title: Intra-DIC (distal intracranial catheter) deployment of the Pipeline embolization device: a novel rescue strategy for failed device expansion.

text: BACKGROUND The Pipeline embolization device (PED) is a braided flow diverter that requires a combination of meticulous maneuvers to assure proper device opening and expansion. Mechanical, anatomical, or technical challenges can result in a partially deployed PED with failed expansion. OBJECTIVE To present a new alternative method of PED deployment using the Navien distal intracranial catheter (DIC) as a salvage maneuver for cases where PED opening fails with standard techniques. METHODS We retrospectively reviewed a prospective, single-center aneurysm database to identify all patients who underwent endovascular treatment of intracranial aneurysms using the PED with the Navien distal intracranial catheter access platform. Cases requiring PED deployment within the Navien catheter were reviewed. Data was collected for patient demographics, aneurysm characteristics, and technical details of the interventional procedure. RESULTS Eleven PED neurointerventions requiring intra-Navien PED deployment to fully open the PED were identified. Mean patient age was 55.5±9.9 years (range 37-76 years). Mean aneurysm size was 12.5 mm±4.9 mm (range 2-42 mm). All aneurysms were located in the anterior circulation (anterior cerebral artery, n=1; supraclinoid, n=1; ophthalmic/paraophthalmic, n=6; cavernous, n=3; petrocervical, n=1). Mean fluoroscopy time was 67.1±20.5 min. The intra-Navien technique was used to open the proximal PED (n=7) and the mid-portion (n=4). Post-processing of the PED with a balloon was used in six cases. CONCLUSIONS When a partially deployed PED remains constrained despite exhaustion of standard maneuvers to facilitate opening, the technique of intra-Navien PED deployment is a valuable rescue strategy. This new alternative method of PED deployment can be used to open a stretched device with successful completion of the PED implantation.


title: Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass.

text: OBJECTIVE The objective of this study was to quantify hormones that regulate energy and glucose homeostasis to establish possible mechanisms for the greater efficacy of Roux-en-Y gastric bypass (RYGB) compared with laparoscopic adjustable gastric banding (LAGB) in achieving weight loss and improved insulin sensitivity. DESIGN Longitudinal study of patients undergoing LAGB (n=15) and RYGB (n=28) who were studied before surgery and at 2, 12, 26 and 52 weeks afterwards. MEASUREMENTS Fasting blood samples were drawn at each visit. Postprandial blood samples were also obtained before surgery and at 26 and 52 weeks. Samples were assayed for peptide YY (PYY), ghrelin, glucagon-like peptide-1 (GLP-1), glucose, insulin, leptin, thyrotropic hormone, free T(4) and free T(3). RESULTS At 1 year there was greater weight loss in RYGB compared with LAGB patients (30 vs 15%), but final body mass index was similar (34 vs 33 kg m(-2)). At week 52, area under the curve (AUC) for PYY in RYGB subjects was greater than LAGB (P<0.01). GLP-1 levels at 30 min after meal were threefold greater after RYGB compared with LAGB (P<0.001). Conversely, ghrelin AUC increased after LAGB at week 52 (P<0.05) but tended to decrease after RYGB. Fasting glucose, insulin, and leptin and homeostasis model of assessment (HOMA-IR) decreased in both groups over time but were significantly lower at week 52 after RYGB compared with LAGB. The change in leptin correlated significantly with weight loss in LAGB (r=0.86) and RYGB (r=0.77), however, HOMA-IR correlated significantly with weight loss only in LAGB (r=0.78), and not RYGB (r=0.15). There was a significant decrease in free T(3) (P<0.01) after RYGB. CONCLUSIONS Differences in levels of gut hormones may play a role in promoting greater weight loss and insulin sensitivity after RYGB compared with LAGB, however, weight loss may be limited by decreases in free T(3) and leptin.


Lack of COVID-19 transmission on an international flight.


title: Neurologic complications after allogeneic transplantation: a meta-analysis.

text: OBJECTIVE Neurologic adverse events remain challenging complications with poor morbidity and mortality post adult allogeneic hematopoietic cell transplantation (allo-HCT) for hematologic diseases. We conducted a systematic review and meta-analysis to determine their spectrum, incidence, and impact on survival. METHODS We searched MEDLINE, COCHRANE, EMBASE through March 2019 for all types of primary studies. Two independent reviewers screened, extracted data, and assessed risk of bias (RoB). RESULTS We identified 552 eligible studies describing 57.972 patients; one randomized controlled trial, two case-control, 17 prospective, 86 retrospective cohort studies, 21 case series, and 425 case reports. RoB ranged from fair to high although case series were low-risk. The majority of studies traced infectious or drug-related neurologic manifestations. Infectious complications were present in 2.7% (95% CI 1.9-3.6) and 3.3% (95% CI 0.8-7.1) of patients in retrospective and prospective cohort studies, respectively. In retrospective studies, 3.4% (95% CI 2.1-4.9) of patients suffered from drug-related neurologic events. In prospective cohorts the equivalent incidence was 13% (95% CI 4.2-24.8). Neurologic complications had a detrimental impact on survival. INTERPRETATION Our study highlights the wide spectrum and significant impact of neurologic complications on survival post allo-HCT. This systematic review summarizes existing data and provides the necessary background information for every physician involved in the management of these patients.


title: A small-size transfer blackbody cavity for calibration of infrared ear thermometers.

text: A small-size transfer blackbody cavity for calibration of infrared ear thermometers (IRETs) was developed and characterized at the Korea Research Institute of Standards and Science. This blackbody cavity consists of a reflector exposed to the air and a radiator with three-step curves immersed in a water-bath, and has an angularly uniform emissivity of higher than 0.9993. The radiance temperature of the blackbody cavity was measured with an IRET. We also calculated the effective emissivity by using the software STEEP322, considering the influence of the shape and temperature of the probe-tip of the IRET on the effective emissivity of the blackbody cavity. The measured and calculated radiance temperatures of the blackbody cavity were compared to those of the ASTM-type blackbody cavity and are in good agreement. Uncertainties (k = 1) of the blackbody cavity are estimated to be less than 44 mK in the temperature range 35-42 °C.


title: Complete genome sequence of a porcine epidemic diarrhea virus variant.

text: In 2011, outbreaks of viral diarrhea were observed on most swine-breeding farms in most of the provinces of China. The disease is characterized by vomiting, severe diarrhea, and a high mortality rate (82.3%) in newborn piglets. The clinical appearance was similar to that of porcine epidemic diarrhea virus (PEDV) infection. PEDVs were detected in samples (feces or small intestines) from most farms. In order to investigate whether there is a PEDV variant circulating in China, we sequenced and analyzed the complete genome of the recently identified field strain, CH/FJND-3/2011. The sequence data indicate that this PEDV variant prevails in China.


title: Prospective, multicenter, observational study of tissue acquisition through EUS-guided fine-needle biopsy using a 25G Franseen needle.

text: Background Recently, EUS-guided fine-needle biopsy (EUS-FNB) using a Franseen needle was developed for histological tissue acquisition. However, the yield of a 25G Franseen needle when acquiring histological core tissue has been unclear. Patients and Methods We performed a prospective, multicenter, and observational cohort study that included 100 solid lesions scheduled for EUS-FNB using a 25G Franseen needle at eight centers in Hokkaido, Japan. Only EUS-FNB specimens acquired at the first pass were evaluated without a rapid on-site evaluation. The tissue acquisition rate, acquisition rate of an adequate specimen for histological assessment, the quality of tissue sample, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic accuracy, and adverse events were evaluated. Results We analyzed a total of 100 solid lesions in 100 patients. The patients were 57 males and 43 females with a median age of 70 years. The technical success rate was 100%. The tissue acquisition rate was 95.0%. The acquisition rate of an adequate specimen for histological assessment was 82.0%. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy were 87.0%, 100%, 100%, 40.0%, and 88.0%, respectively. The adverse event rate was 1.0%, and it was reported in only one patient who had a moderate pancreatic fistula. Conclusions EUS-FNB using the 25G Franseen needle was feasible, and adequate histological core tissue samples were acquired with this method.


Science and Government. Reforming China's S&T system.


Evolving Neuroimaging Findings during COVID-19.


title: Coexistence of DIPNECH and carotid body paraganglioma: is it just a coincidence?

text: Summary We describe the case of a 56 year-old woman with the almost simultaneous appearance of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and a carotid body paraganglioma. Of interest, 6 years earlier, the patient underwent total thyroidectomy due to papillary thyroid carcinoma and, in the meantime, she was submitted to mastectomy to treat an invasive ductal carcinoma of the breast. In order to explain these lesions, an extensive genetic study was performed. Results showed positivity for the presence of the tumor suppressor gene PALB2, whose presence had already been detected in a niece with breast cancer. The patient underwent different procedures to treat the lesions and currently she is symptom-free over 2 years of follow-up. Learning points The presence of two rare neoplasms in a single person should raise the suspicion of a common etiology. To the best of our knowledge, this is the first case that shows the coexistence of DIPNECH and paraganglioma. The contribution of the PALB2 gene in the etiology of these rare neoplasms is a possibility.


title: The use of dextran and carbon dioxide for optical coherence tomography in the superficial femoral artery.

text: The following case report describes using carbon dioxide (CO2) as contrast media for intravascular optical coherence tomography (OCT) imaging in the superficial femoral artery. For initial OCT imaging, 20 mL of iodinated contrast was used during automated pullback. This was followed by 20 mL of hand-injected dextran 40 in normal saline, and finally hand-injected 50 mL of CO2. CO2 gave comparable erythrocyte clearance and imaging quality compared with dextran and iodinated contrast. To our knowledge, this is the first reported case using both dextran and CO2 with OCT imaging of the superficial femoral artery. Using CO2 is a viable option in patients with contraindications to contrast or dextran use.


title: COVID-19 in a severe eosinophilic asthmatic receiving benralizumab - a case study.

text: Introduction: Only little is known about COVID-19 in patients with asthma. There is no data on COVID-19 in patients with severe asthma or patients with asthma who are treated with monoclonal antibodies. Case Study: Here, we present the case of a severe eosinophilic asthmatic in whom benralizumab treatment, an anti-IL-5R monoclonal antibody, was initiated 2 years ago. Prior to benralizumab treatment, every viral infection had resulted in a prolonged course of oral corticosteroids (OCS). Since initiation of benralizumab, the patient has had good asthma control. Mid-March 2020, the patient developed high fever. Results: A SARS-CoV-2-PCR (nasopharyngeal swab) was positive. The patient's symptoms subsided after few days. No OCS was needed. The asthma control questionnaire 6-item scale worsened moderately in the week of the infection and returned to normal levels thereafter. The asthma control test, measuring longer term asthma control, showed no decline. Conclusion: The course of COVID-19 was very mild in this particular patient with severe eosinophilic asthma. So far, there is no evidence that would suggest a more severe course of COVID-19 in patients with asthma. It is worth noting, that prior to the initiation of benralizumab this patient had multiple exacerbations per year triggered by viral infections (4/year), which all required OCS. Whilst only anecdotal, this case study provides the first evidence to support the current recommendation of continuing monoclonal antibodies in patients with severe asthma during the COVID-19 pandemic.


title: Feline infectious peritonitis: still an enigma?

text: Feline infectious peritonitis (FIP) is one of the most important fatal infectious diseases of cats, the pathogenesis of which has not yet been fully revealed. The present review focuses on the biology of feline coronavirus (FCoV) infection and the pathogenesis and pathological features of FIP. Recent studies have revealed functions of many viral proteins, differing receptor specificity for type I and type II FCoV, and genomic differences between feline enteric coronaviruses (FECVs) and FIP viruses (FIPVs). FECV and FIP also exhibit functional differences, since FECVs replicate mainly in intestinal epithelium and are shed in feces, and FIPVs replicate efficiently in monocytes and induce systemic disease. Thus, key events in the pathogenesis of FIP are systemic infection with FIPV, effective and sustainable viral replication in monocytes, and activation of infected monocytes. The host's genetics and immune system also play important roles. It is the activation of monocytes and macrophages that directly leads to the pathologic features of FIP, including vasculitis, body cavity effusions, and fibrinous and granulomatous inflammatory lesions. Advances have been made in the clinical diagnosis of FIP, based on the clinical pathologic findings, serologic testing, and detection of virus using molecular (polymerase chain reaction) or antibody-based methods. Nevertheless, the clinical diagnosis remains challenging in particular in the dry form of FIP, which is partly due to the incomplete understanding of infection biology and pathogenesis in FIP. So, while much progress has been made, many aspects of FIP pathogenesis still remain an enigma.


title: Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy?

text: A new coronavirus, referred to as SARS-CoV-2, is responsible for the recent outbreak of severe respiratory disease. This outbreak first detected in Wuhan, China in December 2019, has spread to other regions of China and to 25 other countries as of January, 2020. It has been known since the 2003 SARS epidemic that the receptor critical for SARS-CoV entry into host cells is the angiotensin-converting enzyme 2 (ACE2). The S1 domain of the spike protein of SARS-CoV attaches the virus to its cellular receptor ACE2 on the host cells. We thought that it is timely to explain the connection between the SARS-CoV, SARS-CoV-2, ACE2 and the rationale for soluble ACE2 as a potential therapy.


title: 99mTc(CO)3-nitrilotriacetic acid: a new renal radiopharmaceutical showing pharmacokinetic properties in rats comparable to those of 131I-OIH.

text: UNLABELLED To develop a (99m)Tc renal tracer with a capacity to measure effective renal plasma flow comparable to that of the clinical gold standard (131)I-o-iodohippurate ((131)I-OIH) and superior to that of (99m)TcO-mercaptoacetyltriglycine, which has a clearance only 50%-60% that of (131)I-OIH, we investigated (99m)Tc-tricarbonyl nitrilotriacetic acid (Na(2)[(99m)Tc(CO)(3)(NTA)]). This radiopharmaceutical, which is based on an aminopolycarboxylate ligand, is formed as a single species and has a dangling carboxylate group favoring tubular transport. METHODS Na(2)[(99m)Tc(CO)(3)(NTA)] was prepared by using commercially available NTA and an IsoLink kit and isolated by high-performance liquid chromatography. The stability of Na(2)[(99m)Tc(CO)(3)(NTA)] in isotonic saline was assessed for 24 h and was further evaluated by incubation in 0.1 M cysteine and histidine for 4 h at 37 degrees C. The biodistribution of Na(2)[(99m)Tc(CO)(3)(NTA)], coinjected with (131)I-OIH as an internal control, was evaluated in 5 normal Sprague-Dawley rats at 10 min, 5 normal Sprague-Dawley rats at 60 min (group A), and 6 rats with renal pedicle ligation at 60 min (group B) after injection. Clearance and extraction fraction studies were conducted in 2 normal Sprague-Dawley rats, and urine and plasma from 2 additional normal rats each were analyzed for metabolites by high-performance liquid chromatography. RESULTS The radiochemical purity of Na(2)[(99m)Tc(CO)(3)(NTA)] was greater than 99%, the complex was stable for 24 h at physiologic pH, and the challenge experiments showed no degradation. In normal rats, the percentage dose in the urine at 10 and 60 min was 108% +/- 9% and 101% +/- 5%, respectively, that of (131)I-OIH; minimal hepatic or gastrointestinal activity was demonstrated. In group B rats, Na(2)[(99m)Tc(CO)(3)(NTA)] was better retained in the blood and had less excretion into the bowel than did (131)I-OIH (P < 0.01). The plasma clearances of Na(2)[(99m)Tc(CO)(3)(NTA)] and (131)I-OIH were comparable, but the extraction fraction of Na(2)[(99m)Tc(CO)(3)(NTA)] was 93.5% +/- 3.8%, compared with 67.9% +/- 6.1% for (131)I-OIH. Plasma protein binding of Na(2)[(99m)Tc(CO)(3)(NTA)] averaged 67% +/- 7%, and red cell uptake was 7% +/- 2%. CONCLUSION Na(2)[(99m)Tc(CO)(3)(NTA)] is stable, exists as a single species, and has pharmacodynamic properties in rats comparable to those of (131)I-OIH.


title: Toxicity of a combined therapy using the mTOR-inhibitor everolimus and PRRT with [177Lu]Lu-DOTA-TATE in Lewis rats.

text: PURPOSE Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA0,TYR3-octreotate ([177Lu]Lu-DOTA-TATE) and the mechanistic target of rapamycin (mTOR) inhibitor everolimus are both approved for the treatment of neuroendocrine tumours (NET). However, tumour progression is still frequent, and treatment strategies need further improvement. One possible approach could be to combine different therapy options. In this study, we investigated the toxicity of a combined treatment with everolimus and [177Lu]Lu-DOTA-TATE in female Lewis rats. METHODS Animals received 200 MBq of [177Lu]Lu-DOTA-TATE once and/or 5 mg/kg body weight everolimus or placebo weekly for 16 weeks and were divided into four groups (group 1, placebo; group 2, everolimus; group 3, placebo + [177Lu]Lu-DOTA-TATE; group 4, everolimus + [177Lu]Lu-DOTA-TATE). Blood levels of creatinine and blood urea nitrogen (BUN) were assessed weekly to monitor nephrotoxicity, and a full blood count was performed at the time of euthanasia to monitor myelotoxicity. Additionally, renal function was analysed by sequential [99mTc]Tc-mercaptoacetyltriglycine ([99mTc]Tc-MAG3) scintigraphies. Histopathological examination was performed in all the kidneys using a standardized renal damage score (RDS). RESULTS Rats receiving everolimus showed a significantly lower increase in creatinine levels than those receiving placebo. Everolimus therapy reduced white blood count significantly, which was not observed for [177Lu]Lu-DOTA-TATE. Functional renal scintigraphies using [99mTc]Tc-MAG3 showed a compromised initial tracer uptake after PRRT and slower but still preserved excretion after everolimus. Histology showed no significant RDS differences between groups. CONCLUSION Renal scintigraphy is a highly sensitive tool for the detection of renal function impairment after a combination of everolimus and PRRT. Additional treatment with everolimus does not increase renal and haematological toxicity of PRRT with [177Lu]Lu-DOTA-TATE.


title: Art therapy in the time of COVID-19.

text: We are fighting two invisible enemies: COVID-19 and mental health challenges due to unmitigated stress and trauma as we follow directions to avoid the spread of the virus. To address the mental health challenges, art therapy is offered as a tool to support individuals during periods of isolation. Art therapy is a wonderful self-care activity that can benefit individuals throughout the life span. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans.

text: Immunomodulators have been shown to improve the outcome of severe pneumonia. We have previously shown that mycophenolic acid (MPA), an immunomodulator, has antiviral activity against influenza A/WSN/1933(H1N1) using a high-throughput chemical screening assay. This study further investigated the antiviral activity and mechanism of action of MPA against contemporary clinical isolates of influenza A and B viruses. The 50 % cellular cytotoxicity (CC50) of MPA in Madin Darby canine kidney cell line was over 50 µM. MPA prevented influenza virus-induced cell death in the cell-protection assay, with significantly lower IC50 for influenza B virus B/411 than that of influenza A(H1N1)pdm09 virus H1/415 (0.208 vs 1.510 µM, P=0.0001). For H1/415, MPA interfered with the early stage of viral replication before protein synthesis. For B/411, MPA may also act at a later stage since MPA was active against B/411 even when added 12 h post-infection. Virus-yield reduction assay showed that the replication of B/411 was completely inhibited by MPA at concentrations ≥0.78 µM, while there was a dose-dependent reduction of viral titer for H1/415. The antiviral effect of MPA was completely reverted by guanosine supplementation. Plaque reduction assay showed that MPA had antiviral activity against eight different clinical isolates of A(H1N1), A(H3N2), A(H7N9) and influenza B viruses (IC50 <1 µM). In summary, MPA has broad-spectrum antiviral activity against human and avian-origin influenza viruses, in addition to its immunomodulatory activity. Together with a high chemotherapeutic index, the use of MPA as an antiviral agent should be further investigated in vivo.


title: Enterovirus 71 induces apoptosis by directly modulating the conformational activation of pro-apoptotic protein Bax.

text: Enterovirus 71 (EVA71), a virus of the genus Enterovirus in the family Picornaviridae, is one of the main causative agents of hand, foot and mouth disease in infected infants and young children. In this study, we report that cells with EVA71 infection exhibit increased levels of cytochrome c release and caspase-3 activation. EVA71 infection induces the conformational activation of pro-apoptotic protein Bax and the subsequent formation of oligomers of Bax in mitochondria. Inhibitors that block caspase-8 activation cannot inhibit apoptosis induced by EVA71 infection. Importantly, cells with Bax but not Bak or caspase-8 knockdown show resistance to apoptosis induced by EVA71 infection. Mitochondria isolated from EVA71-infected cells display clear Bax-binding ability and the subsequent release of cytochrome c. Therefore, these results indicate that EVA71 infection directly impacts the mitochondrial apoptotic pathway by modulating the recruitment and activation of Bax.


title: Single-incision laparoscopic cholecystectomy versus laparoscopic cholecystectomy: a prospective randomized study.

text: This prospective randomized study compared single-incision laparoscopic cholecystectomy (SILC) and laparoscopic cholecystectomy (LC) with respect to estimated blood loss, operative time, postoperative pain levels, and complications. Thirty-four study patients were divided into 2 groups: 17 patients underwent SILC and 17 underwent LC. Operative time was longer for SILC than for LC, and the difference was statistically significant (P<0.001). There was no statistically significant difference in the relationship of body mass index with operative time between SILC and LC (P=0.613, P=0.983, respectively). The 2 groups had no statistically significant differences with respect to visual analog scale scores, estimated blood loss, shoulder pain, or complications (P>0.05). SILC can be the treatment of choice for gallbladder disease. Although the surgeon's first several attempts at SILC require a longer operative time compared with LC, there are no differences in hospital length of stay, blood loss, complication rates, or pain scores between SILC and LC.


title: Prospective Study of Early MRI Appearances following Flow-Diverting Stent Placement for Intracranial Aneurysms.

text: BACKGROUND AND PURPOSE MR imaging findings of aneurysm enlargement, aneurysm wall enhancement, perianeurysmal edema, and embolic phenomena following deployment of flow-diverting stents may be relevant to those patients who subsequently experience procedure-related intracranial hemorrhage. We sought to document the routine early postoperative MR imaging findings following flow-diverting stent insertion. MATERIALS AND METHODS Patients requiring flow-diverting stent placement for treatment or retreatment of cerebral aneurysms were prospectively included in the study during a 26-month period. Early postprocedural MR imaging studies were obtained and compared with preoperative imaging. Patient clinical outcome data were also collected. RESULTS There were 34 stent-placement procedures during the study period. Aneurysm mural enhancement and mild new perianeurysmal edema were present in 50% and 14%, respectively. Any DWI lesion was present in 57% of cases. New or possibly new foci of susceptibility effect were found ipsilateral to the stent and not associated with diffusion restriction in 66% of cases. There were 2 cases (6%) of parenchymal hemorrhage and 2 major clinical complications (6%) causing permanent morbidity. CONCLUSIONS Asymptomatic aneurysm mural enhancement is frequently seen following flow-diverting stent placement and should not necessarily be interpreted as a sign of impending aneurysm rupture. This finding often persists despite complete aneurysm occlusion. New small brain parenchymal susceptibility foci following stent placement have not previously been reported, to our knowledge, but were common in our series.


title: Adaptation and evaluation of Turkish version of the fear of COVID-19 Scale.

text: We investigated the psychometric properties of the Fear of COVID-19 Scale in Turkish among a diverse group with a focus on the prevalence of coronavirus related fear across gender, age intervals, SES, chronic illness situation, and educational level. Based on a confirmatory factor analysis, the Fear of COVID-19 Scale had appropriate psychometric properties for utilization, including excellent goodness-of-fit indices, a Cronbach's alpha value of .86, and discriminant validity, as shown by a significant negative correlation with resilience. Furthermore, group comparison analyses revealed that women reported significantly higher fear of coronavirus. Additionally, individuals from middle SES reported significantly higher fear of coronavirus while the fear of coronavirus did not differ based on participants' educational level, socioeconomic status, and age level. Implications for mental health providers are discussed.


Reactive Psychosis in a Health Care Worker During the COVID-19 Pandemic.


title: Dynamic combinatorial chemistry: a tool to facilitate the identification of inhibitors for protein targets.

text: Dynamic combinatorial chemistry (DCC) has emerged as a powerful strategy to identify ligands for biological targets given that it enables the target to direct the synthesis and amplification of its strongest binder(s) from the library of interconverting compounds. Since the first report of DCC applied to the discovery of binders for a protein, this elegant tool has been employed on a range of protein targets at various stages of medicinal-chemistry projects. A series of suitable, reversible reactions that are biocompatible have been established and the portfolio of analytical techniques is growing. Despite progress, in most cases, the libraries employed remain of moderate size. We present here the most recent advances in the field of DCC applied to protein targets, paying particular attention to the experimental conditions and analytical methods chosen.


title: Anxiety behavior and hypothalamic-pituitary-adrenal axis altered in a female rat model of vertical sleeve gastrectomy.

text: Surgical weight loss results in a host of metabolic changes that culminate in net positive health benefit to the patients. However, the psychological impact of these surgeries has not been fully studied. On one hand, surgical weight loss has been reported to improve standard quality of life and resolution of symptoms of depression. But on the other hand, reports of self-harm and increased ER visits for self-harm suggest other psychological difficulties. Inability to handle anxiety following surgical weight loss has alarming potential ramifications for these gastric surgery patients. In the present study, we used models of diet-induced obesity and vertical sleeve gastrectomy (VSG) to ask whether anxiety behavior and hypothalamic-pituitary-adrenal (HPA) axis gene changes were affected by surgical weight loss under two diet regimens: i.e. low-fat diet (LFD) and high-fat diet (HFD). We show reduced exploratory behavior in the open field test but increased time in the open arms of the elevated plus maze. Furthermore, we show increased plasma levels of corticosterone in female VSG recipients in the estrus phase and increased levels of hypothalamic arginine-vasopressin (avp), pro-opiomelanocortin (pomc), and tyrosine hydroxylase (th). We report reduced dopamine receptor D1 (drd1) gene in prefrontal cortex (PFC) in VSG animals in comparison to Sham. Further we report diet-driven changes in stress-relevant gene targets in the hypothalamus (oxt, pomc, crhr1) and adrenal (nr3c1, nr3c2, mc2r). Taken together, these data suggest a significant impact of both surgical weight loss and diet on the HPA axis and further impact on behavior. Additional assessment is necessary to determine whether molecular and hormonal changes of surgical weight loss are the source of these findings.


title: Near-infrared spectroscopy during cardiopulmonary resuscitation and after restoration of spontaneous circulation: a valid technology?

text: PURPOSE OF REVIEW This article explores the status of using near-infrared spectroscopy and reporting cerebral oximetry (rSO2) for cardiac arrest patients. RECENT FINDINGS Bystander cardiopulmonary resuscitation (CPR) patients have significantly higher rSO2 compared with no bystander CPR patients. It is unclear how quickly rSO2 changes with hemodynamic instability. rSO2 during mechanical CPR varies between 44 and 55% and manual CPR varies between 20 and 40%, representing a significant relative rSO2 increase. Studies have found a relationship between rSO2 and restoration of spontaneous circulation (ROSC) and rSO2 increase can be used as a sign of ROSC. rSO2 evaluation is effective for monitoring quality of resuscitation and neurological prognostication. It seems that cardiac arrest patients with good neurologic outcome have significantly higher rSO2 levels (CPC 1-2 median rSO2 68%, CPC 3-5 median rSO2 58%, P < 0.01) and good neurologic outcome (CPC 1-2) increased 'in proportion to the patients' rSO2 levels irrespective of their ROSC status at hospital arrival'. However, most of the studies are small and a prospective outcome study focusing on rSO2 values is needed. SUMMARY Near-infrared spectroscopy and rSO2 have been used as a monitor during CPR, detection of ROSC, after ROSC, and during post-resuscitation care. Prospective, controlled, randomized clinical studies are needed to document their wide use.


Risk stratification in chronic hepatitis B patients for hepatocellular carcinoma surveillance: management in migrant sub-Saharan African populations.


title: Local infusion analgesia using intra-articular double lumen catheter after total knee arthroplasty: a double blinded randomized control study.

text: PURPOSE Although intra-operative local infiltration analgesia has gained increasing popularity in joint replacement surgery, it is not clear whether postoperative local infusion analgesia using an indwelling catheter provides clinically important additional effects. We, therefore, conducted a randomized controlled trial to clarify the efficacy of the originally developed local infusion analgesia technique in total knee arthroplasty. METHODS Forty patients were randomly allocated to the local infusion analgesia or control group. Patients in the local infusion analgesia group received intermittent bolus intra-articular injection of analgesics consisting of ropivacaine, dexamethasone, and isepamicin until postoperative 48 h. Primary outcome was pain severity at rest using 100-mm visual analogue scale. RESULTS Pain severity in patients of the local infusion analgesia group was lower than control group, and there were significant differences between groups at POD1 (p = 0.025) and POD3 (p = 0.007). Reduction of postoperative pain was associated with a decrease in C-reactive protein level and earlier achievement of straight leg raise. In addition, postoperative drain volume was reduced in the local infusion analgesia group. CONCLUSION Although larger studies are needed to examine its safety, the local infusion analgesia alone provided clinically significant analgesic effects and rapid recovery in total knee arthroplasty.


title: The initial experience of dual port laparoscopy-assisted total gastrectomy as a reduced port surgery for total gastrectomy.

text: Reduced port surgery (RPS), in which fewer ports are used than that in a conventional laparoscopic procedure, is becoming increasingly popular for various surgeries. However, the application of RPS to the field of gastrectomy is still underdeveloped. We started laparoscopy-assisted total gastrectomy through an umbilical port plus another 5 mm port (dual port laparoscopy-assisted total gastrectomy: DP-LATG) as an RPS for laparoscopy-assisted total gastrectomy (LATG). A SILS™ port was inserted into an umbilical incision, while another 5 mm port was inserted at the right flank region. We performed DP-LATG on ten early gastric cancer cases consecutively from May 2011 onwards, with the surgeries all performed by a single surgeon. The results of DP-LATG were compared with the resuls of ten conventional LATGs (C-LATGs) that were performed between March 2010 and April 2011. There were no significant differences in the mean operation time (DP-LATG, 253.0 ± 26.8 min; C-LATG, 235.5 ± 20.6 min; p = 0.119), mean blood loss (33.4 ± 23.7, 39.8 ± 60.4 mL, p = 0.759), and number of lymph nodes dissected (31.6 ± 12.3, 40.9 ± 18.7, p = 0.205). There were no intraoperative complications, there was no need for additional ports, and there were no conversions to open surgery nor postoperative complications in the DP-LATG cases. We successfully and safely performed DP-LATG without incurring any notable differences from C-LATG in terms of operation time, blood loss, and number of lymph nodes dissected.


title: Intractable hemorrhagic cystitis after hematopoietic stem cell tranplantation--is there a role for early urinary diversion in children?

text: PURPOSE Severe hemorrhagic cystitis is a major complication in the pediatric population undergoing hematopoietic stem cell transplantation. Percutaneous nephrostomy tube drainage as a treatment for severe hemorrhagic cystitis has rarely been investigated. We examined children undergoing hematopoietic stem cell transplantation for risk factors associated with severe hemorrhagic cystitis, as well as our experience with percutaneous nephrostomy tube placement as an adjunctive management strategy. MATERIALS AND METHODS Using prospectively collected data from the Blood and Marrow Transplant Database at the University of Minnesota, we reviewed 40 pediatric patients with severe hemorrhagic cystitis from 1996 to 2010. Specific treatment for each patient was administered at the discretion of the attending physician and generally included bladder irrigation before bladder fulguration or percutaneous nephrostomy tube placement. A percutaneous nephrostomy tube was placed in 11 patients due to the intractable nature of the hemorrhagic cystitis. RESULTS Of the 11 patients who underwent percutaneous nephrostomy tube drainage 5 (45%) had improvement of the hemorrhagic cystitis within 30 days and the same number had long-term resolution. Among the patients with long-term resolution hemorrhagic cystitis resolved an average of 12.4 days after percutaneous nephrostomy tube placement, and the tubes were removed an average of 8.8 weeks after placement. Through September 2011 mortality among patients with percutaneous nephrostomy tubes was 55% (6 of 11 patients), which was identical to the overall mortality in the severe hemorrhagic cystitis group (22 of 40). No death could be directly attributed to hemorrhagic cystitis or percutaneous nephrostomy tube placement. CONCLUSIONS Placement of percutaneous nephrostomy tubes for treatment of severe hemorrhagic cystitis results in long-term improvement in intractable hemorrhagic cystitis, and is a safe and viable option for the majority of patients.


China coronavirus: what do we know so far?


title: The effectiveness of a novel neuromuscular electrostimulation method versus intermittent pneumatic compression in enhancing lower limb blood flow.

text: OBJECTIVE This study compares the effectiveness of a neuromuscular electrostimulation device (geko T-1; Firstkind Ltd, High Wycombe, UK) in enhancing lower limb blood perfusion with two leading intermittent pneumatic compression (IPC) devices, the Huntleigh Flowtron Universal (Huntleigh Healthcare Ltd, Cardiff, UK) and the Kendall SCD Express (Covidien plc, Dublin, Ireland). The subjects' tolerance of the devices was also compared. METHODS Ten healthy subjects were recruited. The devices were fitted bilaterally, in a sequential manner, for 30 minutes. Ultrasound and laser Doppler fluxmetry assessments were performed. RESULTS The geko T-1 device was superior to both IPC devices in increasing both venous and arterial blood volume flow by ∼30% (95% confidence interval [CI], 23.7%-82.4%; P ≤ .001). The geko T-1 increased arterial blood velocity by 24% (95% CI, 9.7%-24.5%; P ≤ .001). A substantial increase in the total microcirculatory blood velocity by ∼370% (95% CI, 13.5%-39.7%) was reported after the use of the geko T-1 (P ≤ .001). With use of the visual analog scale, no significant differences in discomfort were found between the geko T-1 device and the IPC devices (P >.05). CONCLUSIONS The geko T-1 device is more effective than the IPC devices in increasing venous, arterial, and microcirculatory blood velocity. The devices studied were safe and well tolerated by healthy subjects.


title: Pancreatic rupture in four cats with high-rise syndrome.

text: Pancreatic trauma and rupture are rare after feline high-rise syndrome; however, should it happen, pancreatic enzymes will leak into the abdominal cavity and may cause pancreatic autodigestion and fatty tissue saponification. If not diagnosed and treated, it can ultimately lead to multiorgan failure and death. In this case series, 700 records of high-rise syndrome cats that presented between April 2001 and May 2006 were analysed, and four cats with pancreatic rupture were identified. Clinical signs, diagnosis using ultrasonography and lipase activity in blood and abdominal effusion, and treatment modalities are reported. Three cats underwent surgical abdominal exploration, one cat was euthanased. Rupture of the left pancreatic limb was confirmed in all cases. Two of the operated cats survived to date. High-rise syndrome can lead to abdominal trauma, including pancreatic rupture. A prompt diagnosis and surgical treatment should be considered.


title: Laparoscopic Treatment of Sclerosing Stromal Tumor of the Ovary in a Woman With Gorlin-Goltz Syndrome: A Case Report and Review of the Literature.

text: Gorlin-Goltz syndrome is a rare hereditary multisystemic disease. Multiple basal cell carcinomas, odontogenic keratocysts, and skeletal abnormalities are the main clinical manifestations of the syndrome, but several organs can be involved. Moreover, this condition is associated with the development of various benign and malignant tumors, even in the genital tract. This report describes a rare association between Gorlin-Goltz syndrome and the sclerosing stromal tumor of the ovary. Because the ultrasound and magnetic resonance imaging patterns of this tumor can be similar to those of a malignant neoplasm, prompt surgical intervention and histological confirmation of diagnosis is mandatory; however, this is a benign lesion and thus can be approached with a laparoscopic fertility-sparing surgery. Gynecologists should be aware of this possible association to provide appropriate counseling for these women, and to take a fertility-sparing laparoscopic approach whenever possible.


Medicaid and COVID-19: At the Center of Both Health and Economic Crises.


title: Canine and feline abdominal arterioportal communications can be classified based on branching patterns in computed tomographic angiography.

text: Arterioportal vascular anomalies are communications between the splanchnic arteries and the portal system that represent a rare cause of presinusoidal portal hypertension in small animals. There is little information concerning the imaging findings of arterioportal communications in small animals and no classification could be found for radiologists and surgeons. The aims of this retrospective descriptive multicentric study were to describe the computed tomographic characteristics of arterioportal communications in a group of cats and dogs, and to propose a classification based on computed tomography (CT) angiographic anatomy. Computed tomography databases from multiple veterinary hospitals were searched for cats and dogs with a diagnosis of arterioportal communication. A total of 36 animals (33 dogs, three cats) met the inclusion criteria. There were 32 intrahepatic arterioportal malformations and four extrahepatic fistulae. The intrahepatic arterioportal malformations were classified as right divisional (11/32) and left divisional (21/32), and the left divisional were subclassified as left medial (16/21) and left lateral (4/21). One patient showed multiple intrahepatic arterioportal communications with concomitant left medial and left lateral conformations. Two patients with intrahepatic arteriovenous malformation showed concomitant congenital intrahepatic shunts. The proposed anatomical classification based on CT angiography could allow veterinary radiologists to have a more systematic approach and help improve the radiologist-surgeon communication.


title: Global Issues of Radiopharmaceutical Access and Availability: a Nuclear Medicine Global Initiative Project.

text: The Nuclear Medicine Global Initiative (NMGI) was formed in 2012 by 13 international organizations to promote human health by advancing the field of nuclear medicine and molecular imaging by supporting the practice and application of nuclear medicine. The first project focused on standardization of administered activities in pediatric nuclear medicine and resulted in two manuscripts. For its second project the NMGI chose to explore issues impacting on access and availability of radiopharmaceuticals around the world. Methods: Information was obtained by survey responses from 35 countries on available radioisotopes, radiopharmaceuticals and kits for diagnostic and therapeutic use. Issues impacting on access and availability of radiopharmaceuticals in individual countries were also identified. Results: Detailed information on radiopharmaceuticals utilized in each country, and sources of supply, was evaluated. Responses highlighted problems in access particularly due to the reliance on a sole provider, regulatory issues and reimbursement, as well as issues of facilities and workforce particularly in low- and middle-income countries. Conclusion: Strategies to address access and availability of radiopharmaceuticals are outlined, to enable timely and equitable patient access to nuclear medicine procedures worldwide. In the face of disruptions to global supply chains by the COVID-19 outbreak, renewed focus on ensuring reliable supply of radiopharmaceuticals is a major priority for nuclear medicine practice globally.


title: Reporting AIDS and the invisible victims in China: official knowledge as news in the People's Daily, 1986-2002.

text: Against the backdrop of the sociology of knowledge as a framework, the purposes of this study are threefold: (1) to examine the discourses surrounding the AIDS news in China; (2) to determine how Chinese people with AIDS and the identification of their social groups are covered at the national level; and (3) to discuss the implications of reporting AIDS as official knowledge for a better understanding of the interplay between the mass media and social structure in China today. Findings indicate that as an epidemic, AIDS in China has not only become invisible in the national news, but also constructed as a nonissue devoid of social consequences in public health communication. It is a disease mostly presented in an "us vs. them" news discourse that helps convey the official knowledge as to how AIDS is to be perceived and understood in the country.


title: Thermogenesis-based interventions for obesity and Type 2 diabetes mellitus.

text: Obesity is one of the key noncommunicable diseases leading to significant comorbidities. In recent years, obesity has become a major public health issue and has threatened the wellbeing of millions of patients. Although there are multiple reasons for people becoming obese, sustained positive energy balance - energy intake is greater than energy expenditure - is the key for accumulating excess bodyfat. Prevention of obesity by lifestyle changes, healthy eating and increased physical activity are more cost effective than pharmacotherapy, bariatric surgery or ultimately treating complications of Type 2 diabetes mellitus (T2DM). Not all patients with obesity experience complications such as T2DM. The distribution of bodyfat is important in determining whether a person is obese and healthy or needs medical attention; however, the use of BMI alone will not differentiate this. Obesity patients with excess abdominal fat have the highest risk for T2DM, insulin resistance and thus, higher incidence of cardiovascular diseases. Obesity-associated complications can be reversed through healthy eating habits and increased duration and intensity of physical activity. Increasing work- and leisure-related physical activities increase the energy expenditure, having salutary effects on weightloss programs. Although treating symptoms of obesity and related disorders is important, it is not a solution for the obesity epidemic. Causes that lead to weight-gain need to be identified in individual patients, who should be educated about the causes of weight gain and ways to prevent it, and be provided with simple and practical interventions to lose weight.


title: Comparison of laparoscopic hepaticojejunostomy and open hepaticojejunostomy. Can stenosis of the hilar hepatic duct affect postoperative outcome?

text: INTRODUCTION The aim of this study was to compare laparoscopic hepaticojejunostomy (LHJ) and open hepaticojejunostomy (OHJ) for choledochal cyst associated with hilar hepatic duct stenosis (HHDS). METHODS Data collection was prospective for LHJ cases from 2009 and retrospective for OHJ cases from 2003 to 2008. Data were compared with respect to HHDS. HHDS was incised longitudinally as required during hilar hepatic ductoplasty. RESULTS Fifty-eight subjects were studied (LHJ: n = 27, 4 boys, 23 girls; OHJ: n = 31; 6 boys, 25 girls). HHDS was present in 10 LHJ cases and 10 OHJ cases. Todani classification of choledochal cyst in LHJ patients was type 1A (n = 16) and type 4A (n = 11), and in OHJ patients, it was type 1A (n = 19) and type 4A (n = 12). There were significant differences between LHJ and OHJ with regard to mean operative time (386 vs 341 min), mean blood loss (5.9 vs 18.4 mL), recommencement of enteral feeding (3.9 vs 6.4 days), and hospital stay (11.7 vs 15.5 days) (all P < 0.05). Hepatic ductoplasty was performed in 23 LHJ patients and in 21 OHJ patients. There were no intraoperative complications and no conversions to OHJ. There were no significant differences between LHJ and OHJ, regardless of the presence of HHDS, for postoperative complications, which included minor bile leakage, anastomotic stricture, and intestinal obstruction. CONCLUSION LHJ is as effective as OHJ for the treatment of choledochal cysts irrespective of the presence of HHDS and the need for hepatic ductoplasty.


Routine vaccination during covid-19 pandemic response.


title: Diary of a parliamentary intern.

text: The Veterinary Policy Research Foundation employs a veterinary intern to assist Lord Trees in advancing veterinary thinking in parliament. Here, the current intern Catrina Prince shares an update.


title: Higher levels of psychiatric symptomatology reported by health professionals working in medical settings in Greece.

text: BACKGROUND Psychological distress in healthcare workers may vary across different specialties. The purpose of this study was to investigate the differences in the rate of anxiety and depression between medical and mental healthcare workers. METHODS The sample was randomly selected and consisted of 229 workers from the medical health sector and 212 from the mental health sector, aged 39.8 ± 7.9 years old. Health workers from University and General Hospitals from all over Greece participated in the study. The Greek version of the Symptoms Rating Scale For Depression and Anxiety (SRSDA) was used. Statistics were processed with SPSS v. 17.0. RESULTS The medical health professionals showed statistically significantly higher scores in all the subscales in comparison with the mental health sector workers, independently of years serving in the department. The rates of a possible psychiatric disorder (score over cutoff points) were significantly elevated on the Beck-21, melancholy and asthenia subscales. CONCLUSIONS Medical healthcare workers appear to suffer from psychological distress more than their colleagues in the mental sector.


title: Anti-SARS coronavirus agents: a patent review (2008 - present).

text: INTRODUCTION A novel coronavirus (CoV), unlike previous typical human coronaviruses (HCoVs), was identified as causative agent for severe acute respiratory syndrome (SARS). SARS first surfaced as a pandemic in late 2002 and originated in southern China. SARS-CoV rapidly spread to > 30 countries by 2003, infecting nearly 8,000 people and causing around 800 fatalities. After 10 years of silence, a 2012 report alarmed researchers about the emergence of a new strain of CoV causing SARS-like disease. AREAS COVERED To combat SARS, scientists applied for patents on various therapeutic agents, including small-molecule inhibitors targeting the essential proteases, helicase and other proteins of the virus, natural products, approved drugs, molecules binding to the virus, neutralizing antibodies, vaccines, anti-sense RNA, siRNA and ribozyme against SARS-CoV. In this article, the patents published from 2008 to the present for the new therapeutics that could potentially be used in the prophylaxis and treatment of SARS are reviewed. EXPERT OPINION The therapeutic interventions or prophylaxis discussed in this review seems to offer promising solutions to tackle SARS. Rather than being complacent about the results, we should envisage how to transform them into drug candidates that may be useful in combating SARS and related viral infections in the future.


title: Reference intervals of common serum analytes of Hong Kong Chinese.

text: AIM Setting up reference intervals from the local service populations is one of the major responsibilities of clinical laboratories. Yet, this task is difficult to achieve because it is costly and time consuming when compared with validating reference intervals from assay manufacturers. METHODS Following the recommendations of the International Federation of Clinical Chemistry, healthy local Chinese adults were recruited to set up reference intervals for common serum analytes. Statistical methods recommended by the National Committee for Clinical Laboratory Standards were used for defining the reference limits. RESULTS Data from 335 subjects were analysed. The reference intervals set up were broadly similar to those provided by the assay manufacturer, except for sodium and potassium. Glomerular filtration rate was estimated by the modification of diet in renal disease equation, with or without modification for Chinese. Body mass index had a significant impact on serum urate and alanine aminotransferase levels. CONCLUSION Reference intervals of common serum analytes have been set up for the local Chinese population. A good example of quality laboratory service has also been set up to provide clinicians with reliable reference intervals that they can confidently rely on for the diagnosis and management of patients.


title: Robotic Platform for an IPAA.

text: INTRODUCTION An IPAA is the preferred operative approach for restoration of intestinal continuity in patients with ulcerative colitis and familial adenomatous polyposis. As minimally invasive approaches have become more widely adopted, their use in IPAA has also become increasingly commonplace. Laparoscopy has the same limitations during the proctectomy portion as seen in operations for rectal cancer, including dissection in the mid-to-lower rectum attributed to angles created by bony confines of the deep pelvis and lack of visibility when constructing the anastomosis. Robotic surgery provides improved 3-dimensional and high-definition visualization of the pelvis and multiple degrees of freedom, which greatly enhance performance during the proctectomy and construction of the anastomosis. TECHNIQUE In the setting of a previous subtotal colectomy, the ileostomy site is taken down and stapled across. A 15-mm balloon trocar is placed in the site to achieve insufflation, and the robotic ports are placed horizontally just above the umbilicus. The lateral mesenteric attachments are mobilized laparoscopically, then the J-pouch is constructed through the ostomy site. The J-pouch is placed back into the abdomen with the anvil in place, and the proctectomy is performed after docking the robot. The rectum is stapled with the robotic stapler and exteriorized from the ileostomy site, and the anastomosis is constructed under direct robotic visualization. RESULTS In addition to the potential ergonomic advantages, the maneuverability and visualization in the pelvis during the proctectomy and construction of the anastomosis are reported by many surgeons to be improved as compared with laparoscopy, especially in male or obese patients. CONCLUSIONS A robotic approach during the proctectomy and IPAA offers significant advantages to a laparoscopic approach, expanding our armamentarium of minimally invasive surgical techniques to IPAA.


title: Safety and Efficacy of a New Bipolar Energy Device for Parenchymal Dissection in Laparoscopic Liver Resection.

text: BACKGROUND Despite emerging technologies, parenchymal transection still remains challenging in liver resection. The aim of this study is to assess the safety and efficacy of a new articulating vessel sealer for laparoscopic hepatectomy. Our hypothesis was that this new device would facilitate parenchymal transection and reduce intraoperative costs in laparoscopic hepatectomy. METHODS Within 18 months, a 5 cm bipolar articulating vessel sealer was used in 32 laparoscopic liver resections (LLR). By excluding 4 patients who underwent concomitant colorectal resections, the outcomes of the remaining 28 patients (group 1) were compared with 28 patients who underwent LLR by the same surgical group using other energy devices (group 2). RESULTS Tumor type was malignant in 71% of patients (n=20) in group 1 and 89% of the patients (n=25) in group 2 (P=0.360). The number and size of tumors were similar in both groups, as well as the type of resections performed. In group 1, there was a less number of adjunctive devices (ie, energy, clip appliers, staplers) used (median 2) compared with group 2 (median 3, P=0.032). Parenchymal transection time (mean±SEM 28.2±3.5 vs. 55.2±4.1 min, respectively, P<0.001) and total operative time (200.1±13.7 vs. 242.7±14.4 min, respectively, P=0.036) were shorter for group 1 versus group 2. Estimated blood loss, transfusion rate, margin status, and length of stay were similar between the groups. There was no mortality. Morbidity was 11% (n=3) in group 1 and 18% (n=5) in group 2 (P=NS). The overall intraoperative costs were an average of $3000 less in group 1 (95% confidence interval, $1090-$4930, P=0.0029) compared with group 2. CONCLUSIONS This study demonstrates the safety and efficacy of a new energy device for LLR. Our experience suggested that this new device provided the functionality of both a vessel sealer and a stapler with its large jaw and articulation.


title: Effect of small interfering RNAs on in vitro replication and gene expression of feline coronavirus.

text: OBJECTIVE To evaluate the ability of small interfering RNAs (siRNAs) to inhibit in vitro viral replication and gene expression of feline coronavirus (FCoV). SAMPLE Cell cultures of Crandell-Rees feline kidney cells. PROCEDURES 5 synthetic siRNAs that each targeted a different region of the FCoV genome were tested individually and in various combinations for their antiviral effects against 2 strains of FCoV (feline infectious peritonitis virus WSU 79-1146 and feline enteric coronavirus WSU 79-1683) in cell cultures. Tested combinations targeted the FCoV leader and 3' untranslated region, FCoV leader region and nucleocapsid gene, and FCoV leader region, 3' untranslated region, and nucleocapsid gene. For each test condition, assessments included relative quantification of the inhibition of intracellular viral genomic RNA synthesis by means of real-time, reverse-transcription PCR analysis; flow cytometric evaluation of the reduction of viral protein expression in infected cells; and assessment of virus replication inhibition via titration of extracellular virus with a TCID₅₀ infectivity assay. RESULTS The 5 siRNAs had variable inhibitory effects on FCoV when used singly. Combinations of siRNAs that targeted different regions of the viral genome resulted in more effective viral inhibition than did individual siRNAs that targeted a single gene. The tested siRNA combinations resulted in approximately 95% reduction in viral replication (based on virus titration results), compared with findings in negative control, nontargeting siRNA-treated, FCoV-infected cells. CONCLUSIONS AND CLINICAL RELEVANCE In vitro replication of FCoV was specifically inhibited by siRNAs that targeted coding and noncoding regions of the viral genome, suggesting a potential therapeutic application of RNA interference in treatment of feline infectious peritonitis.


There is no stopping covid-19 without stopping racism.


title: COVID-19 and Psoriasis: Biologic Treatment and Challenges.

text: Background: There is concern about susceptibility of psoriatic patients on biologics to coronavirus disease 2019 (COVID-19) and its clinical course. Purpose: The aims of present review were to determine whether the biologic treatment of psoriasis increases the risk of SARS-CoV-2 infection and if biologics affect the clinical course of COVID-19 in these patients. Methods: We searched database of MEDLINE (PubMed) for key term of psoriasis biologic and COVID-19 until June 9, 2020 and all published 14 papers and an experience from Iran (10509 cases) related to the psoriatic patients on biologics and COVID-19 along with relevant papers were summarized. In spite of limitation in some reports, due to some of strengths that will be discussed, all papers were included in this review. Results: According to 8769 medical reports around 0.3% of psoriatic patients had COVID-19 and the rate of hospitalization was 0.1%. No death due to COVID-19 was reported among 10509 patients. Reports indicated psoriatic patients on biologics were not more susceptible to COVID-19 and the severe clinical course of disease. Conclusion: While there is not definitive controlled trial data, the available evidence suggests that patients with psoriasis without COVID-19 can continue the biologic therapy for psoriasis.


title: Perforation of gastric volvulus within a giant hiatus hernia secondary to alendronate: A rare complication of bisphosphonate use.

text: INTRODUCTION Bisphosphonates are commonly used in the treatment of metabolic bone disease. However, they are associated with gastrointestinal side effects including acid reflux, mucosal erosion, and oesophageal stricture. We present a rare case of alendronate causing perforated gastric volvulus in a patient with giant hiatus hernia. PRESENTATION OF CASE An 82-year-old woman presented to our hospital with central chest pain, palpitations and new onset atrial fibrillation on the background of 2 weeks of vomiting. Computed tomography (CT) imaging revealed a perforated, mixed type organoaxial/mesoenteroaxial gastric volvulus within a giant hiatus hernia, with partial gastric outlet obstruction. The patient underwent laparoscopic reduction of hiatus hernia and gastric volvulus, conversion to laparotomy, and distal gastrectomy with Bilroth II reconstruction. An alendronate tablet was found in the right mediastinum. The patient had a prolonged post-operative course and was discharged home after completing extensive physical rehabilitation. DISCUSSION Bisphosphonates are widely used to treat metabolic bone disease, however can have devastating adverse effects on the gastrointestinal tract. There are a number of mechanisms postulated for how these medications cause injury to the gastric and oesophageal mucosa. CONCLUSION This case illustrates the importance of considering the gastrointestinal effects associated with bisphosphonates when prescribing them to patients, especially those with functional or anatomical disorders of the gastrointestinal tract. The presence of a large hiatus hernia should be a contraindication to prescribing alendronate.


title: Endovascular therapy versus thrombolysis in patients with anterior circulation stroke in everyday clinical practice.

text: BACKGROUND In patients with large vessel occlusions, endovascular treatment has been shown to be superior to intravenous thrombolysis in recent trials. AIMS The aim of this study was to analyze the impact of endovascular treatment on clinical and radiological outcome in everyday clinical practice. METHODS We compared the rates of good outcome (modified Rankin scale ≤ 2 at discharge), in-hospital death, symptomatic intracranial hemorrhages, and infarct sizes in patients with distal intracranial carotid artery, M1 and M2 occlusions during two time periods. RESULTS From January 2008 to October 2012, a total of 509 patients were treated with intravenous thrombolysis and from November 2012 to December 2014, a total of 270 patients received endovascular treatment with stent retrievers (with or without intravenous thrombolysis). Significantly, more patients in the endovascular treatment group than in the intravenous thrombolysis group had a good outcome (37% vs. 27%, p < 0.01). The infarct sizes were significantly smaller after endovascular treatment than intravenous thrombolysis, whereas the symptomatic intracranial hemorrhages rates and in-hospital mortality were comparable between both treatment groups. The positive impact of endovascular treatment on clinical outcome was most pronounced in patients ≥75 years (31% endovascular treatment vs. 19% intravenous thrombolysis, p < 0.01), in patients with M1 occlusions (43% endovascular treatment vs. 25% intravenous thrombolysis, p < 0.01) and in patients with an admission National Institutes of Health Stroke Scale ≥ 14 (24% endovascular treatment vs. 11% intravenous thrombolysis, p < 0.05). CONCLUSION In everyday clinical practice and compared with intravenous thrombolysis, endovascular treatment significantly improved clinical outcome and was associated with smaller infarctions. This beneficial effect appeared to be highest in older patients, more severely affected patients, and in those with M1 occlusions.


title: New Guidance on Managing Inpatient Hyperglycaemia during the COVID-19 Pandemic.

text: The COVID-19 pandemic has had a dramatic impact on the provision of acute inpatient care with specialists from all disciplines having to manage patients outside of their usual speciality areas. In many UK hospitals diabetes consultants and diabetes inpatient specialist nurses have been redeployed to the wards to care for COVID-19 positive or suspected cases. Consequently, clinicians relatively unfamiliar with managing hyperglycaemia have been required to do so as the usual input from diabetes specialist teams has not been possible in many areas.


title: [Cell-free synthetic biology: an emerging strategy torevolutionize the biomedical industry].

text: Cell-free synthetic biology system can perform biological transcription and translation process in vitro. Because of its advanced features, such as flexible openness, easy control, short expression time and high tolerance to cytotoxicity, this systemhas been successfully used to synthesize proteins that are difficult to express in cells. With the continuous development of cell-free biosensing technology and the lyophilization technology, its applications have widely expanded into many biomedical fields. This review discusses the current research progress of cell-free synthetic biology system in on-demand biopharmaceutical synthesis, portable diagnostics, and others. Further development of the system can lead to even more complicated synthesis of therapeutic proteins with post-translational modifications and evolution of different cell-free biosensors with high sensitivity. Cell-free synthetic biology as an emerging engineering strategy can be a better means applied to high-throughput screening of pharmaceutical proteins, detection of new pathogens, and other important health-care fields in the future.


title: Hyposplenism: comparison of different methods for determining splenic function.

text: Asplenic patients are at risk for pneumococcal sepsis. Patients with hyposplenic function, such as associated with sickle cell disease (SCD), are also at risk. However, tests to assess splenic function are either unavailable or lacking standardization. The aim of this study was to compare different methods for determining splenic function. Eighteen patients with SCD (i.e., 10 heterozygous (SC) and 8 homozygous (SS) SCD patients), and eight splenectomized patients were compared to 10 controls. All subjects underwent spleen scintigraphy, after which functional splenic volumes (FSV) were calculated. FSV was compared to immunological function and B cell-subsets, as well as phagocytic function represented by the presence of Howell Jolly bodies (HJB) and percentages of pitted red cells (PIT). Heterozygous SCD (SC) patients had increased splenic volumes, but diminished FSV, homozygous SCD (SS) patients were asplenic. Splenectomized and SS patients had a strongly reduced phagocytic and immunological function. SC patients had reduced anti-polysaccharide responses without an increase in PIT. FSV correlated significantly with phagocytic and immunological function. HJB were indicative of splenic dysfunction, HJB absence was not indicative of normal functioning splenic tissue. Although visualizing HJB is methodologically advantageous to PIT, both are valid biomarkers of splenic dysfunction. The amount of non-switched memory B cells is strongly correlated to FSV.


title: Bat SARS-Like WIV1 coronavirus uses the ACE2 of multiple animal species as receptor and evades IFITM3 restriction via TMPRSS2 activation of membrane fusion.

text: Diverse SARS-like coronaviruses (SL-CoVs) have been identified from bats and other animal species. Like SARS-CoV, some bat SL-CoVs, such as WIV1, also use angiotensin converting enzyme 2 (ACE2) from human and bat as entry receptor. However, whether these viruses can also use the ACE2 of other animal species as their receptor remains to be determined. We report herein that WIV1 has a broader tropism to ACE2 orthologs than SARS-CoV isolate Tor2. Among the 9 ACE2 orthologs examined, human ACE2 exhibited the highest efficiency to mediate the infection of WIV1 pseudotyped virus. The efficiency of human ACE2 to support WIV1 infectious entry is similar to that of mild SARS-CoV isolate GD03 and two civet cat SL-CoVs, but approximately 50% of that to SARS-CoV Tor2. Our findings thus imply that WIV1 has the potential to infect a wide range of wild animals and may directly jump to humans. We also showed that cell entry of WIV1 could be restricted by interferon induced transmembrane proteins (IFITMs). However, WIV1 could exploit the airway protease TMPRSS2 to activate spike-mediated membrane fusion and partially evade the IFITM3 restriction. Interestingly, we also found that amphotericin B, an antimycotic drug commonly used in clinic for patients with severe fungal infections, could enhance the infectious entry of SARS-CoVs and SL-CoVs by evading IFITM3-mediated restriction. Collectively, our findings further underscore the risk of exposure to animal SL-CoVs and highlight the vulnerability of patients who take amphotericin B to infection by SL-CoVs, including the most recently emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).


title: COVID-19 Contact tracing solutions for mass gatherings.

text: Mass gatherings and high-density activities such as sporting events, conventions and theme parks are consistently included among highest-risk activities given the increased potential for widespread COVID-19 transmission. A more balanced risk management approach is required because absolute suppression of risk is unrealistic in all facets of life. Contact tracing remains a limiting factor in achieving such a balance. The use of Bluetooth or pairing devices is proposed to address this challenge. This simple approach, when applied in a manner that satisfies privacy and trust concerns, would allow high-risk encounters to be quickly identified, namely those where participants have spent 15 or more minutes within 6 feet of each other per current guidelines. If an attendee later tests positive for COVID-19 and tracing is required, the event organizer can provide a limited list of potential close contacts rather than an exhaustive list of all attendees. Contact tracers can therefore limit efforts to this concise list rather than needing to contact thousands of people or conduct mass media communications. Such a system, if institutionalized, supports risk assurance and safety measures for businesses by demonstrating a commitment to staff, customer protection and ensuring high-risk encounters are logged, reinforcing longer-term societal pandemic resilience.


Measuring outcomes in pain clinical trials: the importance of empirical support for measure selection.


title: Rare cause of adult female incontinence: complete duplication of the collecting system and ectopic ureter of the kidney draining into the vagina treated by laparoscopic upper pole heminephrectomy and ureterectomy.

text: A 38-year-old woman presented with a lifelong history of involuntary urinary leakage. The patient reported that she had been operated for her urinary leakage with the diagnosis of stress incontinence with transobturator tape two times at two different institutions. Preoperative computed tomography scan showed complete duplication of the left kidney with poorly functioning upper pole and a tortuous left dilated ureter running down and opening into the vagina. Laparoscopic left upper pole heminephrectomy and ureterectomy were performed uneventfully. Her incontinence improved immediately after surgery.


title: Anorectal malformations.

text: This article reviews the current status of anorectal malformations in the neonate. It begins by discussing the history, epidemiology, and embryology, followed by a discussion of the genetic process causing these diseases. Diagnosis and workup is then discussed, followed by specific details of the surgical treatment of these malformations. The article concludes with a brief review of the complications and long-term outcomes in these children.


title: Endovascular coiling of proximal middle cerebral artery aneurysms: is it safe and durable?

text: BACKGROUND Proximal middle cerebral artery (M1 segment) aneurysms are relatively deeply located in neighboring lenticulostriate arteries, which make them unsuitable for microsurgery. We aimed to investigate the clinical and radiological outcomes of endovascular coiling of M1 segment aneurysms. METHODS Between January 2003 and December 2014, we retrospectively reviewed the medical records of 52 patients (52 aneurysms) from four institutions who underwent endovascular coiling of M1 segment aneurysms. Patients who underwent clinical and radiologic follow-up for more than a year after the procedure were evaluated. RESULTS The aneurysms were located in the early frontal branch, early temporal branch, and lenticulostriate artery in 28, 15, and nine patients, respectively. Endovascular coiling was achieved in 51 cases and failed in one case. Of these 51 cases, 46 (90.2%) and five (9.8%) were non-ruptured and ruptured aneurysms, respectively. Initial angiographic results revealed complete occlusion in 26 (51.0%), residual neck in 16 (31.4%), and residual sac in nine (17.6%) cases. One failed case had a symptomatic procedural complication of thromboembolism. However, there was no permanent morbidity or mortality. Two major recanalization cases (3.9%) were retreated by endovascular coiling. On multivariable logistic regression analysis, aneurysmal recurrence was significantly related to aneurysm height (OR, 1.887; 95% CI, 1.107 to 3.217; p = 0.020), width (OR, 1.836; CI, 1.127 to 2.992; p = 0.015), and neck (OR, 4.017; CI, 1.220 to 13.232, p = 0.022). CONCLUSION Endovascular coiling of M1 segment aneurysms appeared to be a feasible treatment option with a relatively low-retreatment rate. Aneurysm size was statistically significantly associated with recurrence.


title: Novel indication for chimney graft placement in the inferior mesenteric artery in AAA patients with coexistent bilateral internal iliac artery occlusion.

text: PURPOSE To report a novel indication for the use of chimney grafts to preserve flow to the inferior mesenteric artery (IMA) in patients undergoing endovascular aneurysm repair (EVAR) for aortobi-iliac aneurysms with coexistent bilateral occlusion of the internal iliac arteries (IIA). TECHNIQUE Via a cutdown over the left axillary artery, a 5-F vertebral catheter was delivered over a conventional 0.035-inch hydrophilic guidewire to selectively catheterize the IMA via a 7-F shuttle sheath, which was then advanced at least 2 cm into the target vessel. The first chimney graft was advanced into the sheath, and a standard EVAR procedure followed. The chimney graft was deployed at least 2 cm in the IMA; a second chimney graft was advanced and deployed with at least 2 cm overlapping with the first chimney stent parallel and outside of the main abdominal endograft and below the lowest renal artery. The chimney grafts were lined with additional bare nitinol stents. The technique is demonstrated in two male patients who suffered from symptomatic aortobi-iliac aneurysm with patent IMAs and bilateral IIA occlusion. The procedure was completed successfully in both cases without bowel ischemia. At 12 and 6 months, respectively, the chimney grafts remained patent without endoleak. The patients are asymptomatic. CONCLUSION The IMA chimney endovascular technique can be considered in EVAR cases with coexistent bilateral IIA occlusion to minimize the risk for bowel ischemia.


COVID-19, India, lockdown and psychosocial challenges: What next?


title: Detrimental Effects of Filling Laryngotracheal Airways To Excessive Pressure (DEFLATE-P): a quality improvement initiative.

text: BACKGROUND This quality improvement (QI) project was performed at a single center to determine the incidence of postoperative complications associated with use of cuffed airway devices. An educational program was then completed that involved training our anesthesia providers about complications related to excessive cuff pressure and how to utilize a quantitative cuff pressure measurement device (manometer). The impact of this educational initiative was assessed by comparing the incidence of postoperative complications associated with the use of airway devices before and after the training period. METHODS After approval by our institution's Institutional Review Board, a pre-intervention (baseline) survey was obtained from 259 adult patients after having undergone surgery with general anesthesia with the use of an endotracheal tube (ETT) or laryngeal mask airway (LMA). Survey responses were used to determine the baseline incidence of sore throat, hoarseness, and dysphagia. Once these results were obtained, education was provided to the anesthesia department members addressing the complications associated with excessive cuff pressures, appropriate cuff pressures based on manufacturer recommendations, and instructions on the use of a quantitative monitor to determine cuff pressure (manometry). Clinical care was then changed by requiring intraoperative cuff pressure monitoring throughout our institution for all surgical patients. After this educational period, 299 patients completed the same survey describing postoperative airway complications. RESULTS The use of manometry reduced the incidence of moderate-to-severe postoperative sore throat in the pre- vs. post-intervention groups (35 patients vs 31 patients, p = 0.045), moderate to severe hoarseness (30 patients vs 13, patients p = 0.0001), and moderate-to-severe dysphagia (13 patients vs 5 patients, p = 0.03). CONCLUSION Caring for patients in the perioperative setting frequently entails placement of an airway device. This procedure is associated with several potential complications, including sore throat, coughing, and vocal cord damage. Our quality improvement initiative has shown that intraoperative management of intra-cuff pressure based on manometry is feasible to implement in clinical practice and can reduce postoperative airway complications.


title: No Serologic Evidence of Middle East Respiratory Syndrome Coronavirus Infection Among Camel Farmers Exposed to Highly Seropositive Camel Herds: A Household Linked Study, Kenya, 2013.

text: AbstractHigh seroprevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) among camels has been reported in Kenya and other countries in Africa. To date, the only report of MERS-CoV seropositivity among humans in Kenya is of two livestock keepers with no known contact with camels. We assessed whether persons exposed to seropositive camels at household level had serological evidence of infection. In 2013, 760 human and 879 camel sera were collected from 275 and 85 households respectively in Marsabit County. Data on human and animal demographics and type of contact with camels were collected. Human and camel sera were tested for anti-MERS-CoV IgG using a commercial enzyme-linked immunosorbent assay (ELISA) test. Human samples were confirmed by plaque reduction neutralization test (PRNT). Logistic regression was used to identify factors associated with seropositivity. The median age of persons sampled was 30 years (range: 5-90) and 50% were males. A quarter (197/760) of the participants reported having had contact with camels defined as milking, feeding, watering, slaughtering, or herding. Of the human sera, 18 (2.4%) were positive on ELISA but negative by PRNT. Of the camel sera, 791 (90%) were positive on ELISA. On univariate analysis, higher prevalence was observed in female and older camels over 4 years of age (P < 0.05). On multivariate analysis, only age remained significantly associated with increased odds of seropositivity. Despite high seroprevalence among camels, there was no serological confirmation of MERS-CoV infection among camel pastoralists in Marsabit County. The high seropositivity suggests that MERS-CoV or other closely related virus continues to circulate in camels and highlights ongoing potential for animal-to-human transmission.


title: Thoracoscopic Bullectomy for Persistent Air Leak in a 14-Year-Old Child with COVID-19 Bilateral Pulmonary Disease.

text: Introduction: Thoracic surgery in children with coronavirus disease-19 (COVID-19) pulmonary disease is rare, as very limited virus-related lung lesions require intervention. However, some patients may suffer from other pulmonary abnormalities that can be worsened by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and they may consequently require lung surgery. COVID-19 affects the indications, surgical procedure, and postsurgical care of these patients. Background: We present a case of a 14-year-old girl with COVID-19 pulmonary disease and persistent air leak due to right apical bullae that required resection. Clinical, surgical, and safety implications are discussed. The role of thoracic minimally invasive surgery under COVID-19 conditions is also analyzed. Materials and Methods: The thoracoscopic procedure was scheduled earlier than normally expected. The surgery was performed in a COVID-19 reserved theatre with neutral pressure and only the necessary personnel was allowed inside. The use of the required personal protective equipment was supervised by an expert nurse before and after the intervention. Results: The surgeons used a three-port technique to resect the bullae with an endostapler and no mechanical pleural abrasion was added to the procedure. Electrocautery and CO2 insufflation were avoided, and a chest drain with a closed-circuit aspiration system was installed before removing the ports. The child was discharged home 3 days later after the removal of the chest drain. Conclusions: COVID-19 has an impact on the standard indications, surgical strategies and postoperative care of some conditions requiring intervention. Extra safety measures are needed in the operating room to limit the chance of transmission. Minimally invasive surgery for thoracic surgery remains safe if the current safety guidelines are followed closely.


title: Reselection of a genomic upstream open reading frame in mouse hepatitis coronavirus 5'-untranslated-region mutants.

text: An AUG-initiated upstream open reading frame (uORF) encoding a potential polypeptide of 3 to 13 amino acids (aa) is found within the 5' untranslated region (UTR) of >75% of coronavirus genomes based on 38 reference strains. Potential CUG-initiated uORFs are also found in many strains. The AUG-initiated uORF is presumably translated following genomic 5'-end cap-dependent ribosomal scanning, but its function is unknown. Here, in a reverse-genetics study with mouse hepatitis coronavirus, the following were observed. (i) When the uORF AUG-initiating codon was replaced with a UAG stop codon along with a U112A mutation to maintain a uORF-harboring stem-loop 4 structure, an unimpaired virus with wild-type (WT) growth kinetics was recovered. However, reversion was found at all mutated sites within five virus passages. (ii) When the uORF was fused with genomic (main) ORF1 by converting three in-frame stop codons to nonstop codons, a uORF-ORF1 fusion protein was made, and virus replicated at WT levels. However, a frameshifting G insertion at virus passage 7 established a slightly 5'-extended original uORF. (iii) When uAUG-eliminating deletions of 20, 30, or 51 nucleotides (nt) were made within stem-loop 4, viable but debilitated virus was recovered. However, a C80U mutation in the first mutant and an A77G mutation in the second appeared by passage 10, which generated alternate uORFs that correlated with restored WT growth kinetics. In vitro, the uORF-disrupting nondeletion mutants showed enhanced translation of the downstream ORF1 compared with the WT. These results together suggest that the uORF represses ORF1 translation yet plays a beneficial but nonessential role in coronavirus replication in cell culture.


title: Radiofrequency ablation and breast cancer: a review.

text: BACKGROUND Radiofrequency ablation (RFA) use in breast cancer is a developing area of research. There have been a number of published studies over the last decade, which explores the feasibility of minimally invasive techniques in breast cancer treatment. In this review, we will discuss the most recent data on radiofrequency ablation and examine the current methods, outcomes, complications, and limitations of RFA in breast cancer therapy. METHODS Pub Med search for English Language articles on RFA in breast cancer. RESULTS More than 25 studies were reviewed and we searched for number of tumors, average size, electrode used, if they successfully ablated the tumor, when the tumor was then resected and if the patients experienced any complication from the ablation. CONCLUSIONS Radiofrequency ablation is an emerging minimally invasive therapy in small, localized breast cancer. Currently, no clinical trials have been published to directly compare RFA to the current standard of surgical resection. Ultimately, RFA will need clinical trials to evaluate oncologic outcomes involving long interval follow-up to determine survival, local control and disease progression before it becomes a reasonable alternative to surgical resection.


Corrigendum.


title: Characterization of hMTr1, a human Cap1 2'-O-ribose methyltransferase.

text: Cellular eukaryotic mRNAs are capped at their 5' ends with a 7-methylguanosine nucleotide, a structural feature that has been shown to be important for conferring mRNA stability, stimulating mRNA biogenesis (splicing, poly(A) addition, nucleocytoplasmic transport), and increasing translational efficiency. Whereas yeast mRNAs have no additional modifications to the cap, called cap0, higher eukaryotes are methylated at the 2'-O-ribose of the first or the first and second transcribed nucleotides, called cap1 and cap2, respectively. In the present study, we identify the methyltransferase responsible for cap1 formation in human cells, which we call hMTr1 (also known as FTSJD2 and ISG95). We show in vitro that hMTr1 catalyzes specific methylation of the 2'-O-ribose of the first nucleotide of a capped RNA transcript. Using siRNA-mediated knockdown of hMTr1 in HeLa cells, we demonstrate that hMTr1 is responsible for cap1 formation in vivo.


title: Potential Acceptability of a Pediatric Ventilator Management Computer Protocol.

text: OBJECTIVES To examine issues regarding the granularity (size/scale) and potential acceptability of recommendations in a ventilator management protocol for children with pediatric acute respiratory distress syndrome. DESIGN Survey/questionnaire. SETTING The eight PICUs in the Collaborative Pediatric Critical Care Research Network. PARTICIPANTS One hundred twenty-two physicians (attendings and fellows). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We used an online questionnaire to examine attitudes and assessed recommendations with 50 clinical scenarios. Overall 80% of scenario recommendations were accepted. Acceptance did not vary by provider characteristics but did vary by ventilator mode (high-frequency oscillatory ventilation 83%, pressure-regulated volume control 82%, pressure control 75%; p = 0.002) and variable adjusted (ranging from 88% for peak inspiratory pressure and 86% for FIO2 changes to 69% for positive end-expiratory pressure changes). Acceptance did not vary based on child size/age. There was a preference for smaller positive end-expiratory pressure changes but no clear granularity preference for other variables. CONCLUSIONS Although overall acceptance rate for scenarios was good, there was little consensus regarding the size/scale of ventilator setting changes for children with pediatric acute respiratory distress syndrome. An acceptable protocol could support robust evaluation of ventilator management strategies. Further studies are needed to determine if adherence to an explicit protocol leads to better outcomes.


title: Effect of laparoscopic surgery on health care utilization and costs in patients who undergo colectomy.

text: IMPORTANCE Laparoscopic colectomy is safe and effective in the treatment of many colorectal diseases. However, the effect of increasing use of laparoscopy on overall health care utilization and costs, especially in the long term, has not been thoroughly investigated. OBJECTIVE To evaluate the effect of laparoscopic vs open colectomy on short- and long-term health care utilization and costs. DESIGN, SETTING, AND PARTICIPANTS Retrospective multivariate regression analysis of national health insurance claims data was used to evaluate health care utilization and costs up to 1 year following elective colectomy. Data were obtained from the Truven Health Analytics MarketScan Commercial Claims and Encounters database. Patients aged 18 to 64 years who underwent elective laparoscopic or open colectomy from January 1, 2010, through December 31, 2010, were included. Patients with complex diagnoses that require increased non-surgery-related health care utilization, including malignant neoplasm, inflammatory bowel disease, human immunodeficiency virus, transplantation, and pregnancy, were excluded. Of 25 481 patients who underwent colectomy, 4160 were included in the study. MAIN OUTCOMES AND MEASURES Healthcare utilization, including office, hospital outpatient, and emergency department visits and inpatient services 90 and 365 days after the index procedure; total health care costs; and estimated days off from work owing to health care utilization. RESULTS Of 25 481 patients who underwent colectomy, 4160 were included in the study (laparoscopic, 45.6%; open, 54.4%). The mean (SD) net and total payments were lower for laparoscopy ($23 064 [$14 558] and $24 196 [$14 507] vs $29 753 [$21 421] and $31 606 [$23 586]). In the first 90 days after surgery, an open approach was significantly associated with a 1.26-fold increase in health care costs (estimated, $1715; 95% CI, $338-$2853), increased use of heath care services, and more estimated days off from work (2.78 days; 95% CI, 1.93-3.59). Similar trends were found in the full postoperative year, with an estimated 1.18-fold increase (95% CI, 1.04-1.35) in health care expenditures and an increase of 1.15 times (95% CI, 1.08-1.23) the number of health care utilization days compared with laparoscopy. CONCLUSIONS AND RELEVANCE Laparoscopic colectomy results in a significant reduction in health care costs and utilization in the short- and long-term postoperative periods.


title: Clopidogrel-Associated Thrombotic Thrombocytopenic Purpura following Endovascular Treatment of Spontaneous Carotid Artery Dissection.

text: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening multisystem disease secondary to platelet aggregation. We present a patient who developed profound thrombocytopenia and anemia 8 days following initiation of therapy with clopidogrel after stent placement for carotid artery dissection. She did not have a disintegrin and metalloproteinase with thrombospondin domain 13 (ADAMTS 13) deficiency. Management included steroids and therapeutic plasma exchange. Clopidogrel has rarely been associated with TTP. Unlike other causes of acquired TTP, the diagnosis of early clopidogrel-associated TTP is largely clinical given the infrequent reduction in ADAMTS 13 activity.


Minimising the environmental impact of inhaled therapies: problems with policy on low carbon inhalers.


title: Enzyme-catalyzed in situ forming gelatin hydrogels as bioactive wound dressings: effects of fibroblast delivery on wound healing efficacy.

text: In this study, in situ forming gelatin hydrogels via horseradish peroxidase (HRP)-catalyzed cross-linking were developed to serve as bioactive wound dressings with suitable tissue adhesive properties to deliver dermal fibroblasts (DFBs). The DFB-encapsulated gelatin hydrogels with different stiffnesses, GH-soft (1.1 kPa) and GH-hard (6.2 kPa), were prepared by controlling the hydrogen peroxide (H2O2) concentrations. The GH-soft hydrogel was capable of facilitating the proliferation of DFBs and the synthesis of extracellular components, as compared to GH-hard hydrogels. In addition, the subcutaneously injected GH-soft hydrogel with bioluminescent reporter cells provided enhanced cell survival and local retention over 14 days. In vivo transplantation of DFB-encapsulated GH-soft hydrogels accelerated wound contraction, and promoted collagen deposition and neovascularization within the incisions performed on mice skin. Therefore, we expect that HRP-catalyzed in situ forming gelatin hydrogels can be useful for local delivery of cells with high viability in wounds, which holds great promise for advancing wound healing technologies and other tissue engineering applications.


title: Preliminary Experience with Stent-Assisted Coiling of Aneurysms Arising from Small (<2.5 mm) Cerebral Vessels Using The Low-Profile Visualized Intraluminal Support Device.

text: BACKGROUND AND PURPOSE The Low-Profile Visualized Intraluminal Support (LVIS) stent is a new device recently introduced for the treatment of wide-neck intracranial aneurysms. This single-center study presents the authors' preliminary experience using the LVIS stent to treat saccular aneurysms with parent arteries smaller than 2.5 mm. MATERIALS AND METHODS Aneurysms with a LVIS stent used in a small parent vessel (<2.5 mm in diameter) between October 2014 and April 2016 were included. Procedure-related complications, angiographic results, clinical outcomes, and midterm follow-up data were analyzed retrospectively. RESULTS A total of 22 patients was studied, including 5 ruptured and 17 unruptured aneurysms. Most of the aneurysms were located in the anterior circulation (90.9%). Stent placement in the parent arteries measuring 1.7-2.4 mm in diameter (mean, 2.1 mm) was successful in 100% of cases. Procedure-related complication developed in 1 patient (4.5%) who presented with aneurysm rupture. No permanent morbidity and mortality occurred. Immediate angiographic outcome showed complete occlusion in 8 aneurysms (36.4%), neck residual in 8 (36.4%), and residual aneurysm in 6 (27.3%). All patients underwent angiographic follow-up at a mean of 8.3 months, which revealed complete occlusion in 18 (81.8%) patients, neck remnant in 3 (13.6%), and residual sac in 1 (4.5%). No recanalization of the target aneurysm was observed. There was 1 case with asymptomatic in-stent stenosis. CONCLUSIONS Our preliminary results show that the deployment of LVIS stents in small vessels is feasible, safe, and effective in the midterm. Larger studies with long-term follow-up are needed to validate our promising results.


title: Preparing a neurology department for SARS-CoV-2 (COVID-19): Early experiences at Columbia University Irving Medical Center and the New York Presbyterian Hospital in New York City.

text: Beginning in December 2019, a novel coronavirus, SARS-CoV-2 (COVID-19), began spreading rapidly throughout China and now is a global pandemic with cases reported in over 192 countries and territories worldwide. Clinically, COVID-19 ranges from a mild, self-limiting respiratory illness to severe progressive pneumonia and multiorgan failure. The first COVID-19 case was reported at the beginning of March in New York City (NYC), and now just three weeks later, NYC and its suburbs have over 5% of global cases. Worldwide, there is a rapid increase in the number of cases daily, including the number of patients requiring hospitalization and intensive care support.


title: Where future emerging pathogens will come from and what approaches can be used to find them, besides VFARs.

text: A consideration of available evidence for some known and well-characterized waterborne pathogens suggests that the diversity of pathogen virulence mechanisms and properties is too great to specifically predict the emergence and future human health impacts of new waterborne pathogens. However, some future emerging pathogens are existing microbes that will be discovered to cause disease. Some will arise from existing ones by either predictable evolutionary and adaptation changes or by unpredictable changes involving a variety of biotic and abiotic mechanisms. Many, and perhaps most, emerging waterborne human pathogens will be zoonotic agents or come from other non-human reservoirs. The emergence of some waterborne pathogens will be related to antibiotic use, resulting in emerging antibiotic-resistant waterborne pathogens. Reliably predicting pathogen emergence and human health effects based on VFARs or other properties of microbes and their hosts is not possible at this time. This is because of (1) the diversity of microbes and their virulence and pathogenicity properties, (2) their ability to change unpredictably, (3) their intimate and diverse interrelationships with a myriad of hosts and dynamic natural and anthropogenic environments and (4) the subtle variations in the immune status of individuals. The best available approach to predicting waterborne pathogen emergence is through vigilant use of microbial, infectious disease and epidemiological surveillance. Understanding the microbial metagenome of the human body can also lead to a better understanding of how we define and characterize pathogens, commensals and opportunists.