Medicine and Pharmacology

Abstract: Background: Vaginal microbiome dysbiosis is associated with chronic inflammation, pathogen infections, adverse pregnancy outcomes, and increased susceptibility to sexually transmitted infections. However, the current detection methods mainly rely on microscopic examination, enzymology, and culture techniques, lacking precise detection of the species of the pathogen. Methods: A multiplex Droplet digital PCR (ddPCR) detection method of the most common targets related to vaginal diseases-related pathogens were established by retrospective study at Shanghai East Hospital. Swabs of 112 vaginosis patients and 102 non-non-vaginosis patients were detected and quantified the pathogen load of targets in vaginal swabs, targeting Lactobacillus, Gardnerella vaginalis, Candida species, Streptococcus agalactiae, and vaginal Trichomonas to comprehensively describe the vaginal microecological status and compared the results with existing cultivation methods and the double fluorescence staining method. Results: ddPCR test possesses a low limit of detection (LOD) of 5 CFU/mL, achieving PPA values of 87.50%-100.00% across all five targets and significantly increases the detection rate of Candida species (NPA 73.46%, Kappa=0.524 P<0.001), Gardnerella vaginalis (NPA 100%, Kappa=0.241 P<0.001) and Streptococcus agalactia (NPA 89.18%, Kappa=0.606 P<0.001). Excellent inter-assay agreement was observed for Trichomonas (Kappa=0.865, P=1.000) and Lactobacillus (Kappa=0.801, P=0.002). In addition, this assay enables further classification and confirmation of the microbiota in specimens showing “increased small bacilli” or “flora inhibition” on conventional assays. Conclusions: Our study is the first to develop a droplet digital PCR method for multi-target detection and absolute quantification of vaginal microbiome. This method balances both detection efficiency and test convenience. It enables accurate target detection while permitting comprehensive evaluation of the overall vaginal microecology, demonstrating favorable analytical performance and broad clinical application prospects.

Abstract: The relationship between maternal knowledge and Maternal and Child Health (MCH) Handbook utilization may vary across care settings. This secondary analysis examined recorded scores among 120 third-trimester pregnant women recruited consecutively at Samata (urban, n = 63) and Bajeng (rural, n = 57) Primary Health Centres in Gowa, Indonesia, during May–July 2025. Participants attended antenatal care and brought their handbook. Pooled and within-facility correlations and adjusted linear regression assessed the knowledge–utilization association. Mean knowledge scores were 82.14 and 45.70, and utilization scores were 71.13 and 53.40, in Samata and Bajeng, respectively. Knowledge correlated positively with utilization in both facilities (r = 0.640 and 0.506). After adjustment for setting, age, education, employment, and gravidity, each 10-point difference in knowledge corresponded to a 4.24-point difference in utilization (95% confidence interval 3.24–5.24). Exploratory analyses indicated curvature, and differences between setting-specific slopes were sensitive to model specification. Higher knowledge was associated with higher reported utilization among handbook-bringing antenatal attendees. The cross-sectional design and one facility per setting preclude causal conclusions and separation of facility characteristics from rural–urban context.

Abstract: Fetal growth restriction (FGR) is a major obstetric complication associated with increased perinatal morbidity, mortality, and adverse long-term metabolic outcomes in adulthood. Placental dysfunction stands as the principal driver in a substantial proportion of cases, with accumulating evidence indicating that the disruption of placental redox homeostasis plays a central role in its pathophysiology. This review provides a comprehensive synthesis of redox dysregulation in FGR, extending beyond classical oxidative injury to incorporate emerging non-linear paradigms. Excessive production of reactive oxygen species (ROS), coupled with inadequate antioxidant defenses, promotes lipid, protein, and DNA damage, thereby impairing trophoblast function, vascular remodeling, cell survival, and nutrient transport. Crucially, this review integrates recent breakthroughs in the fields of iron-dependent ferroptosis, endoplasmic reticulum stress, and complex redox-epigenetic cross-talk mediated by non-coding RNAs ("redox-miRs"). Furthermore, we address the translational failure of conventional systemic antioxidant therapies, highlighting the newly recognized paradox of reductive stress, where over-supplementation disrupts essential ROS-dependent signaling cascades during early placentation. To resolve these diagnostic and therapeutic limitations, this work evaluates the clinical utility of multi-omics integration for mapping placental metabolic reprogramming and artificial intelligence (AI) machine learning models that combine maternal serum redox biomarkers with longitudinal fetal Doppler metrics for early risk stratification. Finally, we explore next-generation obstetric frontiers, including placenta-targeted nanomedicine for localized drug delivery, Placenta-on-a-Chip microfluidic and organoid screening platforms, and autologous mitochondrial transplantation aimed at rescuing syncytiotrophoblast bioenergetics. Overall, current evidence underscores placental redox dysregulation as an interconnected, systemic failure rather than an isolated molecular defect. Moving toward precision, redox-guided perinatal management requires longitudinal human studies and well-designed clinical trials to validate whether the targeted restoration of redox homeostasis can translate into improved maternal, fetal, and neonatal outcomes.

Abstract: Introduction: Whether maternal and neonatal mortality decline in lockstep determines where obstetric and newborn programmes should co-invest, yet global estimates report them separately. We paired maternal and neonatal causes along a priori care pathways in the Global Burden of Disease Study 2023 (GBD 2023) to test whether they share causes, places and margins.Methods: We develop a dyad synchrony index (DSI) for cause-paired co-movement, analysing deaths from 10 maternal causes (females aged 10–54; six key years) and five neonatal causes (ages 0–27 days), 1990–2023, across 21 GBD regions and five SDI quintiles (n=26 locations, the primary analysis), plus a post-hoc inequality extension over a purpose-built 204-country GBD 2023 extraction (1990, 2023). Three pathway pairs were pre-registered (maternal sepsis×neonatal sepsis; obstructed labour×birth asphyxia; hypertensive disorders×preterm birth). Synchrony used Spearman concordance; declines were decomposed into exposure and fatality margins, and best-frontier avoidable deaths computed.Results: Maternal deaths fell from 422,924 (1990) to 239,929 (166,628–334,199)* in 2023 (−43.3%); neonatal five-cause deaths from 2,841,581 to 1,474,021 (1,168,225–1,840,930*; −48.1%). All three pairs were level-concordant (r≈0.91–0.93), largely reflecting the shared development gradient; synchrony evidence lay in co-movement of change: 1990–2023 declines (Spearman ρ 0.77, 0.57, 0.80) and first differences (ρ 0.58, 0.49, 0.62; p≤2.3×10⁻⁹). Declines ran predominantly on the fatality margin (95.2% of the obstructed-labour decline; exposure contributed 10.9% of the preterm-birth decline). At the 2023 best-SDI frontier, 92.2% (region-frontier sensitivity 97.8%) of maternal direct-cause deaths and 73.5% (sensitivity 92.8%) of neonatal deaths were avoidable (upper bound). Central Asia was the extreme orphan pathway: maternal infection deaths fell 70.2% while neonatal sepsis deaths rose 62.2%.Conclusions: Maternal and neonatal mortality share causes, places and margins; most of the joint toll is avoidable at already-observed performance, and orphan pathways mark where dyad logic breaks. Ending Preventable Maternal Mortality (EPMM) and the Every Newborn Action Plan (ENAP) should be monitored as one dyad with two targets.

Abstract: Chronic stress, circadian disruption, sedentary behaviour, industrialised diets and disturbances in the gut microbiome have created an evolutionary mismatch between ancestral physiology and the modern environment. When midlife women enter the menopausal transition, cumulative exposure to lifestyle and environmental factors may exacerbate the hormonal changes associated with menopause. As a result, midlife women can present with a mixture of vasomotor, somatic, urogenital, psychological and cognitive symptoms that are often poorly diagnosed and treated in isolation. Our previous review described how evolutionary mismatch in Generation X (Gen X) women disrupts perimenopausal physiology through converging endocrine, psychosocial stress and immunometabolic mechanisms, amplifying symptoms and cardiometabolic risk. This included a detailed discussion of the endocrine changes that underpin the menopausal transition, how chronic psychosocial stress overwhelms whole-body stress response systems, and the impact of converging immunometabolism mechanisms such as chronic inflammation and insulin resistance on whole-body energy homeostasis. In the current review, we extend this model by proposing a Gen X clinical phenotype and an evolutionary realignment framework that translates it into an integrated approach to clinical management. The proposed framework addresses circadian alignment, metabolic flexibility, nutritional and lifestyle factors, allostatic load, environmental exposures, cerebral and mitochondrial health, musculoskeletal function, gut–hormone–microbiome signalling and menopausal hormone therapy, offering practitioners a systems-based approach to midlife care that addresses underlying physiological drivers rather than isolated symptoms.

Abstract: Endometriosis is associated with increased cardiovascular risk, but how its subtype heterogeneity informs this association remains unclear. This narrative review examines the biological characteristics of superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE) and their potential cardiovascular relevance. English-language literature identified through PubMed, Scopus, Google Scholar, and reference screening was synthesized across susceptibility factors, molecular and vascular alterations, and treatment exposures. Subtype-related findings highlight differences in anatomical location and tissue microenvironment, including peritoneal immune interactions in superficial lesions, intracystic iron accumulation and oxidative injury in OMA, and inflammatory and fibromuscular remodeling in deep lesions. These features provide a basis for investigating how lesion heterogeneity may relate to systemic lipid dysregulation, inflammation, endothelial dysfunction, and coagulation abnormalities. Ovarian function, surgical history, and hormonal regimens further inform interpretation of these relationships. By integrating phenotype and treatment exposure while distinguishing local findings from circulating biomarkers, vascular measurements, and clinical events, this review identifies evidence gaps linking biological heterogeneity to cardiovascular outcomes. Emerging subtype-related evidence supports further investigation but does not establish differences in cardiovascular event risk among SUP, OMA, and DIE. Prospective studies are needed to determine whether incorporating endometriosis subtype improves cardiovascular risk assessment beyond conventional factors. (Figure 1)

Abstract: Background: Endometrial cancer remains a therapeutic challenge, particularly in advanced and recurrent cases. This study investigated the anticancer effects of three synthetic CDDO derivatives, RTA 404, RTA dh404, and RTA 408, in human endometrial cancer Ishikawa cells. Methods: Cell viability was assessed using the CCK-8 assay, while Ki67 expression, apoptosis, cell cycle distribution, mitochondrial membrane potential, and intracellular reactive oxygen species (ROS) levels were evaluated using immunofluorescence staining and flow cytometry-based assays. Results: All three CDDO derivatives inhibited cell viability in a time- and concentration-dependent manner and reduced Ki67 expression. They also induced apoptosis and cell cycle arrest, with RTA 404 and RTA dh404 promoting G1 phase arrest and RTA 408 inducing G2/M phase arrest. Additionally, all compounds decreased mitochondrial membrane potential and intracellular ROS levels. Conclusion: RTA 404, RTA dh404, and RTA 408 suppress Ishikawa cell growth by inhibiting proliferation, inducing apoptosis, altering cell cycle progression, and disrupting mitochondrial function. These findings support further investigation of CDDO derivatives as potential therapeutic candidates for endometrial cancer.

Abstract: The vaginal microbiota represents a dynamic microbial ecosystem that contributes to mucosal homeostasis and protection against potentially pathogenic microorganisms. Vaginal dysbiosis, characterized by alterations in microbial composition and function, has increasingly been associated with gynecological, reproductive, obstetric, and puerperal conditions. This review summarizes current evidence on the composition and determinants of the vaginal microbiota, with an emphasis on Community State Types and major forms of dysbiosis, including bacterial vaginosis, vulvovaginal candidiasis, aerobic vaginitis, and viral infections. The associations between dysbiosis and sexually transmitted infections are discussed, with particular attention to the distinction between colonization, dysbiosis, and clinically relevant infection. Potential relationships between dysbiosis and infertility are examined, including tubal, cervical, and endometrial factors, as well as outcomes following assisted reproductive technologies. Evidence regarding obstetric and puerperal complications is critically evaluated. Finally, current therapeutic strategies are reviewed, ranging from etiological antimicrobial treatment to probiotics, defined live biotherapeutics, and emerging approaches such as vaginal microbiota transplantation. Although microbiota restoration represents a promising therapeutic concept, uncertainties remain regarding optimal strains, timing, diagnostic criteria, and clinically meaningful outcomes. Overall, vaginal dysbiosis should be regarded not simply as a local microbial imbalance but as a condition capable of modifying mucosal host-pathogen interactions throughout the female reproductive tract.

Abstract: Background: The FAUCS technique has been proposed as an alternative cesarean section approach potentially associated with improved postoperative recovery. Objective: To compare postoperative pain characteristics, functional recovery, analgesic requirements, and psychological outcomes between women undergoing intraperitoneal cesarean section (CS) and FAUCS cesarean section. Methods: A total of 201 women were included in this prospective single-center observational cohort study (CS: n = 101; FAUCS: n = 100). Postoperative pain intensity was assessed using the Numerical Rating Scale (NRS) and the McGill Pain Questionnaire. Functional recovery, emotional status, analgesic intake, and anxiety levels were evaluated during the early postoperative period. Results: FAUCS was associated with significantly lower pain intensity on postoperative day 0 (adjusted β = −1.97, 95% CI −2.63 to −1.32; p < 0.001), lower total McGill Pain Questionnaire scores (adjusted β = −2.85, 95% CI −4.68 to −1.02; p = 0.002), and lower sensory McGill scores (adjusted β = −2.59, 95% CI −4.31 to −0.86; p = 0.003). Time to first sitting and standing was approximately 10 h shorter following FAUCS (both p < 0.001). FAUCS was also associated with lower anxiety levels, better functional independence and overall well-being, and substantially lower weak opioid use (adjusted RR = 0.11, 95% CI 0.03–0.45; p = 0.002). Conclusions: FAUCS was associated with improved early postoperative functional recovery, lower pain burden, lower anxiety levels, and better overall well-being compared with intraperitoneal cesarean section. These findings should be interpreted in the context of the observational, non-randomized study design.

Abstract: Background and Objectives: Preeclampsia (PE) and gestational arterial hypertension (GAH) are major hypertensive disorders of pregnancy with overlapping clinical manifestations, which may complicate their differential diagnosis. Circulating microRNAs (miRNAs) are emerging as potential minimally invasive biomarkers reflecting placental dysfunction, hypoxia, impaired trophoblast invasion, angiogenic imbalance, and endothelial dysfunction. This study aimed to evaluate the expression profile of circulating miRNAs in women with PE and GAH and to identify candidate molecular markers capable of differentiating these conditions. Materials and Methods: A case-control study included 101 pregnant women: 39 women with physiologic pregnancy (control group), 23 women with GAH, and 39 women with PE. Plasma levels of 15 candidate miRNAs were quantified using TaqMan-based quantitative reverse-transcription PCR. Results: Twelve of the 15 investigated miRNAs demonstrated significant differences between PE and the control group and between PE and GAH after multiple-testing correction. The most pronounced decrease in PE was observed for miR-210-3p, with a log2 fold-change of −2.06 versus controls and −2.12 versus GAH. In ROC analysis, miR-210-3p showed the highest discriminatory performance for both comparisons, with an area under the curve (AUC) of 0.830 (95% CI, 0.735–0.925) for PE versus controls and 0.823 (95% CI, 0.720–0.925) for PE versus GAH. Other miRNAs, including miR-144-3p, miR-363-3p, miR-29a-3p, and miR-16-5p, also demonstrated moderate-to-good discriminatory performance. Conclusions: PE is characterized by a distinct circulating miRNA profile that differs from both physiologic pregnancy and GAH, whereas the molecular profile of GAH was broadly comparable to that of controls. Among the investigated candidates, miR-210-3p demonstrated the most consistent discriminatory performance and may represent a promising biomarker candidate for differentiating PE from GAH. A combination of several miRNAs may provide greater diagnostic value than individual markers.

Abstract:

(1) Background: Vaginal dysbiosis is strongly implicated in the pathophysiology of vaginitis and bacterial vaginosis (BV). Standard antimicrobial therapy may temporarily reduce pathogen burden but often disrupts beneficial Lactobacillus species, contributing to recurrence. Topical oxygen treatment may promote selective suppression of anaerobic pathogens and restore Lactobacillus-dominated communities. This preliminary study aimed to evaluate the effect of topical oxygen treatment—alone or adjunctive to systemic antimicrobial treatment—on vaginal microbiota composition. (2) Methods: Twenty-two symptomatic women affected by either BV or vulvovaginitis were enrolled and assigned to either topical oxygen or standard antimicrobial treatment plus topical oxygen. Oxygen delivery (3 L/min for 20 minutes, twice weekly for 2 weeks) was performed by using the Caress Flow device. Vaginal microbiota composition, pH and Lactobacillus presence were evaluated at baseline and 10–14 days post-treatment using the 16S Metagenomic Sequencing Library Preparation, sequencing and analysis. (3) Results: Topical oxygen alone increased the negative swabs from 4 (36.4%) to 9 (81.8%), p=0.06 and maintained stably high the total Lactobacillus spp. 92.60% [67.88–96.16%] at baseline and 91.50% [87.4–95.0%] pre-treatment. Oxygen plus antimicrobial treatment markedly reduced strict anaerobes (pre-treatment: 24.8% [15.3-36.5] to 9.0% [1.3-17.4] after treatment, p=0.05) and decreased BV-associated genera including Atopobium and Sneathia. Both oxygen-based regimens showed trends toward restoration or maintenance of Lactobacillus dominance. (4) Conclusions: Topical oxygen treatment favourably modulates the vaginal microbiota and may accelerate recovery from dysbiosis especially when used combined with standard antimicrobial treatment. These findings support larger trials to assess clinical efficacy and recurrence prevention.

Abstract: Fetal growth restriction (FGR) is a major pregnancy complication linked to placental insufficiency, resulting from defective trophoblast differentiation, impaired maternal-fetal vascular adaptation, and altered nutrient sensing. This review synthesizes current evidence on the interconnected molecular networks driving placental dysfunction. We map the reciprocal crosstalk between the pro-inflammatory shift, highlighted by NLRP3 inflammasome-driven trophoblast pyroptosis, and dysregulated extracellular matrix remodeling mediated by the MMP-9/TIMP system. This hostile microenvironment feeds directly into the angiogenic imbalance defined by the sFlt-1/PlGF ratio, accelerating cellular senescence via p53 and disrupting survival hubs like the PTEN/PI3K/AKT axis. Consequently, downstream metabolic sensors, notably the mTOR pathway, are blunted, causing trafficking failure of essential amino acid (SNAT2, LAT1) and glucose (GLUT) transporters. Crucially, we introduce an original framework integrating emerging spatial transcriptomics and single-cell epigenomics, demonstrating that these pathomechanisms are anatomically regionalized rather than uniform. Finally, we provide a critical evaluation of translation-ready therapeutic targets, emphasizing that strict safety constraints against fetal teratogenesis render ligand-functionalized nanoparticles a non-negotiable prerequisite for placenta-selective drug delivery. Integrating molecular stratification with longitudinal biomarker profiling represents the next milestone for mechanism-based, targeted management of FGR.

Abstract: Objective: To assess whether the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), AST-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) score, derived from first-trimester tests, discriminate intrahepatic cholestasis of pregnancy (ICP) and predict adverse perinatal outcomes within ICP. Materials and Methods: This retrospective case–control study included 115 women with ICP and 64 healthy controls. Indices were derived from 11–14-week values. The composite adverse outcome comprised preterm birth, meconium-stained amniotic fluid, fetal distress, neonatal intensive care admission or a 1-minute Apgar score <7. ROC analysis with DeLong comparisons and logistic regression adjusted for age and body mass index were used. Results: APRI (p < 0.001), NLR (p = 0.002) and SII (p = 0.011) were higher in ICP; FIB-4 was similar. Among derived markers, APRI had the highest area under the curve (AUC 0.786; 95% CI 0.718–0.851); however, ALT alone performed better (AUC 0.895; DeLong p = 0.003), and APRI and SII added nothing to ALT (AUC 0.904; p = 0.465). In the adjusted model, APRI (OR 3.36 per 0.1 unit; 2.16–5.25) and SII (OR 1.45 per 100 units; 1.08–1.96) remained independent. Within the ICP group, no index predicted adverse outcomes; only serum bile acids did (AUC 0.754; OR 2.39 per 10 µmol/L; 1.54–3.69), which persisted, though attenuated, after excluding the protocol-driven preterm component (AUC 0.681). Conclusion: First-trimester APRI and SII carry an early hepatocellular–inflammatory signal in women who later develop ICP, but add no diagnostic value beyond transaminases and do not predict perinatal risk; surveillance and delivery timing should continue to rely on bile acids.

Abstract: Background: Fetal long-bone fractures are rare and may result from maternal trauma, skeletal dysplasia, or, less commonly, apparently spontaneous events. Prenatal diagnosis is primarily based on ultrasonography, while the subsequent course of fetal fracture healing and long-term remodeling remains poorly documented. Case Presentation: A 35-week fetus sustained a displaced mid-diaphyseal fracture of the right femur following a maternal frontal motor vehicle collision. Initial ultrasonography demonstrated approximately 68° of interfragmentary angulation and surrounding soft-tissue edema. Maternal and fetal surveillance over the following 7 days showed no evidence of fetal compromise. Serial ultrasound examinations demonstrated progressive callus formation, with a globular membranous callus at day 7 and a prominent hyperechoic callus with peripheral vascularization and reduced fragment mobility at day 14. Delivery occurred by cesarean section at 39+2 weeks for an obstetric indication. The newborn weighed 3150 g and had Apgar scores of 9 and 10. The fracture was clinically consolidated but remained in severe malunion, with approximately 56° of ventrolateral angulation and a clinically estimated 6.5 cm apparent clinical shortening. No orthopedic intervention was undertaken. Progressive spontaneous correction was documented, with residual angulation of 35° at 3 months and 15° at 6 months. By 10 months, complete angular correction and limb-length equalization were documented. Independent walking was achieved at 12 months. At 12 years of age, the child had normal limb alignment, equal limb lengths, normal gait, and no functional sequelae. Conclusions: This case demonstrates an unusual combination of prenatal fracture healing, severe neonatal malunion, and complete long-term spontaneous correction without orthopedic intervention. The reported 6.5-cm shortening should be interpreted as apparent clinical shortening rather than definitive anatomical shortening because it was not established by standardized radiographic limb-length measurement. Geometric analysis indicates that angular deformity alone could account for only approximately 0.8–1.0 cm of shortening at term. The subsequent course is consistent with substantial growth-related remodeling and provides a rare longitudinal example of the remodeling potential of the immature femur.

Abstract: Background/Objectives: Pelvic organ prolapse (POP) involves anatomical and biomechanical components, yet post-surgical biomechanical changes remain poorly characterized. Vaginal Tactile Imaging (VTI) provides quantitative biomechanical parameters of the vaginal walls and pelvic support structures. This study assessed VTI-derived changes from baseline to 6 months after reconstructive surgery, comparing them with a non-prolapse reference group. Methods: This single-center, prospective cohort study (December 2022–December 2023) enrolled 32 women with POP-Q stage I–IV prolapse scheduled for surgery and 30 women without prolapse. VTI used eight standardized tests generating 46 parameters, with reassessment at 6 months. The primary endpoint was change in the integral pressure parameter P1_I (α = 0.05); secondary endpoints used Bonferroni-adjusted thresholds, with ANCOVA adjusting for age, parity, BMI, and menopausal status. Results: Preoperatively, patients showed markedly lower vaginal wall integrity and stiffness than controls. After adjustment, elasticity differences remained significant, while muscle function differences were largely attenuated. P1_I increased significantly post-operatively (Δ +1.2; 95% CI 0.4–2.0; p = 0.006; d = 0.55). Five secondary endpoints showed nominal improvements (raw p = 0.002–0.033), none surviving correction. Conclusions: Reconstructive surgery significantly improved the primary biomechanical outcome, with modest, unadjusted secondary changes. Findings are hypothesis-generating; confirmation requires powered, matched-control studies with quality-of-life endpoints.

Abstract: Background/Objectives: Menopausal hormone therapy (MHT) and alendronate improve bone mineral density (BMD), but their comparative effects on trabecular bone score (TBS) are unclear. We compared 12-month changes in TBS and site-specific BMD in postmenopausal women treated with MHT or alendronate. Methods: This retrospective cohort included 172 treatment-naïve postmenopausal women with newly diagnosed osteoporosis who initiated MHT (n=87) or alendronate 70 mg/week (n=85). Complete baseline and approximately 12-month DXA/TBS data were available for 164 women (MHT, n=83; alendronate, n=81). The primary outcome was the adjusted between-group difference in lumbar spine TBS at follow-up, assessed by analysis of covariance. Results: The adjusted MHT-minus-alendronate difference in TBS was 0.023 (95% CI, 0.010–0.036; P<0.001). TBS showed no significant within-group change with MHT (0.002 ± 0.044; P=0.699) but decreased with alendronate (−0.018 ± 0.040; P<0.001). BMD increased significantly in both groups, with greater gains with alendronate at the lumbar spine (adjusted difference, −0.014 g/cm²; 95% CI, −0.019 to −0.009; P<0.001), femoral neck (−0.005 g/cm²; 95% CI, −0.009 to −0.001; P=0.013), and total hip (−0.007 g/cm²; 95% CI, −0.011 to −0.003; P<0.001). Conclusions: Both treatments improved BMD, but alendronate produced larger gains, whereas no significant within-group change in TBS was observed with MHT. These findings suggest discordant treatment-related changes in BMD and TBS and warrant cautious interpretation because of the observational design and limitations of serial TBS monitoring.

Abstract: Preeclampsia (PE), a multi-system disorder, is not confined to the puerperium and may represent a sentinel event leading to increased maternal risk for future cardiovascular disease (CVD). Early-onset PE appears to carry a distinct, and possibly more pronounced, vascular signature than late-onset PE. Accumulating data consistently link previous early-onset PE, to an elevated lifetime risk of CVD. Arterial stiffness (AS), most commonly quantified by carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AIx, or AIx corrected to a heart rate of 75 beats per minute, AIx-75), is an established, independent predictor of CVD in the general population and has therefore attracted interest as a candidate marker for postpartum CVD risk stratification. However, whether AS remains elevated once the puerperium has resolved, has been a persistently unsettled question. Existing literature is inconclusive regarding the association between postpartum AS measurements and previous early-onset PE. This comprehensive review synthesizes the available literature on oscillometric AS measurements before and after delivery in pregnancies complicated by early-onset PE and attempts to quantify the differences between ante- and postpartum oscillometric AS measurements. Although not a systematic review, this quantitative review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and MOOSE (Meta-Analysis of Observational Studies in Epidemiology) guidelines. The study protocol was registered at PROSPERO (Prospective Register of Systematic Reviews System) (ID CRD42020167749) a priori. Only longitudinal studies reporting on both pregnancies complicated by early-onset PE (case group) and normotensive pregnancies (control group) were included. cf-PWV, Alx and Alx-75 were assessed both ante- and postpartum. Quantitative synthesis was performed for indices presented among at least 2 studies. Data were presented as standardized mean differences (SMDs) and 95% confidence intervals (95%CIs). Overall, from 14 citations of relevance, 3 studies with a total of 35 cases and 155 controls fulfilled the inclusion/exclusion criteria. In pregnancies complicated by early-onset PE assessed both ante- and postpartum with either cf-PWV (SMD: -0.61, 95%CI: -1.3 to 0.07) and/or Alx (SMD: -0.32, 95%CI: -2.83 to 2.2) and/or Alx-75 (SMD: -0.61, 95%CI: -1.27 to 0.05), there was no statistically significant difference in AS measurements. In conclusion, current literature suggests that AS measurements (cf-PWV, AIx and AIx-75) are not significantly altered in pregnancies complicated by early-onset PE. Alx and Alx-75 should be further evaluated. Substantial heterogeneity in study design, small sample sizes, and inconsistent postpartum follow-up windows continue to limit firm conclusions, underscoring the need for larger, standardized, and adequately powered longitudinal studies before AS measurements can be recommended for routine postpartum CVD risk stratification.

Abstract: Endometriosis is a systemic, estrogen dependent neuroinflammatory-mediated disease affecting approximately 10-15% of women of reproductive age. Clinical manifestations include chronic pelvic pain (CPP), dysmenorrhea, dyspareunia, dyschezia, dysuria, and infertility. Endometriosis-associated pain is multifactorial and comprises overlapping nociceptive, neuropathic, and nociplastic pain phenotypes driven by persistent inflammation, neuroangiogenesis, peripheral nerve involvement, and central sensitization (CS). These mechanisms may sustain pain beyond lesion excision, highlighting the importance of pelvic nervous system (PNS) involvement. This narrative review examines the role of neuropelveology (NP) in endometriosis, focusing on pain mechanisms, diagnostic implications, and surgical decision making. NP integrates pelvic neuroanatomy and neurophysiology into structured neurological assessment, pain mapping, symptom localization, and nerve sparing surgery. Current evidence suggests that NP may complement conventional evaluation in selected patients with refractory pain, neuropathic symptoms, discordance between symptom severity and imaging findings, or suspected involvement of the sacral plexus or sciatic nerve. Recognizing distinct pain phenotypes may support individualized treatment planning by balancing lesion excision with neural preservation and identifying patients who may benefit from multidisciplinary pain management, rehabilitation, neurolysis, or neuromodulation. Although current evidence remains limited, NP should be considered a complementary framework rather than a replacement for established endometriosis management. Prospective multicenter studies using standardized diagnostic criteria and long-term functional outcomes are needed to define its clinical utility.

Abstract: Background: Current guidelines by the American College of Obstetrics and Gynecology require a two-step procedure for diagnosis of gestational diabetes (GD). This two-step procedure is challenging in resource limited settings. We determined if electrocardiography (ECG) done combined with artificial intelligence techniques can predict GD to provide a non-invasive, early gatekeeper strategy for GD risk stratification. Methods: Data for this study came from the Markers of Early Risk-stratification of Gestational Diabetes (MERGD) study and included 10s, 12-lead ECGs collected at the first antenatal visit. Patients were invited to undergo GCT at 24-28 weeks and, if required, an OGTT was conducted. GCT result was considered positive if the 1-hour, 50g glucose load blood glucose level was ≥130 mg/dL. ECGs were preprocessed, filtered, and a synthetic dataset was generated by using features from autoencoders, device-reported variables and heart rate variability parameters. A random forest model (RF-ECG) was trained on the synthetic data and validated first by 10-fold cross-validation, then on a held-out test of the synthetic data and finally on the original data not seen by the model. Results: Total 1,036 quality checked, preprocessed ECGs were used in the study. A total of 123 (11.87%) women developed GD. The fully trained RF-ECG model provided validation performance as follows: 78.28% accuracy, 87.80% sensitivity, 77.00% specificity and a likelihood ratio of positive test of 3.82. The RF-ECG model outperformed existing models of GD risk stratification. Importance metric identified 40 features as contributory to the model’s diagnostic logic. Conclusions: ECGs can accurately predict the likelihood of GD ahead of the final diagnosis. If supported by external validation in future studies, our approach can help noninvasively identify GD risk early during pregnancy in resource limited settings.

Abstract: Background: Maternal overweight, obesity, and inappropriate gestational weight gain (GWG) are increasingly recognized as major contributors to adverse pregnancy outcomes worldwide. Elevated pre-pregnancy body mass index (BMI) is associated with gestational diabetes mellitus (GDM), hypertensive disorders, cesarean delivery, fetal overgrowth, and long-term cardiometabolic risks for both mother and child. Regional contemporary data from Bulgaria remain limited. Objective: To evaluate trends in maternal obesity and gestational weight gain among pregnant women in Southeastern Bulgaria between 2021 and 2025, using a regional cohort from Burgas, and to assess associations with maternal and neonatal outcomes. Methods: This retrospective cohort study included 1,176 singleton pregnancies registered for antenatal follow-up at MC Prime Clinic – Dr. Kirovakov Ltd., Burgas, Bulgaria, between January 2021 and December 2025. Women were classified according to World Health Organization BMI categories as underweight, normal weight, overweight, and obese. Gestational weight gain was categorized as below, within, or above Institute of Medicine recommendations. Maternal and neonatal outcomes were analyzed using comparative statistics and multivariable logistic regression. Results: The mean maternal age was 30.8 ± 5.4 years, and the mean pre-pregnancy BMI was 25.1 ± 4.8 kg/m². BMI distribution was: underweight 7.6%, normal weight 49.8%, overweight 27.9%, and obesity 14.7%. Overall, 42.6% of women entered pregnancy overweight or obese. Mean total GWG was 13.2 ± 5.6 kg. Excessive GWG occurred in 39.0% of women, while only 39.6% remained within recommended ranges. Excessive GWG was significantly more common among obese women (52.8%) than among women with normal BMI (34.7%, p<0.001). Compared with women of normal BMI, obese women had significantly higher rates of gestational diabetes mellitus (16.7% vs 5.8%), hypertensive disorders (12.9% vs 4.2%), preeclampsia (8.4% vs 2.1%), cesarean delivery (47.4% vs 28.6%), macrosomia (14.5% vs 6.1%), and preterm birth (10.7% vs 6.9%) (all p<0.05). In multivariable analysis, maternal obesity independently predicted GDM (aOR 2.94, 95% CI 1.82-4.73), preeclampsia (aOR 3.18, 95% CI 1.87-5.39), cesarean delivery (aOR 2.11, 95% CI 1.42-3.14), macrosomia (aOR 2.46, 95% CI 1.51-4.01), and preterm birth (aOR 1.67, 95% CI 1.02-2.74). Conclusions: Maternal obesity and excessive gestational weight gain were highly prevalent among pregnant women in Southeastern Bulgaria during 2021-2025 and were strongly associated with adverse maternal and neonatal outcomes. These findings support the need for preconception counseling, individualized antenatal weight management, and targeted regional public health strategies.