An integrated picture of chronic pancreatitis derived by mapping variants in multiple disease genes onto pathogenic pathways.

Chronic pancreatitis (CP) is an etiologically and genetically heterogeneous inflammatory syndrome characterised by progressive damage to the exocrine and endocrine components of the pancreas [ 1]. The multigenic paradigm of CP has sparked research in recent years [ 2]. We aimed to expand the current knowledge of genetic susceptibility of pancreatitis in patients of Indian origin. By employing whole-exome sequencing in an Indian hospital cohort, we dissect the genetic landscape associated with CP or recurrent acute pancreatitis (RAP). Notably, all patients had at least one genetic variant identified in a pancreatitis-risk gene, and most had a co-occurrence of a second variant in an additional risk gene. Based on the presence of both acinar and ductal gene variants in individual patients, we propose a two-hit hypothesis where variants in proteins expressed in both acinar and ductal cells are critical for RAP/CP development.

Genes for endosomal pH regulators NHE6 and NHE9 are dysregulated in the substantia nigra in Parkinson's disease.

Endosomal acid base balance functions as a master orchestrator within the cell, engaging with many cellular pathways to maintain homeostasis. Mutations in the endosomal pH regulator Na+/H+ exchanger NHE6 may disrupt this delicate balancing act and cause monogenic Parkinsonism. Here, gene expression studies in post-mortem substantia nigra of Parkinson's disease (PD) patients and normal controls were performed to investigate whether NHE6 represents a pathophysiological link between monogenic and sporadic PD. The substantia nigra in PD displayed down-regulation of NHE6, coincident with a loss of expression of several SNARE signalling pathway members, suggesting impaired membrane fusion and vesicle-recycling. Increased abundance of related NHE9 was also identified in the parkinsonian nigra that could reflect compensatory changes or be a consequence of neuronal dysfunction. The current model suggests the possibility that neurons expressing low levels of NHE6 are more susceptible to injury in PD, potentially directly contributing to the loss of nigral dopaminergic neurons and the genesis of the disease. These results have important implications for disease-modifying therapies as they suggest that endosomal pH correctors, including epigenetic modifiers that regulate NHE6 expression, may be beneficial for PD. Thus, aberrant endosomal acidification in the nigrostriatal pathway is a possible unifying pathomechanism in both monogenic and sporadic PD, with implications for understanding and treating this disorder. Replication of these observations in the post-mortem brains of Alzheimer's disease and frontotemporal dementia patients supports a model of conserved mechanisms underlying injury and death of neurons.

Clinical and laboratory parameters as predictors of mortality in patients with chronic liver disease presenting to emergency department- a cross sectional study.

BACKGROUND: The World Health Organization (WHO) reports that Asia and Africa have the highest Chronic Liver Disease (CLD) mortality rate. Cirrhosis, responsible for 22.2 fatalities per 100,000 people, is India's 10th most common cause of mortality. The increasing prevalence of chronic liver disease necessitates a study to identify predictive factors for patients who visit the emergency department. Identifying elements that enhance the predictive value of mortality in unstable patients with CLD complications is important in emergency departments. This study aims to determine Clinical and Laboratory Parameters as mortality predictors in adult chronic liver disease patients. METHODOLOGY: The study was conducted at the emergency department of a tertiary healthcare center in Northern India. Patients with chronic liver disease above 18 years of age who satisfied the inclusion criteria were clinically evaluated. Clinical and demographic details were collected, and data was analyzed. RESULTS: Two hundred thirty-six patients were enrolled. The mean age was 50.77 ± 14.26 years. 78.4% of the participants were men. Abdominal distension, affecting 59.7% of patients, was the most common presenting ailment, followed by melena and hematemesis, affecting 41.9% and 32.6%, respectively. The mean stay in the emergency department was 10.29 ± 8.10 h. Refractory septic shock, the leading cause of mortality, accounts for 69.2% of all deaths, alongside grade 4 hepatic encephalopathy and massive Upper Gastrointestinal (UGI) bleeding, as identified in our study. Factors such as altered mental sensorium, high respiratory rate, low SpO2, increased heart rate, low systolic blood pressure, low diastolic blood pressure, and low Glasgow Coma Scale (GCS) on Emergency Department (ED) arrival are significantly associated with mortality. CONCLUSIONS: Chronic liver disease, a prevalent condition in India, most commonly seen in middle aged men and lower socioeconomic groups. The parameters independently associated with mortality in our study were presence of altered mental sensorium, Glasgow coma scale, Child Pugh class and need for ICU admission. Understanding the presentation pattern, and mortality predictors can help ED physicians in managing acute events and follow-ups.

An Endosomal Acid-Regulatory Feedback System Rewires Cytosolic cAMP Metabolism and Drives Tumor Progression.

Although suppressed cAMP levels have been linked to cancer for nearly five decades, the molecular basis remains uncertain. Here, we identify endosomal pH as a novel regulator of cytosolic cAMP homeostasis and a promoter of transformed phenotypic traits in colorectal cancer. Combining experiments and computational analysis, we show that the Na+/H+ exchanger NHE9 contributes to proton leak and causes luminal alkalinization, which induces resting [Ca2+], and in consequence, represses cAMP levels, creating a feedback loop that echoes nutrient deprivation or hypoxia. Higher NHE9 expression in cancer epithelia is associated with a hybrid epithelial-mesenchymal (E/M) state, poor prognosis, tumor budding, and invasive growth in vitro and in vivo. These findings point to NHE9-mediated cAMP suppression as a pseudostarvation-induced invasion state and potential therapeutic vulnerability in colorectal cancer. Our observations lay the groundwork for future research into the complexities of endosome-driven metabolic reprogramming and phenotype switching and the biology of cancer progression. IMPLICATIONS: Endosomal pH regulator NHE9 actively controls cytosolic Ca2+ levels to downregulate the adenylate cyclase-cAMP system, enabling colorectal cancer cells to acquire hybrid E/M characteristics and promoting metastatic progression.

Sequential Human Histology Results of the Subperiosteal Minimally Invasive Aesthetic Ridge Augmentation Technique (SMART): A Chronologic Wound Healing Proof-of-Principle Study.

Traditional GBR procedures have been associated with frequent complications and compromised peri-implant esthetics. Tunneling techniques have been proposed as a promising alternative in this regard. More recently, a subperiosteal minimally invasive aesthetic ridge augmentation technique (SMART) was reported to have been clinically successful in a prospective case series. This technique includes the use of a bone graft/recombinant human platelet-derived growth factor-BB combination delivered to the site by a tunneling method. However, published histologic information regarding the nature of the regenerated tissue has been limited. The current study evaluated the histologic and histomorphometric findings of four human specimens harvested at 2, 5, 9, and 14 months after ridge augmentation using the SMART method. Evaluations of the wound healing and bone regeneration sequence over time found that the ridge augmentation was the result of extensive new bone formation that progressed through the woven bone to lamellar bone stages, with remodeling of the xenogeneic graft material and replacement by patient bone. This is the first study utilizing sequential human specimens to histologically examine the chronology of wound healing following alveolar ridge augmentation.

Differential Gene Expression Analysis of Human Ovarian Follicular Cumulus and Mural Granulosa Cells Under the Influence of Insulin in IVF Ovulatory Women and Polycystic Ovary Syndrome Patients Through Network Analysis.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a commonly occurring reproductive disorder among the reproductive-aged women. Its global occurrence varies based on diagnostic guidelines, ethnicities, and locations of concern. Insulin resistance (IR) is commonly observed around 65-70% of women diagnosed with PCOS, representing a prevalent association. Consequently, the study was designed with an objective of illustrating the effect of insulin on mural and cumulus granulosa cells (GCs) of PCOS patients in comparison to normal ovulating women. METHODOLOGY: This study is a case-control design, wherein a total of 80 participants were recruited meeting criterion of inclusion and exclusion, divided into 8 groups with each group consisting of 10 samples. The process involves the isolation and culturing of mural granulosa cells (MGC) and cumulus granulosa cells (CGC) with and without exposure to insulin. The proteins released by untreated GCs and insulin-treated GCs were extracted, and complex protein mixtures were digested with trypsin, followed by tandem mass spectrometry analysis and data processing using bioinformatics. RESULTS: We found 595 proteins in both control and PCOS samples, of which 310 were contributed by MGCs and 285 by CGCs. The PCOS MGCs expressed 20%, both the normal MGCs and CGCs have equal representation of 16% by each, whereas the PCOS CGCs proteins contributed 15% of the total of the proteomic expression. However, the poor expression observed with the Insulin exposure, the Insulin treated PCOS CGCs contributes 13%, PCOS MGCs contributes 8%. The normal MGCs upon the Insulin treatment give 8% then and there only 4% of proteins expressed by normal CGCs after Insulin treatment. The Venn analysis widened on their precise expression topographies. The examination of strings exhibited important protein-protein interaction pathways. CONCLUSION: This is a pioneering investigation aimed to establish the link between hyperinsulinemia in localized follicular GCs and PCOS mechanisms by comparing them to control group. The examination of various attributes, mechanisms, and traits shown by genes and proteins in individuals with PCOS compared to control populations, alongside the investigation of the dynamics of these genes and proteins following exposure to insulin, holds promise for the formulation of novel hypotheses and strategies in the identification of new biomarkers.

Protein Expression and Bioinformatics Study of Granulosa Cells of Polycystic Ovary Syndrome Expressed Under the Influence of DHEA.

Background: The reproductive system is heavily dependent on ovarian follicles, which are made up of germ cells (oocytes) and granulosa cells (GCs), including cumulus granulosa cells (CGCs) and mural granulosa cells (MGCs). Understanding their normal and steroid-induced functions is the key to understanding the pathophysiology of endocrinal diseases in women. Objective: This study investigated the differentially expressed proteins by CGCs and MGCs of patients with polycystic ovarian syndrome (PCOS) and without subsequent exposure to dehydroepiandrosterone sulfate (DHEAS) and functional differentiation. Design: The present study was observational and experimental study carried out in hospital involving 80 female patients undergoing IVF for infertility. Methods: In this study, we isolated CGCs and MGCs from the follicular fluid of both PCOS and non-PCOS patients undergoing in vitro fertilization (IVF). The cells were cultured and treated with DHEAS for 48 hours, and these cells were extracted, digested, and analyzed by tandem mass spectrometry followed by processing of the results using open-source bioinformatics tools. Results: The present investigation discovered 276 and 341 proteins in CGCs and MGCs, respectively. DHEAS reduced the number of proteins expressed by CGCs and MGCs to 34 and 57 from 91 and 94, respectively. Venn results of CGCs revealed 49, 53, 36, and 21 proteins in normal CGCs, PCOS-CGCs, post-DHEAS, and PCOS-CGCs, respectively. Venn analysis of MGCs showed 51 proteins specific to PCOS and 29 shared by normal and PCOS samples after DHEAS therapy. MGCs express the most binding and catalytic proteins, whereas CGCs express transporter-related proteins. A protein pathway study demonstrated considerable differences between normal and PCOS samples, while DHEAS-treated samples of both cell lines showed distinct pathways. String findings identified important network route components such as albumin, actin, apolipoprotein, complement component C3, and heat shock protein. Conclusion: This is the first study to show how DHEAS-induced stress affects the expression of proteins by MGCs and CGCs isolated from normal and PCOS patients. Further studies are recommended to identify PCOS biomarkers from CGCs and MGCs expressed under the influence of DHEAS.

Stereospecific Conversion of Boronic Esters into Enones using Methoxyallene: Application in the Total Synthesis of 10-Deoxymethynolide.

Enones are widely utilized linchpin functional groups in chemical synthesis and molecular biology. We herein report the direct conversion of boronic esters into enones using commercially available methoxyallene as a three-carbon building block. Following boronate complex formation by reaction of the boronic ester with lithiated-methoxyallene, protonation triggers a stereospecific 1,2-migration before oxidation generates the enone. The protocol shows broad substrate scope and complete enantiospecificity is observed with chiral migrating groups. In addition, various electrophiles could be used to induce 1,2-migration and give a much broader range of α-functionalized enones. Finally, the methodology was applied to a 14-step synthesis of the enone-containing polyketide 10-deoxymethynolide.

Trans-aortic DORV repair.

Double-outlet right ventricle (DORV) is a group of complex ventriculoarterial connections. In the literature, there are reports of trans-aortic correction of tetralogy of Fallot, as well as ventricular septal defects and complex DORV without right ventricular outflow tract obstruction. However, a pure trans-aortic approach for DORV ventricular septal defect (VSD) right ventricular outflow tract obstruction repair is not reported in the literature. We present a case of pure trans-aortic repair of DORV VSD pulmonary stenosis (PS) in an adult. A 20-year-old male with a known case of DORV, VSD, and PS presented with cyanosis. A pure trans-aortic repair of DORV was done. Complete trans-aortic DORV VSD PS repair is yet to be reported in the literature. The trans-aortic approach avoids a right atriotomy, right ventriculotomy, and injury to coronary arteries in cases of complicated tetralogy of Fallot and avoids injury to the tricuspid valve. This approach can be used in selected patients for intracardiac repair. The advantages are excellent visualization of the defects and avoidance of injury to the aortic cusps and bundle of His. In addition, placement of the VSD patch on the left ventricular outflow side may prevent residual shunts after repair. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01564-x.

Prospective observational study on clinical and epidemiological profile of adult patients presenting to the emergency department with suspected upper gastrointestinal bleed.

BACKGROUND AND OBJECTIVE: Bleeding from the upper gastrointestinal (GI) tract is one of the common medical emergencies. In this study, we assessed patients' socio-demographic and clinical characteristics and the association of clinical characteristics with treatment outcomes among patients with suspected upper gastrointestinal bleed (UGIB) presenting to the emergency department (ED). At present, there is a scarcity of data on UGIB in Northern part of India. MATERIAL AND METHOD: The study was a single-center, prospective observational study conducted at an urban tertiary care center. Consecutive patients with suspected UGIB were enrolled in the study from August 2020 to February 2022. A detailed history was obtained, including demographic data such as age and sex, presenting complaints, history of presenting illness, history related to co-morbidities, addiction, and drug history. Pre-endoscopic Rockall and Glasgow-Blatchford Score were calculated for each patient. The patients were subsequently followed up till discharge from the hospital. The final outcomes with regard to mortality, need for blood transfusion, length of emergency department stay, and discharge were noted. RESULT: 141 patients were included in the study. The mean age of the patients with suspected UGIB was 48 ± 14 years. 115 (81.6%) patients were male. The most common co-morbidity was chronic liver disease (40;28.4%). The most frequent presenting complaint in this study was hematemesis (96; 68.1%), followed by melena (76;53.9%). The mean (Standard Deviation, SD) of the Rockall Score was 2.46 ± 1.75. The mean (SD) of the Glasgow Blatchford Score was 12.46 ± 3.15 in patients with UGIB. CONCLUSION: In our study, hematemesis was the most prevalent symptom of suspected UGIB, followed by melena. Portal hypertension was the most common cause of UGIB. Most frequent comorbidities in patients suspected of UGIB were alcohol intake, Nonsteriodal Antiinflammatory Drugs (NSAIDs) abuse, and co-morbidities such as underlying chronic liver disease, hypertension, and diabetes. Early endoscopy can be of great utility to reduce morbidity and mortality.

Maternal Tuberculosis Leading to Congenital Tuberculosis: A Case Report.

In India, tuberculosis (TB) is a severe public health concern. We report a case of a 45-day male baby who had respiratory distress and fever, whose mother was diagnosed with pulmonary TB infection prior to delivery which was confirmed by a positive Cartridge-Based Nucleic Amplification Test (CBNAAT) from the sputum and was on antitubercular therapy (ATT). Due to the symptoms, signs, and maternal TB history, congenital TB was strongly suspected. A positive CBNAAT result from the gastric lavage further supported this suspicion. This case emphasizes the value of obtaining details on the mother's TB history to aid in the early diagnosis of congenital TB and expedite the treatment and prognosis.

Correlation and agreement between arterial and venous blood gas analysis in patients with hypotension-an emergency department-based cross-sectional study.

BACKGROUND: Blood gas analysis is integral to assessing emergency department (ED) patients with acute respiratory or metabolic disease. Arterial blood gas (ABG) is the gold standard for oxygenation, ventilation, and acid-base status but is painful to obtain. Peripheral venous blood gas (VBG) is a valuable alternative as it is less painful and easy to collect. The comparability of ABG and VBG was studied in various conditions. But in hypotension, previous findings were inconsistent. So, we studied the correlation and agreement between ABG and VBG in hypotensive patients. METHODOLOGY: The study was conducted at the emergency department of a tertiary healthcare center in Northern India. Patients with hypotension above 18 years who satisfied the inclusion criteria were clinically evaluated. Patients who require ABG as a part of routine care were sampled. ABG was collected from the radial artery. VBG was obtained from the cubital or dorsal hand veins. Both samples were collected within 10 min and were analyzed. All ABG and VBG variables were entered in premade proforma. The patient was then treated and disposed of according to institutional protocol. RESULTS: A total of 250 patients were enrolled. The mean age was 53.25 ± 15.71 years. 56.8% were male. The study included 45.6% septic, 34.4% hypovolemic, 18% cardiogenic, and 2% obstructive shock patients. The study found a strong correlation and agreement for ABG and VBG pH, pCO2, HCO3, lactate, sodium, potassium, chloride, ionized calcium, blood urea nitrogen, base excess, and arterial/alveolar oxygen ratio. Hence, regression equations were made for the aforementioned. There was no correlation observed between ABG and VBG pO2 and SpO2. Our study concluded that VBG could be a reasonable alternative for ABG in hypotensive patients. We can also mathematically predict values of ABG from VBG using regression equations derived. CONCLUSIONS: ABG sampling causes most unpleasant experiences to patients and is associated with complications like arterial injury, thrombosis, air or clotted-blood embolism, arterial occlusion, hematoma, aneurysm formation, and reflex sympathetic dystrophy. The study has shown strong correlations and agreements for most ABG and VBG parameters and can predict ABG mathematically using regression formulas formulated from VBG. This will decrease needle stick injury, consume less time, and make blood gas evaluation easy in hypotensive settings.

Monkeypox epidemiology, clinical presentation, and transmission: a systematic review.

BACKGROUND: The new zoonotic viral infection, monkeypox, is a global health issue. Our study aimed at studying the epidemiology, clinical presentation, complications, case fatality rate, and transmission among the present cases of monkeypox infection. METHODS: Articles were searched in PubMed, Google Scholar, and Science Direct databases using the keywords "Monkeypox" [MeSH] or "Monkeypox virus" (MeSH). Narrative reviews, conference abstracts, commentaries, and articles in languages other than English were excluded. RESULTS: From three databases, 1442 studies were identified. Seven hundred ten articles were excluded because they included data before 2022, leaving 732 items for screening. After filtering 320 data due to data duplication, 412 remained. Due to the inclusion of systematic reviews, meta-analyses, reviews, comments, and articles in languages other than English, 257 were excluded. Eligibility based on full-text review was applied to the remaining 155, excluding 129. So, the study covered a total of remaining 26 articles. We studied 2352 confirmed cases from published literature, accounting for approximately 4% of infected cases worldwide. Around 81.71% of patients have a bisexual or men having sex with men (MSM) preference. Approximately 30.18% of confirmed cases were HIV positive. Male sex was also identified as a risk factor in our review. CONCLUSION: Monkeypox human-to-human and human-to-animal transmission are rising. Thus, it is essential to do research on the prevention, clinicodemographic trends, and treatment of monkeypox. Understanding this will enable us to treat monkeypox patients with a targeted and focused approach.

Bone Regeneration in Maxillary Sinus Augmentation Using Advanced Platelet-Rich Fibrin (A-PRF) and Plasma Rich in Growth Factors (PRGF): A Pilot Randomized Controlled Trial

The purpose of this pilot randomized controlled trial was to analyze and compare the effects of advanced platelet-rich fibrin (A-PRF) and plasma rich in growth factors (PRGF) combined with deproteinized bovine bone mineral (DBBM) on bone regeneration outcomes in maxillary sinus augmentation (MSA) procedures. A total of 15 patients in need of MSA were consecutively recruited. Maxillary sinuses were grafted with DBBM alone (control group), DBBM mixed with A-PRF (PRF group), or DBBM mixed with PRGF (PRGF group). After a 6-month healing period, bone core biopsy samples were collected prior to implant placement for histologic and histomorphometric analyses. The mean percentage of mineralized tissue (MT) was 20.33 ± 11.50 in the control group, 32.20 ± 7.29 for the PRF group, and 34.80 ± 6.83 for the PRGF group, with no statistically significant differences across the three groups (P > .05). The mean percentage of remaining bone grafting material (RBGM) was 24.00 ± 7.94 for the control group, 26.00 ± 7.78 for the PRF group, and 15.80 ± 8.23 for the PRGF group, with no statistically significant differences across the three groups (P > .05). Finally, the mean percentage of nonmineralized tissue (NMT) was 55.66 ± 7.77 for the control group, 41.40 ± 8.32 for the PRF group, and 49.60 ± 5.68 for the PRGF group, with no statistically signifcant differences across the three groups (P > .05). These findings suggest that the addition of A-PRF and PRGF to DBBM does not enhance new bone formation outcomes in maxillary sinus augmentation procedures. Neither of the two platelet concentrates were superior to the other in any of the variables assessed.

Endosomal Acid-Base Homeostasis in Neurodegenerative Diseases.

Neurodegenerative disorders are debilitating and largely untreatable conditions that pose a significant burden to affected individuals and caregivers. Overwhelming evidence supports a crucial preclinical role for endosomal dysfunction as an upstream pathogenic hub and driver in Alzheimer's disease (AD) and related neurodegenerative disorders. We present recent advances on the role of endosomal acid-base homeostasis in neurodegeneration and discuss evidence for converging mechanisms. The strongest genetic risk factor in sporadic AD is the ε4 allele of Apolipoprotein E (ApoE4), which potentiates pre-symptomatic endosomal dysfunction and prominent amyloid beta (Aß) pathology, although how these pathways are linked mechanistically has remained unclear. There is emerging evidence that the Christianson syndrome protein NHE6 is a prominent ApoE4 effector linking endosomal function to Aß pathologies. By functioning as a dominant leak pathway for protons, the Na+/H+ exchanger activity of NHE6 limits endosomal acidification and regulates ß-secretase (BACE)-mediated Aß production and LRP1 receptor-mediated Aß clearance. Pathological endosomal acidification may impact both Aß generation and clearance mechanisms and emerges as a promising therapeutic target in AD. We also offer our perspective on the complex role of endosomal acid-base homeostasis in the pathogenesis of neurodegeneration and its therapeutic implications for neuronal rescue and repair strategies.

Flies trade off stability and performance via adaptive compensation to wing damage.

Physical injury often impairs mobility, which can have dire consequences for survival in animals. Revealing mechanisms of robust biological intelligence to prevent system failure can provide critical insights into how complex brains generate adaptive movement and inspiration to design fault-tolerant robots. For flying animals, physical injury to a wing can have severe consequences, as flight is inherently unstable. Using a virtual reality flight arena, we studied how flying fruit flies compensate for damage to one wing. By combining experimental and mathematical methods, we show that flies compensate for wing damage by corrective wing movement modulated by closed-loop sensing and robust mechanics. Injured flies actively increase damping and, in doing so, modestly decrease flight performance but fly as stably as uninjured flies. Quantifying responses to injury can uncover the flexibility and robustness of biological systems while informing the development of bio-inspired fault-tolerant strategies.

Human Histologic Analysis of Implant Osseointegration in a Healed Site Grafted with Nondemineralized Autologous Tooth-Derived Graft Material.

Autologous tooth-derived grafts (ATDGs) have gained popularity as bone substitute biomaterials, owing to their promising healing dynamics in vivo and to patient preference for repurposing hopeless teeth. Nonetheless, concerns exist regarding the biologic response of these ATDGs in preparation for implant placement and subsequent osseointegration. After 12 weeks of extraction socket healing, an implant with an acid-etched surface was placed using osseodensification osteotomy preparation and was retrieved after 16 weeks of integration. Histologic analysis revealed ≥ 64% of direct bone-to-implant contact at multiple regions of interest along the implant surface. Residual dentin particles were scarce and were never found in contact with the implant, suggesting that the ATDG did not interfere with implant osseointegration. Despite the overall trabecular structure of the adjacent maxillary bone with large marrow spaces, the implant surface was delineated with a continuous dense mineralized zone (thickness of 2 to 5 cell layers) with vital osteoblasts in the lacunae. These results suggest that the healing dynamics of ATDG are well aligned with implant osseointegration dynamics.

Snakebite Causing Facial and Lingual Tremors: A Case Report.

Snakebite is a significant public health problem causing around 2.7 envenomations and 138,000 deaths globally. History may sometimes be unclear or misleading, which can cause a delay in diagnosis. Neuroparalytic, hemotoxic, and myotoxic are the common snake bite manifestations. Neuroparalytic snake bites rarely cause involuntary movements. Here we report a case of a 26-year-old female patient who sustained a snake bite and developed tremors in the face and tongue. She improved with mechanical ventilation, anti-snake venom, atropine-neostigmine, and calcium gluconate. She was discharged after seven days of hospital stay and now maintaining regular follow-up in the outpatient clinic.

The Dowd-Beckwith Reaction: History, Strategies, and Synthetic Potential.

Ring-expansion strategies are valuable synthetic tools that take benefit of existing ring structures and evade the unfavorable enthalpic-and entropic effects that arise with end-to-end cyclizations. One potentially important class of such reactions is the Dowd-Beckwith reaction, the ring-expansion of ketones via alkoxy radicals. The exciting advancement in this research area is starting to show its potential, as demonstrated by applying this methodology in strategy-level bond formation to synthesize complex natural products. This Review aims to provide the first comprehensive survey of the development of the Dowd-Beckwith reaction spanning three decades from the initial report to the present day, thus providing the readers with great detail about the contributions of this reaction to organic synthesis. We hope that this review will further disclose the salient features of the Dowd-Beckwith reaction for synthetic applications and encourage the development of new, more advanced applications.

Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities.

Receptor Guanylyl Cyclase C (GC-C) was initially characterized as an important regulator of intestinal fluid and ion homeostasis. Recent findings demonstrate that GC-C is also causally linked to intestinal inflammation, dysbiosis, and tumorigenesis. These advances have been fueled in part by identifying mutations or changes in gene expression in GC-C or its ligands, that disrupt the delicate balance of intracellular cGMP levels and are associated with a wide range of clinical phenotypes. In this review, we highlight aspects of the current knowledge of the GC-C signaling pathway in homeostasis and disease, emphasizing recent advances in the field. The review summarizes extra gastrointestinal functions for GC-C signaling, such as appetite control, energy expenditure, visceral nociception, and behavioral processes. Recent research has expanded the homeostatic role of GC-C and implicated it in regulating the ion-microbiome-immune axis, which acts as a mechanistic driver in inflammatory bowel disease. The development of transgenic and knockout mouse models allowed for in-depth studies of GC-C and its relationship to whole-animal physiology. A deeper understanding of the various aspects of GC-C biology and their relationships with pathologies such as inflammatory bowel disease, colorectal cancer, and obesity can be leveraged to devise novel therapeutics.