screening for cancer in patients with unprovoked venous thromboembolism: protocol for a systematic review and individual patient data meta-analysis.

text: INTRODUCTION Occult cancer is present in 4%-9% of patients with unprovoked venous thromboembolism (VTE). Screening for cancer may be considered in these patients, with the aim to diagnose cancers in an early, potentially curable stage. Information is needed about the risk of occult cancer, overall and in specific subgroups, additional risk factors and on the performance of different screening strategies. METHODS AND ANALYSIS MEDLINE, Embase and CENTRAL databases were searched from November 2007 to January 2016 for prospective studies that had evaluated protocol-mandated screening for cancer in patients with unprovoked VTE and with at least 12 months' follow-up. Two reviewers independently assessed articles for eligibility. Ten eligible studies were identified and individual patient data were obtained from each of them. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool . Generalised linear mixed-effects models was used to calculate estimates in a one-stage meta-analytic approach, overall and in a number of subgroups, including patients undergoing limited screening only, elderly patients, patients with previous VTE, smokers and patients using oestrogens. ETHICS AND DISSEMINATION Ethical approval is not required for this systematic review and individual patient data meta-analysis. Findings have been submitted for publication in peer-reviewed journals and presentations at national and international conferences to provide clinicians and other decision-makers with valid and precise risk estimates of occult cancer, overall and in specific clinical subgroups, with risk factors for occult cancer, with estimates of the diagnostic performance of limited screening and with an exploration of the benefit of extensive screening strategies.


title: MHC class I A loci polymorphism and diversity in three Southeast Asian populations of cynomolgus macaque.

text: Cynomolgus macaques (Macaca fascicularis, Mafa) have emerged as important animal models for biomedical research, necessitating a more extensive characterization of their major histocompatibility complex polymorphic regions. The current information on the polymorphism or diversity of the polygenetic Mafa class I A loci is limited in comparison to the more commonly studied rhesus macaque Mafa class I A loci. Therefore, in this paper, to better elucidate the degree and types of polymorphisms and genetic differences of Mafa-A1 among three native Southeast Asian populations (Indonesian, Vietnamese, and Filipino) and to investigate how the allele differences between macaques and humans might have evolved to affect their respective immune responses, we identified 83 Mafa-A loci-derived alleles by DNA sequencing of which 66 are newly described. Most alleles are unique to each population, but seven of the most frequent alleles were identical in sequence to some alleles in other macaque species. We also revealed (1) the large and dynamic genetic and structural differences and similarities in allelic variation by analyzing the population allele frequencies, Hardy-Weinberg's equilibrium, heterozygosity, nucleotide diversity profiles, and phylogeny, (2) the difference in genetic structure of populations by Wright's FST statistic and hierarchical analysis of molecular variance, and (3) the different demographic and selection pressures on the three populations by performing Tajima's D test of neutrality. The large level of diversity and polymorphism at the Mafa-A1 was less evident in the Filipino than in the Vietnam or the Indonesian populations, which may have important implications in animal capture, selection, and breeding for medical research.


title: Complete endoscopic/transgastric retrieval of eroded gastric band: description of a novel technique and review of the literature.

text: Complications of laparoscopic adjustable gastric banding (LAGB) include band slippage, material infection, and band erosion. Band erosion can lead to chronic infection, obstruction, delayed perforation, and ineffectiveness; therefore, removal is indicated. A myriad of approaches exist for band removal and many authors have described novel techniques. A minimally invasive approach, including laparoscopic or endoscopic assistance, is favored given the reduction of postoperative complications compared with laparotomy. We present a novel approach to band retrieval following partial erosion involving a complete endoscopic/transgastric technique. Perioperative management and a review of the literature also are described.


title: Disaster preparedness of families with young children in Hong Kong.

text: AIMS The aims of this study were to explore the perception of disaster among the head of household mainly responsible for family matters of Hong Kong families with young children, and the extent of their preparedness for disasters. BACKGROUND Being prepared for disasters can minimize damage to our health, lives, and property. Families with young children are particularly vulnerable during disasters. METHODS A questionnaire was distributed to a convenience sample of families with young children in March and September in 2008. RESULTS A total of 198 out of 220 questionnaires distributed to heads of households were collected and analyzed for this study. Most of the householders (94.4%) considered the SARS outbreak in Hong Kong in 2003 to have been a disaster. They considered that the disastrous events most likely to occur in Hong Kong were infectious disease outbreaks (96.5%) and major transport accidents (94.4%). In preparing for unexpected events, these families reported having stocked up on ''young children's necessities'' (82.8%, 73.7%) and ''medications'' (82.8%, 60.1%) sufficient for three and seven days respectively. These families also kept a flashlight with adequate batteries (74.7%), extra blankets (69.2%), and a first aid kit (60.6%) at home for safety. They reported ''panic buying'' for necessities during previous typhoon strikes (68.2%) and infectious disease outbreaks (46.0%). Only 9.1% considered themselves adequately prepared for disasters (9.1%). CONCLUSIONS Although the families with young children in this study are prepared for disaster to some extent, their preparedness is still considered grossly inadequate and in need of public attention.


Forced social isolation due to COVID-19 and consequent mental health problems: lessons from hikikomori.


title: Internal dressings for healing perianal abscess cavities.

text: BACKGROUND A perianal abscess is a collection of pus under the skin, around the anus. It usually occurs due to an infection of an anal gland. In the UK, the annual incidence is 40 per 100,000 of the adult population, and the standard treatment is admission to hospital for incision and drainage under general anaesthetic. Following drainage of the pus, an internal dressing (pack) is placed into the cavity to stop bleeding. Common practice is for community nursing teams to change the pack regularly until the cavity heals. Some practitioners in the USA and Australia make a small stab incision under local anaesthetic and place a catheter into the cavity which drains into an external dressing. It is removed when it stops draining. Elsewhere in the USA, simple drainage is performed in an outpatient setting under local anaesthetic. OBJECTIVES To assess the effects of internal dressings in healing wound cavities resulting from drainage of perianal abscesses. SEARCH METHODS In May 2016 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL Plus. We also searched clinical trial registries to identify ongoing and unpublished studies, and searched reference lists of relevant reports to identify additional studies. We did not restrict studies with respect to language, date of publication, or study setting. SELECTION CRITERIA Published or unpublished randomised controlled trials (RCTs) comparing any type of internal dressing (packing) used in the post-operative management of perianal abscess cavities with alternative treatments or different types of internal dressing. DATA COLLECTION AND ANALYSIS Two review authors independently performed study selection, risk of bias assessment, and data extraction. MAIN RESULTS We included two studies, with a total of 64 randomised participants (50 and 14 participants) aged 18 years or over, with a perianal abscess. In both studies, participants were enrolled on the first post-operative day and randomised to continued packing by community district nursing teams or to no packing. Participants in the non-packing group managed their own wounds in the community and used absorbant dressings to cover the area. Fortnightly follow-up was undertaken until the cavity closed and the skin re-epithelialised, which constituted healing. For non-attenders, telephone follow-up was conducted.Both studies were at high risk of bias due to risk of attrition, performance and detection bias.It was not possible to pool the two studies for the outcome of time to healing. It is unclear whether continued post-operative packing of the cavity of perianal abscesses affects time to complete healing. One study reported a mean time to wound healing of 26.8 days (95% confidence interval (CI) 22.7 to 30.7) in the packing group and 19.5 days (95% CI 13.6 to 25.4) in the non-packing group (it was not clear if all participants healed). We re-analysed the data and found no clear difference in the time to healing (7.30 days longer in the packing group, 95% CI -2.24 to 16.84; 14 participants). This was assessed as very low quality evidence (downgraded three levels for very serious imprecision and serious risk of bias). The second study reported a median time to complete wound healing of 24.5 days (range 10 to 150 days) in the packing group and 21 days (range 8 to 90 days) in the non-packed group. There was insufficient information to be able to recreate the analysis and the original analysis was inappropriate (did not account for censoring). This second study also provided very low quality evidence (downgraded four levels for serious risk of bias, serious indirectness and very serious imprecision).There was very low quality evidence (downgraded for risk of bias, indirectness and imprecision) of no difference in wound pain scores at the initial dressing change. Both studies also reported patients' retrospective judgement of wound pain over the preceding two weeks (visual analogue scale, VAS) as lower for the non-packed group (2; both studies) compared with the packed group (0; both studies); (very low quality evidence) but we have been unable to reproduce these analyses as no variance data were published.There was no clear evidence of a difference in the number of post-operative fistulae detected between the packed and non-packed groups (risk ratio (RR) 2.31, 95% CIs 0.56 to 9.45, I(2) = 0%) (very low quality evidence downgraded three levels for very serious imprecision and serious risk of bias).There was no clear evidence of a difference in the number of abscess recurrences between the packed and non-packed groups over the variable follow-up periods (RR 0.72, 95% CI 0.22 to 2.37, I(2) = 0%) (very low quality evidence downgraded three levels for serious risk of bias and very serious imprecision).No study reported participant health-related quality of life/health status, incontinence rates, time to return to work or normal function, resource use in terms of number of dressing changes or visits to a nurse, or change in wound size. AUTHORS' CONCLUSIONS It is unclear whether using internal dressings (packing) for the healing of perianal abscess cavities influences time to healing, wound pain, development of fistulae, abscess recurrence or other outcomes. Despite this absence of evidence, the practice of packing abscess cavities is commonplace. Given the lack of high quality evidence, decisions to pack may be based on local practices or patient preferences. Further clinical research is needed to assess the effects and patient experience of packing.


title: COVID-19 in Patient with Sarcoidosis Receiving Long-Term Hydroxychloroquine Treatment, France, 2020.

text: Because of in vitro studies, hydroxychloroquine is under evaluation as a preexposure or postexposure prophylaxis for coronavirus disease (COVID-19) and as a possible COVID-19 curative treatment. We report a case of COVID-19 in a patient with sarcoidosis who was receiving long-term hydroxychloroquine treatment, despite adequate plasma concentrations.


title: Radiofrequency ablation is a valid treatment option for lung metastases: experience in 566 patients with 1037 metastases.

text: BACKGROUND Minimal invasive methods are needed as an alternative to surgery for treatment of lung metastases. PATIENTS AND METHODS The prospective database of two cancer centers including all consecutive patients treated with radiofrequency ablation (RFA) for lung metastasis over 8 years was reviewed. RFA was carried out under general anesthesia, with computed tomography guidance using a 15-gauge multitined expandable electrodes RF needle. RESULTS Five hundred sixty-six patients including 290 men (51%), 62.7 ± 13.2 years old with primary tumor to the colon (34%), rectum (18%), kidney (12%), soft tissue (9%) and miscellaneous (27%) received 642 RFA for 1037 lung metastases. Fifty-three percent of patients had 1 metastasis, 25% had 2, 14% had 3, 5% had 4 and 4% had 5-8. Metastases were unilateral (75%), or bilateral (25%). The median diameter [extremes] of metastases was 15 mm (4-70). Twenty-two percent of patients had extrapulmonary disease amenable to local therapy including 49 liver, 16 bone and 60 miscellaneous metastases. Median follow-up was 35.5 months. Median overall survival (OS) was 62 months. Four-year local efficacy was 89%. Four-year lung disease control rate was 44.1%, with patient retreated safely up to four times. Primary origin, disease-free interval, size and number of metastases were associated with OS in multivariate analysis. Progression at RFA site was associated with poor OS [P = 0.011, hazard ratio (HR): 1.69 (95% confidence interval 1.13-2.54)]. In the 293 colorectal cancer metastases, size >2 cm (HR = 2.10, P = 0.0027) and a number of metastases ≥3 (HR = 1.86, P = 0.011) remained significantly associated with OS. A prognostic score made of three groups based on the four above-mentioned prognostic factors demonstrated 3-year OS rates of respectively 82.2%, 69.5% and 53.6% (log-rank test, P ≤ 0.0001) among the three groups in the overall population, and of 81.3%, 72.8% and 57.9% (log-rank test, P = 0.005) in the colorectal cancer patients. CONCLUSION Radiofrequency is an option for treatment of small size lung metastases, namely the ones below 2-3 cm.


docid: qroiwzhs

title: Sirt3 Protects Against Ischemic Stroke Injury by Regulating HIF-1α/VEGF Signaling and Blood-Brain Barrier Integrity.

text: Sirtuin 3 (Sirt3) is a member of the Sirtuin family proteins and known to regulate multiple physiological processes such as metabolism and aging. As stroke is an aging-related disease, in this work, we attempt to examine the role and potential mechanism of Sirt3 in regulating ischemic stroke by using a permanent middle cerebral artery occlusion (pMCAO) model in wild type (WT) and Sirt3 knockout (KO) mice, coupled with oxygen glucose deprivation (OGD) experiments in cultured primary astrocytes. Sirt3 deficiency aggravated neuronal cell apoptosis and neurological deficits after brain ischemia. In addition, Sirt3 KO mice showed more severe blood-brain barrier (BBB) disruption and inflammatory responses compared with WT group in the acute phase. Furthermore, specific overexpression of Sirt3 in astrocytes by injecting glial fibrillary acidic protein (GFAP)::Sirt3 virus in ischemic region showed protective effect against stroke-induced damage. Mechanistically, Sirt3 could regulate vascular endothelial growth factor (VEGF) expression by inhibiting hypoxia inducible factor-1α (HIF-1α) signaling after ischemia (OGD). Our results have shown that Sirt3 plays a protective role in ischemic stroke via regulating HIF-1α/VEGF signaling in astrocytes, and reversal of the Sirt3 expression at the acute phase could be a worthy direction for stroke therapy.


title: Global genetic variation at OAS1 provides evidence of archaic admixture in Melanesian populations.

text: Recent analysis of DNA extracted from two Eurasian forms of archaic human shows that more genetic variants are shared with humans currently living in Eurasia than with anatomically modern humans in sub-Saharan Africa. Although these genome-wide average measures of genetic similarity are consistent with the hypothesis of archaic admixture in Eurasia, analyses of individual loci exhibiting the signal of archaic introgression are needed to test alternative hypotheses and investigate the admixture process. Here, we provide a detailed sequence analysis of the innate immune gene OAS1, a locus with a divergent Melanesian haplotype that is very similar to the Denisova sequence from the Altai region of Siberia. We resequenced a 7-kb region encompassing the OAS1 gene in 88 individuals from six Old World populations (San, Biaka, Mandenka, French Basque, Han Chinese, and Papua New Guineans) and discovered previously unknown and ancient genetic variation. The 5' region of this gene has unusual patterns of diversity, including 1) higher levels of nucleotide diversity in Papuans than in sub-Saharan Africans, 2) very deep ancestry with an estimated time to the most recent common ancestor of >3 myr, and 3) a basal branching pattern with Papuan individuals on either side of the rooted network. A global geographic survey of >1,500 individuals showed that the divergent Papuan haplotype is nearly restricted to populations from eastern Indonesia and Melanesia. Polymorphic sites within this haplotype are shared with the draft Denisova genome over a span of ∼90 kb and are associated with an extended block of linkage disequilibrium, supporting the hypothesis that this haplotype introgressed from an archaic source that likely lived in Eurasia.


title: Antineoplastic drug exposure in an ambulatory setting: a pilot study.

text: BACKGROUND Exposure to antineoplastic drugs confers health risks to workers, yet little is known about the exposure after a drug spill, nor has the relationship between exposure and organizational factors such as staffing and work environment been studied. OBJECTIVE The aim of this study was to evaluate drug spills prospectively using biological measures and correlate drug spills with organizational factors. METHODS Prospective questionnaires with 8-hour timed urine samples were collected from nursing and pharmacy personnel who reported drug spill events in 1 academic health center's infusion center. Urine was collected similarly from workers who did not report a spill. Liquid chromatography tandem mass spectrometry techniques identified detectable drug levels. After the prospective sampling period, workers were surveyed on workloads, practice environment, and safety behaviors. RESULTS From 81 eligible individuals, 40 participated in the prospective study and 19 completed retrospective questionnaires. Four spills were reported by 9 personnel, as multiple employees were exposed to drug spills. Four participants who reported a spill showed detectable levels of antineoplastic drugs. Four participants who did not report a spill had detectable levels of docetaxel. Compared with respondents who did not report a spill, collegial relations with physicians were significantly poorer for workers who reported spills. CONCLUSIONS The study protocol successfully captured drug spill reports and biological samples. Workers have detectable levels of antineoplastic drugs through both drug spills and environmental contamination. IMPLICATIONS FOR PRACTICE Multisite research studies and practice-based quality improvement approaches are needed to improve adherence to personal protective equipment use and safe handling procedures.


title: Dengue virus in bats from southeastern Mexico.

text: To identify the relationship between landscape use and dengue virus (DENV) occurrence in bats, we investigated the presence of DENV from anthropogenically changed and unaltered landscapes in two Biosphere Reserves: Calakmul (Campeche) and Montes Azules (Chiapas) in southern Mexico. Spleen samples of 146 bats, belonging to 16 species, were tested for four DENV serotypes with standard reverse transcriptase polymerase chain reaction (RT-PCR) protocols. Six bats (4.1%) tested positive for DENV-2: four bats in Calakmul (two Glossophaga soricina, one Artibeus jamaicensis, and one A. lituratus) and two bats in Montes Azules (both A. lituratus). No effect of anthropogenic disturbance on the occurrence of DENV was detected; however, all three RT-PCR-positive bat species are considered abundant species in the Neotropics and well-adapted to disturbed habitats. To our knowledge, this study is the first study conducted in southeastern Mexico to identify DENV-2 in bats by a widely accepted RT-PCR protocol. The role that bats play on DENV's ecology remains undetermined.


title: Ventricular assist devices as rescue therapy in cardiogenic shock after subarachnoid hemorrhage.

text: We review the journey to myocardial and neurologic recovery of a 42-year-old mother with severe acute cardiogenic shock and multiorgan failure after extensive subarachnoid hemorrhage, who was salvaged successfully using a CentriMag short-term biventricular assist device.


Deep Learning Localization of Pneumonia: 2019 Coronavirus (COVID-19) Outbreak.


title: Supervised exercise, stent revascularization, or medical therapy for claudication due to aortoiliac peripheral artery disease: the CLEVER study.

text: BACKGROUND Treatment for claudication that is due to aortoiliac peripheral artery disease (PAD) often relies on stent revascularization (ST). However, supervised exercise (SE) is known to provide comparable short-term (6-month) improvements in functional status and quality of life. Longer-term outcomes are not known. OBJECTIVES The goal of this study was to report the longer-term (18-month) efficacy of SE compared with ST and optimal medical care (OMC). METHODS Of 111 patients with aortoiliac PAD randomly assigned to receive OMC, OMC plus SE, or OMC plus ST, 79 completed the 18-month clinical and treadmill follow-up assessment. SE consisted of 6 months of SE and an additional year of telephone-based exercise counseling. Primary clinical outcomes included objective treadmill-based walking performance and subjective quality of life. RESULTS Peak walking time improved from baseline to 18 months for both SE (5.0 ± 5.4 min) and ST (3.2 ± 4.7 min) significantly more than for OMC (0.2 ± 2.1 min; p < 0.001 and p = 0.04, respectively). The difference between SE and ST was not significant (p = 0.16). Improvement in claudication onset time was greater for SE compared with OMC, but not for ST compared with OMC. Many disease-specific quality-of-life scales demonstrated durable improvements that were greater for ST compared with SE or OMC. CONCLUSIONS Both SE and ST had better 18-month outcomes than OMC. SE and ST provided comparable durable improvement in functional status and in quality of life up to 18 months. The durability of claudication exercise interventions merits its consideration as a primary PAD claudication treatment.


title: Histologic Analysis of Retrieved Clots in Acute Ischemic Stroke: Correlation with Stroke Etiology and Gradient-Echo MRI.

text: BACKGROUND AND PURPOSE It is unclear whether clot composition analysis is helpful to predict a stroke mechanism in acute large vessel occlusion. In addition, the relationship between early vessel signs on imaging studies and clot compositions has been poorly understood. The purpose of this study was to elucidate the relationship between clot composition and stroke etiology following mechanical thrombectomy and to investigate the effect of varied clot compositions on gradient-echo MR imaging of clots. MATERIALS AND METHODS Histopathologic analysis of retrieved clots from 37 patients with acute MCA occlusion was performed. Patients underwent gradient-echo imaging before endovascular therapy. Retrieved clots underwent semiquantitative proportion analysis to quantify red blood cells, fibrin, platelets, and white blood cells by area. Correlations between clot compositions and stroke subtypes and susceptibility vessel signs on gradient-echo imaging were assessed. RESULTS Stroke etiology was classified as cardioembolism in 22 patients (59.4%), large-artery atherosclerosis in 8 (21.6%), and undetermined in 7 (18.9%). The clots from cardioembolism had a significantly higher proportion of red blood cells (37.8% versus 16.9%, P = .031) and a lower proportion of fibrin (32.3% versus 48.5%, P = .044) compared with those from large-artery atherosclerosis. The proportion of red blood cells was significantly higher in clots with a susceptibility vessel sign than in those without it (48.0% versus 1.9%, P < .001), whereas the proportions of fibrin (26.4% versus 57.0%, P < .001) and platelets (22.6% versus 36.9%, P = .011) were significantly higher in clots without a susceptibility vessel sign than those with it. CONCLUSIONS The histologic composition of clots retrieved from cerebral arteries in patients with acute stroke differs between those with cardioembolism and large-artery atherosclerosis. In addition, a susceptibility vessel sign on gradient-echo imaging is strongly associated with a high proportion of red blood cells and a low proportion of fibrin and platelets in retrieved clots.


title: Role of p38 protein kinase in the ligand-independent ubiquitination and down-regulation of the IFNAR1 chain of type I interferon receptor.

text: Phosphorylation-dependent ubiquitination and degradation of the IFNAR1 chain of type I interferon (IFN) receptor is a robust and specific mechanism that limits the magnitude and duration of IFNα/β signaling. Besides the ligand-inducible IFNAR1 degradation, the existence of an "inside-out" signaling that accelerates IFNAR1 turnover in the cells undergoing the endoplasmic reticulum (ER) stress and activated unfolded protein responses has been recently described. The latter pathway does not require either presence of ligands (IFNα/β) or catalytic activity of Janus kinases (JAK). Instead, this pathway relies on activation of the PKR-like ER kinase (PERK) and ensuing specific priming phosphorylation of IFNAR1. Here, we describe studies that identify the stress activated p38 protein kinase as an important regulator of IFNAR1 that acts downstream of PERK. Results of the experiments using pharmacologic p38 kinase inhibitors, RNA interference approach, and cells from p38α knock-out mice suggest that p38 kinase activity is required for priming phosphorylation of IFNAR1 in cells undergoing unfolded protein response. We further demonstrate an important role of p38 kinase in the ligand-independent stimulation of IFNAR1 ubiquitination and degradation and ensuing attenuation of IFNα/β signaling and anti-viral defenses. We discuss the distinct importance of p38 kinase in regulating the overall responses to type I IFN in cells that have been already exposed to IFNα/β versus those cells that are yet to encounter these cytokines.


title: Treatment with potassium bromide mitigates ataxia and reduces tremor in lambs with perennial ryegrass toxicosis.

text: AIMS To assess the use of potassium bromide (KBr) as a therapeutic intervention for perennial ryegrass toxicosis (PRGT) in lambs fed ryegrass seed containing lolitrem B. METHODS Male lambs aged 10-12 months (n = 43) were assigned to received ryegrass seed containing lolitrem B, at a dose of 0.16 mg/kg/day (Groups 2, 3 and 4), or lucerne chaff and molasses (Groups 1 and 5). Lambs in Groups 2 and 3 were observed for clinical signs and gait changes until defined signs of PGRT were observed, when they were transferred, with lambs in Group 1, to the Testing phase of the trial. Lambs in Group 3 were then treated with a single oral dose of 300 mg/kg bromide. Lambs in Groups 4 and 5 received KBr daily from the start of the trial (540 mg/kg bromide over 3 days then 20 mg/kg daily) and were transferred to the Testing phase after 18 days. Clinical examination and gait assessment, and surface electromyography of the triceps muscle, measuring root-mean-square (RMS) voltages, were carried out on Days 0, 1 and 2 of the Testing phase followed by necropsy, histopathology, measurement of concentrations of bromide in serum and CSF and faecal cortisol metabolites (FCM). RESULTS In Group 3 lambs, mean composite gait scores decreased between Testing phase Day 0 and Days 1 and 2 (p < 0.001), but increased in lambs in Group 2 between Day 0 and Day 2 (p = 0.015). Scores for lambs in Group 3 on Day 2 were lower than for lambs in Group 2 (p < 0.001). Mean RMS voltages on Day 2 were higher in lambs in Group 2 than Group 3 (p = 0.045). Mean concentrations of bromide in serum were >800 µg/mL in lambs in Groups 3 and 4 on Day 2. Concentrations of FCM were higher in lambs from Group 2 than in Groups 1 or 5, but were similar in Groups 2, 3 and 4. Histopathological findings in the cerebellum of lambs from Groups 2, 3 and 4 were similar, showing pyknosis of neurons within the granular layer of the cerebellum and Purkinje neuron proximal axonal spheroid formation. CONCLUSIONS AND CLINICAL RELEVANCE A single oral dose of 300 mg/kg bromide in lambs with neurological signs of PRGT resulted in reduced composite gait scores and reduced RMS voltages, indicating a significant improvement in clinical signs of ataxia, movement disorder and muscle tremor associated with the neurotoxic effects of lolitrem B.


Last haircut in Amwaj: COVID-19 in Bahrain.


title: Modified Graded Repair of Cerebrospinal Fluid Leaks in Endoscopic Endonasal Transsphenoidal Surgery.

text: OBJECTIVE Complete sellar floor reconstruction is critical to avoid postoperative cerebrospinal fluid (CSF) leakage during transsphenoidal surgery. Recently, the pedicled nasoseptal flap has undergone many modifications and eventually proved to be valuable and efficient. However, using these nasoseptal flaps in all patients who undergo transsphenoidal surgery, including those who had none or only minor CSF leakage, appears to be overly invasive and time-consuming. METHODS Patients undergoing endoscopic endonasal transsphenoidal tumor surgery within a 5 year-period were reviewed. Since 2009, we classified the intraoperative CSF leakage into grades from 0 to 3. Sellar floor reconstruction was tailored to each leak grade. We did not use any tissue grafts such as abdominal fat and did not include any procedures of CSF diversions such as lumbar drainage. RESULTS Among 200 cases in 188 patients (147 pituitary adenoma and 41 other pathologies), intraoperative CSF leakage was observed in 27.4% of 197 cases : 14.7% Grade 1, 4.6% Grade 2a, 3.0% Grade 2b, and 5.1% Grade 3. Postoperative CSF leakage was observed in none of the cases. Septal bone buttress was used for Grade 1 to 3 leakages instead of any other foreign materials. Pedicled nasoseptal flap was used for Grades 2b and 3 leakages. Unused septal bones and nasoseptal flaps were repositioned. CONCLUSION Modified classification of intraoperative CSF leaks and tailored repair technique in a multilayered fashion using an en-bloc harvested septal bone and vascularized nasoseptal flaps is an effective and reliable method for the prevention of postoperative CSF leaks.


docid: ztkmvupw

title: Audiometric Outcomes and Middle Ear Disease following Cerebrospinal Fluid Leak Repair.

text: OBJECTIVE To investigate audiometric outcomes and incidence of chronic ear disease following lateral skull base repair (LSBR) of cerebrospinal fluid (CSF) leaks. STUDY DESIGN Retrospective review. SETTING Tertiary skull base center. SUBJECTS AND METHODS Consecutive adults undergoing LSBR of CSF leaks between 2012 and 2018 were reviewed. Audiometric data included mean air conduction pure-tone average (PTA), air-bone gap (ABG), speech recognition threshold (SRT), and word recognition score (WRS). The incidence and management of the following were collected: effusion, retraction, otitis media and externa, perforation, and cholesteatoma. RESULTS Seventy-three patients underwent transmastoid (n = 5), middle cranial fossa (n = 2), or combined approach (n = 67) for repair of spontaneous leaks (sCSFLs, n = 41) and those occurring in the setting of chronic ear disease (ceCSFLs, n = 32). ABG decreased 7.23 dB (P = .01) in sCSFL patients. Perforations (P = .01) were more likely in ceCSFL. No sCSFL patient developed a cholesteatoma, perforation, or infection. Effusions (n = 7) were transient, and retractions (n = 2) were managed conservatively in the sCSFL cohort. Eight ceCSFL patients required tubes, 3 underwent tympanoplasties with (n = 2) and without (n = 1) ossicular chain reconstruction (OCR), and 1 had tympanomastoidectomy with OCR. CONCLUSION Lateral skull base repair of CSF leaks maintained or improved hearing. Patients with preexisting chronic ear disease were more likely to require additional intervention to sustain adequate middle ear aeration compared to the sCSFL cohort. LSBR of sCSFL does not appear to increase risk for developing chronic ear disease.


title: Carotid stenting and intracranial thrombectomy for treatment of acute stroke due to tandem occlusions with aggressive antiplatelet therapy may be associated with a high incidence of intracranial hemorrhage.

text: BACKGROUND Acute stroke from tandem extracranial carotid artery and intracranial large vessel occlusion poses challenges for emergency endovascular treatment. Establishing and maintaining patency of the carotid artery and avoiding intracranial hemorrhage are competing concerns. METHODS Twenty-three consecutive cases of emergency carotid stenting followed by mechanical thrombectomy identified by retrospective review of the endovascular ischemic stroke database maintained prospectively at our institution since January 2011 form the basis for this report. No cases were lost to follow-up. RESULTS Patients were selected with CT angiography or MR angiography and diffusion weighted imaging. Carotid stenting was successful in all cases, and establishment of Thrombolysis in Cerebral Ischemia 2A, 2B or 3 flow was successful in 21/23 (91%). 12/23 (52%) patients achieved a modified Rankin Scale score of 0-2 at 90 days. Symptomatic intracranial hemorrhage (SICH) occurred in 5/23 patients (22%). Of 13 patients receiving an intravenous loading dose of abciximab during the procedure, 4/13 had SICH (31%) compared with 1/10 (10%) of those who did not. Of seven patients who received intravenous tissue plasminogen activator prior to the procedure, none had SICH. 90-day mortality was 9/23 (39%). All patients who had SICH were above the median age. CONCLUSIONS Primary stenting of the extracranial carotid artery combined with intracranial mechanical thrombectomy can be an effective treatment for tandem occlusions, can be performed with a high rate of technical success, and can achieve good clinical outcomes in selected patients. However, the incidence of SICH may be higher than in other patient populations and may be associated with the use of abciximab and advanced patient age.


Diagnostic Value of Chest CT in Coronavirus Disease 2019 (COVID-19).