Nevin Manimala

Microb Genom. 2025 Sep;11(9). doi: 10.1099/mgen.0.001496.

ABSTRACT

Riboswitches are widely distributed RNA regulatory elements primarily found in prokaryotes. Over a decade ago, it was discovered that certain genes are regulated either by multiple tandemly arranged riboswitches or by riboswitches with tandem sensor domains.Riboswitches consist of a sensor domain, also known as an aptamer, and an expression platform, primarily regulating gene expression through transcription or translation attenuation, although other mechanisms such as RNA splicing or stability modulation are also possible. In tandemly arranged riboswitches, the first riboswitch is often positioned far from the ribosome binding site of the target gene, making transcriptional regulation a likely primary mechanism. In contrast, riboswitches with adjacent aptamers have a single expression platform, which may be located at varying distances from the regulated gene. Consequently, no inherent bias towards either transcriptional or translational regulation is expected in this case.Considering the reported enrichment of transcriptional riboswitches in certain phylogenetic clades, the present study analyses the distribution of tandemly arranged riboswitches and riboswitches with adjacent aptamers across various phylogenetic groups, as well as the tendencies of different riboswitch families to regulate genes in a contiguous fashion. Our results indicate that Bacillota is the phylum with the most notable families of tandemly arranged riboswitches. In contrast, regulation of gene expression via tandem sensor domains was predominantly associated with the Pseudomonadota phylum. On the other hand, our statistical analysis identified the T-box and cyclic dimeric guanosine monophosphate as the most prominent members of tandemly arranged riboswitches, while the glycine riboswitch is the most relevant family to be composed of adjacent aptamers.In addition, this article presents a comprehensive analysis of all relevant orthologous gene groups regulated by contiguous riboswitches, highlighting trends in cases where strict regulation is necessary due to the high metabolic cost of a pathway. Finally, we provide an in-depth discussion of the observed regulatory tendencies.

PMID:40961346 | DOI:10.1099/mgen.0.001496

Am Fam Physician. 2025 Sep;112(3):301-312.

ABSTRACT

Autism is a lifelong neurodevelopmental condition that affects approximately 1 in 31 US children and 1 in 45 US adults; autism spectrum disorder includes a wide range of neurologic diversity, symptoms, challenges, strengths, and abilities. The Diagnostic and Statistical Manual of Mental Disorders, 5th ed., text revision criteria for autism spectrum disorder require deficits in three areas of communication and social interaction across multiple settings, with at least two restricted or repetitive behaviors, not explained by another condition, and causing functional impairment. The American Academy of Pediatrics recommends screening for autism at ages 18 and 24 months in addition to routine developmental surveillance, whereas screening in adults is not recommended. Diagnosis should include a multidisciplinary team and a multidimensional assessment. Autistic individuals have a 20- to 30-year lower life expectancy than nonautistic people and experience higher rates of many chronic conditions, such as diabetes, epilepsy, gastrointestinal concerns, feeding disorders, and mental health disorders (eg, attention-deficit/hyperactivity disorder, depression, anxiety, schizophrenia). Treatment of children with autism spectrum disorder focuses on minimizing core deficits, maximizing functional independence, and preventing problem behaviors. Pharmacologic therapy may be indicated for related conditions or symptoms, such as sleep disorders, seizures, mental health conditions, behavior problems, and gastrointestinal issues. Melatonin effectively reduces sleep symptoms and improves daytime behaviors with minimal adverse effects. The SPACE (sensory, predictability, acceptance, communication, empathy) framework provides specific interventions that make health care more accessible and affirming to autistic patients.

PMID:40961308

Nutr Health. 2025 Sep 17:2601060251378785. doi: 10.1177/02601060251378785. Online ahead of print.

ABSTRACT

BackgroundLifestyle factors, including dietary fasting and structured eating habits, may influence neurodegenerative processes in Huntington’s disease (HD), yet little is known about dietary behaviors in this population.AimEvaluate the frequency of fasting habits, identify meal timing characteristics, and explore dietary composition choices in individuals with or at-risk for HD.MethodsAn electronic survey was distributed within the HD community. Responses were collected for one year and statistically analyzed.ResultsAmong 116 respondents, 42% reported practicing a fasting protocol, with 36% sustaining it for over a year and 40% applying it as a weight loss strategy. The most common type was daily 16:8 fasting. Mediterranean, low-carbohydrate, and vegetarian diets were the most frequently adopted structured dietary patterns.ConclusionsFasting and structured eating habits are common in the HD community, suggesting dietary interventions may be feasible and relevant. Future studies are needed to evaluate their safety and effects in HD.

PMID:40961265 | DOI:10.1177/02601060251378785

J Biomech Eng. 2025 Sep 17:1-21. doi: 10.1115/1.4069774. Online ahead of print.

ABSTRACT

This study introduces a novel framework for generating personalized musculoskeletal models to predict tibial strains from video data. By integrating a statistical shape model (SSM) with markerless motion capture, this approach enables strain prediction without requiring medical scans or marker-based data collection, making it particularly useful in settings like Basic Combat Training. Additionally, we evaluate the impact of using single versus multiple principal components in estimating musculoskeletal injury risk indicators, such as tibial strains. Data from seven participants performing a one-legged hop were used to evaluate this framework. To determine the impact of using single versus multiple PCs on tibial strain predictions, the same loading profile was applied to the personalized models. Based on the observed effects, we selected the appropriate number of PCs and applied personalized loading profiles to the corresponding finite element (FE) models to predict tibial strains. Our findings indicate that using only the first PC to develop FE musculoskeletal models leads to differences in strain predictions compared to models incorporating multiple PCs, as the latter capture subtle morphological variations. The first PC primarily accounts for variability in overall size and relying solely on it may result in similar strain predictions for subjects of comparable stature. This study highlights the importance of incorporating higher-order PCs to better capture morphological differences, ultimately influencing strain distribution and injury risk assessment. The approach presented in this study offers a scalable, efficient solution for personalized biomechanical modeling, with applications in both individual and population-level injury risk analysis.

PMID:40960884 | DOI:10.1115/1.4069774

Clin Chem Lab Med. 2025 Sep 10. doi: 10.1515/cclm-2025-0949. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the relationship between uracilemia (U) and dihydropyrimidine dehydrogenase (DPD) activity in peripheral blood mononuclear cells (PBMC) and whether they are influenced by renal or hepatic impairment.

METHODS: This retrospective study included 176 cancer patients with pre-treatment U (UPLC-MSMS assay) and PBMC-DPD (radioenzymatic assay) analyzed the same day (routine phenotyping). Blood renal (creatinine, BUN) and hepatic (ALT, AST, GGT, ALP, albumin, bilirubin) work-up was performed within 15 days before or up to 4 days after DPD phenotyping. Biochemical markers were categorized according to CTCAEv5.0 grade (G). Glomerular filtration rate (eGFR) was estimated (CKD-EPI and EKFC). Non-parametric statistical tests were used.

RESULTS: Prevalence of partial deficiency was 3.4 % based on PBMC-DPD (i.e. ≤100 pmol/min/mg) and 6.3 % based on U (i.e. ≥16 μg/L). No complete deficiency was observed. Fifteen patients out of 176 (8.5 %) exhibited discordant DPD status between PBMC activity and U. The correlation between PBMC-DPD and U was significant but weak (r= -0.309, p<0.001). PBMC-DPD (mean 246, median 235, range 62-926 pmol/min/mg prot) was not influenced by renal or hepatic impairment. U (mean 9.6, median 8.5, range 1.7-57.8 μg/L) was significantly higher in patients with elevated BUN (normal vs. >1-UNL, p=0.009), GGT (G0 vs. G1 vs. G2 vs. G3, p<0.001), AST (G0 vs. G≥1, p=0.015), or with hypoalbuminemia (G0 vs. G ≥ 1, p=0.045). Categorized creatinine or eGFR did not influence U.

CONCLUSIONS: It remains unclear whether renal and/or hepatic impairment acts as a confounding factor affecting the accuracy of uracilemia testing, or whether truly impacts DPD activity, suggesting caution in U interpretation.

PMID:40960875 | DOI:10.1515/cclm-2025-0949

J Med Internet Res. 2025 Sep 17;27:e65939. doi: 10.2196/65939.

ABSTRACT

BACKGROUND: Individual-level dietary intake data are fundamental for developing nutrition policy and programs. In low- and lower-middle-income countries, proxy measures of individual intake (household consumption and expenditure surveys and food balance sheets) are often used, with limited implementation of new technology-assisted applications.

OBJECTIVE: We aimed to determine the relative validity, test-retest reliability, and acceptability of the Voice-Image Solution for Individual Dietary Assessment (VISIDA) system in a sample of Cambodian women and their children aged ≤5 years.

METHODS: Mothers and one of their children were recruited from 3 locations (rural, semirural, and urban) in Siem Reap province, Cambodia. Dietary intake data were collected for each participant using 2 methods across 3 recording periods over approximately 4 weeks. In week 1, intake was recorded using VISIDA for 3 nonconsecutive days, followed by 3 interviewer-administered, multiple-pass 24-hour recalls collected in weeks 2 to 3. In week 4, VISIDA was used again to collect a 3-day food record. After the third intake recording period, the mothers completed a feedback survey. Differences in estimated nutrient intakes for the 3 recording periods for mothers and children were examined using a linear mixed model approach.

RESULTS: The analysis included 210 participants (n=119, 56.7% mothers and n=91, 43.3% children). Estimated mean nutrient intakes reported in both VISIDA recording periods were mostly lower compared to intakes reported using the 24-hour recalls. Compared to the 24-hour recalls, statistically significant differences were found for the VISIDA recording periods for 80% (16/20) of nutrients for mothers and 32% (6/19) of nutrients for children. Nutrient intakes estimated from both VISIDA recording periods showed no statistically significant differences for mothers and children. For mothers, the differences of model weighted marginal means in energy intakes (kcal) were -296 (95% CI -410 to -181; VISIDA period 1 minus 24-h recall), -274 (95% CI -390 to -158; VISIDA period 2 minus 24-h recall), and -22 (95% CI -131 to 87; VISIDA period 1 minus VISIDA period 2). For children, the differences in model weighted marginal means in energy intakes (kcal) were -158 (95% CI -227 to -89; VISIDA period 1 minus 24-h recall), -127 (95% CI -198 to -57; VISIDA period 2 minus 24-h recall), and -31 (95% CI -98 to 37; VISIDA period 1 minus VISIDA period 2). Most mothers reported that the VISIDA smartphone app was “easy to use” (68/108, 63%) or “very easy to use” (23/108, 21.3%) for collecting dietary intake data.

CONCLUSIONS: The VISIDA system produced lower estimates of nutrient intakes when compared to the 24-hour recalls in a sample of mothers and children in Siem Reap province, Cambodia. However, the estimated nutrient intakes for the 2 VISIDA recording periods were similar. The participating mothers reported high acceptability for using the VISIDA smartphone app to collect intake data.

PMID:40960862 | DOI:10.2196/65939

JAMA Netw Open. 2025 Sep 2;8(9):e2532319. doi: 10.1001/jamanetworkopen.2025.32319.

ABSTRACT

IMPORTANCE: Implicit bias recognition and management (IBRM) training is a promising strategy for improving clinician communication but is underevaluated.

OBJECTIVE: To describe the development and psychometric properties of the Respect, Empathize, Listen, Ask, Talk, and Engage (RELATE) rating scale, based on a theoretical framework of communication skills, to mitigate negative influences of implicit bias by using strategies for interrupting unconscious decision-making in patient-centered communication.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, between September 2019 and April 2022, standardized patients used the RELATE rating scale to evaluate communication skills of participating clinical trainees at an academic medical center who completed an IBRM training and engaged in simulated clinical encounters with standardized patients representing those with low socioeconomic status and African American, Latino or Hispanic, and African immigrant patients. Statistical analyses were ongoing from June 2021 to January 2024.

MAIN OUTCOME AND MEASURES: Gwet agreement coefficient (AC) was calculated using data from the 2019 to 2020 cohort year to assess standardized patient interrater reliability (IRR). To assess construct validity and internal consistency reliability, factor analysis techniques were used, and Cronbach α was calculated using data from 3 cohorts (2019-2020, 2020-2021, and 2021-2022).

RESULTS: Twenty-seven standardized patients generated 226 independent RELATE ratings for 123 consenting clinical trainees (14 family medicine residents [11.4%], 48 internal medicine residents [39.0%], and 61 doctor of nursing practice students [49.6%]; mean [SD] age, 30.4 [4.1] years; 82 [66.7%] female), who each had 2 RELATE scores. Of the 3-level item responses of whether a behavior was observed (“present,” “partial,” or “absent”), for all 19 items, at least 1 trainee (0.4%) was noted who did not complete the evaluated behavior, and all items had some responses of “partial” (range, 13 [5.8%] to 70 [31.0%]). Twelve of the 19 RELATE items (63.2%) showed either substantial or almost perfect IRR (Gwet AC, >0.60), and 6 items (31.6%) had moderate IRR (Gwet AC, 0.41-0.60). Factor analyses resulted in a final 4-factor solution with excellent model fit indices and strong factor loadings: respect (4 items), empathy (5 items), listening and talking (6 items), and engaging in partnership with patients (4 items). Each factor showed sound internal consistency (Cronbach α range, 0.64-0.77).

CONCLUSIONS AND RELEVANCE: This cross-sectional study of the RELATE rating scale demonstrated high construct validity and good internal consistency in simulated clinician-patient encounters. The findings suggest that the RELATE rating scale is an efficient, theoretically consistent tool to evaluate implicit bias-management communication behavior among clinicians.

PMID:40960826 | DOI:10.1001/jamanetworkopen.2025.32319

JAMA Netw Open. 2025 Sep 2;8(9):e2532334. doi: 10.1001/jamanetworkopen.2025.32334.

ABSTRACT

IMPORTANCE: Although advanced airway (AA) practice patterns have varied over time, their association with out-of-hospital cardiac arrest (OHCA) outcomes is unknown.

OBJECTIVE: To determine the association between AA temporal practice patterns of emergency medical service (EMS) agencies and OHCA outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from multicenter EMS agencies participating in the Cardiac Arrest Registry to Enhance Survival database. The study included adults (aged ≥18 years) with OHCA treated by EMS agencies that had 25 or more OHCA episodes annually from January 1, 2016, through December 31, 2022.

EXPOSURE: AA interventions included supraglottic airway (SGA) device use or endotracheal intubation (ETI). Patients were categorized into groups using the following EMS agency-level patterns defined by predominant AA use before and after 2019: (1) ongoing ETI, (2) ongoing SGA use (ongoing SGA), (3) transitioning from ETI to SGA use (ETI to SGA), or (4) transitioning from SGA use to ETI (SGA to ETI).

MAIN OUTCOMES AND MEASURES: Mixed-effects logistic regression models accounting for EMS agency clustering and adjusting for Utstein variables were used to evaluate the association between EMS agency AA practice patterns and OHCA outcomes including return of spontaneous circulation (ROSC) and survival. Subanalyses were also conducted for agencies in the lowest survival quartile. Odds ratios (ORs) are reported with 95% CIs.

RESULTS: This study included 350 216 patients with OHCA treated by 254 eligible EMS agencies. The 214 EMS agencies (n = 305 341 patients) with a predominant AA pattern were grouped as follows for temporal pattern analysis: ongoing ETI (n = 72 [33.6%]), ongoing SGA (n = 66 [30.8%]), ETI to SGA (n = 67 [31.3%]), or SGA to ETI (n = 9 [4.2%]). Patients were predominantly male (62.2%), with a median age of 64 (IQR, 52-76) years, and most (81.7%) presented with nonshockable rhythms. ROSC occurred in 30.8% of patients, and 10.4% of patients survived to hospital discharge. Predominant SGA use among EMS agencies increased from 65 agencies in 2016 to 113 in 2022. ROSC decreased in all 4 groups from before to after 2019 as follows: from 36.5% to 30.7% (OR, 0.80 [95% CI, 0.77-0.82]) for ongoing ETI, from 32.4% to 26.4% (OR, 0.75 [95% CI, 0.73-0.78]) for ongoing SGA, from 32.1% to 28.5% (OR, 0.88 [95% CI, 0.85-0.91]) for ETI to SGA, and from 36.7% to 33.3% (OR, 0.92 [95% CI, 0.83-1.03]) for SGA to ETI. For the 15 lower-performing agencies (n = 20 860 patients) that transitioned from ETI to SGA after vs before 2019, an association with higher ROSC (from 25.7% to 29.1%; OR, 1.16 [95% CI, 1.09-1.24]) and survival (from 5.6% to 6.3%; OR, 1.17 [95% CI, 1.04-1.32]) was observed.

CONCLUSIONS AND RELEVANCE: In this cohort study, SGA use among EMS agencies increased over time. Although ROSC declined for all AA temporal practice patterns, the transition from ETI to SGA use at EMS agencies with lower baseline survival was associated with improved outcomes. Future studies are warranted to confirm these findings and to evaluate whether the observed associations are consistent across diverse populations.

PMID:40960825 | DOI:10.1001/jamanetworkopen.2025.32334

JAMA Surg. 2025 Sep 17. doi: 10.1001/jamasurg.2025.3581. Online ahead of print.

ABSTRACT

IMPORTANCE: Robot-assisted surgery (RAS) is increasingly used for abdominal procedures; however, postoperative pulmonary complications (PPCs) are more frequent in patients undergoing RAS compared with patients undergoing conventional laparoscopic surgery (CLS).

OBJECTIVE: To compare the incidence of PPCs after CLS and RAS and to determine which patient-, surgery-, and anesthesia-related factors are associated with PPCs.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the Laparoscopic and Robot-Assisted Surgery (LapRAS) database, a pooled dataset containing individual patient data of 2 worldwide prospective cohort studies: the Local Assessment of Ventilatory Management During General Anaesthesia for Surgery (LAS VEGAS) study and the Assessment of Ventilatory Management During General Anesthesia for Robotic Surgery and Its Effects on Postoperative Pulmonary Complications (AVATaR) study. Data were collected from adult patients requiring intraoperative ventilation during general anesthesia for CLS or RAS surgical procedures from 163 centers and 31 countries in the Americas, Europe, the Middle East, and North Africa from January 2013 to March 2019. Data were analyzed from December 2023 to October 2024.

EXPOSURES: Type of surgical approach (CLS vs RAS), duration of intraoperative ventilation, and intensity of mechanical ventilation, assessed using the 4 times the driving pressure (DP) plus respiratory rate (RR) estimator (4DP + RR).

MAIN OUTCOME AND MEASURES: The primary outcome was occurrence of 1 or more PPCs in the first 5 postoperative days. Mixed-effects logistic regression assessed associations with PPCs; mediation and matched cohort analyses served as sensitivity analyses.

RESULTS: A total of 2738 patients (median [IQR] age, 56 [41-66] years; 1456 female [53.1%]) were included. PPCs occurred in 172 of 903 patients (19.0%) in the RAS group and 174 of 1835 patients (9.5%) in the CLS group (P < .001). Duration of intraoperative ventilation was longer in RAS compared with CLS (median [IQR] duration, 219 [180-270] vs 95 [68-145] minutes; P < .001) and the intensity of mechanical ventilation was higher (median [IQR] intensity, 84 [69-100] vs 72 [60-87] 4DP + RR; P < .001). PPCs were independently associated only with duration of ventilation (adjusted odds ratio [aOR], 1.49; 95% CI, 1.33-1.66; P < .001), not with the surgical approach (ie, RAS vs CLS; aOR, 1.35; 95% CI, 0.72-2.54; P = .35) nor the intensity of ventilation as measured by 4DP + RR (aOR, 1.01; 95% CI, 1.01-1.01; P = .21). A post hoc analysis showed a more pronounced association of intensity of ventilation in surgical procedures of shorter duration.

CONCLUSIONS AND RELEVANCE: In this cohort study, patients who received RAS vs CLS had a higher incidence of PPCs and received longer and more intense mechanical ventilation; however, only the duration of ventilation rather than intensity of ventilation or type of surgical approach (ie, RAS vs CLS) was independently associated with the occurrence of PPCs, indicating that the longer duration of ventilation in RAS underlies the higher incidence of PPCs observed in those who undergo this type of surgery.

PMID:40960804 | DOI:10.1001/jamasurg.2025.3581

Br Poult Sci. 2025 Sep 17:1-7. doi: 10.1080/00071668.2025.2559391. Online ahead of print.

ABSTRACT

1. The following reports an in-vivo study to investigate the toxicity profile of the azithromycin drug in broilers.2. Ninety, 1-d-old Hubbard chicks were purchased from Dakahliah Poultry Company, Egypt and, on d 25 of age, were subdivided into three groups. Group 1 (G1, control) received only drinking water, Group 2 (G2, treatment 1) received 50 mg azithromycin/kg body weight (BW) and Group 3 (G3, treatment 2) received 300 mg azithromycin/kg BW. All treatments were administered orally. Immunological, histopathological, and immunohistochemical assays were performed to evaluate the effect of azithromycin on broiler health.3. The weights of bursa of Fabricius and spleen in azithromycin-treated broilers decreased, particularly in G3. A decrease in both the phagocytic activity and index was evident in the treated groups (G2 and G3). Prominent degenerative changes and necrosis of immune organs were observed in treated chicks. Furthermore, strong immunoreactivity to caspase-3 was observed in the G3 group, which indicated elevated apoptosis in immune organs following exposure to a high-dose of azithromycin.4. It was concluded that administering azithromycin in broilers at a dose of 300 mg/kg impaired the immune function, promoted apoptosis and induced many microscopical alterations in different organs.

PMID:40960799 | DOI:10.1080/00071668.2025.2559391