Mazandaran University of Medical Sciences

Major depressive disorder (MDD) is a common condition that negatively affects individuals’ emotions, thinking, and overall functioning. The primary objective of this study was to investigate the potential utility of DISC1 gene expression as a peripheral blood biomarker for the diagnosis and monitoring of treatment response in individuals with MDD. 80 healthy control participants and 80 patients diagnosed with Major Depressive Disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. The MDD patients were randomly assigned to two distinct treatment groups: one group received a standardized dose of fluoxetine (20 mg/day) (n = 40), while the other group underwent a 12-session cognitive-behavioral therapy (CBT) intervention (n = 40). The expression levels of the DISC1 gene were quantitatively assessed in both control and patient samples via qPCR before and after treatment in each group. Patients with depression had significantly lower levels of the DISC1 gene expression than the healthy control (p = 0.0025). In the fluoxetine therapy group, there was a notable reduction in the expression of the DISC1 gene (p = 0.005), while the expression in the psychotherapy group remained relatively unchanged from pre-treatment levels (p = 0.177). The expression of the Disc1 gene may serve as a putative blood biomarker for the diagnosis of MDD. Notably, the differential effects of fluoxetine and CBT on DISC1 expression highlight distinct therapeutic mechanisms. CBT may be a more effective treatment strategy for compensating the decline in DISC1 gene expression observed in patients with MDD.

The Rumpel-Leede (R-L) phenomenon represents acutely developing purpuric macules that often occur after rupture of dermal capillaries caused by proximal compressive forces and may sometimes appear as petechiae following the application of vascular pressure. In this context, the present report describes a woman who developed this phenomenon related to non-invasive blood pressure (NIBP) monitoring during electroconvulsive therapy (ECT). The patient, a 53-year-old woman, was admitted to the psychosomatic ward of a general university hospital in northern Iran in November 2023 due to a severe episode of major depressive disorder and non-compliance with pharmacological and nonpharmacological treatments. . During the sixth ECT session, her blood pressure transiently increased from 120/80 mmHg to 140/90 mmHg and returned to 120/70 mmHg post-procedure. At the end of this session, purpuric lesions were observed on her right forearm distal to the tourniquet site, these lesions faded and completely resolved within 48 h. This case is notable for the combination of ECT, an uncontrolled depressive episode, and metabolic comorbidities, in the absence of chemotherapy or other known high-risk factors. Physicians, anesthesiologists, and psychiatrists should be aware of acute dermal capillary rupture following tourniquet or cuff pressure during ECT, particularly in patients with a history of DM or chronic hypertension. This case underscores the importance of clinician awareness of the R-L phenomenon during ECT to prevent unnecessary investigations.

BACKGROUND:Aedes aegypti is the main vector of arboviral diseases worldwide. The species invaded and became established in southern Iran in 2020. Insecticide-based interventions are primarily used for its control. With insecticide resistance widespread, knowledge of resistance mechanisms is vital for informed deployment of insecticidal interventions, but information from Iranian Ae. aegypti is lacking. METHODS:Fifty-six Ae. aegypti specimens were collected from the port city of Bandar Lengeh in Hormozgan Province in the South of Iran in 2020 and screened for kdr mutations. The most common kdr mutations in Latin America and Asia (V410L, S989P, V1016G/I and F1534C), especially when present in combinations, are highly predictive of DDT and pyrethroid resistance were detected. Phylogenetic analyses based on the diversity of S989P and V1016G/I mutations were undertaken to assess the phylogeography of these kdr mutations. RESULTS:Genotyping all four kdr positions of V410L, S989P, V1016G/I and F1534C revealed that only 16 out of the 56 (28.57%) specimens were homozygous wild type for all kdr mutation sites. Six haplotypes including VSVF (0.537), VSVC (0.107), LSVF (0.016), LSIF (0.071), VPGC (0.257) and LPGC (0.011) were detected in this study. For the first time, 11 specimens harbouring the V410L mutation, and 8 samples with V1016I mutation were found. V410L and V1016I were coincided in 8 specimens. Also, six specimens contained 1016G/I double mutation which was not reported before. CONCLUSIONS:The relatively high frequency of these kdr mutations in Iranian Ae. aegypti indicates a population exhibiting substantial resistance to pyrethroid insecticides, which are used widely in control operations and household formulations. The detection of the 410L/1016I kdr mutant haplotype in Iranian Ae. aegypti suggests possible convergence of invasive populations from West Africa or Latin America. However, as Iran has very limited maritime/air connections with those African countries, a Latin American origin for the invasive Ae. aegypti in Iran is more plausible.

OBJECTIVES:To assess the effects of lifestyle interventions on gestational diabetes, determine whether the effects vary by maternal body mass index, age, parity, ethnicity, education level, or intervention, and rank interventions by effectiveness. DESIGN:Individual participant data (IPD) and network meta-analysis. DATA SOURCES:Major electronic databases (January 1990 to April 2025). METHODS:This meta-analysis included randomised trials on the effects of lifestyle interventions (physical activity based, diet based, or mixed) in pregnancy on gestational diabetes. Main outcomes were gestational diabetes defined by any criteria and by UK NICE (National Institute for Health and Care Excellence) criteria; other outcomes included IADPSG (International Association of Diabetes in Pregnancy Study Group) and modified IADPSG defined gestational diabetes. A two stage IPD meta-analysis estimated summary odds ratios and 95% confidence intervals and interactions (subgroup effects), along with absolute risk reduction estimates. Aggregate data from non-IPD trials were added to the meta-analysis when possible. Intervention effects were ranked using network meta-analysis. RESULTS:104 randomised trials (35 993 women) were included, with IPD for 68% of participants (24 391 women; 54 studies). Lifestyle interventions reduced gestational diabetes defined by any criteria by 10% in IPD trials (odds ratio 0.90, 95% confidence interval (CI) 0.80 to 1.02; absolute risk reduction 1.3%, 95% CI -0.3% to 2.6%), and by 20% when combining IPD and non-IPD trials (odds ratio 0.80, 95% CI 0.73 to 0.88; absolute risk reduction 2.6%, 95% CI 1.6% to 3.6%), and no reduction was observed using NICE criteria (odds ratio 0.98, 95% CI 0.84to 1.13). Lifestyle interventions reduced gestational diabetes defined using IADPSG criteria by 14% in IPD trials (odds ratio 0.86, 95% CI 0.75 to 0.97; absolute risk reduction 2.7%, 95% CI 0.6% to 5.0%) and by 18% when combining IPD and non-IPD trials (odds ratio 0.82, 95% CI 0.72 to 0.93; absolute risk reduction 3.5%, 95% CI 1.3% to 5.7%). Effects did not vary by maternal characteristics, except for education. Although women of all educational levels benefited from the intervention, the benefit was less in those with low education (low v middle interaction: odds ratio 0.68, 95% CI 0.51 to 0.90; low v high interaction: odds ratio 0.71, 95% CI 0.54 to 0.93). Benefits did not vary by intervention characteristics, except for greater effectiveness with group format (odds ratio 0.81, 95% CI 0.68 to 0.97; absolute risk reduction 2.5%, 95% CI 0.4% to 4.3%) and newly trained facilitators (odds ratio 0.82, 95% CI 0.69 to 0.96; absolute risk reduction 2.4%, 95% CI 0.5% to 4.2%). Physical activity based interventions ranked highest (mean rank 1.1, 95% CI 1 to 2) in preventing gestational diabetes. CONCLUSIONS:Lifestyle interventions in pregnancy are likely to prevent gestational diabetes, with effects varying according to diagnostic criteria. Implementation strategies should address inequalities by maternal education, and consider group formats, provider training, and physical activity based interventions to prevent gestational diabetes. STUDY REGISTRATION:PROSPERO CRD42020212884.

Chemotherapy remains a foundation of cancer care but is limited by multidrug resistance, systemic toxicities, and suboptimal selectivity, prompting interest in adjunctive strategies that improve efficacy and tolerability without adding significant burden to patients or healthcare systems. This review highlights evidence on natural bioactive compounds, including polyphenols, alkaloids, terpenoids, and fungal metabolites, as adjuvants to standard chemotherapeutics, with objectives to: first, delineate mechanisms by which these agents enhance cytotoxic efficacy and overcome resistance; second, summarize preclinical and clinical combination data; and third, evaluate their potential to mitigate chemotherapy-induced organ toxicities through pathway modulation. Natural bioactives modulate key oncogenic and stress-response pathways, such as NF-κB, PI3K/AKT/mTOR, and NRF2/HO-1, thereby sensitizing tumors to chemotherapy, attenuating pro-survival signaling, and enhancing apoptosis while reducing inflammatory and oxidative injury in normal tissues. Exemplary combinations, including curcumin with 5‑fluorouracil and resveratrol with cisplatin, have demonstrated improved antitumor activity and reduced toxicity in preclinical models, with early clinical observations supporting feasibility and safety in selected settings. Additionally, several compounds exhibit organ-protective effects against cardiotoxicity, nephrotoxicity, neurotoxicity, and gastrointestinal injury induced by chemotherapy, suggesting dual benefits on efficacy and tolerability profiles. Integrating natural bioactives with conventional chemotherapy represents a promising strategy to enhance therapeutic index by concurrently amplifying antitumor mechanisms and mitigating dose‑limiting toxicities, though broader clinical validation and standardized quality controls are needed for routine adoption. •Cancer incidence and mortality rates are rising worldwide, posing significant public health challenges •Chemotherapy remains the primary treatment despite tumor resistance and severe patient side effects. •Combination therapies targeting multiple pathways improve efficacy and reduce harmful chemotherapy side effects.