Alterations in the pH of pancreatic juice are associated with chymotrypsin C inactivation and lithostathine precipitation in chronic pancreatitis patients: a proteomic approach.

Background: The progression of chronic pancreatitis (CP), an inflammatory disease of the pancreas, causes pancreatic stones to form within the pancreatic ductal lumen/parenchyma, which occurs via protein plug formation. Pain is the most common symptom that necessitates clinical attention, and pain relief is the therapeutic goal for these patients. Endoscopic therapy and surgery are complimentary forms of therapy for pain relief.

Design and synthesis of novel halogen rich salicylanilides as potential antileishmanial agents.

The available therapeutic treatment for leishmaniasis is inadequate and toxic due to side effects, expensive and emergence of drug resistance. Affordable and safe antileishmanial agents are urgently needed and toward this objective, we synthesized a series of 32 novel halogen rich salicylanilides including niclosamide and oxyclozanide and investigated their antileishmanial activity against amastigotes of Leishmania donovani. In vitro data showed fifteen compounds inhibited intracellular amastigotes with an IC of below 5 μM and selectivity index above 10.

Production and possible reduction of greenhouse gases produced during GI endoscopy activity: a systematic review of available literature.

Background And Aims: Greenhouse gases (GHGs) that trap heat in the atmosphere are composed of carbon dioxide (CO), methane, nitrous oxide and fluorinated gases (synthetic hydrofluorocarbons, perfluorocarbons and nitrogen trifluoride). In the USA, the health sector accounts for 8.5% of total GHG emissions.

ΔNp63 drives dysplastic alveolar remodeling and restricts epithelial plasticity upon severe lung injury.

The lung exhibits a robust, multifaceted regenerative response to severe injuries such as influenza infection, during which quiescent lung-resident epithelial progenitors participate in two distinct reparative pathways: functionally beneficial regeneration via alveolar type 2 (AT2) cell proliferation and differentiation, and dysplastic tissue remodeling via intrapulmonary airway-resident basal p63 progenitors. Here we show that the basal cell transcription factor ΔNp63 is required for intrapulmonary basal progenitors to participate in dysplastic alveolar remodeling following injury. We find that ΔNp63 restricts the plasticity of intrapulmonary basal progenitors by maintaining either active or repressive histone modifications at key differentiation gene loci.

Identification of genomic regions governing moisture and heat stress tolerance employing association mapping in rice (Oryza sativa L.).

Background: Rice crop is damaged extremely by abiotic stress world-wide. The best approach to enhance drought tolerance in rice varieties is to identify and introgress yield QTLs with major effects. The Association mapping approach helps in the identification of genomic regions governing physiological, yield and yield attributes under moisture and heat stress conditions in diverse collections of crop germplasm, based on historic recombination events and linkage disequilibrium across the genome.

Isobolographic analysis of adjunct antiseizure activity of the FDA-approved cannabidiol with neurosteroids and benzodiazepines in adult refractory focal onset epilepsy.

Epilepsy is a serious neurological disorder associated with recurrent and unpredictable seizures and extensive neuropsychiatric comorbidities. There is no cure for epilepsy, and over one third of epileptic patients have been diagnosed with drug-refractory epilepsy, indicating the critical need for novel antiseizure medications (ASMs). Cannabidiol (CBD) has been shown to decrease seizures in pediatric epilepsies, such as Dravet and Lennox-Gastaut syndromes; however, it has not been rigorously tested for adult seizures or in models of refractory focal epilepsy.

Establishing normal ranges for fetal and neonatal small and large intestinal lengths: results from a prospective postmortem study.

Objective: To establish reference intervals (RIs) for fetal and neonatal small and large intestinal lengths.

Methods: Linear measurements on small and large intestines were made upon postmortem examination of 131 preterm and term infants with gestational ages between 13 and 41 weeks. All cases were referred from the Eastern Ontario and Western Québec regions to a tertiary care hospital.

The Outcome of Placing the Medial K-wire First and Then the Lateral K-wire in Treating Supracondylar Humerus Fractures in Children Treated by Closed Reduction.

Background Displaced Gartland type III and IV supracondylar fractures are difficult to reduce and invariably require closed pining. After closed reduction, taking the anteroposterior (AP) view does not present any problem but when the elbow is placed in flexion and the limb is rotated internally to take a lateral view, the reduction is invariably lost. However, the reduction stays when the arm is rotated outwards, keeping the medial condyle up.

Prospective Validation and Comparison of Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) and Site Other Than Lower Limb, Immunosuppression, Age, Renal Impairment, and Inflammatory Markers (SIARI) Scoring Systems for Necrotizing Fasciitis.

Introduction: Necrotizing fasciitis (NF) is a rapidly progressing infection of the soft tissues associated with high morbidity and mortality and hence it is a surgical emergency. Early diagnosis and treatment are of paramount importance. LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) and SIARI (Site other than lower limb, Immunosuppression, Age, Renal impairment, and Inflammatory markers) scoring systems have been established for early and accurate diagnosis of necrotizing fasciitis.

Anomalous H NMR chemical shift behavior of substituted benzoic acid esters.

Benzoic acid esters represent key building blocks for many drug discovery and development programs and have been advanced as potent PDE4 inhibitors for inhaled administration for treatment of respiratory diseases. This class of compounds has also been employed in myriad industrial processes and as common food preservatives. Recent work directed toward the synthesis of intermediates for a proprietary medicinal chemistry program led us to observe that the H NMR chemical shifts of substituents ortho to the benzoic acid ester moiety defied conventional iterative chemical shift prediction protocols.

Poor immune response to coronavirus disease vaccines in decompensated cirrhosis patients and liver transplant recipients.

Background And Aims: Recent studies have reported poor humoral immune response to mRNA vaccines in patients with chronic liver disease (CLD). However, the immunogenicity of ChAdOx1 (vector-based) and BBV152 (inactivated virus) vaccines in patients with CLD and liver transplant recipients (LTRs) is unknown. Therefore, we aimed to assess the immunogenicity of ChAdOx1 and BBV152 vaccines in patients with CLD (including cirrhosis patients) and LTRs.

Paraspeckles interact with SWI/SNF subunit ARID1B to regulate transcription and splicing.

Paraspeckles are subnuclear RNA-protein structures that are implicated in important processes including cellular stress response, differentiation, and cancer progression. However, it is unclear how paraspeckles impart their physiological effect at the molecular level. Through biochemical analyses, we show that paraspeckles interact with the SWI/SNF chromatin-remodeling complex.

Influence of Proline Chirality on Neighbouring Azaproline Residue Stereodynamic Nitrogen Preorganization.

We report herein the first systematic crystal structural investigation of azaproline incorporated in homo- and heterochiral diprolyl peptides. The X-ray crystallography data of peptides 1-5 illustrates that stereodynamic nitrogen in azaproline adopted the stereochemistry of neighbouring proline residue without depending on its position in the peptide sequence. Natural bond orbital analysis of crystal structures indicates O -C' of peptides 4 and 5 participating in n→π* interaction with stabilization energy about 1.

Diagnostic yield and technical performance of the novel motorized spiral enteroscopy compared with single-balloon enteroscopy in suspected Crohn's disease: a prospective study (with video).

Background And Aims: Both single-balloon enteroscopy (SBE) and the novel motorized spiral enteroscopy (NMSE) are effective techniques for device-assisted enteroscopy (DAE). To date, no study has prospectively compared both modalities in suspected Crohn's disease (CD).

Methods: Patients with suspected CD undergoing either SBE or NMSE between March 2021 and December 2021 in a high-volume tertiary center were prospectively compared for technical success (ability to reach the lesion), diagnostic yield, depth of maximal insertion (DMI), procedure time, and total enteroscopy rates.

Application of Deep Learning Models to Improve Ulcerative Colitis Endoscopic Disease Activity Scoring Under Multiple Scoring Systems.

Background And Aims: Lack of clinical validation and inter-observer variability are two limitations of endoscopic assessment and scoring of disease severity in patients with ulcerative colitis [UC]. We developed a deep learning [DL] model to improve, accelerate and automate UC detection, and predict the Mayo Endoscopic Subscore [MES] and the Ulcerative Colitis Endoscopic Index of Severity [UCEIS].

Methods: A total of 134 prospective videos [1550 030 frames] were collected and those with poor quality were excluded.

Experimental and Clinical Biomarkers for Progressive Evaluation of Neuropathology and Therapeutic Interventions for Acute and Chronic Neurological Disorders.

This article describes commonly used experimental and clinical biomarkers of neuronal injury and neurodegeneration for the evaluation of neuropathology and monitoring of therapeutic interventions. Biomarkers are vital for diagnostics of brain disease and therapeutic monitoring. A biomarker can be objectively measured and evaluated as a proxy indicator for the pathophysiological process or response to therapeutic interventions.

Long-term Outcome of Peroral Endoscopic Myotomy in Esophageal Motility Disorders: A Systematic Review and Meta-analysis.

Background And Aim: Peroral endoscopic myotomy (POEM) is an established treatment for achalasia. In this systematic review and meta-analysis, we aimed to analyze the mid and long-term outcomes of POEM in esophageal motility disorders.

Methods: Literature search was performed in databases including PubMed, Embase, Cochrane databases, and Google scholar from January 2010 to May 2021.

Efficacy of the FDA-approved cannabidiol on the development and persistence of temporal lobe epilepsy and complex focal onset seizures.

Presently there is no drug therapy for curing epilepsy. Despite many advancements in epilepsy research, nearly 30% of people with epilepsy remain refractory to current antiseizure medications (ASM). Cannabidiol (CBD) has recently been approved as an ASM for pediatric refractory seizures, but it has not been widely tested for adult epileptogenesis and focal onset seizures.

Soft self-expandable metal stent to treat painful pancreatic duct strictures secondary to chronic pancreatitis: a prospective multicenter trial.

Background And Aims: Fully covered self-expandable metal stents (FCSEMSs) may offer a treatment option for pain associated with a dilated pancreatic duct (PD) in chronic pancreatitis (CP), but optimal patient selection and FCSEMS design, efficacy, and safety remain uncertain. We studied an investigational pancreatic FCSEMS for treatment of CP-associated pain.

Methods: Patients with painful CP, a dominant distal PD stricture, and PD dilation upstream were enrolled in a prospective, multicenter, single-arm trial studying 6-month indwell of a 4- to 6-cm-long soft pancreatic FCSEMS.

Therapeutic and clinical foundations of cannabidiol therapy for difficult-to-treat seizures in children and adults with refractory epilepsies.

Novel and effective antiseizure medications are needed to treat refractory and rare forms of epilepsy. Cannabinoids, which are obtained from the cannabis plant, have a long history of medical use, including for neurologic conditions. In 2018, the US Food and Drug Administration approved the first phytocannabinoid, cannabidiol (CBD, Epidiolex), which is now indicated for severe seizures associated with three rare forms of developmental and epileptic encephalopathy: Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex.