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Comparative evaluation of long-term ophthalmic sequelae following first versus second-line antibiotic treatment for congenital syphilis

Int J Retina Vitreous. 2025 Jun 10;11(1):63. doi: 10.1186/s40942-025-00689-y.

ABSTRACT

PURPOSE: Congenital syphilis (CS) is associated with interstitial keratitis, chorioretinitis, uveitis, and optic atrophy mainly in inadequately treated patients. We conducted a retrospective cohort analysis evaluating ocular findings in children born in 2015 with CS treated with ceftriaxone at the time of delivery during the period of penicillin shortage in a city located at Northeast of Brazil and compared them with those adequately treated.

METHODS: 469 children were reported with CS at birth during the penicillin shortage period and 171 were actively searched and invited to an ophthalmological assessment and retrospective analysis of their information recorded in the medical records of the municipality’s health services.

RESULTS: A total of 68 children came to the assessment, median age 8 years of age (range 7-8 years), 48 were treated with penicillin (70.5%) and 20 with ceftriaxone (29.5%). There were no significant differences in demographic or perinatal characteristics between the groups. The majority of children had a completely normal ophthalmological examination (67.6%). Regarding findings that are more associated with CS, one child in ceftriaxone group (5.0%) had optic atrophy in one eye and one in the penicillin group (2.9%) had glaucomatous optic disc changes. No interstitial keratitis was found. There was no significant association between the child’s treatment and the prevalence of ophthalmologic findings (p = 0.663). There was also no association between the medication and a current reactive VDRL (p = 1.000).

CONCLUSION: After an 8-year follow-up, no statistically significant difference was observed in the incidence of ophthalmologic manifestations among individuals treated for CS with either penicillin or ceftriaxone. These findings suggest that ceftriaxone may serve as an effective alternative for the prevention of CS and its associated ocular complications.

PMID:40495236 | DOI:10.1186/s40942-025-00689-y

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Beyond the brain: early autonomic dysfunction in Alzheimer’s disease

Acta Neuropathol Commun. 2025 Jun 10;13(1):128. doi: 10.1186/s40478-025-02042-8.

ABSTRACT

Alzheimer’s disease (AD) is classically defined by central hallmarks such as amyloid-beta plaques, tau hyperphosphorylation, and synaptic failure. However, mounting evidence suggests that dysfunction outside the brain, particularly in the peripheral nervous system, may also play a significant role in disease progression. The adrenal medulla-a key regulator of systemic neurotransmission and stress response-has received little attention in this context. In this study, we investigated whether chromaffin cells (CCs) from the triple transgenic AD mouse model (3xTg) exhibit functional alterations that could contribute to peripheral neurochemical imbalance. Using electrophysiology, high-resolution amperometry, and neurotransmitter quantification, we identified early and progressive defects in CC function. Remarkably, even at two months of age-prior to cognitive decline-3xTg CCs showed impaired exocytosis, reduced vesicle release, and slower fusion pore kinetics. These changes were accompanied by diminished sodium (INa), calcium (ICa), and nicotinic (IACh) currents, compromising CC excitability. With age, a shift toward increased potassium (IK) currents and enhanced catecholamine secretion may reflect compensatory adaptations aimed at preserving output. These functional deficits were paralleled by structural remodeling of the actin cytoskeleton and systemic neurotransmitter disturbances. Noradrenaline levels increased in both plasma and brain, while dopamine decreased peripherally but paradoxically increased in the prefrontal cortex and hippocampus. Serotonin levels consistently declined across compartments. These imbalances correlated with altered behavior: 3xTg mice displayed increased exploration of exposed areas and heightened behavioral despair, pointing to anxiety- and depression-like phenotypes. Together, our findings identify the adrenal medulla as a previously underrecognized site of early catecholaminergic dysregulation in AD. The observed associations between peripheral CC dysfunction, systemic neurotransmitter imbalance, and behavioral changes point to a potential link between peripheral neuroendocrine alterations and central disease features. These results broaden the current understanding of AD pathophysiology and support the adrenal medulla as a promising candidate for further investigation as a therapeutic target and source of peripheral biomarkers.

PMID:40495232 | DOI:10.1186/s40478-025-02042-8

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Primary healthcare delivery adaptations in war-induced population displacement

Isr J Health Policy Res. 2025 Jun 10;14(1):35. doi: 10.1186/s13584-025-00698-0.

ABSTRACT

BACKGROUND: Impact of war on civilians in high-income countries has been relatively underexplored in research. Internal displacement of populations within a country during war challenges healthcare universal access, utilization, and continuity of care. Healthcare systems can prepare and adjust to mitigate detrimental effects. Therefore, our objective was to examine primary healthcare delivery adaptations during war-induced population displacement and the effects on primary healthcare utilization.

METHODS: Observational, repeated cross-sectional study based on Clalit Health Services (CHS) electronic medical records (EMR) data. Outcomes were the rates of visits in primary care during five months following the war, compared to the previous year, by population group. All CHS members were included, 4.86 million, classified into four groups: (1) evacuated municipalities in the South (ES); (2) evacuated municipalities in the North (EN); (3) areas of restricted activity (RA) (4) rest of the Country (RC). The considered exposures were the state of war and internal displacement of populations, extended periods of restricted activities for areas under threat, and primary healthcare delivery adaptation measures. The main outcomes and measures were primary care visit rates grouped into four consecutive weeks clusters. Visits were further classified as in-person or telehealth visits.

RESULTS: Healthcare delivery adaptation measures included fast set-up of pop-up primary clinics in evacuated population concentrations, services expansion (online visits 24/7, medication delivery range), and expanded services for internally displaced persons (designated call center lines and text-based nursing service). During the initial weeks following the outbreak of war overall visits declined, mainly in displaced populations (by 43.9% (95% CI: 42.2-45.6%) and 19.1% (95% CI: 17.1 – 21.1%) in the first month in ES and EN, respectively). Visits rates gradually recovered in all population groups, returning to baseline within 12 weeks. This was driven by a sharp initial decline of in-person visits, and attenuated by increased usage of telehealth, mainly observed in displaced populations.

CONCLUSIONS: The outbreak of war and population displacement was associated with decreased primary care visits, while telehealth service utilization increased significantly. This increase was partly facilitated by telehealth consultations provided by patients’ regular primary care physicians, often themselves displaced, thereby preserving continuity of care through existing trust and rapport. Healthcare systems should proactively integrate telehealth solutions into emergency preparedness plans, prioritizing continuity of patient-provider relationships even during displacement. Future research is needed to evaluate the quality and equity implications of telehealth adaptations and their impact on long-term health outcomes.

PMID:40495226 | DOI:10.1186/s13584-025-00698-0

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Providing food security in Gaza for the “day after”

Isr J Health Policy Res. 2025 Jun 10;14(1):34. doi: 10.1186/s13584-025-00700-9.

ABSTRACT

Poverty, conflict and war are the most prominent reasons for food insecurity worldwide including for the population of Gaza since October 7, 2023. It has been shown that at least during the seven-month period between January and July, 2024, an adequate supply of food was delivered to Gaza. However, a distinction must be made between food availability (entering Gaza), and food accessibility (food supply actually reached at the household level). The latter was apparently controlled by Hamas; and there are no reliable data available on the actual distribution of food. A prerequisite for achieving a better “day after” for the population of Gaza depends on achieving a permanent end to the hostilities between Hamas and other Gazan militants with Israel. That must be a top priority for policymakers. Nonetheless, understanding the elements involved in the planning for a successful “day after” can begin now. We know that most of the population needs housing, as well as sufficient, adequate and accessible food, water, energy sources, adequate health services for acute and chronic medical and surgical conditions, mental health, and preventive care. In this article, we focus on planning for food and nutrition security for the “day after,” a process that will require actions along the six dimensions of food security- availability, accessibility, utilization, stability, sustainability, and agency. We outline these dimensions and their necessary components.

PMID:40495200 | DOI:10.1186/s13584-025-00700-9

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High prevalence of co-infections with latent tuberculosis, syphilis and hepatitis B and C among people with HIV in Ghana: a call for integrating screening into routine care

AIDS Res Ther. 2025 Jun 10;22(1):61. doi: 10.1186/s12981-025-00756-2.

ABSTRACT

BACKGROUND: People with HIV (PWH) are at risk of co-infections, such as latent tuberculosis (LTBI), hepatitis B (HBV), hepatitis C (HCV), and syphilis; hence, routine screening is critical. However, evaluation of routine screening is not being fully implemented in Ghana. This study assessed the prevalence of these co-infections among PWH in Accra, Ghana.

METHODS: The HIV Cure Research Infrastructure Study (H-CRIS) followed 390 PWH from three HIV treatment centres in Accra. A cross-sectional study was conducted within this cohort, and participants were screened for LTBI, hepatitis B, hepatitis C, and syphilis using standardized assays. LTBI was detected using the QuantiFERON-TB Gold Plus assay. Syphilis testing included treponemal and non-treponemal assays. HBV and HCV were tested using rapid test kits. Data was collected on demographics, viral load, CD4 count, ART regimen, and therapy duration. Descriptive statistics used frequency and proportion, while inferential analysis employed chi-square tests, t-tests, and odds ratios (OR) to assess associations.

RESULTS: Among 390 participants, median age: 45 years (IQR: 39-52 years), 69% (269/390) were virologically suppressed, and 80% (312/390) had CD4 counts above 350 cells/µL. The prevalence of co-infections was 12% (48/390) for HBV, 10.8% (42/390) for LTBI, 12.5% (40/320) for syphilis, and 1% (4/390) for HCV, with 2% (8/390) having more than two co-infections. LTBI was associated with age (> 60 years; OR = 3.5) and years of HIV diagnosis (> 10 years; OR = 2.2).

CONCLUSION: The significant burden of co-infections among PWH in Ghana highlights the urgent need to integrate routine screening into HIV care.

PMID:40495197 | DOI:10.1186/s12981-025-00756-2

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Noninvasive markers for warning premature ovarian insufficiency: a Mendelian randomisation study

J Ovarian Res. 2025 Jun 10;18(1):127. doi: 10.1186/s13048-025-01696-1.

ABSTRACT

BACKGROUND: Early diagnosis and early delivery are the main strategies for the treatment of premature ovarian insufficiency (POI). However, POI warning markers, especially those that can be detected through noninvasive methods, are very limited; therefore, the identification of noninvasive markers for POI is urgent.

METHODS: We acquired POI GWAS summary statistics from the FinnGen database. The metabolome, circulating plasma proteins, gut microbiota, immunophenotypes, circulating microRNAs (miRNAs), and two proteomes were obtained for two-sample Mendelian randomization (MR). Specifically, we employed inverse variance weighted (IVW) as the main method to calculate the MR effect estimates. eQTL data (from the eQTLGen Consortium) were employed for SMR. Hub genes were identified using the String database and Cytoscape software. Potential mechanisms of POI were identified via pathway enrichment analysis of the identified genes and miRNAs.

RESULTS: Three metabolites (sphinganine-1-phosphate levels, X-23636 levels, 4-methyl-2-oxopentanoate levels), two circulating plasma proteins (fibroblast growth factor 23 levels, neurotrophin-3 levels), one gut microbiota (faecalibacterium abundance), one immunophenotype (HVEM on naive CD8 + T cells), 23 miRNAs (miR-500a-3p, miR-555, miR-584-5p, miR-642a-5p, miR-671-3p, miR-1324, miR-6870-3p, miR-1468-5p, miR-146a-3p, miR-221-3p, miR-3121-5p, miR-3184-3p, miR-3185, miR-335-5p, miR-4302, miR-4506, miR-6808-5p, miR-6894-5p, miR-145-5p, miR-149-3p, miR-23a-3p, miR-3141, and miR-374b-5p), and three hub genes (ESR1, ERBB2, and GART) serve as warning markers for POI. Enrichment analysis indicated that pathways such as glutathione metabolism and the PI3 kinase pathway may be involved in mechanisms regulating POI.

CONCLUSION: Our results are the first to identify noninvasive predictors for POI via MR, providing contributions for early warning and fertility guidance for clinical POI patients.

PMID:40495196 | DOI:10.1186/s13048-025-01696-1

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HCV-related hepatocellular carcinoma: gene signatures associated with TERT promoter mutations and sex

J Transl Med. 2025 Jun 10;23(1):639. doi: 10.1186/s12967-025-06560-w.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a rapidly progressing disease, frequently caused by hepatitis C virus (HCV) infection and a higher prevalence in males than females. Over 60% of HCCs harbour frequent activating mutations in the telomerase reverse transcriptase promoter (TERTp). However, the relationship between TERTp status, sex, and expression of specific genes remains poorly understood.

METHODS: We conducted a literature search to identify genes that were significantly upregulated in HCV-related HCC, compared to the respective peri-tumour tissues, in at least two independent studies. We identified 90 genes and validated their expression in 59 matched HCV-related HCC and peri-tumour tissues using a custom multiplex array qPCR. HCV-related HCC patients were stratified by TERTp mutations and sex. Statistical analysis was performed to identify relationships between different variables.

RESULTS: Overall, validation analysis confirmed the upregulation of 39 out of 90 genes. Expression levels of 24 genes differed significantly between HCV-related HCC with mutant and wild type TERTp. The expression of FASTK and FLVCR1 genes correlated with TNM and tumour size (p < 0.05). High expression of NUCKS1 was associated with mortality, particularly in male patients. Overall, the expression of 57 genes was sex-linked, with 26 and 48 genes significantly overexpressed in males and in females, respectively, some of which were also associated with mutant TERTp status.

CONCLUSIONS: We identified unique molecular signatures in TERTp mutant HCC associated with the activation of specific genes. Such results suggest that TERTp mutant HCC might represent a distinct clinical entity. Furthermore, the up-regulation of several genes in HCV-related HCC is sex-linked. These results are crucial for understanding the mechanisms underlying TERTp mutations in tumour progression and sex-related HCC risk and for developing more effective diagnostic and prognostic biomarkers.

PMID:40495193 | DOI:10.1186/s12967-025-06560-w

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Branched-chain amino acid and cancer: metabolism, immune microenvironment and therapeutic targets

J Transl Med. 2025 Jun 10;23(1):636. doi: 10.1186/s12967-025-06664-3.

ABSTRACT

Cancer is one of the major diseases threatening human health in the world. According to the latest global cancer statistics from the International Agency for Research on Cancer (IARC), there were approximately 20 million new cancer cases and 10 million cancer deaths worldwide. Amidst this global health concern, branched chain amino acids have emerged as key players, playing an important role in the occurrence and development of cancer. In certain malignancies like colorectal cancer, the average level of BCAA in tumor tissues is twice that in normal tissues. BCAA metabolism is intricately associated with the progression of multiple tumors and is modulated by diverse enzymes, including BCAT, BCKDH, and BCKDK. The metabolism of BCAA involves multiple enzymes and biochemical processes via signaling pathways such as PI3K/AKT/mTOR and AMPK/mTOR, etc. In addition, mTOR inhibitors show potential value in cancer treatment by regulating the metabolism and signaling pathways of tumor cells, which provides a new direction for anticancer efforts. Simultaneously, BCAAs are closely associated with tumor immunity, including NK cells, CD4+ T cells, and CD8+ T cells. At present, the research on BCAA metabolism and related enzymes and signaling pathways is still in progress, aiming at identifying new targets and ideas for cancer therapy, and combined therapy will become an important trend in the future. In this review, we discuss the role and mechanisms of BCAA metabolism in human cancer.

PMID:40495192 | DOI:10.1186/s12967-025-06664-3

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Advantages of a new improved oblique Retractor in oblique lateral lumbar interbody fusion: a retrospective study

J Orthop Surg Res. 2025 Jun 10;20(1):581. doi: 10.1186/s13018-025-05992-w.

ABSTRACT

A clear surgical field of view is one of the key factors for a smooth operation. Whether a new modified oblique retractor can improve the field of view during oblique lumbar interbody fusion (OLIF) surgery and thus shorten the surgical time and reduce blood loss needs to be evaluated. A total of 64 patients who were diagnosed with L4‒5 segment lumbar spondylolisthesis, lumbar spinal stenosis, or lumbar disc herniation and who underwent OLIF surgery in our hospital between January 2023 and December 2023 were retrospectively enrolled. They were divided into two groups on the basis of whether the new modified oblique retractor was used: 32 cases with the new modified oblique retractor and 32 cases with a traditional right-angle retractor. Clinical efficacy was compared between the two groups using the visual analogue scale (VAS) for lower limb pain and the Oswestry Disability Index (ODI). The safety in the perioperative period was compared between the two groups using indicators such as surgical time, intraoperative blood loss, the vertebral canal area, and complications. No statistically significant differences were found in the baseline data (age, sex, or BMI) between the two groups (P > 0.05). There were no significant differences in the postoperative VAS score, postoperative ODI, postoperative vertebral canal area, or incidence of complications between the two groups (P > 0.05). There was a statistically significant difference in surgical time and intraoperative blood loss (P < 0.05) between the two groups. Compared with traditional right-angle retractors, the newly improved oblique retractor is more suitable for the surgeon’s field of view, thereby shortening the surgical time to some extent and reducing blood loss. By reducing traction on the psoas major muscle, the possibility of psoas muscle weakness can be decreased. Although there are differences in overall efficacy between the two groups of patients, these differences are small. The newly improved oblique retractor is better in terms of the appropriate surgical field of view angle and provides easier assistant cooperation, thus it is worth promoting and applying in clinical practice.

PMID:40495186 | DOI:10.1186/s13018-025-05992-w

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Association between the triglyceride glucose index and long-term outcomes in patients with acute coronary syndrome and chronic kidney disease

Diabetol Metab Syndr. 2025 Jun 11;17(1):206. doi: 10.1186/s13098-025-01775-9.

ABSTRACT

BACKGROUND: Despite the association between the triglyceride-glucose (TyG) index and major adverse cardiovascular events (MACE) has been reported, a notable research gap persists regarding its predictive value in patients with acute coronary syndrome (ACS) and chronic kidney disease (CKD). This study endeavors to bridge this gap by investigating the relationship between the TyG index and outcomes among this unique patient cohort.

METHODS: Patients having ACS with CKD were recruited from January 2013 to December 2021. Outcomes included all-cause mortality and MACE. The potential linear relationship was visualized by the restricted cubic spline (RCS) curve. Cox proportional hazards models were employed to rigorously examine the association between the TyG index and study outcomes. Furthermore, to assess the incremental value of the TyG index, we conducted analyses using C-statistics, the continuous net reclassification index (cNRI), and the integrated discrimination index (IDI).

RESULTS: A total of 1094 patients were included in the final analysis. Over a median follow-up period of 30.1 months (IQR: 16.5 to 40.0 months), we recorded 167 (15.3%) all-cause mortality events and 285 (26.1%) MACE. Additionally, each 1-unit increase of it was significantly associated with a 61% elevation in the risk of all-cause mortality (95% CI: 1.28-2.03, P < 0.001) and a 72% increase in the risk of MACE (95% CI: 1.45-2.05, P < 0.001). These associations between TyG index (as quantitative or categorical variables) and endpoints remained robust even after multivariable adjustment. RCS analysis showed linear relationships between TyG and endpoints (all P for non-linear > 0.05). Moreover, subgroup analysis revealed significant interactions of dialysis and renal function (P for interaction = 0.008 and 0.011, respectively) with all-cause mortality. Lastly, combining with the established risk score significantly enhanced the discrimination and reclassification performance of TyG, as evidenced by the C-statistic, cNRI, and IDI values (all P < 0.05).

CONCLUSION: For patients with both ACS and CKD, TyG index is associated with both MACE and all-cause death. Prognostic classification is enhanced by the TyG index. The results collectively suggest that the TyG index serves as a reliable predictor of outcomes among patients with ACS and CKD, offering a novel metabolic perspective.

PMID:40495184 | DOI:10.1186/s13098-025-01775-9