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

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


docid: ympwtyqw

title: Covid-19: a digital epidemic.


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

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


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

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


docid: nvmncuzn

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

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


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

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


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

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


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

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


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

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


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

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


docid: emeeawfw

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

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


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

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


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

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


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

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


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


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


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

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


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

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


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

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


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

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


Pneumoperitoneum after Percutaneous Endoscopic Gastrostomy.


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

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


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

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


docid: ovrxoexc

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

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


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

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


title: Hydroxychloroquine use in the COVID-19 patient.

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


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

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


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


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

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


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

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


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

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


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

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


Analysis of Dual Antiplatelet Therapy.


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

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


title: Strength of a bifurcated H bond.

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


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

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


Electronic health record: what do you expect from them?


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


title: Imaging selection for acute stroke intervention.

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


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


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

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


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

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


title: A multicentre prospective cohort study assessing the effectiveness of budesonide MMX® (Cortiment®MMX®) for active, mild-to-moderate ulcerative colitis.

text: Background Cortiment®MMX® (budesonide MMX®) is currently approved for the induction of remission in mild-to-moderate ulcerative colitis (UC) patients when 5-ASA treatment is not sufficient. Data in real-life settings are lacking. Methods This was a multicentre observational prospective cohort study conducted in Europe and Canada. Effectiveness, safety, and tolerability of Cortiment®MMX® in a real-life setting of patients treated for mild-to-moderate UC was investigated. Patients were prescribed Cortiment®MMX® in accordance with the Summary of the Product Characteristics (SmPC).The primary endpoint was the clinical benefit of Cortiment® MMX® in routine practice (improvement ≥ 3 points in the clinical sub-scores of the Ulcerative Colitis Disease Activity Index, UCDAI). Results Data from 326 patients with mild-to-moderate UC were analysed for the primary endpoint. Clinical benefit was achieved in 60.1% (196/326) of patients at the end of Cortiment®MMX® treatment. Clinical remission (UCDAI clinical sub-score ≤ 1), full symptoms resolution (rectal bleeding (RB) = 0 and stool frequency (SF) = 0) and symptoms resolution (RB = 0 + SF ≤ 1) at the end of the Cortiment®MMX® treatment were achieved in 51.8%, 45.1% and 63.2% of patients, respectively. The median time to symptoms resolution was 30 days (range 29.0-36.0 days). Fifty patients (14.3%) had to discontinue Cortiment®MMX® due to adverse events; 17.5% of patients (n = 61) reported at least one adverse event related to the study drug. Conclusions This was the first time that a large cohort study was conducted with Cortiment®MMX® in a real-life setting. It demonstrated that Cortiment®MMX® is effective, safe and well tolerated in about 60% of UC patients.


title: Pure transvaginal laparoscopic appendectomy.

text: BACKGROUND Natural orifice transluminal endoscopic surgery has been at the forefront of minimally invasive surgery. Benefits include no visible scars, less pain, and shorter recovery time. We describe a video of a 37-year-old female who underwent a pure transvaginal appendectomy (TVA) for acute appendicitis. This is 1 of 18 successfully performed TVAs at Yale-New Haven Hospital. Appropriate Institutional Review Board was obtained preoperatively. METHODS The patient was positioned in steep Trendelenburg and then a weighted speculum was introduced into the vagina allowing exposure of the posterior vaginal fornix. The cervix was grasped with a single-toothed tenaculum on the posterior cervical lip and the posterior vaginal fornix was visualized. Access to the peritoneum was achieved by electrocautery and then sharp dissection. A SILS™ port (Covidien, Mansfield, MA, USA) was introduced and pneumoperitoneum up to 15 mmHg was achieved. Two 5-mm trocars and one 12-mm trocar were used. A 5-mm 30° angled endoscope, a flexible reticulating endograsper, and straight standard instruments were used. The identified appendix was dissected and a stapler was used to divide the mesoappendix from the appendix. Following confirmation of good hemostasis and no spillage of bowel contents, the appendix was removed from the abdomen within a retrieval bag and the culdotomy was closed with a running absorbable suture. The patient tolerated the 27 min procedure well and was discharged home in good condition on postoperative day 1.


docid: nbalshmi

title: Cutting-edge progress in viral immunology.


title: A novel interaction between sympathetic overactivity and aberrant regulation of renin by miR-181a in BPH/2J genetically hypertensive mice.

text: Genetically hypertensive mice (BPH/2J) are hypertensive because of an exaggerated contribution of the sympathetic nervous system to blood pressure. We hypothesize that an additional contribution to elevated blood pressure is via sympathetically mediated activation of the intrarenal renin-angiotensin system. Our aim was to determine the contribution of the renin-angiotensin system and sympathetic nervous system to hypertension in BPH/2J mice. BPH/2J and normotensive BPN/3J mice were preimplanted with radiotelemetry devices to measure blood pressure. Depressor responses to ganglion blocker pentolinium (5 mg/kg i.p.) in mice pretreated with the angiotensin-converting enzyme inhibitor enalaprilat (1.5 mg/kg i.p.) revealed a 2-fold greater sympathetic contribution to blood pressure in BPH/2J mice during the active and inactive period. However, the depressor response to enalaprilat was 4-fold greater in BPH/2J compared with BPN/3J mice, but only during the active period (P=0.01). This was associated with 1.6-fold higher renal renin messenger RNA (mRNA; P=0.02) and 0.8-fold lower abundance of micro-RNA-181a (P=0.03), identified previously as regulating human renin mRNA. Renin mRNA levels correlated positively with depressor responses to pentolinium (r=0.99; P=0.001), and BPH/2J mice had greater renal sympathetic innervation density as identified by tyrosine hydroxylase staining of cortical tubules. Although there is a major sympathetic contribution to hypertension in BPH/2J mice, the renin-angiotensin system also contributes, doing so to a greater extent during the active period and less during the inactive period. This is the opposite of the normal renin-angiotensin system circadian pattern. We suggest that renal hyperinnervation and enhanced sympathetically induced renin synthesis mediated by lower micro-RNA-181a contributes to hypertension in BPH/2J mice.


title: Human serum amyloid P functions as a negative regulator of the innate and adaptive immune responses to DNA vaccines.

text: The utility of DNA vaccines has been limited by their failure to elicit sufficiently potent immune responses in many human applications, whereas DNA vaccinations in mice have been very successful. However, the underlying mechanisms remain unknown. We hypothesize that serum amyloid P component (SAP), which has a species-specific, DNA-binding ability, contributes to the differences between human and mice and then limits DNA vaccine's efficacy in vivo. In our study, DNA vaccine-induced adaptive immune responses were also significantly decreased in the human SAP (hSAP) transgenic mice. Using human promonocytic cell line THP-1-derived macrophages as a cell model, we found that cells incubated with a hSAP-DNA complex showed significant defects in innate immune activations, whereas mouse SAP had similar, albeit very weak, activities. hSAP also significantly inhibited the functions of two identified DNA sentinels, high-mobility group B protein 1 and antimicrobial peptide LL37, and redirected DNA update to FcRs leading to endocytosis and endosomal degradation. We also found that a chemical SAP inhibitor strongly recovered the suppressed innate immune responses to DNA in the presence of human serum and enhanced the immunogenicity of DNA vaccines in vivo. Our data indicated that SAP is a key negative regulator for innate immune responses to DNA and may be partly responsible for the insufficient immune responses after DNA vaccinations in humans. SAP suppression may be a novel strategy for improving efficacy of human DNA vaccines and requires further clinical investigations.


title: Evaluation of fibrin sealants for central nervous system sealing in the mongrel dog durotomy model.

text: BACKGROUND Watertight repair of the dura is imperative after neurosurgical procedures involving the brain or spinal cord because inadequately treated leakage of cerebrospinal fluid (CSF) from punctured dura can have serious consequences such as meningitis, arachnoiditis, or epidural abscess. OBJECTIVE To assess the efficacy of Evicel Fibrin Sealant (Human) to prevent CSF leakage using a 2.0-cm durotomy mongrel dog repair model and to compare the tissue response with Tisseel (a fibrin sealant) and Duraseal (a synthetic polyethylene glycol [PEG] hydrogel sealant). METHODS The canine durotomy repair model was used. This well-characterized model assesses the ability of sealants to achieve intraoperative watertight seals of the dura mater, as well as long-term safety and efficacy. This study included 27 mongrel dogs and had a 28-day duration. RESULTS The 3 sealants were 100% effective in preventing CSF leakage intraoperatively at 15 mm Hg. The 2 fibrin sealants were 100% effective in postoperative sealing; the PEG hydrogel was not. Microscopically, the tissue changes induced by Evicel at the durotomy site were similar in nature except for foamy macrophages seen only with the PEG hydrogel. The extent and severity of adhesions at 28 days were less with the fibrin sealants than with the PEG hydrogel. CONCLUSION Evicel, a fibrin sealant, was safe and effective in achieving and maintaining a watertight seal of the dura. The performance of the fibrin sealants was similar to that of the synthetic PEG hydrogel sealant with the exception of a Duraseal seal, which leaked.


title: Use of the Outreach Distal Access Catheter for microcatheter stabilization during intracranial arteriovenous malformation embolization.

text: The Outreach DAC is an intermediate-sized catheter designed for use with the Merci clot retriever in acute stroke. We investigated its utility as an adjunctive device during AVM pedicle embolization. In the authors' opinion, the DAC provided additional guide-catheter and microcatheter support, improved selective angiographic visualization of AVM angioarchitecture, aided microcatheter removal from its embedded position in the AVM Onyx cast, and enhanced local microcatheter control and safety, compared with embolization with the guide and microcatheter alone.


title: Laparoscopic versus open colectomy for patients with American Society of Anesthesiology (ASA) classifications 3 and 4: the minimally invasive approach is associated with significantly quicker recovery and reduced costs.

text: BACKGROUND Conceivably, the benefits of earlier recovery associated with a minimally invasive technique used in laparoscopic colectomy (LC) may be amplified for patients with comorbid disease. The dearth of evidence supporting the safety of laparoscopy for these patients led to a comparison of outcomes between LC and open colectomy (OC) for patients with American Society of Anesthesiology (ASA) classifications 3 and 4. METHODS Data for all ASA 3 and 4 patients who underwent elective LC were reviewed from a prospectively maintained laparoscopic database. The patients who underwent LC were matched with OC patients by age, gender, diagnosis, year, and type of surgery. Estimated blood loss, operation time, time to return of bowel function, length of hospital stay, readmission rate, and 30-day complication and mortality rates were compared using chi-square, Fisher's exact, and Wilcoxon tests as appropriate. A p value <0.05 was considered statistically significant. RESULTS In this study, 231 LCs were matched with 231 OCs. The median age of the patients was 68 years, and 234 (51%) of the patients were male. There were 44 (19%) conversions from LC to OC. More patients in the OC group had undergone previous major laparotomy (5 vs. 15%; p < 0.001). Estimated blood loss, return of bowel function, length of hospital stay, and total direct costs were decreased in the LC group. Wound infection was significantly greater with OC (p = 0.02). When patients with previous major laparotomy were excluded, the two groups had similar overall morbidity. The other benefits of LC, however, persisted. CONCLUSION The findings show that LC is a safe option for patients with a high ASA classification. The LC approach is associated with faster postoperative recovery, lower morbidity rates, and lower hospital costs than the OC approach.


title: Fast-track hip and knee arthroplasty: clinical and organizational aspects.

text: Fast-track hip and knee arthroplasty aims at giving the patients the best available treatment at all times, being a dynamic entity. Fast-track combines evidence-based, clinical features with organizational optimization including a revision of traditions resulting in a streamlined pathway from admission till discharge – and beyond. The goal is to reduce morbidity, mortality and functional convalescence with an earlier achievement of functional milestones including functional discharge criteria with subsequent reduced length of stay and high patient satisfaction. Outcomes are traditionally measured as length of stay; safety aspects in the form of morbidity/mortality; patient satisfaction; and – as a secondary parameter – economic savings. Optimization of the clinical aspects include focusing on analgesia; DVT-prophylaxis; mobilization; care principles including functional discharge criteria; patient-characteristics to predict outcome; and traditions which may be barriers in optimizing outcomes. Patients should be informed and motivated to be active participants and their expectations should be modulated in order to improve satisfaction. Also, organizational aspects need to be analyzed and optimized. New logistical approaches should be implemented; the ward ideally (re)structured to only admit arthroplasties; the staff educated to have a uniform approach; extensive preoperative information given including discharge criteria and intended length of stay. This thesis includes 9 papers on clinical and organizational aspects of fast-track hip and knee arthroplasty (I–IX). A detailed description of the fast-track set-up and its components is provided. Major results include identification of patient characteristics to predict length of stay and satisfaction with different aspects of the hospital stay (I); how to optimize analgesia by using a compression bandage in total knee arthroplasty (II); the clinical and organizational set-up facilitating or acting as barriers for early discharge (III); safety aspects following fast-track in the form of few readmissions in general (IV) and few thromboembolic complications in particular (V); feasibility studies showing excellent outcomes following fast-track bilateral simultaneous total knee arthroplasty (VI) and non-septic revision knee arthroplasty (VII); how acute pain relief in total hip arthroplasty is not enhanced by the use of local infiltration analgesia when multi-modal opioid-sparing analgesia is given (VIII); and a detailed description of which clinical and organizational factors detain patients in hospital following fast-track hip and knee arthroplasty (IX). Economic savings following fast-track hip and knee arthroplasty is also documented in studies, reviews, metaanalyses and Cochrane reviews – including the present fast-track (ANORAK). In conclusion, the published results (I–IX) provide substantial, important new knowledge on clinical and organizational aspects of fast-track hip and knee arthroplasty – with concomitant documented high degrees of safety (morbidity/mortality) and patient satisfaction. Future research strategies are multiple and include both research strategies as efforts to implement the fast-track methodology on a wider basis. Research areas include improvements in pain treatment, blood saving strategies, fluid plans, reduction of complications, avoidance of tourniquet and concomitant blood loss, improved early functional recovery and muscle strengthening. Also, improvements in information and motivation of the patients, preoperative identification of patients needing special attention and detailed economic studies of fast- track are warranted.


title: Conservative management of an unusual bilioduodenal fistula post laparoscopic Duodeno-Ileal Switch (SADI-S) case report.

text: INTRODUCTION Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is an advanced operation for morbid obesity. To our knowledge, no internal Biliodigestive Fistula has yet been reported as specific complication in the field of metabolic and bariatric Biliopancreatic diversion. CASE PRESENTATION In this case report, we detail the case of a 57-year-old man who underwent a Single Anastomosis Duodeno-Ileal Switch (SADI-S) bariatric procedure for morbid obesity. Upon admission 3 weeks after the SADI-S procedure acute sepsis caused by a delayed choledoco-duodenal Fistula was diagnosed. A conservative management of this rare complication was successful. DISCUSSION We highlight the differential diagnosis and optional treatment in such a rare complication, and how we succeeded in its conservative management, without any need for endoscopic nor surgical intervention. A review of the literature on different types of Internal Biliodigestive Fistulae and their appropriate management are reported and briefly discussed. CONCLUSION The aim of this case report is to highlight the existence of such a rare complication, and its successful multidisciplinary conservative medical management.


Anatomy and physiology of coronary blood flow.


title: Comparisons of surgical outcomes between transperitoneal and retroperitoneal approaches in robot-assisted laparoscopic partial nephrectomy for lateral renal tumors: a propensity score-matched comparative analysis.

text: OBJECTIVE To compare the surgical outcomes between the transperitoneal (TP) and retroperitoneal (RP) approaches in robot-assisted laparoscopic partial nephrectomy (RAPN) for lateral tumors. METHODS This study included patients who underwent RAPN for lateral renal tumors between 2013 and 2019. Lateral tumors were defined as X of A factors in the RENAL nephrometry score. In total, 290 and 48 patients with TP and RP, respectively, were included in the analysis. To minimize the effects of selection bias, the following variables were adjusted using 1:1 propensity score matching: age, sex, body mass index, American Society of Anesthesiologists score, preoperative estimated glomerular filtration rate, tumor size, and RENAL nephrometry score. RESULTS After matching, 48 patients were allocated to each group. The mean age was 55 years, and the mean preoperative estimated glomerular filtration rate (eGFR) was 68-69 mL/min/1.73 m2. The mean tumor size was 30-31 mm. The RP group had a shorter operative time (124 vs. 151 min, p = 0.0002), shorter console time (74 vs. 110 min, p < 0.0001), shorter warm ischemic time (14 vs. 17 min, p = 0.0343), lower estimated blood loss (EBL) (33 vs. 52 ml, p = 0.0002), and shorter postoperative length of hospital stay (PLOS) (3.3 vs. 4.0 days, p < 0.0001) than the TP group. The change in eGFR, incidence rate of perioperative complication, and positive surgical margin rate did not significantly differ between the two groups. CONCLUSION RP had better surgical outcomes, including shorter operative time, lower EBL, and shorter PLOS for lateral renal tumors, which may suggest that RP is the optimal approach for selected lateral renal tumors.


title: Emergence of Porcine epidemic diarrhea virus in the United States: clinical signs, lesions, and viral genomic sequences.

text: During the 10 days commencing April 29, 2013, the Iowa State University Veterinary Diagnostic Laboratory received the first 4 of many submissions from swine farms experiencing explosive epidemics of diarrhea and vomiting affecting all ages, with 90-95% mortality in suckling pigs. Histology revealed severe atrophy of villi in all segments of the small intestines with occasional villus-epithelial syncytial cells, but testing for rotaviruses and Transmissible gastroenteritis virus (Alphacoronavirus 1) were negative. Negative-staining electron microscopy of feces revealed coronavirus-like particles and a pan-coronavirus polymerase chain reaction (PCR) designed to amplify a conserved region of the polymerase gene for all members in the family Coronaviridae produced expected 251-bp amplicons. Subsequent sequencing and analysis revealed 99.6-100% identity among the PCR amplicons from the 4 farms and 97-99% identity to the corresponding portion of the polymerase gene of Porcine epidemic diarrhea virus (PEDV) strains, with the highest identity (99%) to strains from China in 2012. Findings were corroborated at National Veterinary Services Laboratories using 2 nested S-gene and 1 nested N-gene PCR tests where the sequenced amplicons also had the highest identity with 2012 China strains. Whole genome sequence for the virus from 2 farms in 2 different states using next-generation sequencing technique was compared to PEDV sequences available in GenBank. The 2013 U.S. PEDV had 96.6-99.5% identity with all known PEDV strains and the highest identity (>99.0%) to some of the 2011-2012 Chinese strains. The nearly simultaneous outbreaks of disease, and high degree of homology (99.6-100%) between the PEDV strains from the 4 unrelated farms, suggests a common source of virus.


title: The spread of awareness and its impact on epidemic outbreaks.

text: When a disease breaks out in a human population, changes in behavior in response to the outbreak can alter the progression of the infectious agent. In particular, people aware of a disease in their proximity can take measures to reduce their susceptibility. Even if no centralized information is provided about the presence of a disease, such awareness can arise through first-hand observation and word of mouth. To understand the effects this can have on the spread of a disease, we formulate and analyze a mathematical model for the spread of awareness in a host population, and then link this to an epidemiological model by having more informed hosts reduce their susceptibility. We find that, in a well-mixed population, this can result in a lower size of the outbreak, but does not affect the epidemic threshold. If, however, the behavioral response is treated as a local effect arising in the proximity of an outbreak, it can completely stop a disease from spreading, although only if the infection rate is below a threshold. We show that the impact of locally spreading awareness is amplified if the social network of potential infection events and the network over which individuals communicate overlap, especially so if the networks have a high level of clustering. These findings suggest that care needs to be taken both in the interpretation of disease parameters, as well as in the prediction of the fate of future outbreaks.


title: Integrating the selection of PHA storing biomass and nitrogen removal via nitrite in the main wastewater treatment line.

text: A novel scheme was developed for the treatment of municipal wastewater integrating nitritation/denitritation with the selection of polyhydroxyalkanoates (PHA) storing biomass under an aerobic/anoxic, feast/famine regime. The process took place in a sequencing batch reactor (SBR) and the subsequent PHA accumulation in a batch reactor. The carbon source added during the selection and accumulation steps consisted of fermentation liquid from the organic fraction of municipal solids waste (OFMSW FL) (Period I) and OFMSW and primary sludge fermentation liquid (Period II). Selection of PHA storing biomass was successful and denitritation was driven by internally stored PHA during the famine phase. Under optimum conditions of SBR operation ammonia removal was 93%, reaching a maximum nitrite removal of 98%. The treated effluent met the nitrogen limits, while PHA-storing biomass was successfully selected. The maximum accumulation of PHA was 10.6% (wt.) since the nutrients present in the carbon source promoted bacterial growth.


Single-incision laparoscopic hernioplasty with the assistance of the Radius Surgical System.


title: Repurposing of Kinase Inhibitors as Broad-Spectrum Antiviral Drugs.

text: The high cost of drug development and the narrow spectrum of coverage typically provided by direct-acting antivirals limit the scalability of this antiviral approach. This review summarizes progress and challenges in the repurposing of approved kinase inhibitors as host-targeted broad-spectrum antiviral therapies.


title: Quantitative margin assessment of radiofrequency ablation of a solitary colorectal hepatic metastasis using MIRADA RTx on CT scans: a feasibility study.

text: BACKGROUND Compared to surgery, radiofrequency ablation(RFA) for colorectal liver metastasis(CRLM) is associated with higher local recurrence(LR) rates. A wide margin (at least 5 mm) is generally recommended to prevent LR, but the optimal method to assess ablation margins is yet to be established. The aim of our study was to evaluate the feasibility and reproducibility of CT-CT co-registration, using MIRADA software, in order to assess ablation margins of patients with CRLM. METHODS In this retrospective study, pre- and post-ablation contrast-enhanced CT scans of 29 patients, treated with percutaneous RFA for a solitary CRLM, were co-registered. Co-registration was performed by two independent radiologist, based on venous structures in proximity to the tumor. Feasibility of CT-CT co-registration and inter-observer agreement for reproducibility and ablation margins was determined. Furthermore, the minimal ablation margin was compared with the occurrence of LR during follow-up. RESULTS Co-registration was considered feasible in 18 patients (61% male, 63.1(±10.9) year), with a perfect inter-observer agreement for completeness of ablation: κ = 1.0(p < 0.001). And substantial inter-observer agreement for measurement of the minimal margin (≤ 0 mm, 1-5 mm, ≥ 5 mm): κ = 0.723(p-value < 0.001). LR occurred in eight of nine(88.9%) incompletely ablated CRLM and in one of the nine completely ablated CRLM(11.1%). CONCLUSION Co-registration using MIRADA is reproducible and potentially a valuable tool in defining technical success. Feasibility of co-registration of pre- and post-ablation CT scans is suboptimal if scans are not acquired concordantly. Co-registration may potentially aid in the prediction of LR after percutaneous ablation.


title: Pipeline embolization device for the treatment of a traumatic intracranial aneurysm in a child.

text: INTRODUCTION Traumatic intracranial aneurysms in children are rare and may occur as the result of closed or penetrating head trauma. Their natural history seems to be more aggressive. Most traumatic aneurysms have complex shape, tending to have a large neck or even a fusiform morphology. CASE REPORT We present a case of a traumatic carotid artery aneurysm in a 9-year-old girl that was successfully treated with pipeline embolization device. DISCUSSION Due to its dissecting nature, wall friability and lack of a substantial neck can make surgical clipping and selective coiling difficult and risky. Although endovascular parent artery occlusion is the best approach in the acute phase, in some situations it is not possible or very risky. In such scenario the use of flow diverter devices would be an alternative approach. Additionally, we discuss the potential advantages and risks of flow diverter deployment inside a developing vessel.


Fecal testing for SARS-CoV-2 in patients undergoing elective lower gastrointestinal endoscopy.


title: The Arg719 residue at the C-terminal end of the stem region in hepatitis C virus JFH-1 E2 glycoprotein promotes viral infection.

text: Hepatitis C virus (HCV) envelope glycoprotein E2 is involved in virus assembly and initial entry into host cells. The tertiary organization of the E2 ectodomain is mainly composed of domains I-III, followed by the stem (ST) region and transmembrane (TM) domain. The ST region is critical for reorganizing the envelope glycoproteins during the membrane fusion process. While this region is relatively flexible, the physicochemical properties of its amino acid residues are conserved. Whether and how this physicochemical conservation is required for HCV infection is still unclear. The last residue of the E2 ST region evolved to be either an arginine or lysine among different HCV strains, suggesting that the residues confer different functions during HCV infection. To address this possibility, we constructed an R719K point mutant in the JFH-1 strain (genotype 2a) in the context of the cell-culture derived HCV (HCVcc) system. Compared with wild-type (wt) HCV, the R719K mutant exhibited decreased growth, and its extracellular and intracellular infectivity were also significantly decreased at 48 and 72 h post-electroporation. Correspondingly, less RNA and HCV core protein was observed in the supernatant for the R719K mutant, as well as less efficient RNA replication and protein expression. These findings indicate that the 719th residue of arginine on E2 is critical to promote HCV replication and infection. The data provide new clues for the biochemical function of E2, which is required for efficient HCV assembly and infection.


Impact of the COVID-19 Pandemic on the Urology Residency Match in Singapore.


title: Biochemistry, hormones and adipocytokines in prepubertal children born with IUGR evoke metabolic, hepatic and renal derangements.

text: Children born with IUGR develop features of the metabolic syndrome and exhibit deranged markers of hepatorenal physiology. Metabolic and hepatorenal biochemistry and the rs9939609 FTO polymorphism were investigated in prepubertal children born with IUGR. Ninety-eight prepubertal children (46 IUGR and 52 AGA), subdivided in <5 years and >5 years old groups were included. Anthropometry; creatinine, eGFR, urea, AST, ALT, triglycerides, uric acid, total cholesterol, HDL-c, LDL-c, glucose, C-peptide, insulin and glucagon z-scores; HOMA-IR; leptin and adiponectin concentrations; rs9939609 FTO polymorphism frequency were measured. In males, weight and ALT were higher and adiponectin was lower, in IUGR < 5 years; C-peptide, insulin and leptin were higher in IUGR > 5 years; C-peptide was higher in all IUGR, than the respective AGA. In females, creatinine and triglycerides were higher in IUGR < 5 years old; creatinine was higher and eGFR was lower in all IUGR, than the respective AGA. In males and females, creatinine was higher in all IUGR, than the respective AGA; C-peptide, insulin and HOMA-IR were lower, and AST was higher in IUGR < 5 than in IUGR > 5 years old. FTO rs9939609 frequency did not differ between IUGR and AGA. In conclusion prepubertal males born with IUGR increased weight, insulin and leptin and decreased adiponectin, as compared to males born AGA, emerge as early metabolic syndrome characteristics. The concentrations of these hormones do not differ between prepubertal males and females born with IUGR. Weight control, healthy nutrition and physical exercise should be recommended to these children. The deranged renal (particularly evident in females below the age of 5) and liver biochemistry in prepubertal children born with IUGR suggests that hepatorenal derangements might commence in utero. Regular checkup of biochemical and lipid profile is recommended for all children born with IUGR.


title: Liver Enzyme Elevation in Coronavirus Disease 2019: A Multicenter, Retrospective, Cross-Sectional Study

text: INTRODUCTION: Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized. METHODS: Hospitalized patients with COVID-19 in Zhejiang Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared. RESULTS: Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median [interquartile range {IQR}] age, 47.0 [35.0–55.0] years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2–6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11–16). No differences in disease severity and clinical outcomes were noted between the groups. DISCUSSION: We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.


Middle East respiratory syndrome coronavirus: epidemic potential or a storm in a teacup?


Cardiovascular pipeline decline quantified.


title: Single port sigmoidectomy in an experimental model with survival.

text: INTRODUCTION Single port laparoscopic access could reduce morbidity associated with additional trocar placement and, through the development of a hybrid intermediate, facilitate the clinical adoption of evolving techniques such as natural orifice transluminal endoscopic surgery. Advanced trocar technology, as much as adapted surgical technique, seems necessary to best facilitate this, however. METHODS A novel port (Airseal, Surgiquest) that uses vortex technology to create an air-curtain seal to maintain the pneumoperitoneum while facilitating the simultaneous passage of multiple working instruments was trialed. For this, 6 pigs (30 kg each) underwent sigmoid resection and reanastomosis using the port as the sole laparoscopic access for conventional instrumentation. All animals were thereafter survived for observation during a 2-week convalescence before undergoing repeat general anesthesia, sigmoidoscopy for anastomotic assessment, and forensic laparotomy for determination of intraperitoneal healing and complications. RESULTS The operation was technically feasible via a single port within a short time in every animal (mean duration 12.3 minutes). One anastomosis had to redone because of staple misfire but this too was accomplishable without additional port placement. All animals survived and convalesced normally without evincing clinical complication. At follow-up, all anastomoses were patent at sigmoidoscopy and only 1 animal had evidence of complicated anastomotic healing (the same animal that had needed anastomotic refashioning). CONCLUSIONS Single port colonic resection and reanastomosis is readily achievable in this animal model. As an operative approach, it may both advance in its own right as much as facilitate the evolution and clinical incorporation of other developmental access routes.


title: Endoscopic surgery for patients with syndromic craniosynostosis and the requirement for additional open surgery.

text: OBJECTIVE Recent reports have described early endoscopic suturectomy as a treatment option for patients with syndromic craniosynostosis, but such patients often require subsequent calvarial remodeling. The authors describe their experience with this patient population and seek to identify predictors of sufficiency of endoscopic surgery alone. METHODS The medical records of patients with syndromic craniosynostosis who underwent endoscopic repair were retrospectively reviewed. Demographic data, operative details, and follow-up data were collected. RESULTS A total of 6 patients with syndromic craniosynostosis underwent endoscopic surgery followed by helmet therapy during the study period. Of these, 3 patients were male. The involved syndromes included Crouzon, Pfeiffer, Jackson-Weiss, Muenke, Saethre-Chotzen, and craniosynostosis-3 (n = 1 each). The patients underwent endoscopic surgery at a median age of 2.1 months (range 0.9-4.1 months). The median estimated blood loss was 30 ml (range 20-100 ml), with 2 patients requiring a transfusion. The median length of stay in the hospital was 1.5 days (range 1-4 days), and the median follow-up was 29.0 months (range 16.8-81.7 months), with 1 patient (16.7%) requiring an open revision. Three patients (50%) were classified as Whitaker Category I at the last follow-up. The patients for whom additional open surgery was performed or recommended (Whitaker Category IV) were the oldest patients in the cohort, ranging from 2.6 to 4.1 months at the time of surgery. CONCLUSIONS This series demonstrates that endoscopic surgery can be sufficient to treat syndromic craniosynostosis without subsequent open calvarial remodeling over a median follow-up period of at least 2 years. The findings suggest that younger age at the time of endoscopic surgery may be an important factor in determining the sufficiency of this procedure. Even among patients who require subsequent open calvarial remodeling, early endoscopic surgery may allow for growth and development of the brain and skull while delaying the need for open remodeling until the patient is older and can better tolerate the procedure.


title: Global Health Security Demands a Strong International Health Regulations Treaty and Leadership From a Highly Resourced World Health Organization.

text: If the Ebola tragedy of West Africa has taught us anything, it should be that the 2005 International Health Regulations (IHR) Treaty, which gave unprecedented authority to the World Health Organization (WHO) to provide global public health security during public health emergencies of international concern, has fallen severely short of its original goal. After encouraging successes with the 2003 severe acute respiratory syndrome (SARS) pandemic, the intent of the legally binding Treaty to improve the capacity of all countries to detect, assess, notify, and respond to public health threats has shamefully lapsed. Despite the granting of 2-year extensions in 2012 to countries to meet core surveillance and response requirements, less than 20% of countries have complied. Today it is not realistic to expect that these gaps will be solved or narrowed in the foreseeable future by the IHR or the WHO alone under current provisions. The unfortunate failures that culminated in an inadequate response to the Ebola epidemic in West Africa are multifactorial, including funding, staffing, and poor leadership decisions, but all are reversible. A rush by the Global Health Security Agenda partners to fill critical gaps in administrative and operational areas has been crucial in the short term, but questions remain as to the real priorities of the G20 as time elapses and critical gaps in public health protections and infrastructure take precedence over the economic and security needs of the developed world. The response from the Global Outbreak Alert and Response Network and foreign medical teams to Ebola proved indispensable to global health security, but both deserve stronger strategic capacity support and institutional status under the WHO leadership granted by the IHR Treaty. Treaties are the most successful means the world has in preventing, preparing for, and controlling epidemics in an increasingly globalized world. Other options are not sustainable. Given the gravity of ongoing failed treaty management, the slow and incomplete process of reform, the magnitude and complexity of infectious disease outbreaks, and the rising severity of public health emergencies, a recommitment must be made to complete and restore the original mandates as a collaborative and coordinated global network responsibility, not one left to the actions of individual countries. The bottom line is that the global community can no longer tolerate an ineffectual and passive international response system. As such, this Treaty has the potential to become one of the most effective treaties for crisis response and risk reduction worldwide. Practitioners and health decision-makers worldwide must break their silence and advocate for a stronger Treaty and a return of WHO authority.


title: Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses.

text: BACKGROUND The novel swine-origin influenza A H1N1 virus (S-OIV) causes the current pandemic. Its tissue tropism and replication in different cell lines are not well understood. OBJECTIVE Compare the growth characteristics of cell lines infected by S-OIV, seasonal influenza A H1N1 (sH1N1) and avian influenza A H5N1 (H5N1) viruses and the effect of temperature on viral replication. STUDY DESIGN Cytopathic effect (CPE), antigen expression by immunofluorescence (IF) and viral load profile by quantitative RT-PCR in 17 cell lines infected by S-OIV, sH1N1 and H5N1 were examined. Comparison of their replication efficiency in chick embryo was performed. The effect of temperature on viral replication in Madin-Darby canine kidney (MDCK) cells was determined by TCID(50) at 33 degrees C, 37 degrees C and 39 degrees C for 5 consecutive days. RESULTS S-OIV replicated in cell lines derived from different tissues or organs and host species with comparable viral load to sH1N1. Among 13 human cell lines tested, Caco-2 has the highest viral load for S-OIV. S-OIV showed a low viral load with no CPE or antigen expression in pig kidney cell PK-15, H5N1 demonstrated the most diverse cell tropism by CPE and antigen expression, and the highest viral replication efficiency in both cell lines and allantoic fluid. All three viruses demonstrated best growth at 37 degrees C in MDCK cells. CONCLUSION Cell line growth characteristics of S-OIV, sH1N1 and H5N1 appear to correlate clinically and pathologically with involved anatomical sites and severity. Low replication of S-OIV in PK-15 suggests that this virus is more adapted to human than swine.


title: Evolution of minimally invasive surgery for donor nephrectomy and outcomes.

text: BACKGROUND Laparoscopic donor nephrectomy was introduced into Australia in 1997 by this unit. However, some donors may be considered unsuitable, and few modifications to the existing technique can tailor this procedure for an individual donor. Recently, further changes including clustering of ports and single-port methods have been investigated. METHODS The laparoscopic method was offered to all but 3 donors from May 1997 to October 2009. Data were collected on all 289 donors who underwent laparoscopic procedures. RESULTS All but 5 donor procedures were completed laparoscopically, and in 4 of them conversion to open was necessary due to hemorrhage. The fifth was a planned conversion in our first right LDN. Delayed graft function was seen in 7 recipients and 5 required dialysis postoperatively. Two kidneys were lost due to arterial thrombosis, and 5 patients underwent segmental infarction with decreased renal function. Mean hospital stay was 2.35±1.67 days. There were no donor deaths or serious morbidity. CONCLUSIONS Although the benefits to the donor of the laparoscopic method are well recognized, our modifications will benefit those who may be precluded from this method.


title: Correction: Neuroprotection by Argon Ventilation after Perinatal Asphyxia: A Safety Study in Newborn Piglets.

text: [This corrects the article DOI: 10.1371/journal.pone.0113575.].


title: Dual-ports laparoscopy-assisted distal gastrectomy compared with conventional laparoscopy-assisted distal gastrectomy.

text: PURPOSE We performed laparoscopic gastrectomy using an umbilical port in addition with one other port (dual-ports laparoscopy-assisted distal gastrectomy, DP-LADG) since December 2009. We describe a retrospective study to evaluate the possibility of DP-LADG compared with conventional LADG (C-LADG). METHODS The indication for DP-LADG was preoperative clinical Stage IA gastric cancer. We compared 20 patients who underwent DP-LADG with 24 patients of clinical Stage IA patients who underwent C-LADG. RESULTS The mean operation time was significantly longer for DP-LADG (250.5 min) than for C-LADG (197.5 min); however, the mean operation time for the last 5 patients undergoing DP-LADG (209 ± 31.1 min) was almost the same as that for C-LADG. There were no significant differences between DP-LADG and C-LADG in terms of blood loss, number of lymph nodes dissected, rates of conversion to open surgery, postoperative complications, and length of postoperative hospital stay. CONCLUSIONS DP-LADG is technically feasible.