Balkan Medical Journal最新文献

Background: Endocrine resistance remains a significant therapeutic challenge in estrogen receptor-positive (ER+) breast cancer, the most common subtype, contributing to increased morbidity and mortality. The interaction between ER and HER family receptors, particularly HER2 and epidermal growth factor receptor (EGFR), drives resistance to standard therapies such as tamoxifen and trastuzumab by activating key signaling pathways, including PI3K/AKT and RAS/MAPK. Dysregulated miRNAs, which are non-coding gene expression regulators, have been linked to therapy response.

Aims: To investigate the role of miR-99b-5p in ER-HER2/EGFR crosstalk in BT-474 cells.

Study design: Experimental study.

Methods: The expression profile and prognostic significance of miR- 99b-5p in breast cancer were analyzed using The Cancer Genome Atlas (TCGA) database. BT-474 cells were transfected with miR-99b-5p mimics and inhibitors, followed by treatment with tamoxifen and trastuzumab to assess their impact on cell proliferation and ER-HER2/EGFR crosstalk. Western blotting was performed to quantify EGFR, HER2, and ESR1 protein levels. Real-time proliferation analysis evaluated changes in cell growth following miRNA transfection and drug treatment.

Results: The study revealed that miR-99b-5p is significantly overexpressed in tumors compared to normal tissues and is associated with poor patient survival and enhanced ER signaling. Transfection with miR-99b-5p mimics increased ESR1 expression and cell proliferation, even in the presence of tamoxifen or trastuzumab, indicating that miR-99b-5p contributes to therapy resistance through receptor crosstalk. Conversely, miR-99b-5p inhibition significantly restored drug sensitivity, reducing proliferation and enhancing the effectiveness of tamoxifen and trastuzumab.

Conclusion: These findings establish miR-99b-5p as a key regulator of endocrine and HER2-targeted therapy resistance. Targeting miR-99b-5p could represent a potential therapeutic strategy to improve treatment outcomes in ER+/HER2+ breast cancer. Further research is needed to clarify the underlying molecular mechanisms and validate the therapeutic potential of miR-99b-5p inhibition in clinical applications.

Background: Numerous studies have reported neurodevelopmental disorders in children with a history of early-life iron deficiency (ID), though findings vary.

Aims: To evaluate the long-term impact of early childhood ID on neurodevelopmental outcomes.

Study design: Systematic review.

Methods: A literature search was conducted across five electronic databases (PubMed, Cochrane, Scopus, Sage, and Embase) using the keywords “iron deficiency anemia” and “infant.” The JBI critical appraisal tool for cohort studies was used to evaluate study quality.

Results: Seventeen relevant cohort studies were identified through the systematic search. Of these, 14 were rated as high quality, while 3 were classified as moderate quality. The neurodevelopmental domains assessed included cognitive deficits (seven studies), motor deficits (four studies), verbal deficits (seven studies), behavioral deficits (nine studies), auditory function (one study), and neuroendocrine function (two studies).

Conclusion: Early-life ID disrupts neurodevelopment, leading to persistent cognitive, motor, behavioral, and neuroendocrine impairments. Children with a history of early childhood ID demonstrate poorer cognitive, motor, and behavioral outcomes compared with their non-ID counterparts. Preventing ID within the first 1,000 days of life is essential to mitigate irreversible deficits in motor, cognitive, and behavioral functions.

Background: Studies on the burden and epidemiological aspects of substance-use disorders in the Middle East and North Africa (MENA) are limited.

Aims: To evaluate the burden and epidemiology of substance-use disorders in MENA countries during 1990-2019.

Study design: Ecological study.

Methods: Data from the global burden of disease study were used in the current study. The incidence, prevalence, mortality, years of life lost from mortality, years of healthy life lost due to disability, and disability-adjusted life years (DALY) rates attributable to each group of disorders across age groups, genders, years, and countries were retrieved along with their corresponding age-standardized values. Age-standardized DALYs rates of alcohol-use disorders, drug-use disorders, and substanceuse disorders associated with sociodemographic index across MENA countries and over 30 years were examined.

Results: The age-standardized DALY rate of substance-use disorders in MENA had risen from 190.1 in 1990 to 234.93 per 100,000 in 2019, indicating a 23.57% increase. In both genders, the DALY rate was highest in the 25-29-years age group in 2019 (440.81 per 100,000 in females and 645.97 per 100,000 in males). In addition, in 2019, age-standardized DALY rates of alcohol-use disorder were the highest in the United Arab Emirates (77.08 per 100,000), Afghanistan (67.77 per 100,000), and Bahrain (60.35 per 100,000). In almost all these countries, opioid-use disorder had the highest age-standardized DALY rate in 2019.

Conclusion: The burden of substance-use disorders has increased from 1990 to 2019 in the MENA region in contrast to the global trend. This study findings highlight that the current interventions and laws implemented in this region to address drug trafficking and substance-use disorders may be insufficient and ineffective, warranting further international collaboration and implementation of more effective strategies to reduce the overall burden of substance-use disorders.

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly impacted global mortality, albeit Türkiye has been largely excluded from mortality studies owing to delayed data release and a lack of nationwide analyses.

Aims: To identify the excess mortality rates in Türkiye between 2020 and 2022, analyze the temporal trends and regional differences, and determine factors associated with excess deaths at the regional level.

Study design: A cross-sectional ecological analysis.

Methods: We analyzed all-cause mortality data from the Turkish Statistical Institute from January 2015 to December 2022. The projected deaths during 2020-2022 were derived from Quasi-Poisson Regression models applied to the 2015-2019 provincial mortality data, adjusting for seasonal trends, population offsets, and overdispersion. The results were aggregated to national and socioeconomic levels for comparative analyses. Excess deaths were calculated as the difference between observed and projected deaths. P-scores and excess mortality per 100,000 inhabitants were utilized as standardized metrics. Socioeconomic disparities were examined using the Socioeconomic Development Ranking of Provinces and Regions (SEGE-2017). We assessed the associations between excess mortality and vaccination coverage, elderly population ratio, intensive care unit beds per 100,000 population, and population per family physician.

Results: Türkiye experienced 247,640 excess deaths [95% confidence interval (CI): 176,405-315,204] from 2020 to 2022. Excess mortality peaked in 2021 with 121,426 excess deaths (27.2% P-score, 143.5 per 100,000 population). Lower vaccination coverage [estimate: -0.51, 95% CI: (-0.81, -0.20), p = 0.001] and higher population per family physician [estimate: 0.01, 95% CI: (0.00, 0.02), p = 0.005] were significantly associated with higher excess mortality. A higher elderly population ratio was positively associated with excess deaths [estimate: 1.41, 95% CI: (0.50, 2.32), p = 0.003]. Socioeconomically less developed regions (SEGE 5 and SEGE 6) exhibited higher P-scores (21.3% and 20.2%, respectively), indicating greater relative increases in mortality when compared with the relatively more developed regions.

Conclusion: Excess mortality in Türkiye during the COVID-19 pandemic was substantial, particularly in 2021, and was influenced by regional socioeconomic disparities, vaccination coverage, and healthcare access. These findings underscore the importance of addressing sociodemographic factors and strengthening primary healthcare services in pandemic responses.

Background: The literature on the clinical presentations of nail unit melanoma (NUM) in different countries is limited.

Aims: To assess the specific clinical characteristics of NUM in Türkiye.

Study design: A retrospective cross sectional study.

Methods: Patients with NUM in two centers were retrospectively evaluated for their clinicopathological features, including the location, laterality, destruction of the nail plate, erosion or ulceration, presence of longitudinal melanonychia (LM), Hutchinson's sign (HS), and the absence of pigmentation and Breslow thickness. These variables were compared in terms of the main location of the NUMs (fingernail versus toenail).

Results: A total of 37 patients (54.1% female) of mean age 61.9 ± 14.8 years were enrolled. In most cases, NUMs were located in the fingernails (62.2%), with the most common location being the thumbnails (45.9%), followed by the big toenails (32.4%). Five cases had in situ melanoma presenting with LM. The mean Breslow thickness of invasive NUM lesions (n = 26) was 4.7 ± 4.1 mm (median: 3). Although all in situ NUMs were located on the hands, no statistically significant difference was noted in the Breslow thickness of invasive NUMs on the toenails and fingernails. NUMs were hypomelanotic/amelanotic in 10 (27%) patients. LM was clinically evident in 40.5% of the patients and was significantly more frequently observed on fingernails. The HS of the nail folds was noted in 40.5% of the patients, with the proximal (73.3%) and distal (73.3%) nail folds being most commonly involved. Total or partial destruction of the nail plate was recorded in 24.3% and 51.4% of the patients, respectively. Erosion and/or ulceration on the surface of the NUM was clinically present in most (75.7%) cases. Invasive NUMs associated with LM (n = 10) displayed partial destruction of the nail plate (n = 9), erosion and/or ulceration on the tumor surface (n = 7), and HS (n = 6).

Conclusion: The clinical characteristics of patients with NUM, such as more common localization on the hands, a high rate of preference for thumbnail and big toe, and the ratio of HS, were similar to the studies reported from diverse countries. Partial destruction of the nail plate is an important clinical feature of NUM. Furthermore, LM is more frequently observed in NUMs on the fingernails.