Abstract:

Background/Objectives: Sarcopenia, obesity, and sarcopenic obesity (SO) are common in older adults and may be associated with functional limitations in basic (ADL) and instrumental (IADL) activities of daily living. This study aimed to evaluate the association between body composition phenotypes and ADL/IADL limitations among older adults. Methods: A cross-sectional study included 440 community-dwelling adults aged ≥60 years (281 women, 159 men; mean age 74.7 ± 7.8 years). Sarcopenia was diagnosed according to EWGSOP2 criteria, obesity was defined as percent body fat >42% in women and >30% in men, and SO was classified based on the ESPEN/EASO recommendations. Participants without obesity or sarcopenia were categorized as ‘normal’ phenotype. Functional status was evaluated using the Katz and Lawton scales, with limitations defined as ADL ≤5 and IADL ≤26 points, respectively. Multivariate logistic regression analysis was performed to determine factors associated with ADL and IADL limitations. Results: Over half of the participants (57.1%) had abnormal body composition: 31.6% obesity, 11.4% sarcopenia, and 13.2% SO. SO was associated with a nearly threefold higher risk of ADL limitations (OR = 2.86; p = 0.003) and a 3.7-fold higher risk of IADL limitations (OR = 3.68; p < 0.001) compared to the normal phenotype. Sarcopenia was associated with IADL limitations in the unadjusted model (OR = 2.44; p = 0.010). Independent predictors of ADL and IADL limitations included reduced muscle strength, a higher number of chronic diseases, and a worse nutritional status. Conclusions SO was linked to higher risk of both ADL and IADL limitations, while sarcopenia was associated only with IADL deficits. Obesity severity may be relevant, but its impact on daily functioning in older adults requires further study.

Abstract:

Introduction: We hypothesised that vitamin K (VK) may have potential effect on insulin secretion and FGF-19 and FGF 21 may modulate the vitamin K/insulin pathway. We investigated whether vitamin K1 or K2 supplementation for 18 months can affect insulin secretion and FGF19 and FGF21 production. Methods: We conducted exploratory analyses using stored samples from an 18-month randomised double-blind placebo controlled trial of VK1 (1 mg/day) or VK2 (menaquinone-4, MK4 45 mg/day)) in 105 post-menopausal women with osteoporosis (PMO) aged between 55-85 years which looked at the effect of VK supplementation on bone mineral density. In the current study, plasma insulin (primary outcome), FGF19 and FGF21 (secondary outcomes) were measured at baseline, 6 and 18 months. Results: Plasma insulin at 6 and 18 months increased significantly compared to baseline value in both treatment arms (VK1 and VK2 (MK4) ) (Median Insulin [IQR] VK1: baseline : 41.2 [29.3, 54.3] pmol/L, 6 months: 59.7 [37.8, 89.5] pmol/L p<0.001, 18 months: 54.3[43.5, 73] pmol/L (p= 0.05), VK2 (MK4) arm (Median Insulin [IQR]: baseline: 44.3[30.6, 60.9], 6 months: 63.2[43.5, 97] pmol/L p=0.011, 18 months: 54.2[40.7, 103.5] pmol/L p=0.05) in within-group analyses. No significant changes were seen in the placebo group. Circulating FGF21 tended to be higher at 6 months (p=0.045) compared to baseline following VK2 (MK4) only. Conclusions: Improving VK status in post-menopausal women may improve insulin secretion. Our data suggest that MK4’s effect on the insulin axis may be mediated, at least in part, by FGF21. Further studies are needed for confirmation.

Abstract:

In endemic regions where simultaneous larval tick bites are common, early species-level information obtained from eschar lesions can meaningfully change pre-symptomatic triage. We report a 78-year-old woman found after ~24 hours of wandering with multiple clustered eschars on the legs and attached ticks on the trunk. PCR and Sanger sequencing of two removed ticks and ten representative eschars identified Amblyomma testudinarium in all samples. Because A. testudinarium is a known vector of severe fever with thrombocytopenia syndrome (SFTS) virus but not of Rickettsia japonica, we deprioritized Japanese spotted fever and focused targeted monitoring on early SFTS features. The patient remained asymptomatic and was transferred to long-term care. This case illustrates that, particularly in high-incidence settings with numerous bite sites, selective PCR of representative eschars provides a rapid and resource-sparing means to infer vector species and tailor risk assessment before symptom onset. Emphasizing eschar-based species identification in endemic areas can concentrate testing where pretest probability is highest, streamline surveillance, and support shared decision-making in frontline practice.

Abstract:

Background/Objectives: Biomarker-based prevention is rapidly expanding, driven by advances in molecular diagnostics, genetic profiling, and commercial direct-to-consumer (DTC) testing. General practitioners (GPs) increasingly encounter biomarker results of uncertain relevance, often introduced outside the guideline frameworks. This creates new challenges in interpretation, communication, and equitable resource use in primary care. Methods: This narrative review synthesizes evidence from population-based studies, guideline frameworks, consensus statements, and communication research to evaluate the predictive value, limitations, and real-world implications of biomarkers in asymptomatic adults. Attention is given to polygenic risk scores, DTC genetic tests, neurodegenerative and cardiovascular biomarkers, and emerging multi-omics and aging markers. Results: Several biomarkers, including high-sensitivity cardiac troponins, N-terminal pro–B-type natriuretic peptide, lipoprotein(a), coronary artery calcium scoring, and plasma p-tau species, showed robust predictive validity. However, many widely marketed biomarkers lack evidence of clinical utility, offer limited actionable benefits, or perform poorly in primary care populations. Unintended consequences, such as overdiagnosis, false positives, psychological distress, diagnostic cascades, and widening inequities, are well documented. Patients often misinterpret unvalidated biomarker results, whereas DTC testing amplifies demand without providing adequate counseling or follow-up. Conclusions: Only a minority of biomarkers currently meet the thresholds of analytical validity, clinical validity, and clinical utility required for preventive use in general practices. GPs play a critical role in contextualizing biomarker results, guiding shared decision-making, and mitigating potential harm. The responsible integration of biomarkers into preventive medicine requires clear communication, strong ethical safeguards, robust evidence, and system-level support for equitable, patient-centered care.

Abstract: Background: Squamous cell carcinoma of the skin (SCC) is the second most common neoplasm in humans and the most frequent in Brazil (80% in the head and neck region, 20% mortality). Brazil is a world leader in organ transplants (more than 30,000 transplants in 2019). The risk of transplant patients (Tx) developing SCC is 65-250 times higher, with deeper infiltration, advanced stage, higher local recurrence, occult metastases and worse survival. Objective: To investigate the prognostic factors of locally advanced cutaneous squamous cell carcinoma (LASCC) of the head and neck region in transplant patients. Methods:16-year retrospective, single-center series of patients with LASCC in the head and neck region who underwent surgical treatment. Were analyzed: clinical and Tx data, clinical/pathological stage, surgical treatment, parotid/regional and distant metastases, recurrence and survival. Results: 156 patients were included: 69.2% women, 65.3 years; mean primary size: 4.24 cm, 66% T3/T4 tumors, 71% grade 2/3 differentiation, 20.5% transplant recipients, follow-up: 33.6 months. Most affected regions: malar/nasal (28.8%), auricular (19.2%). Surgeries: wide resection with reconstruction (58.9%), exenteration (14.1%), temporalectomy (11.5%). Univariate analysis: Recurrence: immunosuppressor drugs (p=0.009), transplanted (p=0.006), compromised margin (p=0.049), Mortality: immunosuppression (p=0.028), Total Resection and reconstruction (p=0.013), Stage(8ed) III-IV (p&lt;0.001), compromised margin (p&lt;0.001), neck metastasis with extranodal extension (p=0.018). Multivariate analysis: Recurrence: Transplanted HR:3.69 (p&lt;0.001), Neck metastasis extranodal extension HR:5.41 (p&lt;0.001), Evolution to Distant metastasis HR:5.27 (p&lt;0.001); Mortality: Neck metastasis extranodal extension HR:1.94, (p=0.032), Compromised Margins HR:1.87 (p=0.001), Main Surgical Procedures: Temporalectomy HR:2.83 (p=0.007); Major Rhinectomy HR:2.47 (p=0.005); Worst Overall Survival: Tx compared to NonTx (p=0.069), Worst Survival with Recurrence: Tx compared to NonTx (p=0.005). Conclusions: The LASCC and Transplanted (immunosuppressed) group present low survival, worse prognosis, high risk of recurrence and mortality outcome, formulation of specific guidelines to standardize treatment and predict outcomes in this population are strictly necessary.

Abstract:

Background/Objectives: Cardiovascular disease (CVD) remains the leading cause of global morbidity and mortality. Although substantial therapeutic advances have been made over the past decades, the years 2024–2025 mark a turning point characterized by the emergence of mechanistically innovative, disease-modifying therapies that go beyond conventional risk-factor control. This narrative review aims to synthesize transformative pharmacological and regulatory milestones reshaping contemporary cardiovascular practice and establishing a roadmap for precision medicine implementation. Methods: We conducted a comprehensive narrative review of pivotal clinical trials, regulatory approvals and mechanistic frameworks for emerging cardiovascular therapeutics approved or under investigation during 2024–2025. The analysis encompasses novel agents across multiple disease domains including transthyretin amyloid cardiomyopathy (ATTR-CM), resistant hypertension, dyslipidemia, pulmonary arterial hypertension, hypertrophic cardiomyopathy, and cardiometabolic disease, with emphasis on their molecular targets, clinical efficacy, and practice-changing implications. Results: Key therapeutic advances include acoramidis and vutrisiran for ATTR-CM demonstrating significant reductions in cardiovascular mortality and hospitalization; aprocitentan for resistant hypertension alongside investigational angiotensinogen silencers and aldosterone synthase inhibitors; RNA-based dyslipidemia therapies (inclisiran, lepodisiran, pelacarsen, olezarsen) enabling durable lipid control; sotatercept introducing disease modification in pulmonary arterial hypertension; cardiac myosin inhibitors (mavacamten, aficamten) transforming hypertrophic cardiomyopathy management; and GLP-1 receptor agonist semaglutide receiving FDA approval for cardiovascular risk reduction in obesity. These agents collectively demonstrate mechanistic targeting, genetic precision, and disease modification beyond traditional risk-factor management. Conclusions: Cardiovascular medicine is transitioning from symptomatic palliation toward an era defined by molecular pathway targeting, individualized therapy, and durable disease control, establishing a new paradigm for precision cardiovascular care.

Abstract: Implant-based breast reconstruction (IBBR) remains the most common form of post-mastectomy reconstruction worldwide, offering patients a reliable and accessible option to restore breast contour. Advances in surgical technique, biomaterials, and implant technology have driven rapid evolution in the field, with the dual goals of improving aesthetic outcomes and minimizing patient morbidity. The prepectoral plane has been popularized due to the eliminated risk of animation deformity and reduced postoperative pain. Some concerns remain regarding mastectomy flap thickness and long-term oncologic and aesthetic outcomes. Concurrently, nipple-sparing mastectomy has improved aesthetic results and enabled surgeons to move beyond just restoring breast form and improve functional recovery as well, as demonstrated by surgical efforts aimed at restoring nipple–areolar complex (NAC) sensation. Adjunctive use of biologic matrices and synthetic meshes has broadened reconstructive options while next-generation implants seek to further enhance outcomes. Balanced against these innovations are important oncologic and systemic safety concerns, including breast implant-related cancers and the ongoing debate over breast implant illness (BII). This review highlights eight current “hot topics” in implant-based breast reconstruction: (1) prepectoral reconstruction, (2) nipple-sparing mastectomy, (3) oncoplastic techniques (4) nipple areolar complex (NAC) neurotization, (5) biologic matrices and synthetic meshes, (6) next-generation implants, (7) optimizing aesthetic outcomes, and (8) implant-associated cancer and systemic concerns. Together, these areas define the current landscape of innovation, controversy, and future directions in implant-based reconstruction.

Abstract: Adolescents who show both obsessive-compulsive behaviour and pronounced, labile mood present a treatment challenge: the usual recommendation of lithium, valproate or other mood stabilisers can bring metabolic and cognitive costs, yet withholding them risks an antidepressant-induced switch to mania. A 17-year-old boy illustrates an alternative course. He had childhood ADHD and long-standing checking rituals; while at boarding school overseas he developed intense rumination, wide mood swings and passive suicidal thoughts. Low-dose risperidone failed to help. Rather than add a conventional mood stabiliser, we introduced an oral glutamatergic stack aimed at reproducing ketamine-like plasticity: dextromethorphan for NMDA antagonism, piracetam to potentiate AMPA transmission and 10 mg fluoxetine nightly to slow dextromethorphan metabolism. Within weeks mood steadied, intrusive thoughts abated and function at school improved. The patient remained well without therapeutic-dose mood stabilisers. This experience suggests that carefully layered oral glutamatergic therapy may, in selected adolescents, deliver both anti-obsessional and mood-stabilising benefits while avoiding the burdens of traditional agents.

Abstract:

Background: Street sex workers (SSWs) experience some of the highest levels of health inequality in the UK yet face persistent barriers to accessing NHS healthcare. These barriers are shaped by structural disadvantage, stigma, and the complex realities of their lives. Despite significant health needs, engagement with services remains low, and existing models of care often fail to accommodate the lived experiences of this population. Aims: This study explores how SSWs access, experience, and navigate NHS healthcare. It aims to understand the barriers and enablers of access, identify areas for improvement, and offer recommendations to inform the development of more inclusive service provision. Methods: An ethnographic approach was undertaken within a South Yorkshire charitable organisation. Data collection involved participant observation and an arts-based scrapbook intended to facilitate trauma-informed, flexible engagement. Thematic analysis was used to analyse the data, organised around a dynamic, processual access using the candidacy framework. Findings: Barriers to care were present across all stages of healthcare engagement, including minimisation of health needs, administrative exclusion, lack of continuity, and stigma from professionals. Participants frequently described systems as inaccessible. Key enablers included supportive organisational staff, and consistent, trusted relationships with specific providers. Areas for Improvement and Recommendations: Findings highlight the need to simplify registration processes, provide in-person options, and reduce reliance on digital communication. Greater continuity of care and gender-sensitive, trauma-informed approaches were consistently requested. Services should not be evaluated solely by uptake but by how well they accommodate marginalised users. Healthcare settings that prioritise safety, trust, and consistency were shown to improve engagement. SW spoke of the work of access of care which for many way too hard to gain. Conclusions: SSWs are not disengaged from healthcare but are routinely excluded by systems that fail to meet their needs. Service redesign must begin from the realities of those most marginalised through co-production, to reduce health inequity and build meaningful access.

Abstract: Recurrent depressive disorder (RDD) and bipolar disorder (BD) are the most common affective disorders worldwide. However, the pathogenesis of these disorders remains far from understood. Macromolecular proton fraction (MPF) mapping is a sensitive and specific quantitative MRI method for the assessment of brain tissue myelination, but its clinical value for affective disorders remains unknown. This cross-sectional study employed fast MPF mapping on a 1.5T MRI scanner using single-point synthetic reference method to investigate myelin abnormalities in white matter of RDD and BD patients. ANOVA revealed a significant main effect of the group (RDD vs. BD vs. 2 age-matched control groups; F (3.76) =7.42, p&lt;0.001, η²=0.227). MPF values were significantly reduced in RDD versus BD patients (p&lt;0.001). BD showed elevated MPF compared to controls (p=0.01). MPF levels showed significant weak-to-moderate correlations with clinical scales of affective disorders. These findings demonstrate divergent cerebral myelination patterns—hypomyelination in RDDversus an increased myelin content in BD. In conclusion, MPF mapping demonstrated a promise as a marker of myelin content changes in affective disorder.

Abstract: Background: Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity worldwide, yet its mechanisms remain poorly understood. Dysregulated innate im-munity, specifically aberrant complement activation and excessive neutrophil extracel-lular traps (NETs) formation, contributes to endothelial dysfunction and inflammation in preeclampsia. However, the interaction between complement activation and NETs, as well as the differences between these immune pathways in early-onset and late-onset preeclampsia, remain unclear. To address this gap, we assessed complement components and NET markers across various preeclampsia phenotypes and examined their rela-tionships. Methods: Plasma samples were collected from 56 women with early-onset preeclampsia (EO-PE) before 34 weeks, 32 with late-onset preeclampsia (LO-PE) after 34 weeks, and 32 healthy pregnant women in the control group. Complement components (C1q, C3, C3a, C4, and the terminal complement complex, TCC) and NETs markers (MPO-DNA, cit-rullinated histone H3, and cathepsin G) were measured using ELISA. Group differences were assessed with non-parametric tests, and associations between markers and clinical variables were analyzed using Spearman correlations. Results: We observed higher levels of C1q, C3, C3a, and TCC in pregnant women with severe preeclampsia compared with healthy pregnancies (p < 0.001), while C4 levels remained unchanged. Among neutrophil trap biomarkers, MPO-DNA levels were el-evated in EO-PE (p = 0.019), while CitH3 and cathepsin G levels did not differ significantly between groups. Strong correlations were observed between MPO-DNA and TCC (ρ = 0.30, p = 0.013), as well as between cathepsin G and C3a (ρ = 0.40, p = 0.0007), indicating NETs–complement interactions. Patterns of complement and NETs activation were similar in early and late preeclampsia, despite differences in gestational age. Conclusions: The observed associations between MPO-DNA and TCC, and between cathepsin G and C3a, indicate meaningful crosstalk between NETs and complement ac-tivation. These findings support the role of innate immune dysregulation in preeclampsia and highlight NETs–complement interactions as potential targets for diagnostic and therapeutic approaches.

Abstract: (1) Background: MicroRNAs (miRNAs) are candidate biomarkers of therapeutic re-sponse; this study sequenced tumor miRNAs before and after neoadjuvant chemoradi-ation (CRT) in cohorts with locally advanced rectal cancer undergoing total mesorectal excision. (2) Materials and Methods: A total of 79 tumor samples, with 36 in the pre-operative (pre-OP) and 43 in the post-operative (post-OP) group, underwent miRNA profiling with the NanoString nCounter Human v3 assay and functional tar-get/pathway analysis using miRDB and TargetScanHuman. (3) Results: NanoString nCounter profiling of 798 miRNAs showed an overall higher expression in post-OP versus pre-OP samples, with 93 miRNAs upregulated in the post-OP group. Tar-get/pathway analyses of the top upregulated miRNAs indicated enrichment across 37 KEGG pathways—including MAPK and Ras signaling and proteoglycans in can-cer—and qRT-PCR validated significant post-OP increases in six miRNAs (miR-143-3p, miR-145-5p, miR-99a-5p, miR-125b-5p, miR-100-5p, and let-7c-5p). (4) Conclusion: We found and validated significant differentially expressed (DE) miRNAs in the post-OP group compared to the pre-OP group in patients with rectal cancer undergoing con-current CRT. These DE miRNAs might serve as the key molecules in CRT-induced suppression of tumor progression and immunomodulation. The further role of DE miRNAs as significant biomarkers needs to be explored in future studies.

Abstract: Objectives: This prospective study aimed to assess noise levels in otolaryngology operating rooms (OR), explore noise variation across subspecialties, and examine the correlation between noise, verbal communication, and surgery complexity. Study Design: Prospective trial. Setting: Single academic institution. Methods: Noise levels and surgeon feedback from 60 otolaryngology surgeries at a Tertiary Academic Medical Center were collected between May 2023 and March 2024. Cases were randomly selected based on staff availability, excluding emergency surgeries. The cohort included 13 general ENT, 13 facial plastics, 8 head and neck, 13 laryngology, and 13 rhinology surgeries. Noise data was recorded with a Curconsa Sound Level Meter SL720. Surgeons reported communication ease and case complexity via survey, with communication deemed impaired with the incidence of repeated information in the OR. Case complexity was rated from grade 1 (lowest) to grade 4 (highest). Results: Noise differences between subspecialties’ ORs were statistically significant (p < 0.001), but the Effect size was small (η² ≈ 0.04). The Rhinology OR showed higher average noise levels compared to Facial Plastic (Rhinology louder by ~2.2 dB) and Head-Neck (Rhinology louder by ~2.6 dB). Noise did not significantly impair communication in the OR (p=0.526). Higher noise in the OR did not significantly influence surgical complexity (p=0.547). Conclusion: Noise levels in otolaryngology operating rooms varied modestly across subspecialties. No significant association between noise levels and either communication impairment or surgical complexity was observed.

Abstract: Background and Objectives: In the context of free access to antiretroviral treatment for pregnant women in Romania since 2001 and the proven efficacy in vertical transmission of HIV, the impact on newborns exposed to HIV and antiretroviral drugs is concerning. The study focused on prematurity and low birth weight in antiretroviral HIV exposed children in two major Romanian centers, Bucharest and Constanța. Materials and Methods: A retrospective observational study was performed including couples of HIV infected women and their live singleton newborns from 2006 and 2012. Preterm delivery was defined as birth before week 37 and low birth weight was defined as birth weight less than 2500g. Results: The total number 352 children and 313 women were enrolled. Mean maternal age at delivery was 23.1 years. Mean newborns birth weight was 2726g. In the children group 191 (54.2%) were boys and the rate of HIV transmission was 13.9%.The prematurity rate was 21.5% and low birth rate was 25.56%. Preterm birth was associated with high HIV RNA in the third trimester, and HIV positive final status in infants and vaginal delivery. Low birth weight was associated with lack of antiretroviral treatment during pregnancy and HIV positive status in infants. Prematurity and low birth weight were not associated with antiretroviral class, any specific antiviral drug, maternal number of regimens or duration of antiretroviral treatment prior conception, nor with maternal exposure during puberty. Conclusions: Prematurity rate was higher in HIV vertically infected newborns and those exposed to high level of maternal viral replication during the last trimester of pregnancy. Low birth weight rate was associated with lack of in utero antiretroviral exposure. Prematurity and low birth weight were not associated with any antiretroviral class or specific antiretroviral drug, duration and number of regimens before conception or with maternal exposure during childhood and puberty.

Abstract: Multiple myeloma is a malignant tumor disease that affects plasma cells and is one of the most common tumors of lymphoid origin. In the process of oncogenesis, that is, the formation of a tumor, there is a significant change in the immune balance in the body, which leads to the suppression of the immune response to the tumor. This suppression is one of the reasons why the tumor can progress and cause serious health problems for the patient. One of the key factors that affect immune balance is innate lymphoid cells (ILCs). ILCs play an important role in regulating the immune response and can both promote and hinder the development of tumor processes, depending on their functional state and interaction with other cells of the immune system. It has been shown that the number of immature CD5+ILC2s cells in the peripheral blood of patients with multiple myeloma is comparable to that of healthy individuals. However, autologous hematopoietic stem cell transplantation in MM patients leads to an increase in the relative number of CD5+ILC2s.

Abstract: Tuberculosis (TB) persists as a devastating global health crisis, exacting a disproportionate burden on low-middle-income countries (LMIC), within which the burgeoning pediatric TB population is especially vulnerable to severe TB manifestations. Rifampicin, a cornerstone of the first-line TB regimen, is indispensable; yet its therapeutic potential is substantially constrained by intrinsic poor aqueous solubility, limited permeability, physicochemical instabilities, and deleterious drug-drug interactions with drugs such as isoniazid. Although current research focuses on formulating rifampicin into fixed-dose combinations – some reporting improved outcomes – the variable and often suboptimal rifampicin bioavailability in such formulations remains a critical concern. Consequently, the development of a stable, independent rifampicin oral formulation should be prioritized to ensure effective TB treatment. There are currently no commercially available rifampicin-only liquid preparations, despite the urgent need for palatable, flexible, age-appropriate formulations. This paucity constitutes a profound and persistent gap in pediatric TB, compromising accurate weight-based dosing, treatment adherence, and therapeutic outcomes while contributing to rifampicin resistance. This paper highlights the key characteristics and formulation challenges of rifampicin, with particular emphasis on pediatric TB. It further discusses liquid self-emulsifying drug delivery systems (SEDDSs) as a novel approach to enhance oral rifampicin delivery. These feasible lipid-based delivery systems offer notable promise, as they are capable of maintaining rifampicin in a solubilized and stable state throughout the gastrointestinal tract, which in turn will likely improve bioavailability. The possible development of a stable liquid rifampicin SEDDS represents a paradigm shift in addressing the longstanding neglect of pediatric TB treatment.

Abstract: Comorbid obsessive–compulsive symptoms in bipolar disorder remain difficult to manage because serotonin-reuptake agents can trigger mood elevation while conventional mood stabilisers seldom relieve obsessions. Rapid-acting glutamatergic interventions such as intravenous ketamine improve both mood and intrusive thinking (1,2) yet are costly and logistically demanding. We describe three consecutive adults with bipolar disorder who showed severe, mood-congruent obsessive–compulsive phenomena—including trichotillomania, onychophagia and distressing somatic ruminations—despite multiple trials of high-dose SSRIs, SNRIs, atypical antipsychotics and standard mood stabilisers. During routine outpatient care between May and November 2025 each patient began an oral ketamine-mimetic programme — the Cheung Glutamatergic Regimen — built around dextromethorphan (NMDA antagonism) whose exposure was extended with a CYP2D6 inhibitor, then augmented with piracetam (AMPA positive allosteric modulation) and, when required, L-glutamine for presynaptic glutamate replenishment. All three individuals entered sustained remission of depressive, anxious and obsessive–compulsive symptoms after the sequential addition of piracetam to the dextromethorphan base, and the gains persisted through follow-up. Treatment was generally well tolerated; transient hypomanic activation was contained by reducing dextromethorphan or its metabolic inhibitor while maintaining piracetam. These naturalistic observations suggest that a wholly oral, low-cost NMDA–AMPA modulation strategy may offer a rapid and durable option for the "bipolar-OCD" phenotype. Formal controlled studies are needed to confirm efficacy, define optimal dosing and clarify long-term safety.

Abstract:

Cadherin 13 (CDH13), also known as T-cadherin or H-cadherin, is a member of the cadherin superfamily. CDH13 is anchored to the plasma membrane via glycosylphosphatidylinositol. CDH13 plays an essential role in the development of the heart and nervous systems, including the brain. Many reports have identified CDH13 as a risk factor for neurodevelopmental disorders. Furthermore, CDH13 has been shown to be expressed in numerous cancers, but its role as a cancer-promoting or -suppressing factor remains unclear. Therefore, the development of highly sensitive and specific anti-CDH13 monoclonal antibodies (mAbs) is necessary to elucidate the biological and pathological functions of CDH13. In this study, we established a novel anti-human CDH13 mAb (clone Ca₁₃Mab-4) using the Cell-Based Immunization and Screening (CBIS) method. Ca₁₃Mab-4 can be used for flow cytometric analysis. Ca₁₃Mab-4 binds specifically to CDH13 and not to other cadherin family members. The dissociation constant values of Ca₁₃Mab-4 for CDH13-overexpressed CHO-K1 and U87MG glioma cells were determined as 2.5 (± 0.6) x 10^-8 M and 8.9 (± 2.1) x 10^-9 M, respectively. Furthermore, Ca₁₃Mab-4 clearly detected CDH13 in the western blot and immunohistochemistry of cell sections. Therefore, the Ca₁₃Mab-4, established by CBIS method, could be a valuable tool for basic research and is expected to contribute to elucidating the relationship between CDH13 and diseases, including neurodevelopmental disorders and cancer.

Abstract:

Objectives: Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults, and consolidation with autologous hematopoietic stem cell transplantation (HSCT) in AML patients represents an alternative therapeutic option in the absence of related or unrelated donors, in the elderly or in patients with good or standard risk. In this retrospective analysis, the data were evaluated from a total of 47 AML patients who underwent autologous hematopoietic stem cell transplantation between November 2012 and March 2023 at the Bone Marrow Transplantation Unit of Medicalpark Izmir Hospital. The present study also investigates the factors affecting overall survival (OS) and progression-free survival (PFS). Methods: This study is a retrospective evaluation of the data obtained from 47 patients with AML who underwent an autologous HSCT. Results: 24 patients were female, and 23 patients were male. The median age at diagnosis was 39 years (range: 18-68 y). The mean OS from diagnosis to the last follow-up or death was 26 months (4-116 months), and the PFS was 20 months (3-69 months). An assessment of the factors that influenced OS and PFS showed no significant association of NPM positivity, gender, risk group, response to first-line chemotherapy, transplantation at CR (Complete remission) 1 or CR2, LDH (lactade dehidrogenase) , CD34 count, and the day of neutrophil engraftment with OS or PFS. In patients with FLT3(fms benzeri tirozin kinaz 3) positivity, OS was significantly shorter (p < 0.05), while PFS was not significantly different (p=0.21). Conclusions: Consolidation with auto-HSCT in AML patients can be preferred in subjects with good or intermediate 1 risk category according to ELN (European leukemia net )criteria, or in subjects with intermediate 2 or poor-risk category who have no related or unrelated donor.

Abstract: Objective: Impairment of the Fas/FasL apoptotic pathway is a mechanism contributing to the malignant transformation of multiple cell types The aim of this study was to evaluate the clinical usefulness of soluble forms of both Fas receptor (sFas) and its ligand (sFasL) in the serum of patients with pancreatic and papilla of Vater adenocarcinomas. Methods: Soluble levels of Fas and FasL were measured by an ELISA in the serum of 53 healthy controls and in 82 pancreatic and in 14 Vater carcinoma patients both before surgery and 30 days after surgery. The association between preoperative levels, clinicopathological features and patient survival, and their changes following surgery were evaluated. Results: Cancer patients had significantly higher sFas and lower sFasL levels compared to healthy controls and correlated significantly with both lymph node and distant metastases and advance disease stage. Elevated sFas and decreased sFasL levels correlated significantly with poor overall survival with sFas being an independent prognostic factor. Following radical tumor resection preoperative sFas levels decreased whereas sFasL levels increased. These levels remained unchanged in cases of unresectable disease. Conclusions: Increased sFas secretion by pancreatic or Vater adenocarcinomas could contribute to the escape of cancer cells from apoptosis induction. Serum levels of sFas and sFasL could be useful tumor markers with prognostic value for pancreatic or Vater adenocarcinomas.