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PubMed2026

Same-day initiation of tenofovir alafenamide-based pre-exposure prophylaxis with drug-level feedback for transgender women in Uganda.

OBJECTIVE: To evaluate the feasibility and acceptability of same-day initiation of emtricitabine/tenofovir alafenamide (F/TAF) pre-exposure prophylaxis (PrEP) and test the impact of drug-level feedback on PrEP adherence among transgender women (TGW) in Uganda. DESIGN: Randomized controlled trial. METHODS: HIV-negative TGW were randomly assigned 1 : 1 to intervention (drug-level feedback with tailored adherence counseling) or standard-of-care (SOC), and followed quarterly for 12 months (November 2021-July 2023; NCT04491422). Quarterly clinic visits included demographic and socio-behavioral data collection, PrEP refills, STI testing, and quarterly PrEP adherence assessment using tenofovir levels in dried blood spots (DBS; long-term) and urine (short-term). RESULTS: We enrolled 200 TGW (100 per arm), median age 21 years. Same-day F/TAF PrEP initiation was 100%. Tenofovir detection in urine (intervention arm) was 79, 80, 85, and 70% at the 3, 6, 9, and 12-month visits, respectively. Tenofovir detection in DBS was 46, 40, 35, and 31% at 3, 6, 9, and 12 months, respectively. Median tenofovir DBS concentrations were 40.6 and 47.0 fmol/punch in intervention and SOC arms, respectively. There was no intervention effect on PrEP adherence (DBS tenofovir levels) [adjusted incidence rate ratio (aIRR) 1.06; 95% CI: 0.82-1.37]. Never being harassed by police for being transgender (aIRR 1.66; 95% CI: 1.24-2.23), history of taking daily medication for more than 7 days (aIRR 1.51; 95% CI: 1.18-1.93) and higher monthly income (aIRR 1.44; 95% CI: 1.10-2.04) were associated with PrEP adherence. CONCLUSION: Oral F/TAF PrEP adherence among TGW in Uganda was low and not affected by drug-level feedback or tailored adherence counseling. Long-acting injectable PrEP formulations should be considered for this population.

Humans↗

PubMed2026

Lung function after randomization to metformin, lifestyle intervention or placebo in the Diabetes Prevention Program Outcomes Study (DPPOS).

INTRODUCTION: Metformin and physical activity have been suggested as beneficial for chronic lung disease; however, there are no prior randomized trials. METHODS: The Diabetes Prevention Program (DPP) was a 3-year trial that randomized 3234 individuals at risk for diabetes to metformin, lifestyle intervention or placebo. After the DPP, 88% of participants enrolled in the DPP Outcomes Study that offered lifestyle intervention to all and open-label continuation of metformin. Spirometry was performed at approximately 19 and 22 years post-randomization. Lung function measures were compared in an intention-to-treat (ITT) analysis by original randomization group. Models were unadjusted and adjusted for demographics, body size, smoking and sitting/standing at spirometry. Additional analyses tested prevalence of obstruction (FEV1/FVC <70%), restrictive pattern (FVC < LLN and FEV1/FVC ≥70%), preserved ratio impaired spirometry (PRISm: FEV1 <80% predicted, FEV1/FVC ≥70%) and symptoms (COPD Assessment Test [CAT] score ≥10). RESULTS: The 1888 participants with spirometry were a mean (±SD) age of 68.2 ± 9.3 years, 70% female and 6% currently smoked and 33% had previously smoked cigarettes. Mean follow-up time was 19.0 ± 0.8 years. The mean FEV1 was 2.14 ± 0.60 L, FVC 2.74 ± 0.74 L, FEV1/FVC 78.4 ± 6.4%, mean BMI was 32.4 ± 6.7 kg/m2 and 58% had diabetes. In both unadjusted and adjusted ITT analyses, randomization group was not associated with FEV1, FVC or FEV1/FVC. Likewise, rates of obstruction, restrictive pattern, PRISm or symptoms did not differ by randomization group. CONCLUSIONS: In this long-term follow-up after a randomized trial, we found no significant associations between randomization to metformin or lifestyle intervention and lung function or respiratory symptoms.

Humans↗

PubMed2026

Complementary feeding patterns in preterm and term infants.

Complementary feeding is essential for infants' nutritional status and development, marking the transition to solid foods when breast milk or formula alone is insufficient. Despite its importance, clear recommendations on which foods to introduce when initiating complementary feeding in preterm infants are lacking. By using data from our previously published randomized controlled trial on the timing of complementary feeding in preterm infants, the current study explores the complementary feeding patterns of preterm infants and compares them with those of term-born infants, providing insights into parental decision-making and potential long-term health impacts. Complementary feeding practices differed significantly between preterm (n = 255) and term (n = 159) infants, with preterm infants more often receiving vegetables as their first solid food (85.4% versus 68.8%, difference 17.6% with 95% CI 12-35%). The group with early introduction of vegetables had a lower BMI-for-age z-scores (β -0.28 [95% CI -0.55 - 0.02]) and weight-for-height z-scores (β -0.27 [95% CI -0.53 to -0.01]) at two years of age. Additionally, preterm infants showed a greater variety in the numbers of different fruits and vegetables consumed by six months (corrected) age than term-born counterparts (8.29 (SD 3.65) versus 6.26 (SD 3.47), p < 0.001). These results indicate that complementary feeding patterns in preterm infants differ from term-born infants, with potential positive implications on growth. These data contribute to the development of accurate feeding protocols for preterm infants. Given that feeding practices are culturally influenced, further multinational research is essential to refine complementary feeding guidelines for preterm infants and support caregivers in informed decision-making.

Humans↗

PubMed2026

2024-2025 BNT162b2 KP.2 COVID-19 full season vaccine effectiveness from vaccine registries linked to administrative claims in two states: A cohort study in non-immunocompromised adults.

BACKGROUND: Data on effectiveness of COVID-19 vaccinations during the 2024-2025 respiratory season are limited, particularly among those with underlying medical conditions (UMC). We estimated BNT162b2 KP.2 vaccine effectiveness (VE) against COVID-19-associated hospital admission, emergency department (ED), and urgent care (UC) visits in two U.S. states. METHODS: Retrospective cohort study of non-immunocompromised adults living in Louisiana or California, with ≥1 year prior continuous enrollment in insurance plans contributing to the HealthVerity claims database beginning August 22, 2024. The effectiveness of BNT162b2 KP.2 vaccine (2024-2025 formulation, hereafter referred to as BNT162b2), measured as a time-varying exposure against hospital admission, ED, or UC encounters with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code U07.1 was calculated as 1 - adjusted hazard ratio using Cox proportional hazard models adjusted for age group, sex, state, insurance payor, presence or absence of UMCs, and pre-index healthcare utilization. Stratifications included those aged 65 years and older, those aged 18-64 years with UMCs, and those aged 18-64 years without UMCs. RESULTS: The cohort included 6,256,421 individuals (93% California, 7% Louisiana); 330,565 (5%) received the BNT162b2 vaccine. Vaccinated individuals were older and had more comorbidities, wellness visits, and prior influenza vaccination. Overall, 66% of the study population had ≥1 UMC; the most prevalent conditions were obesity (25%), history of immunocompromised conditions (23%), and mental health conditions (19%). COVID-19-related encounter rates for ED, UC or hospitalization were lower among vaccinated compared to unvaccinated persons (25.1 vs 36.3 per 100,000 person-months). Among all adults, VE was 37% against hospitalization, 12% against ED/UC encounters, and 16% against ED/UC/hospitalization encounters. Results were similar across age groups and UMCs. CONCLUSIONS: BNT162b2 provided protection against COVID-19-associated outcomes of ED, UC or hospitalization among non-immunocompromised U.S. adults, including those with UMCs, over the course of the 2024-2025 respiratory virus season, supporting continued vaccine recommendations. REGISTRATION: This study was posted on clinicaltrials.gov prior to analyses (NCT06923137).

Adolescent↗

PubMed2026

Age at menopause and subjective cognitive symptoms predict digital cognitive outcomes at the gynecological Well-Woman visit.

INTRODUCTION: Women are at increased risk for Alzheimer's Disease (AD). Growing evidence suggests that the menopausal transition may represent a vulnerable window for development of AD-related pathology. Yet, women are diagnosed with AD later than men. Conducting routine cognitive screenings and integrating information about both cognitive symptoms and age at menopause may help address sex-based disparities in detection and prevention. This study investigated whether subjective cognitive symptoms, in combination with age at menopause, were associated with performance on a digital cognitive task in postmenopausal women. METHODS: 183 postmenopausal women (mean age = 63.8, range = 45-85) were recruited after their Well-Woman visit. Participants completed the Screener for Cognitive Problems in Everyday Life (SCoPE) to assess subjective cognitive symptoms, followed by a sensitive measure of objective cognition: the Linus Health Digital Clock and Recall (DCR™). Information was also collected on age at menopause. We examined associations of subjective cognitive symptoms and age at menopause with digital cognitive performance, adjusting for age, education and depression. Model fit was evaluated using adjusted R2, AIC, and BIC. RESULTS: 48.1% of women reported one or more cognitive symptoms on the SCoPE. On objective testing, 73.2% scored in the normal range, 20.8% in the borderline range, and 6.0% in the impaired range. SCoPE total score was negatively associated with objective cognitive performance in adjusted models (B = -.12, p = .03). Age at menopause showed a significant quadratic association with cognitive performance (B = -0.006, p<.001). SCoPE total was not associated with DCR subtests, while age at menopause predicted both Delayed Recall and Clock Drawing. CONCLUSION: Subjective cognitive symptoms and age at menopause were associated with lower performance on a sensitive, objective cognitive test. Findings support routine cognitive screening and suggest that subjective cognitive symptoms as well as age at menopause are associated with cognitive function.

Humans↗

PubMed2026

Clinical Outcomes and Genomic Epidemiology of Multidrug-Resistant Methicillin-Resistant Staphylococcus aureus Keratitis.

PURPOSE: To characterize the clinical features, management, antimicrobial resistance patterns, and genomic epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) keratitis at two North American centers. DESIGN: Retrospective interventional case series combined with laboratory investigation PARTICIPANTS: Seventy eyes of 67 patients presenting laboratory-confirmed MRSA keratitis were included METHODS: We performed a multicenter retrospective case series of patients with culture-proven MRSA keratitis treated between 2005 and 2022. Demographic and clinical data were collected. Antimicrobial susceptibility testing was conducted, and multidrug resistance (MDR) was defined as resistance to ≥3 antibiotic classes. A subset of isolates underwent whole-genome sequencing with core genome multilocus sequence typing. Vancomycin susceptibility, heteroresistance screening, and tolerance testing were performed on available isolates. MAIN OUTCOME MEASURES: Antimicrobial susceptibility and multidrug resistance rates, vancomycin phenotypic profiles, MRSA genotypic distribution, and final best-corrected visual acuity RESULTS: Median age was 63.5 years, and 61.4% were female. Ocular surface disease (67.7%) and prior ocular surgery (65.2%) were common. Only 25.4% had significant healthcare exposure in the preceding year. Most isolates (85.7%) were MDR. Fluoroquinolone susceptibility was low (moxifloxacin 19.7%). All isolates were susceptible to vancomycin (MIC₉₀ 2 µg/mL), and no vancomycin-intermediate, heteroresistant, or tolerant phenotypes were identified. Whole genome sequencing (n = 41) demonstrated predominance of clonal complexes 5 (68.3%) and 8 (29.2%). Visual outcomes were poor, with most patients (85.2%) having a final visual acuity worse than 20/60 among those with follow-up. CONCLUSIONS: MRSA keratitis is associated with high rates of multidrug resistance and poor visual outcomes despite guideline-based therapy. Infections were predominantly caused by CC5 MDR strains despite limited recent healthcare exposure. These findings highlight the persistence of highly resistant MRSA lineages in community-associated corneal infection and underscore the need for ongoing antimicrobial surveillance and optimized treatment strategies.

Humans↗

PubMed2026

Quality assessment, prognostic factors, and biomarkers for brain tumor analysis: a comprehensive systematic review.

The brain tumors possess different causative factors and properties, making their diagnosis and treatment difficult. Growth of these cancers usually leads to compression of the adjacent nerves and obstruction of the flow of cerebrospinal fluid, thus leading to increase in intracranial pressure. This affects the working of brain in many ways; thus, the difficulty involved in its treatment. With the improvements in technology in neuroimaging, including Diffusion Tensor Imaging (DTI), Positron Emission Tomography (PET), and multiparametric Magnetic Resonance Imaging (mpMRI), the diagnosis process has become easy. The effectiveness of any form of therapy in such patients depends primarily on their prognosis. While it is a common practice that physicians determine the prognosis of the disease by considering the age of the patient, histological grade of the tumor, and resection status, now this method has become more comprehensive by adding molecular signature and genetic analyses to the list of criteria. Next-generation sequencing (NGS) allows a reliable molecular classification. It increases the level of risk stratification, facilitating the application of therapies tailored to individual patients. Thus, molecular oncology has greatly changed our views on brain tumors' pathology and prognosis while neoadjuvant treatments aim at increasing the survival rate. On the other hand, radiogenomics is a field of study that combines non-invasive imaging phenotypes and genomic information in order to find unique molecular signatures of tumors without collecting samples from tumors. Molecular biomarkers are absolutely essential in the diagnosis of cancer, treatment monitoring, and recurrence of cancer. Advances in liquid biopsy technology, particularly the methods for circulating tumor DNA (ctDNA) and Extracellular Vesicle (EV) based analysis, have enabled the possibility of non-invasive monitoring of the progression of the tumors over time. This review highlights key studies and important scientific works about imaging technologies, biomarkers, and prognostic factors of malignant brain tumors.

Humans↗

PubMed2026

Prevalence and cardiometabolic impact of mild autonomous cortisol secretion in primary aldosteronism: a systematic review and meta-analysis.

Many primary aldosteronism (PA) patients harbor concomitant mild autonomous cortisol secretion (MACS), termed "Connshing syndrome." The prevalence and cardiometabolic impact of this co-secretion have not been quantitatively synthesized. To determine the pooled prevalence of MACS in PA and evaluate its association with cardiovascular (CV) events, type 2 diabetes mellitus (T2DM), and obesity. PubMed, Embase, Cochrane, Web of Science, and Scopus through January 2026. Following PRISMA 2020 and MOOSE guidelines (PROSPERO: CRD420261334965), studies reporting MACS prevalence [post-1 mg dexamethasone suppression test (DST) cortisol ≥1.8 μg/dl] in PA were included. Prevalence was pooled using random-effects models. Odds ratios (ORs) were calculated for cardiometabolic outcomes. Certainty was evaluated using GRADE. Fourteen studies (2356 patients) were included. Pooled MACS prevalence was 26.2% [95% confidence interval (CI): 24.1-28.4; I2 = 24.2%; prediction interval: 21.6-31.4%], consistent across European (27.0%) and East Asian (25.2%) cohorts ( P = 0.62). MACS + PA patients had higher odds of CV events (OR 1.60; 95% CI: 1.07-2.38; P = 0.021) and T2DM (OR 1.37; 95% CI: 1.00-1.86; P = 0.048), but not obesity (OR 1.10; P = 0.411). Sensitivity analyses confirmed robustness. GRADE certainty was moderate for prevalence and low for CV events. Approximately one in four PA patients has MACS, associated with a 60% higher CV event risk. These findings support routine DST screening in PA and have implications for perioperative management and cardiometabolic risk stratification.

Humans↗

PubMed2026

The Efficacy of Erector Spinae Plane Block Versus Subcostal Transversus Abdominis Plane Block in Laparoscopic Nephrectomy: A Randomized Clinical Trial.

OBJECTIVES: This study compared the efficacy and safety of erector spinae plane block (ESPB) versus subcostal transversus abdominis plane (TAP) block in reducing postoperative pain among patients undergoing laparoscopic nephrectomy. METHODS: This randomized clinical trial enrolled 70 adult patients, ASA physical status I or II, who underwent total (radical) laparoscopic nephrectomy under general anesthesia. Patients were randomly assigned to 2 groups. Group ESPB received an ultrasound-guided ESPB at the T7 transverse process level, while group TAP received an ultrasound-guided subcostal TAP block. The primary outcome was the total amount of morphine consumed at 6 and 24 hours postoperatively. Secondary outcomes included the incidence of patients requiring opioid analgesia, time to rescue analgesia, visual analog scale of pain intensity, time to postoperative ambulation, intraoperative and postoperative hemodynamics, arterial partial pressure of oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 or P /F) ratio, and incidence of complications. RESULTS: Compared with the TAP group, the ESPB group exhibited significantly lower median morphine consumption at 24 hours ( P =0.032), prolonged time to first analgesic rescue ( P =0.049), and lower incidence of rescue morphine requirement (OR=0.23; 95% CI=0.06-0.94; P =0.031), with lower visual analog scale pain scores at 12, 18, and 24 hours postoperatively ( P <0.001). The mean arterial blood pressure and heart rates were comparable between groups. No significant adverse effects from either approach. DISCUSSION: In laparoscopic nephrectomy, ultrasound-guided ESPB may safely and effectively be used to improve pain management and reduce pain intensity, with stable hemodynamics and a comparable risk of postoperative complications to the ultrasound-guided subcostal TAP block.

Humans↗

PubMed2025

Preoperative Patient Education on Opioid Use and Pain After Surgery: A Randomized Trial.

OBJECTIVE: To evaluate the impact of preoperative analgesic education on postoperative opioid consumption, pain scores, and patient satisfaction with analgesia. BACKGROUND: Effective postoperative pain management is crucial for patient recovery and satisfaction, yet opioid use poses risks of tolerance and addiction. Preoperative patient education offers a potential avenue to mitigate opioid reliance and improve pain management outcomes. METHODS: This single-center randomized trial was conducted at the Cleveland Clinic Main Campus between October 2021 and October 2023. Adult patients scheduled for hip arthroplasty or laparoscopic-assisted abdominal surgery with an ASA physical status of 1 to 4 were eligible. Patients with a history of prolonged opioid use, planned regional block or epidural analgesia, or limited English fluency were excluded. Participants were randomized 1:1 to receive either an analgesic educational video or a generic video about surgery and hospitalization. The primary outcome was opioid consumption during the initial 72 postoperative hours. Secondary outcomes included time-weighted average pain scores and patient satisfaction with analgesia. RESULTS: Among 957 analyzed patients, preoperative analgesic education did not significantly reduce opioid consumption (adjusted ratio of geometric means, 1.01; 95% CI, 0.86-1.18; P =0.890) or improve pain scores (adjusted mean difference, -0.1; 95% CI, -0.3 to 0.2; P =0.617). Patient satisfaction scores also did not differ significantly between groups (adjusted mean difference, -0.1; 95% CI, -0.3 to 0.2; P = 0.611). CONCLUSIONS: Preoperative analgesic education did not result in clinically meaningful reductions in opioid consumption or improvements in pain management outcomes. Further research may explore more intensive educational interventions to optimize postoperative pain management strategies.

Humans↗

PubMed2026

A systematic review and meta-analysis of radiation-induced oral complications in head and neck cancer: Prevalence and clinical outcomes.

BACKGROUND: Radiation-induced oral complications, notably xerostomia and oral mucositis (OM), are common and debilitating in patients with head and neck cancer (HNC), adversely affecting swallowing, nutritional intake, and overall quality of life (QoL). OBJECTIVES: This review aimed to quantify the prevalence of radiation-induced xerostomia and OM and synthesize their impact on dysphagia and nutritional status among HNC patients undergoing radiotherapy (RT). METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. Comprehensive searches were performed in MEDLINE, Scopus, SciFinder, Embase, and PubMed for studies published between January 2019 and December 2025. Data from 51 studies were extracted and synthesized. RESULTS: The pooled prevalence was 85% (95% CI: 81.6-87.9%) for xerostomia and 88.3% (95% CI: 73.9-95.3%) for any-grade OM. Severe OM (Grade 3-4) had a prevalence of 39.5% (95% CI: 23.1-58.8%). These complications were strongly interrelated and significantly associated with dysphagia (69.8%; 95% CI: 53.1-83.7%), malnutrition (66.6%; 95% CI: 37.3-95.9%), and poor QoL (pooled mean QoL score: 64.13/100). Studies employing advanced radiation techniques (e.g., IMRT) demonstrated a lower prevalence of xerostomia (OR = 0.58, 95% CI: 0.42-0.80) compared to conventional RT. CONCLUSION: Radiation-induced oral complications (xerostomia & OM) remain prevalent and clinically significant burden in HNC patients, contributing to a cascade of functional impairments and diminished QoL. These findings highlight the need for preventive strategies, symptom management interventions, and the broader adoption of advanced RT techniques. Longitudinal research is warranted to further evaluate long-term outcomes and guide patient-centered care models.

Humans↗

PubMed2026

Transforming Curcuma longa leaf waste into cellulose scaffolds.

The constant dearth of transplantable tissues and organs in India required the development of substitute biomaterials for tissue engineering. Plant-based decellularized scaffolds have become attractive options because of their abundance, ethical acceptability, architectural diversity, and lower risks of zoonotic transmission. Curcuma longa leaves were investigated in this study as a possible source of cellulose-based scaffolding for use in biomedical applications. After cuticle removal, an immersion decellularization technique utilizing sodium dodecyl sulphate (SDS) and triton-X-100 was developed to successfully remove cellular and nuclear material while maintaining leaf parenchyma architecture. Histology, DAPI staining, scanning electron microscopy, and a notable decrease in leftover DNA content all demonstrated efficient decellularization. When contrasted with native leaves, the resultant decellularized C. longa leaf scaffolds showed significant increase in porosity, water vapor transmission rate and swelling percent, and significantly lower contact angle with an optimum surface roughness promoting cell adhesion. Mechanical test manifest higher tensile strength with decreased stiffness. Fourier transform infrared spectra of leaf scaffold reveals persistence of different components except cuticle but the intensity of different peaks was decreased. The leaf scaffolds showed superior hemocompatibility and excellent compatibility with Madin-Darby canine kidney cells (MDCK) which is demonstrated by cell attachment and proliferation. MTT assay of seeded scaffold showed significantly higher metabolically active cell. In vivo subcutaneous implantation of decellularized scaffolds showed host tissue incorporation, accumulation of collagen, and neovascularization. C. longa leaf scaffolds can be utilized as cost effective and sustainable biomaterials for soft tissue engineering and regenerative medicine.

Curcuma↗

PubMed2026

Prevalence of POMC allele associated with obesity in feline population in Vietnam.

Feline obesity is an increasingly important health problem influenced by both genetic predisposition and husbandry practices. This study investigated the prevalence and phenotypic relevance of the feline proopiomelanocortin (POMC) c.28G > C (p.Gly10Arg) variant in a Vietnamese cat population and evaluated environmental factors associated with obesity. A total of 63 clinically healthy cats were classified as normal weight (body condition score [BCS] 5-6/9; n = 40) or obese (BCS ≥7/9; n = 23). Genotyping was performed using a newly developed PCR-restriction fragment length polymorphism assay and validated by Sanger sequencing. Ventral subcutaneous adipose tissue (VSAT) thickness was measured ultrasonographically as an objective indicator of adiposity. Genotyping revealed a high prevalence of the risk-associated C allele, with 45/63 cats (71.4%) carrying the GC genotype and 18/63 (28.6%) carrying the CC genotype, whereas the GG genotype was not detected, giving a Callele frequency of 64.3%. Obese cats had significantly greater body weight and VSAT thickness than normal-weight cats. Neuter status and ad libitum feeding were significantly associated with obesity, whereas diet type, housing, exercise frequency, and begging behavior were not. Although genotype distribution did not differ significantly between normal and obese cohorts, obese CC cats showed significantly greater VSAT thickness than obese GC cats, indicating an allele-dosage effect on adiposity. These findings suggest that the POMC c.28G > C variant is a useful risk-informative marker and that combining genetic screening with objective fat assessment may support earlier identification and prevention of feline obesity in Vietnam under routine laboratory conditions and guide personalized management strategies in practice.

Animals↗

PubMed2026

Saliva-based RT-LAMP assays support heat shock protein 70 as a promising transcript marker for estrus identification in buffaloes.

Buffaloes do not exhibit overt estrus signs particularly during summer, leading to a significant economic loss to farmers. Previous studies have identified several candidate transcripts (HSP70, TIMP1, TLR4 and HSD17B1), abundant in buffalo saliva during estrus stage. However, there is no widely applicable technology for estrus detection targeting these transcripts. Therefore, the present study aimed to develop reverse transcription loop mediated isothermal amplification (RT-LAMP) assays for these candidate transcripts using buffalo saliva. Saliva samples were collected from 10 cyclic buffaloes and RT-LAMP assays were optimized for salivary RNA as well as direct saliva. Among the four candidate transcripts, HSP70 showed a statistically significant colour change (p-value = 0.0191) at the estrus stage compared to the diestrus stage. This abundance of HSP70 was also supported in large simulated population datasets (10,000 animals) generated using R. Further, the RT-LAMP assays were tested using direct saliva without RNA isolation, and the colour change in the samples during estrus suggested the feasibility of estrus identification using direct saliva, overcoming the tedious step of RNA isolation. The detection of HSP70 using either direct saliva or salivary RNA indicated its potential as a marker for estrus identification. Similarly, TLR4 appeared to be another potential biomarker for RT-LAMP reaction using direct saliva, but it needs further validation in both RNA and direct saliva samples. Overall, the proof-of-concept on RT-LAMP assays optimized for salivary transcripts in the present study would be useful for estrus identification in tropical production systems following further validation on a larger sample size.

Animals↗

PubMed2026

Accelerated Diagnostic Pathways for Suspected Acute Coronary Syndrome in Practice: A Randomized Trial of 0/1-Hour vs 0/3-Hour Troponin Testing.

BACKGROUND: For suspected acute coronary syndrome (ACS), guidelines recommend using high-sensitivity troponins (hs-cTn) in accelerated diagnostic pathways (ADPs) with 0/1-hour recommended over 0/3-hour ADP. However, implementation of these ADPs, with universal use of hs-cTns, has not been directly compared in randomized trials OBJECTIVES: This study sought to compare the efficiency and safety of the European Society of Cardiology (ESC) 0/1-hour and a 0/3-hour ADP when implemented in real-world clinical practice. METHODS: This pragmatic, randomized, noninferiority implementation trial compared the safety and efficiency of clinician decision making using these 2 pathways. To prevent incorporation bias, an independent hs-cTnI was used for formal adjudication using the fourth universal definition of myocardial infarction (MI). Efficiency was judged by the proportion of patients discharged within 4 hours. The safety endpoint was major adverse cardiac events (MACE) within 30 days (adjudicated index or representation type 1 MI, cardiovascular death, and urgent coronary revascularization) for those who were considered not to have ACS and discharged. The noninferiority margin, for absolute difference in sensitivity, between the ESC 0/1-hour and the 0/3-hour ADP was set at 3%, assessed with a 1-sided 97.5% CI. RESULTS: From December 2021 to July 2024, of 13,983 screened 3,543 individual patients with suspected ACS were recruited and consented from 2 major emergency departments in North-West England, with 100% follow-up achieved for all representations to any national hospital. The median age was 60 years (IQR: 49.5-70.5 years), 53% were men, 6.7%, and 7.6% had adjudicated index type 1 MI and MACE within 30 days, respectively. The turnaround time from sample to result for central laboratory hs-cTnT was 81 minutes (IQR: 69-101 minutes). The proportion of patients discharged within 4 hours was relatively low and did not differ substantially (21.8% vs 19.2%, P = 0.07). In addition, the 0/1-hour pathway was noninferior for safety, in patients discharged, compared with the 0/3-hour pathway, absolute difference in sensitivity was +4.2% (1-sided 97.5% CI: -2.5) in favor of the 0/1-hour pathway. The calculated sensitivities were 93.7% (95% CI: 88.4%-97.1%) vs 89.5% (95% CI: 82.7%-94.3%), respectively. CONCLUSIONS: Implementation of the ESC 0/1-hour pathway failed to discharge significantly more patients within 4 hours of presentation compared with the 0/3-hour ADP. In addition, The ESC 0/1-hour was noninferior to the 0/3-hour hs-cTn pathway for safety of discharge, although safety for both pathways was less than that imputed by observational studies. This trial demonstrates that perceived benefits to emergency department efficiency of a reduced sampling interval are mitigated by central laboratory turnaround times as well as system constraints. (Pragmatic Randomised Trial of the ESC 0/1 Versus 0/3 Hour Troponin Pathway [MACROS2]; NCT05322395).

Acute Coronary Syndrome↗

PubMed2026

Trade-offs in avian parental care: a review of theory and meta-analysis of brood size manipulations.

The selective forces shaping parental care have been studied for over 50 years. While theoretical and experimental work has yielded qualitative progress, the large body of empirical work testing predictions about parental investment based on life-history trade-offs has yet to be synthesized. We first provide an overview of the core life-history theory exploring how selection might shape parental care. We then conduct a systematic review and meta-analysis on studies that experimentally manipulated brood size in birds, a widely used experimental approach to manipulate parental investment. We extracted 313 estimates from 62 studies representing 31 species of birds from 19 different families and tested key predictions on trade-offs in parental care derived from theory. Our analysis provides strong support for some predictions about life-history trade-offs in parental care, but weak or equivocal support for others. Specifically, we found that overall, avian parents respond to brood size manipulations as predicted by life-history theory: they increased care in response to brood enlargement, and decreased care in response to brood reductions. Furthermore, for the same relative manipulation size, responses to brood reductions were greater than responses to brood enlargements. This finding is consistent with predictions derived from life-history theory based on some types of non-linear utility curves. However, many predictions derived from theory are not well supported by our comparative analysis. Species' life-history traits such as clutch size (a measure of current reproduction), adult survival, and broods per year (two measures of future reproduction), explained little, if any, among-species variation in response to brood size manipulations. Several factors may explain this. We highlight that brood size manipulations may affect more than just perception of the value of current reproduction, such as altering parents' perception of predation risk. Importantly, these unintended consequences could lead to asymmetric responses like those we observed. Other common experimental approaches - such as hormone manipulations, altering a partner's effort, and food supplementation - often affect multiple traits or fitness components simultaneously, or may involve cues that poorly match the evolved mechanisms guiding parental behaviour. Our review of both theory and experimental approaches suggests that there are multiple opportunities for more precise experiments. We offer several recommendations for effective designs. One is improved understanding of the biology underlying the functions relating to costs and benefits, with careful consideration of not only how the manipulation will affect only one of those, but also the mechanisms that might alter how parents perceive the manipulation. We also emphasize general principles, such as assessing alternative hypotheses and devising multiple independent tests. Armed with these recommendations, we believe there are new opportunities to increase the strength of inference achieved from studies aimed at understanding the trade-offs affecting the evolution of parental care.

Animals↗

PubMed2026

Performance of Automated Hematology Analyzer Criteria in Detecting Peripheral Blood Smear Abnormalities: A Systematic Literature Review.

OBJECTIVES: Criteria for visual examination of stained peripheral blood smear (PBS) differ among institutions in the United States and internationally. In an effort to standardize review criteria, the International Consensus Group for Hematology Review (ICGHR) proposed in 2005 a consensus list of rules for CBC findings that should trigger a review of automated cell counter results and potentially lead to further testing or blood smear review. The primary aim of this paper is to report on the published literature in the past 20 years regarding PBS review criteria and their ability to identify relevant peripheral blood abnormalities. METHODS: We performed a systematic review of the published literature from 2005 to 2025 to investigate and summarize PBS review criteria and performance in the context of automated hematology analyzers in clinical laboratories. RESULTS: Of 5351 citations, 68 studies met our search criteria. These studies included 22 countries and all major hematology analyzer manufacturers. Marked variability was observed in study populations, analyzer flagging criteria, details of PBS visual review, definitions of a "positive" smear, and approaches to statistical data analysis. Across studies, the blast flag sensitivity ranged from 18% to 100% while the blast flag specificity ranged from 17% to 100%. Wide ranges in sensitivity/specificity were also seen for atypical and/or abnormal lymphocyte flags across studies. For studies analyzing the same patient population, less striking variation was seen across instruments. CONCLUSIONS: This systematic review provides a 20-year overview of the literature, highlighting significant variability in PBS review criteria, dependence on study design and hematology analyzer, and the importance of developing harmonized evidence-based guidelines.

Humans↗

PubMed2026

Diverse structures of mcr-10-bearing plasmids and high colistin resistance in Enterobacter cloacae complex clinical isolates from South Korea.

BACKGROUND: The emergence of mcr-mediated colistin resistance in Enterobacter cloacae complex (ECC) poses a significant threat to antimicrobial therapy. Among mcr variants, mcr-10 has been identified in various environments, but its genetic diversity, structural context, and functional role in colistin resistance remain unclear. METHODS: We investigated 183 ECC isolates and identified 60 colistin-resistant strains through minimum inhibitory concentration (MIC) testing. The presence of mcr-10 was screened using reference genomes from NCBI, and whole plasmid sequencing was conducted on mcr-10-positive isolates. The genetic environment of mcr-10 was analyzed via synteny and structural annotation. RESULTS: Whole-plasmid sequencing of eight mcr-10-positive ECC isolates identified three replicon types among the mcr-10-harboring plasmids: IncFIB (n=3), IncFII (n=3), and IncFII/IncFIB (n=2). Although all plasmids shared the xerC-mcr-10 cassette, they lacked a conserved backbone and showed diverse genetic contexts with variable insertion sequences near mcr-10, indicating marked structural heterogeneity. No additional antimicrobial resistance genes were detected on these plasmids. When introduced into E. coli DH5α, the plasmids increased colistin MICs only modestly, whereas representative plasmids transferred into colistin-susceptible E. roggenkampii and E. kobei conferred high-level resistance comparable to that of the parental mcr-10-positive isolates. Consistently, qRT-PCR showed higher mcr-10 expression in ECC transformants than in E. coli under colistin exposure, supporting a hostdependent effect on mcr-10-mediated colistin resistance. CONCLUSION: These findings highlight the diversity of mcr-10-carrying plasmids and suggest that mcr-10-mediated colistin resistance is shaped by the host genetic background. Further studies are needed to clarify the mechanisms underlying mcr-10 expression.

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