Background: To relieve acute and inflammatory pain, preparations of plant and animal origin have been used. The present work aimed to study the analgesic and anti-inflammatory effectiveness of a combined preparation based on viper venom and essential oil. Determining effective routes of exposure, optimal doses, the duration of action of the preparation, and possible mechanisms of their action were the areas of interest. Methods: Experiments were carried out on murine. Essential oil content was determined by gas chromatography– mass spectrometry equipment. The formalin, carrageenan, and hot plate tests were used. Certain methods for determining side effects were used as well. To determine the participation of cannabinoid and opioid receptors in the antinociceptive action of combined preparation, SR144528 and naloxone were used. Results: The treatment of the ointment version of the preparation reduced inflammatory pain by more than 68% and decreased the volume of inflammatory edema by up to 36%. The involvement of cannabinoid receptors in the analgesic mechanism of the ointment was approximately 73%, and, for the opioid receptors, about 64%. Physiologically significant side effects were not observed. Conclusions The active components of the ointment are principally different in their mechanism of action and make it possible to relieve pain and inflammation both through the blockade of pain receptors of afferent nociceptive neurons (venom) as well as via cannabinoid and opioid receptors (essential oil).

Purpose: Metabolic diseases such as diabetes mellitus may play a role in the development and progression of prostate cancer (PC); however, this association remains to be explored in the context of specific PC stages. The objective of this study was to systematically review the evidence for an association between diabetes and overall, early, or advanced PC risk. Materials and Methods: A systematic review with meta-analysis was performed (MEDLINE, EMBASE, and CINAHL) from inception until September 2023. Cohort and case-control studies that assessed PC risk in adult males (≥18 years) associated with type 2 diabetes mellitus or diabetes (if there was no distinction between diabetes type) were included. The Newcastle-Ottawa Scale (NOS) was used to assess study bias; those with NOS<7 were excluded. Evidence certainty was assessed with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method. Results: Thirty-four studies (n=26 cohorts and n=8 case-controls) were included. Of these, 32 assessed diabetes and all PC stages combined, 12 included early PC stages, and 15 included advanced PC stages. Our meta-analysis showed diabetes had a protective effect against early PC development (n=11, risk ratio [RR]=0.71; 95% confidence interval [CI]=0.61–0.83, I2=84%) but no association was found for combined (n=21, RR=0.95; 95% CI=0.79–1.13, I2=99%) or advanced PC stages (n=15, RR=0.96; 95% CI=0.77–1.18, I2=98%) at diagnosis. According to GRADE, the evidence certainty was very low. Conclusions Diabetes may be protective against early PC stages, yet evidence linking diabetes to risk across all stages, and advanced PC specifically, is less conclusive. High heterogeneity may partially explain discrepancy in findings and was mostly associated with study design, method used for PC diagnosis, and risk measures. Our results may aid risk stratification of males with diabetes and inform new approaches for PC screening in this group, especially considering the reduced sensitivity of prostate-specific antigen values for those with diabetes.

Background: Type 1 diabetes (T1D) results in autoreactive T cells chronically destroying pancreatic islets. This often results in irreplaceable loss of insulin-producing beta cells. To reverse course, a combinatorial strategy of employing glucose-responsive insulin restoration coupled with inhibiting autoreactive immune responses is required. Methods: Non-obese diabetic mice received a single intraperitoneal implantation of a novel biomaterial co-seeded with insulin-producing islets and T regulatory cells (Tregs). Controls included biomaterial seeded solely with islets, or biomaterial only groups. Mice were interrogated for changes in inflammation and diabetes progression via blood glucose monitoring, multiplex serum cytokine profiling, flow cytometry and immunohistochemistry assessments. Results: Islet and Tregs co-seeded biomaterial recipients had increased longevity, insulin secretion, and normoglycemia through 180 days post-implantation compared to controls. Serum profile revealed reduced TNFα, IFNγ, IL-1β and increased IL-10, insulin, C-Peptide, PP and PPY in recipients receiving co-seeded biomaterial. Evaluation of the resected co-seeded biomaterial revealed reduced infiltrating autoreactive CD8 + and CD4 + T cells concomitant with sustained presence of Foxp3 + Tregs; further analysis revealed that the few infiltrated resident effector CD4+ or CD8+ T cells were anergic, as measured by low levels of IFNγ and Granzyme-B upon stimulation when compared to controls. Interestingly, studies also revealed increased Tregs in the pancreas. However, there was no restoration of the pancreas beta cell compartment, suggesting normoglycemia and production of insulin levels were largely supported by the implanted co-seeded biomaterial. Conclusion These studies show the efficacy of a combinatorial approach seeding Tregs with pancreatic islets in a novel self-assembling organoid for reversing T1D.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

Purpose: This study aimed to evaluate our institution's experience in using artificial intelligence (AI) decision support (DS) as part of the clinical workflow to triage patients with Breast Imaging Reporting and Data System (BI-RADS) 3 sonographic lesions whose follow-up was delayed during the coronavirus disease 2019 (COVID-19) pandemic, against subsequent imaging and/or pathologic follow-up results. Methods: This retrospective study included patients with a BI-RADS category 3 (i.e., probably benign) breast ultrasound assessment from August 2019–December 2019 whose follow-up was delayed during the COVID-19 pandemic and whose breast ultrasounds were re-reviewed using Koios DS Breast AI as part of the clinical workflow for triaging these patients. The output of Koios DS was compared with the true outcome of a presence or absence of breast cancer defined by resolution/stability on imaging follow-up for at least 2 years or pathology results. Results: The study included 161 women (mean age, 52 years) with 221 BI-RADS category 3 sonographic lesions. Of the 221 lesions, there were two confirmed cancers (0.9% malignancy rate). Koios DS assessed 112/221 lesions (50.7%) as benign, 42/221 lesions (19.0%) as probably benign, 64/221 lesions (29.0%) as suspicious, and 3/221 lesions (1.4%) as probably malignant. Koios DS had a sensitivity of 100% (2/2; 95% confidence interval [CI], 16% to 100%), specificity of 70% (154/219; 95% CI, 64% to 76%), negative predictive value of 100% (154/154; 95% CI, 98% to 100%), and false-positive rate of 30% (65/219; 95% CI, 24% to 36%). Conclusion When many follow-up appointments are delayed, e.g., natural disaster, or scenarios where resources are limited, breast ultrasound AI DS can help triage patients with probably benign breast ultrasounds.

Objective: To explore sleep patterns in individuals with essential tremor (ET) and essential tremor plus (ET-Plus) compared with healthy controls and assess differences between ET and ET-Plus, given the lack of established polysomnography (PSG) data on these groups and the potential for sleep disturbances to serve as clinical markers. Methods: We conducted a prospective cross-sectional study at National Institute of Mental Health and Neurosciences, Bengaluru, from November 2021 to August 2023 on 45 patients (26 ET, 19 ET-Plus) and 45 controls. Tremor severity was assessed using The Essential Tremor Rating Assessment Scale (TETRAS) and Fahn‐Tolosa‐Marin Clinical Rating Scale (FTMRS). Sleep symptoms were assessed via the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Mayo Sleep Questionnaire, restless legs syndrome questionnaire, Berlin questionnaire, Generalized Anxiety Disorder Scale 7, and Patient Health Questionnaire-9. All patients and controls underwent overnight video PSG. Sleep scoring was manually performed by a trained sleep research technician and the first author following the American Academy of Sleep Medicine (2017) guidelines, with data analyzed using R studio. Results: Compared with ET-Plus patients, ET patients had a younger onset age (46.8±11.1 years versus 30.8±16.7 years, respectively). Compared with ET patients, ET-Plus patients had higher TETRAS and FTMRS scores (p<0.005). Compared with controls, both ET patients and ET-Plus patients presented poorer sleep quality, excessive daytime sleepiness, rapid eye movement (REM) sleep behavior disorder, and restless legs syndrome symptoms. PSG findings supported these clinical observations, showing an elevated apnea‒hypopnea index, reduced total sleep time, prolonged REM latency, decreased sleep efficiency, increased N1 stage duration, and reduced N2/N3 durations and percentages in patients versus controls. Conclusion The study highlights significant sleep architecture abnormalities in both ET and ET-Plus patients compared with healthy controls, with no differences between the ET groups.

Background/Aims: Panenteric gastrointestinal dysmotility in diabetic gastroenteropathy remains incompletely understood. We aim to (1) compare gastrointestinal transit times, contractile activity, and pH levels between individuals with and without diabetic gastroenteropathy and (2) investigate associations between symptoms and contractile activity. Methods: We compared 37 healthy individuals to 68 individuals with diabetic gastroenteropathy. Gastrointestinal segmental transit times, contractile activity, and pH were measured with SmartPill. The Gastroparesis Cardinal Symptom Index and the Gastrointestinal Symptom Rating Scale were used to evaluate symptoms. Results: Compared to controls, individuals with diabetic gastroenteropathy had prolonged median gastric emptying time (3.3 [IQR, 2.5-4.4] vs 2.5 [IQR, 1.9-3.6] hours, P = 0.023), antroduodenal transition time (23 [IQR, 8-52] vs 11 [IQR, 2-25] minutes, P = 0.015), colonic transit times (36.0 [IQR, 17.3-53.5) vs 20.8 [IQR, 14.0-28.8] hours, P = 0.004), and whole-gut transit time (46.1 [IQR, 24.3-72.9] vs 28.7 [IQR, 22.0-42.7] hours, P = 0.002). The diabetes group had lower antral contraction frequency (1.5 [IQR, 0.9-2.1] vs 2.5 [IQR, 1.5-3.9] contractions per minute, P = 0.004) and sum of amplitudes (1941 [1377-2763] vs 2975 [1734-5337] mmHg, P = 0.004).In contrast, the diabetes group had higher colonic sum of amplitudes and area under the contraction curve. The antral contraction frequency was unassociated with gastrointestinal symptoms. Still, the overall stomach contraction frequency increased by 30% (P < 0.001) and 15% (P = 0.003) in individuals with diabetes for each incremental increase in nausea and reflux scores, respectively. Conclusions Gastrointestinal transit times, as well as antral and colonic contractile activity, differed between individuals with diabetic gastroenteropathy and controls. The overall gastric contraction frequency was associated with symptom severity.

Background/Aims: Pediatric patients with suspected gastroparesis often undergo antroduodenal manometry (ADM) and gastric emptying scintigraphy (GES) for diagnostic purposes. However, it is unknown if delayed gastric emptying (DGE) correlates with manometric findings. This study evaluates whether ADM parameters differ between normal and abnormal GES in pediatric patients. Methods: Data from pediatric patients undergoing ADM and GES at Nationwide Children’s Hospital from 2011-2020 were retrospectively reviewed. Manometry parameters including motility index (Ln [sum of amplitudes × number of contractions + 1]), number of antral contractions, and direction of the phase III migrating motor complex (MMC) were compared to GES results from age-matched patients with DGE (n = 32) and normal gastric emptying (NGE) (n = 32) of similar sex, body mass index, and weight. Results: Children with DGE had a lower post-prandial antral motility index and antral contraction number than those with NGE (9.4 vs 11.2, P = 0.005; 21.8 vs 49.6, P < 0.001). The gastric emptying percentage at 4 hours was lower in patients with retrograde phase III (59.2% vs 83.9%,P = 0.022) and in those without an antral component in the fasting phase III of the migrating motor complex (70.3% vs 86.5%, P = 0.003). Post-prandial antral hypomotility occurred more frequently in the DGE group than in the NGE group (41% vs 9%, P = 0.008). Conclusions ADM findings differ between children with DGE and NGE. Children with DGE are more likely to have abnormal fasting phase III patterns and decreased post-prandial antral activity during ADM testing.

Objective: To investigate the characteristics of public health emergencies in Jinhua City, Zhejiang Province from 2014 to 2023, so as to provide the reference for prevention and control of public health emergencies. Methods: Data of public health emergencies and related information in Jinhua City from 2014 to 2023 were collected through Emergency Public Reporting System of Chinese Disease Prevention and Control Information System. Attack rates, and distribution of time, areas and places were descriptively analyzed. Results: A total of 276 public health emergencies were reported in Jinhua City from 2014 to 2023. There were 10 324 reported cases and 7 deaths, with an attack rate of 0.32%. There were 53 Ⅳ-level (19.20%) and 223 unclassified public health emergencies (80.80%). Infectious disease emergencies were predominant types, accounting for 97.83% (270 events). The three most common infectious disease emergencies were other infectious diarrhea (42.03%), influenza (21.01%) and COVID-19 (16.30%). The reported public health emergencies peaked in November and December, with 66 and 45 events reported, respectively. The three most counties (cities, districts) included Yiwu City, Wucheng District and Lanxi City, accounting for 24.28% (67 events), 18.48% (51 events) and 11.96% (33 events), respectively. School and preschool institutions were predominant places where public health emergencies occurred (198 events, 71.74%). Conclusions The public health emergencies in Jinhua City from 2014 to 2023 were Ⅳ-level and unclassified emergencies, and infectious disease emergencies were predominant. November and December were the peak reporting periods, and schools and preschool institutions were the main places where these events occurred.