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Gut microbial diversity at baseline conditions the clinical, microbiome, and metabolic response to paraprobiotic Lactiplantibacillus plantarum LRCC5282 in overweight adults.

The gut microbiota is increasingly recognized as a target for obesity management; however, whether baseline gut microbial diversity conditions responsiveness to microbiota-targeted interventions remains unclear. We aimed to investigate whether baseline gut microbial diversity is associated with responsiveness to a paraprobiotic derived from Lactiplantibacillus plantarum LRCC5282 (LP5282-P) in overweight adults. In a 12-week, randomized, double-blind, placebo-controlled, multicenter trial of 120 overweight adults, LP5282-P produced no significant between-group differences in any clinical outcome across the overall per-protocol population. However, in the low-diversity subgroup, LP5282-P was associated with significant reductions in body weight, body mass index, and circulating leptin levels. These clinical changes were accompanied by compositional shifts in the gut microbiota, including higher relative abundances of Christensenellaceae, Faecalibacterium, and Alistipes. Fecal metabolite profiles showed elevated acetate and butyrate concentrations and altered bile acid composition. Within the low-diversity subgroup, changes in the relative abundances of Akkermansia and Eubacterium were inversely correlated with changes in body weight, body fat mass, and leptin levels. In contrast, the high-diversity subgroup exhibited no consistent response across the outcome domains examined. Overall, baseline gut microbial diversity was associated with differential responsiveness to LP5282-P, supporting its potential use as a stratification variable in future microbiota-targeted intervention trials. Further studies integrating direct measures of microbial activity and host response are warranted to elucidate the biological pathways underlying this diversity-dependent responsiveness. Trial registration: Clinical Research Information Service (CRIS), KCT0008119.

Humans

Melatonin Levels in 89 Individuals With Smith Magenis Syndrome.

In patients with Smith-Magenis syndrome (SMS), an inverted circadian rhythm of melatonin (MT) contributes to the sleep disturbance. Standard treatment of sleep disturbance with MT often leads to extremely high daytime MT levels, resulting in even more sleep disorders. We therefore retrospectively evaluated the MT data of 89 SMS patients. Mean MT levels in participants on exogenous MT were significantly higher than in participants that did not use MT (p&#x2009;=&#x2009;<&#x2009;0.0001). In 9 participants with very high MT levels, these dropped significantly after discontinuation of exogenous MT (p&#x2009;=&#x2009;0.0037). In 12 participants, MT levels were significantly higher after MT therapy start compared to MT levels before MT start (p&#x2009;=&#x2009;0.028). MT is catabolized principally by the CYP1A2 enzyme, with a half-life of about 40&#x2009;min. CYP1A2 genotyping was performed in five participants with high MT levels during MT use. Although clinically suspected to be a poor CYP1A2 metabolizer, all five turned out to have haplotype CYP1A2*1F, which is associated with increased enzyme activity. This shows that genotyping of CYP1A2 is not suitable to estimate the level of CYP1A2 enzyme activity. When prescribing MT, it is strongly recommended to measure a MT level prior to treatment in order to determine the dose to be given. Checks of the MT level during treatment are necessary due to the frequent occurrence of poor CYP1A2 metabolism. Since CYP1A2 genotyping does not provide adequate information about the level of CYP1A2 enzyme activity, we propose a simple way to determine CYP1A2 phenotype.

Humans

Written vs. verbal sleep hygiene strategies administration in track and field athletes: a randomized controlled trial study.

BACKGROUND: Sleep hygiene strategies (SHS) are practical, evidence-informed recommendations to enhance both the quantity and quality of sleep in athletes. However, little is known about how these strategies could be communicated and implemented in practice. The primary objective of this study is to investigate how different methods of delivering SHS (written vs. verbal) affect sleep hygiene and sleep parameters in athletes. METHODS: The study was a three-arms randomized controlled trial (ClinicalTrials.gov Identifier: NCT07083544) involving track and field athletes competing at the regional or national level (N.=66). Athletes were randomized to either a control group (CON=22), a written SHS group (W-SHS=22), or a verbal SHS group (V-SHS=22). Sleep characteristics were assessed by actigraphy and sleep diary during a ten-day baseline period (T0) and a ten-day intervention period (T1). Six objective sleep parameters and the Sleep Regularity Index were assessed. Participants also completed a training diary and the Sleep Hygiene Index (SHI). RESULTS: No statistical differences were found between and within groups in training and sleep parameters, but SHI scores improved significantly in the intervention groups between T0 and T1, with differences compared to the control group. A non-significant improvement in total sleep time was observed in the intervention groups, primarily due to earlier bedtimes. CONCLUSIONS: While significant differences in objective sleep measures were not observed, the trends suggest that both written and verbal SHS interventions can modestly improve sleep-related behaviors, particularly by encouraging earlier bedtimes and slightly extending total sleep duration.

Humans

Pathways of onward HIV disclosure in relationships among young people living with vertically acquired HIV receiving antiretroviral therapy: A qualitative analysis from the BREATHER Plus trial, South Africa.

For young people living with HIV (YPLHIV) navigating their status since birth, managing onward disclosure of a potentially stigmatising condition in relationships is challenging, and may or may not lead to social support, with implications for wellbeing. In a clinical trial setting in KwaZulu-Natal, South Africa, we investigate how young people living with vertically acquired HIV navigate onward disclosure. Data were from the qualitative component of the BREATHER Plus randomised controlled trial evaluating the efficacy, safety and acceptability of short-cycle dolutegravir/tenofovir-based triple antiretroviral therapy (ART) in young people aged 12-19 years. We analyse data on 35 participants receiving ART engaged in clinical trials at the research site: 29 in longitudinal in-depth interviews (IDIs) and 12 across three focus group discussions (FGDs), including 6 in IDIs and FGDs. The Disclosure Processes Model was applied in the thematic analysis. Pre-disclosure was characterised by social assessments of potential confidants. During disclosure, reciprocal vulnerability and partial information-sharing were employed. Post-disclosure processes entailed linear and non-linear feedback trajectories, impacting future disclosures. The findings show that the study cohort of young people receiving ART navigated many bidirectional disclosure pathways to maintain social connections in relationships, and counselling guidelines need to be responsive to this.

Humans

Effectiveness of different anaesthetic techniques, agents and adjunctive interventions in handling pain during dental treatment of MIH-affected teeth: a systematic review.

BACKGROUND: Molar incisor hypomineralisation (MIH) is frequently associated with hypersensitivity, dental anxiety and reduced efficacy of local anaesthesia, complicating pain control during dental treatment in children. AIM: To evaluate, based exclusively on randomised controlled trials (RCTs), the effectiveness of different local anaesthetic techniques, agents and adjunctive interventions in reducing pain during dental treatment of MIH-affected teeth in children. METHODS: A systematic review was conducted following PRISMA 2020 guidelines and registered in PROSPERO (CRD420251150485). MEDLINE, Cochrane Central, ScienceDirect, SCOPUS, EBSCO, and LILACS were searched up to September 2025. Eligible studies were RCTs involving children and adolescents (6 - 18&#xa0;years-of-age) with MIH, assessing pain outcomes during dental procedures. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE approach. RESULTS: Eight RCTs were included. Low-certainty evidence suggested that intraosseous anaesthesia and 4% articaine may reduce intra-operative pain compared with conventional techniques or 2% lidocaine. Adjunctive cryotherapy and pre-emptive ibuprofen showed potential benefits, but evidence was of very low certainty and limited to single trials. Findings for photobiomodulation were inconsistent across studies. Most trials were judged to be at high risk of bias, primarily due to lack of blinding and reliance on subjective pain outcomes. CONCLUSION: Current evidence supporting specific pain management strategies for MIH-affected teeth is limited and of low certainty. Whilst 4% articaine and intraosseous anaesthesia appear promising, well-designed, adequately powered RCTs with standardised pain outcomes are required to inform robust clinical recommendations.

Local anaesthesia

Operationalizing Local Ecological Knowledge for Aquatic Biodiversity Conservation: A Systematic Review and Management Framework.

Effective conservation and management of aquatic biodiversity is severely constrained by the absence of long-term ecological data in small-scale, tropical, and data-poor fisheries, where roughly one-quarter to one-third of freshwater fish species and 37.5% of elasmobranchs are threatened with extinction once Data Deficient species are accounted for. Conventional monitoring and stock-assessment tools are often financially and technically inaccessible in these systems, leaving managers without the evidence needed to prioritize conservation action or implement precautionary governance. Local Ecological Knowledge (LEK) is a largely underutilized resource for natural resource management that can provide temporal depth, spatial resolution, and species-specific ecological insights unavailable from scientific records. We conducted a systematic review and bibliometric synthesis of 60 peer-reviewed studies (1997-2025) applying LEK to assess fish conservation status, examining how, where, and through what methods this knowledge has been used. Our analysis identifies four complementary pathways through which LEK informs conservation management: reconstructing multi-decadal population changes, documenting spatial contraction and habitat loss, detecting extreme rarity and local extirpation, and characterizing intrinsic sensitivity to exploitation based on life-history traits. Despite growing methodological rigor, freshwater systems and African fisheries remain critically underrepresented, and formal integration of LEK into fisheries governance and biodiversity assessment remains the exception rather than the rule. We propose a practical three-stage framework to operationalize LEK within existing management and conservation systems. Recognizing fishing communities as legitimate co-producers of ecological knowledge is both scientifically necessary and an equity imperative for achieving global biodiversity commitments under the Kunming-Montreal Global Biodiversity Framework.

Biodiversity

Psychometric Evaluation of the Breast Inflammatory Symptom Severity Index Versions 2 and 3 Among Lactating Women.

OBJECTIVE: To evaluate the psychometric properties of Versions 2 and 3 of the Breast Inflammatory Symptom Severity Index (BISSI). DESIGN: Secondary data analysis of clinical trial data. SETTING: Private physiotherapy practices, a public tertiary hospital, and a community in Melbourne, Australia. PARTICIPANTS: Women more than 7 days after birth with inflammatory conditions of the lactating breast (N = 43). METHODS: We performed confirmatory factor analysis of the BISSI Version 2 to examine item loading, which informed development of the BISSI Version 3 (V3). We assessed convergent validity by comparing total BISSI V3 scores with human milk sodium to potassium ratio (Na+:K+) at Trial Days 1, 3, and 10 using Bland-Altman plots. We compared item-level scores for size of affected area with objective receiver operating characteristic curve analysis to assess discriminant validity for symptom severity and Cronbach's alpha for internal reliability. RESULTS: After confirmatory factor analysis, we removed two items, resulting in a six-item BISSI V3. All retained items demonstrated comparable loading on the overall scale. Limits of agreement for total BISSI V3 scores and item-level scores for size of affected area were acceptable at all time points, with more than 90% of observations falling within 2 standard deviations of the mean difference, supporting convergent validity. Discriminant validity of the BISSI V3 was supported. We found high internal reliability at both time points CONCLUSION: Our findings provide evidence for the validity and reliability of the BISSI V3 and support its continued development and for clinical use of the BISSI V3 and human milk Na+:K+ analysis to enhance management of inflammatory conditions of the lactating breast.

breastfeeding

Quantifying the aromatic amino acid metabolome: UPLC-MS/MS analysis of aromatic amino acids and their host and co-metabolites in plasma.

Aromatic amino acids (AAAs), tryptophan, phenylalanine, and tyrosine along with their pathway metabolites have been implicated in the pathogenesis of diseases ranging from cardiovascular, neurological, inflammatory, and cancer diseases, among others. As such, the measurement of the primary AAAs, their host pathway metabolites, and microbiome derived co-metabolites in blood can provide a sensitive reflection of systemic health. The aim of the study was to develop a method for the quantification of 17 metabolites, the three AAAs and various of their metabolites in plasma using a high-throughput ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. The method demonstrated a dynamic range (1 to 16,700&#xa0;ng/mL), with detection limits (LOD) as low as 0.05&#xa0;ng/mL. Quantification limits ranged from 3 to 5019&#xa0;ng/mL (LLOQ) and up to 16,700&#xa0;ng/mL (ULOQ). Recovery at LQC, MQC, and HQC was satisfactory and consistent across most metabolites, with significant matrix effects observed only for 4-ethylphenol sulfate. Furthermore, intra and inter-day accuracy and precision met all acceptance criteria at all quality control concentrations for most of the metabolites. Measurement of NIST SRM 1950 showcased the method's accuracy for most of the metabolites. Finally, the method was applied on the analysis of plasma samples from 55 individuals (13 males and 42 females) providing information on AAAs and their pathway metabolites relevant concentrations in human plasma.

Amino Acids, Aromatic

Health bill beneath the plastic feast: A phthalate contamination alert from takeout food containers.

The rapid growth of takeout food consumption in China has raised concerns regarding exposure to phthalic acid esters (PAEs) from food packaging. This study investigated the presence, source, contribution, and health risk of PAEs in commonly used takeout containers. Widespread contamination was observed, with total PAE concentrations ranging from below the limit of detection to 222,000 ng/g. Diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), and bis(2-ethylhexyl) phthalate (DEHP) were identified as the predominant compounds, accounting for 7.50 %, 14.7 %, and 18.7 % of the total concentration, respectively. These PAEs may originated from additives during manufacturing and potential contamination of raw materials. Human exposure assessment showed that daily exposure doses of DIBP, DBP, and DEHP via container ranged from 0.00 to 2340 ng/(kg&#xb7;day) among frequent takeout consumers, contributing substantially to overall PAE body burdens. To further assess exposure and associated risks, a nationwide online questionnaire survey was conducted across China. Based on this national-scale behavioral dataset, the health risks among Chinese residents were evaluated. Although the modeled non-carcinogenic risks of DIBP, DBP, and DEHP remained within acceptable limits, the simulation suggested that approximately 70 % of participants may experience potential exceedance of the carcinogenic risk threshold for DEHP. The frequency of takeout food consumption was identified as the most important factor affecting PAE exposure. These findings underscore the importance of limiting takeout frequency and reducing reliance on plastic containers to mitigate health risks. This study provides scientific evidence to support the development of safer packaging materials and informs public health strategies.

Phthalic Acids

Influence of ovarian maturity, age, and mating status on&#xa0;the antennal responses of wild and laboratory reared Xyleborus affinis (Coleoptera: Curculionidae: Scolytinae) to ethanol.

Xyleborus affinis Eichthoff is a neotropical ambrosia beetle that, in certain regions such as the United States and Mexico, has been associated with exotic phytopathogenic fungi causing extensive tree mortality. Although studies relating its olfactory response to volatile compounds and trapping systems have been published, factors such as the insect's physiological condition, which can affect its recognition or response to odors, have not been studied. Here, we evaluated the electroantennographic (EAG) response of wild and&#xa0;laboratory reared X. affinis females to 70% ethanol, a compound known to attract these insects. The experimental design was developed to consider and compare the following conditions: (i) females collected inside and outside host-galleries, (ii) sexual maturity (with mature and immature ovaries), (iii) age (0, 1, 3, and 5&#x2009;d after emergence), and (iv) mating status (virgins and mated). Our results indicate that most of the wild females located outside the galleries were sexually mature but exhibited significantly lower EAG response than those inside the galleries. Regarding mating status, mated females exhibited significantly stronger antennal responses compared to virgins, whereas age did not affect antennal sensitivity. Finally, we provide images of the hitherto undescribed reproductive system of X. affinis females, a key element that enabled this investigation. The information generated offers a useful foundation for future studies aimed at understanding the physiological mechanisms and other critical factors related to sensory perception and reproductive condition. For example, factors that may influence the behavior and attraction of X. affinis females to host semiochemicals.

Animals

Left ventricular hypertrophy in hypertension: a systematic review and meta-analysis of echocardiographic studies published from 2011 to 2025.

AIM: An updated meta-analysis targeting the prevalence of left ventricular hypertrophy (LVH), a cardinal marker of hypertensive heart disease (HHD), over the last 15&#x200a;years is lacking. Thus, we analyzed the literature in order to provide a comprehensive information on LVH prevalence, as assessed by echocardiography, in the hypertensive setting. METHODS: The PubMed, OVID-MEDLINE, and Cochrane Library databases were analyzed to search English-language articles published from 1 January 2011 up to 31 December 2025. Studies were identified by using MeSH terms and crossing the following search items: 'left ventricular hypertrophy', 'left ventricular mass', 'hypertensive heart disease', 'echocardiography', 'hypertension', and 'subclinical cardiac damage'. RESULTS: A total of 51 studies including 74&#x200a;632 hypertensive patients were considered. Overall, the prevalence of LVH in the pooled cohort, defined according to criteria recommended by echocardiographic guidelines, was 36.6% (95% CI: 33.4-40%). Data provided by 18 studies ( n &#x200a;=&#x200a;40&#x200a;108 patients) showed that the probability of having LVH was lower in men than in women (OR&#x200a;=&#x200a;0.62, CI: 0.48-0.80, P &#x200a;<&#x200a;0.0001). Among patients with LVH (17 studies), the risk of concentric LVH was almost twice as high as eccentric (OR&#x200a;=&#x200a;1.94, CI: 1.52-2.49, P &#x200a;<&#x200a;0.0001). CONCLUSION: Our meta-analysis suggests that the high contemporary prevalence of LVH reflects the failure of therapeutic strategies worldwide in the prevention and treatment of HHD. From a clinical perspective, these data imply the need for a more aggressive treatment of hypertension and related cardiovascular risk factors leading to LVH, especially in women.

Humans

Systems Factors Contributing to Racial/Ethnic Disparities in Maternal Health: A Systematic Review.

INTRODUCTION: Despite ongoing efforts to reduce adverse maternal outcomes, including maternal mortality and severe maternal morbidity, racial/ethnic disparities in outcomes persist in high-income countries, including the United States (US) and Canada. Limited research has examined hospital-level factors that may drive disparities and contribute to adverse outcomes. This systematic review summarizes factors within the health system contributing to adverse outcomes and racial/ethnic disparities in the US and Canada to inform future policies and practices. METHOD: We searched SCOPUS, PubMed, EBSCOhost, and ProQuest Healthcare Administration for studies that reported hospital-level factors contributing to adverse maternal outcomes and racial/ethnic disparities. The review followed a two-stage screening process. The risk of bias of the included studies was evaluated using the Mixed Methods Appraisal Tool. The System Engineering Initiative for Patient Safety (SEIPS) 2.0 framework guided the identification and categorization of factors. RESULTS: Of 2441 studies retrieved, 30 met the inclusion criteria. Twenty-eight studies were conducted in the US, and 2 were conducted in Canada. The review included 16 qualitative, 11 quantitative, and 3 mixed-methods studies. We identified 60 factors associated with different system components, including person(s) (12%), tasks (28%), tools and technology (7%), internal environment (10%), organization (28%), and external environment (15%). Shortage of resources, including staffing, poor care coordination, and discriminatory organizational practices, were key factors described in the studies. CONCLUSION: Addressing health system factors in addition to broader societal factors is important to reduce adverse outcomes and promote equity for all women and birthing persons.

Humans

The application of artificial intelligence in healthcare practice: A mapping review of systematic reviews.

Artificial intelligence (AI) is rapidly transforming healthcare practice, with growing evidence supporting its use in diagnosis, prognosis, treatment planning, and operational decision-making. The proliferation of systematic reviews in recent years underscores the need for an updated synthesis of the literature to inform research, policy, and practice. We searched PubMed, Web of Science, Scopus, IEEE Xplore, and CINAHL for systematic reviews and meta-analyses published between 2019 and February 2026. Eligible reviews focused on AI applications in healthcare practice, were peer-reviewed, and written in English. A total of 368 reviews met the inclusion criteria. Publication volume increased steadily, peaking in 2025. AI research was concentrated in high-density domains, such as radiology, oncology, and critical care. Across reviews, diagnostic imaging, electronic health record (EHR) data, and biomarkers/laboratory results accounted for 68% of training data sources, though newer data types, such as wearable device and sensor data, emerged from 2022 onward. Diagnosis, prognosis, and treatment comprised over 80% of AI applications, with novel uses emerging in recent years, such as AI-assisted clinical documentation (e.g., ambient documentation tools) and patient education. Ethical concerns were reported in 78.5% of reviews, with privacy, model accuracy, data and algorithmic bias, and explainability as recurrent themes. The proportion of reviews reporting ethical concerns increased from 2021 to 2025. AI applications in healthcare are expanding in scope, diversifying in data sources, and evolving toward novel clinical and operational uses. The human-centered AI or augmented intelligence paradigm, integrating computational precision with clinical expertise, holds significant promise but will require parallel advances in governance, regulatory frameworks, and ethical oversight to ensure safe adoption.

Artificial Intelligence

Determinants of private health insurance uptake and its association with healthcare utilization in Gulf Cooperation Council countries: a systematic review.

All Gulf Cooperation Council (GCC) countries have a multi-payer healthcare system that comprises governmental health coverage (GHC), funded by the government, and private health insurance (PHI), mainly sponsored by employers and purchased by individuals. Both are expected to influence healthcare utilization and contribute to system efficiency and patient well-being. This systematic review explored the determinants of PHI uptake and its association with healthcare service utilization in the presence of GHC in GCC countries. We systematically searched CINAHL, PubMed, Scopus, Web of Science, and Cochrane Library for peer-reviewed studies published between January 2012 and October 2022. Study quality was assessed using the Critical Appraisal Skills Programme (CASP) checklists for both quantitative and qualitative studies, following PRISMA guidelines. Twenty-six studies met the inclusion criteria. Determinants of PHI uptake were mapped to Andersen's Behavioral Model of Health Services Use (BMHSU) and categorized into (1) predisposing factors (sex, age, marital status, and education), (2) enabling factors (employment/income and health system-related factors such as access and perceived service quality), and (3) need factors (health status, including chronic noncommunicable diseases). PHI uptake was positively associated with being male, married, highly educated, employed with a high income, and having chronic diseases. PHI was positively associated with healthcare utilization, particularly routine check-ups, preventive services, and the use of prescribed medicines. In GCC countries, PHI uptake is influenced by sociodemographic and socioeconomic characteristics, health status, and perceived service quality. PHI is also associated with higher healthcare utilization, underlining the need for evidence-informed policies that enhance equity and expand coverage.

Humans

Mitomycin C in the Endoscopic Treatment of Airway Stenosis: A Systematic Review and a Meta-Analysis.

OBJECTIVE: To assess the efficacy of adjuvant MMC in the endoscopic treatment of airway stenoses. DATA SOURCES: PubMed/MEDLINE, Cochrane Library, Scopus, Embase, and Google Scholar databases. REVIEW METHODS: A literature search was conducted following PRISMA guidelines. The PICOS tool was used to determine the eligibility criteria for this study. A single arm meta-analysis was performed for stenosis resolution, the rate of patients requiring multiple endoscopic procedures, and the rate of patients requiring other surgical treatments. RESULTS: A total number of 358 patients (median age: 48.0&#x2009;years; 95% CI 44.8-50.8) were included. The median follow-up was 25.2&#x2009;months (n&#x2009;=&#x2009;244/358; 95% CI 15.4-38.3). Overall, the cumulative stenosis resolution rate was 76.37% (n&#x2009;=&#x2009;187/254; 95% CI 59.72-89.64), the rate of patients requiring multiple endoscopic procedures was 52.33% (n&#x2009;=&#x2009;131/260; 95% CI 32.03-72.25), and the rate of patients requiring other surgical treatments was 4.08% (n&#x2009;=&#x2009;26/310; 95% CI 0.37-11.48). The median intervention-free interval was 366&#x2009;days (n&#x2009;=&#x2009;155/358; 95% CI 270-696). CONCLUSIONS: Current evidence does not allow definitive conclusions regarding the efficacy of adjuvant MMC in reducing recurrence or prolonging intervention-free intervals in airway stenosis. Further well-designed prospective studies are needed to clarify the role of MMC and to inform evidence-based guidelines for patient selection and treatment use. LEVEL OF EVIDENCE: NA.

Humans

Macroprolactinemia as a diagnostic pitfall in hyperprolactinemia: a systematic review and quantitative synthesis.

CONTEXT: Macroprolactinemia is a well-recognized cause of hyperprolactinemia and an important diagnostic pitfall in endocrine practice. However, interpretation of published quantitative prolactin data remains sparse as studies vary in confirmation method, assay platform, polyethylene glycol (PEG) recovery cutoff, and reporting of prolactin measurement. EVIDENCE ACQUISITION: PubMed, Embase, Scopus, Web of Science, the Cochrane Library, and Google Scholar were systematically searched. Eligible studies reported macroprolactinemia-specific quantitative prolactin data in patients with confirmed macroprolactinemia defined by PEG precipitation, gel filtration chromatography (GFC), or both. Two reviewers independently performed study selection, data extraction, and quality assessment. Findings were summarized using study-level descriptive synthesis. The review was prospectively registered in PROSPERO and conducted in accordance with PRISMA 2020 guidelines. EVIDENCE SYNTHESIS: Forty-five studies encompassing 2853 macroprolactinemia cases from 21 413 screened patients with hyperprolactinemia across 22 countries were included. Among 33 studies eligible for primary quantitative analysis, the median study-level central total prolactin attributed to macroprolactinemia was 61.4 ng/mL ([IQR] 42.0-80.0; range 28.1-137.6), and the median study-level post-PEG monomeric prolactin was 11.7 ng/mL (IQR 8.3-13.2; range 4.0-17.0)). The median study-level maximum total prolactin was 264.5 ng/mL (IQR 97.0-425.5; range 81.8-663.0); extreme elevations were attributable to coexisting prolactinomas. CONCLUSION: In confirmed macroprolactinemia, total prolactin elevation is typically moderate, and post-PEG monomeric prolactin is usually within or near the normal range. The post-PEG monomeric prolactin value, rather than percent recovery alone, is the most informative parameter for distinguishing isolated macroprolactinemia from coexisting true hyperprolactinemia. These quantitative benchmarks may help clinicians to avoid unnecessary investigation or treatment.

Humans

Utero-placental calcium and magnesium ion channels: A systematic review of obstetric implications of their alterations.

Despite the established roles of calcium (Ca2+) and magnesium (Mg2+) in placental function and uterine contractility, limited information exists on how dysregulation of major ion channels contributes to poor pregnancy outcomes. We synthesized data on the consequences of Ca2+ and Mg2+ channelopathies in uterine and placental functions. Using PubMed, Wiley Online, AJOL, and Web of Science databases for article search, a systematic review of forty-nine papers published between 2000 and March 2026 was carried out and reported in accordance with the PRISMA 2020 guideline. Based on the PICO framework, eligible studies involving human, animal, and in vitro designs were chosen and subjected to narrative analysis. L-type and T-type voltage-gated Ca2+ channels, together with transient receptor potential channels, emerged as principal mediators of placental Ca2+ transport and myometrial contractility. Mechanosensitive Piezo1 channels mediate stretch-activated Ca2+ influx, while store-operated Ca2+ entry pathways involving STIM1-Orai1 sustain intracellular Ca2+ homeostasis. Potassium-Ca2+ coupling channels modulated membrane hyperpolarization and anti-labor effects, and intracellular regulators such as PMCA and RYR1 fine-tuned Ca2+ homeostasis. The Mg2+ transporters are essential for preserving Mg2+ homeostasis and regulating Ca2+-dependent excitability. Dysregulation of these ion channel systems was consistently linked to abnormal uterine contractility, preterm birth, preeclampsia, fetal growth restriction, and adverse pregnancy outcomes. Both Ca2+ and Mg2+ ion channelopathies represent both a potential therapeutic target and a mechanistic factor underlying key obstetric complications.

Female

Evolution of Candidaemia and azole resistance in Italy: A multicentre retrospective study.

PURPOSE: Candidaemia is the most common healthcare-associated invasive fungal infection. The evolution of the epidemiology of candidaemia in Italy has not been assessed, except at the local level. The primary objective of this study is monitoring changes in the epidemiology of candidaemia and in the susceptibility profiles of Candida isolates between 2015 and 2023. METHODS: This retrospective multicentre study (2015-2023), involved 11 tertiary-care hospital microbiology laboratories across the Italian country. The confirmed candidaemia episodes were included and demographic data, hospital ward, species identification, and antifungal susceptibility profiles (Sensititre Yeast One) were collected. RESULTS: 6,927 candidaemia cases were identified; incidence increased from 1.1/1000 hospitalisations in 2017 to 2.3/1000 in 2020-2021, peaking during the COVID-19 pandemic, and declined in 2023 while remaining above prepandemic levels. Patients older than 65 years accounted for most infections. Medical wards represented the main setting of occurrence, followed by intensive care units, especially during pandemic years. C. albicans remained the most common species (45.4%), followed by C. parapsilosis (24.7%), C. glabrata (11.8%), and C. tropicalis (11.4%). Echinocandin resistance remained low (<&#x2009;2% for C. albicans and C. glabrata), whereas azole resistance increased markedly, particularly in C. parapsilosis, reaching fluconazole resistance rates of 25.6% in 2022. CONCLUSIONS: Candidaemia increased during the 9-year study period in Italy, particularly in the COVID-19 pandemic, in medical wards and ICU. Emerged a growing azole resistance, underscoring the need for enhanced surveillance and informed empirical treatment strategies.

Candida species etiology