Holttierney6433

Purpose Wolf-Hirschhorn syndrome (WHS) is a rare inherited disease caused by the deletion in short arm of 4th chromosome. Various ocular manifestations in WHS have been described previously. We present an extraordinary clinical case of WHS associated with optic nerve head malformation and optic nerve sheath enlargement in the same eye.Methods Case reportResults A male infant was delivered by Caesarean section at 38 weeks with a birth weight of 2040 gr and admitted to neonatal intensive care unit due to multi-systemic abnormalities. The infant had multiple congenital anomalies; a cleft palate, microcephalia, micrognathia, renal pelvicalyceal ectasia, atrial septal defect, transvers arcus hypoplasia, patent ductus arteriosus, hypospadias and undescended testicle. Fundus examination revealed optic disc coloboma of both eyes. Two weeks later, at the second examination, the left optic disc margins were indistinct with vessels radiating from the disc margins which resembles morning glory disc anomaly (MGDA). The MRI demonstrated corpus callosum agenesis and a T1 hypointense, T2 hyperintense, 12 × 9 mm optic nerve sheath enlargement in the retrobulbar area.Conclusion The case presented here demonstrates that, the optic nerve head malformations and optic nerve sheath enlargement may be due to incomplete closure of choroidal fissure and subsequent accumulation of cerebrospinal fluid may result in a spectrum of optic nerve head malformations.

Patients with end-stage liver disease (ESLD) have impaired physical, psychological, and social functions, which can diminish patient quality of life, burden family caregivers, and increase health-care utilization. For those with a life expectancy of less than six months, these impairments and their downstream effects can be addressed effectively through high-quality hospice care, delivered by multidisciplinary teams and focused on the physical, emotional, social, and spiritual wellbeing of patients and caregivers, with a goal of improving quality of life.

In this review, we examine the evidence supporting hospice for ESLD, we compare this evidence to that supporting hospice more broadly, and we identify potential criteria that may be useful in determining hospice appropriateness.

Despite the potential for hospice to improve care for those at the end of life, it is underutilized for patients with ESLD. Increasing the appropriate utilization of hospice for ESLD requires a better understanding of patient eligibility, which can be based on predictors of high short-term mortality and liver transplant ineligibility. Such hospice criteria should be data-driven and should accommodate the uncertainty faced by patients and physicians.

Despite the potential for hospice to improve care for those at the end of life, it is underutilized for patients with ESLD. Increasing the appropriate utilization of hospice for ESLD requires a better understanding of patient eligibility, which can be based on predictors of high short-term mortality and liver transplant ineligibility. Such hospice criteria should be data-driven and should accommodate the uncertainty faced by patients and physicians.

Celiac disease (CD) is commonly found in women. Given the sex differences in diagnosed patients, we hypothesized sex differences in physicians obtaining biopsies for CD may exist.

We retrospectively reviewed duodenal biopsies for suspected CD excluding pre-existing CD patients. Appropriate biopsy practice was defined as ≥5 specimens per ACG guidelines.

We included 125 patients (females, 92). There were 85 properly (68%) biopsied. Presence of a female endoscopist was associated with better adherence to biopsy guidelines (OR, 2.99, 95% CI, 1.19-7.54;

 = .02) which remained significant after multivariable adjustment (adjusted OR, 2.7;

 = .047).

Physician sex-based differences in biopsy patterns may exist.

Physician sex-based differences in biopsy patterns may exist.Ethylene spent caustic with strong alkalinity, high chemical oxygen demand (COD) and toxicity could not be directly discharged without pretreatment. In this paper, the composition of spent caustic from a petrochemical enterprise was analyzed. Effects of oxidants, reaction temperature, pressure and residence time on the removal ratio of COD in the spent caustic were investigated. The oxidation reaction mechanism of main organic sulphides in the spent caustic was discussed. Results show that COD of the ethylene spent caustic is ∼ 24.5 g/L, the main compositions are S2- and disulphides including a small amount of ketones and phenolic organics. The removal ratio of S2- in spent caustic is up to 100%, and the removal ratio of COD is over 83% at 180 °C with the pressure of 2 MPa and residence time of 15 min using oxygen as an oxidant. Taking dimethyl disulphide as an example, dimethyl disulphide with HO• firstly produces methyl thiosulphonate and methyl sulphenic acid, then further oxidized to generate methanesulphonic acid, and the C-S bonds in the methanesulphonic acid were broken to generate sulphuric acid and formic acid. So the oxidative degradation products of organic sulphides are sulphuric acid, formic acid and a small amount of acetic acid.Background Oculocutaneous albinism (OCA) is a Mendelian disorder characterized by hypopigmentation of the skin, hair, and eyes, hypoplastic fovea, and low vision, known to be caused by mutations in the Tyrosinase (TYR) gene. Among the known TYR variants, some reduce but do not completely eliminate tyrosinase activity, allowing residual production of melanin and resulting in a contradictory assignment as either pathogenic or benign, preventing a precise clinical diagnostic.Materials and Methods In the present work, we performed Whole Exome Sequencing and subsequent Sanger sequencing in a young male clinically diagnosed with OCA.Results Whole-exome sequencing analysis revealed the identification of two variants in trans in TYR. The first, corresponds to a known pathogenic variant G47D, while the second S192Y, was considered a polymorphism due to its relatively high frequency in the European population.Conclusion The lack of other pathogenic variants in TYR, the reported reduced enzymatic activity (ca. buy MK-0752 40% respect to wt) for S192Y, together with the structural in-silico analysis strongly suggest that both reported variants are jointly disease-causing and that S192Y should be considered as likely pathogenic, especially when it is found in trans with a null variant.Objectives Because only one head-to-head randomized trial of biologics for moderate-to-severe UC has been performed, indirect treatment comparisons remain important. This systematic review and network meta-analysis examined efficacy and safety of biologics and tofacitinib for moderate-to-severe UC, using vedolizumab as reference.Methods Relevant studies (N = 19) of vedolizumab, adalimumab, infliximab, golimumab, ustekinumab, and tofacitinib were identified. Study design differences were addressed by assessing efficacy outcomes conditional on response at maintenance initiation. Primary analysis used fixed-effect models to estimate odds ratios for efficacy and safety endpoints.Results Compared with vedolizumab 300 mg, adalimumab 160/80 mg was associated with less clinical remission (odds ratio, 0.69 [95% credible interval, 0.54-0.88]), and infliximab 5 mg/kg was associated with more clinical remission (1.67 [1.16-2.42]) and response (1.63 [1.15-2.30]). Adalimumab 40 mg, golimumab 50 mg, and ustekinumab 90 mg Q12W had significantly lower clinical remission rates during maintenance (0.62 [0.45-0.86], 0.55 [0.32-0.95], and 0.59 [0.35-0.99]) versus vedolizumab 300 mg Q8W. Response results were similar. Tofacitinib 10 mg had the highest maintenance treatment efficacy estimates and highest infection risk.Conclusion Network meta-analysis and novel integrated benefit-risk analysis suggest a potentially favorable efficacy-safety balance for vedolizumab vs adalimumab and other advanced UC therapies.The outbreak of the second severe acute respiratory syndrome coronavirus (SARS-CoV-2) known as COVID-19 has caused global concern. No effective vaccine or treatment to control the virus has been approved yet. Social distancing and precautionary protocols are still the only way to prevent person-to-person transmission. We hope to identify anti-COVID-19 activity of the existing drugs to overcome this pandemic as soon as possible. The present study used HEX and AutoDock Vina softwares to predict the affinity of about 100 medicinal structures toward the active site of 3-chymotrypsin-like protease (3Clpro) and RNA-dependent RNA polymerase (RdRp), separately. Afterwards, MOE software and the pharmacophore-derived query methodology were employed to determine the pharmacophore model of their inhibitors. Tegobuvir (19) and compound 45 showed the best binding affinity toward RdRp and 3Clpro of SARS-CoV-2 in silico, respectively. Tegobuvir -previously applied for hepatitis C virus- formed highly stable complex with uncommon binding pocket of RdRp (E total -707.91 Kcal/mol) in silico. In addition to compound 45, tipranavir (28) and atazanavir (26) as FDA-approved HIV protease inhibitors were tightly interacted with the active site of SARS-CoV-2 main protease as well. Based on pharmacophore modelling, a good structural pattern for potent candidates against SARS-CoV-2 main enzymes is suggested. Re-tasking or taking inspiration from the structures of tegobuvir and tipranavir can be a proper approach toward coping with the COVID-19 in the shortest possible time and at the lowest cost.Drug resistance seriously limits the efficacy of chemotherapy drugs and hinders successful treatment in patients with gastric cancer. Endoplasmic reticulum (ER) and autophagy are recognized to be one of the mechanisms involving the drug resistance of gastric cancer. The mechanisms of action of JAK2/STAT3 pathway were investigated in AGS cells with drug resistance of 5-fluorouracil (5-FU) by corresponding inhibitors. We firstly analyzed the effects of JAK2/STAT3 inhibitor on the expression of drug resistance genes, autophagy markers, and ER stress-related markers on AGS/5-FU cells by Western blot. Whether JAK2/STAT3 pathway regulated the transcription of ATF6 was investigated through luciferase reporter assay. The expression of LC3B was detected by immunofluorescence assay. Next, ER stress inhibitor and ATF6 overexpression plasmid were respectively used to treat AGS/5-FU cells for analyzing whether JAK2/STAT3 pathway regulated ER stress. The results showed that JAK2 inhibitor or STAT3 inhibitor significantly altered the expression of these proteins and suppressed the activities of ATF6 promoter. Intriguingly, ATP6 overexpression could markedly reverse their effects. Moreover, similar effects to JAK2 inhibitor or STAT3 inhibitor appeared in ER stress inhibitor-treated group. These findings indicated that the involvement of JAK2/STAT3 pathway in regulating ER stress affected the 5-FU resistance of AGS cells and autophagy, which was mediated by ATF6. Targeting JAK2/STAT3 pathway could be a potential approach to decrease the 5-FU resistance of gastric cancer and enhance the sensitivity of gastric cancer to 5-FU. Additionally, our study offers new insights into the molecular mechanisms underlying the resistance of gastric cancer to 5-FU.