Introduction: Diabetes mellitus is associated with systemic complications, including the development of pulmonary injury, characterized mainly by excessive accumulation of extracellular matrix components and inflammatory cell infiltration in lung tissue. This process is driven by oxidative stress and chronic inflammation, both caused and exacerbated by hyperglycemia. N-acetylcysteine (NAC) and glycine, known for their antioxidant and anti-inflammatory effects, offer potential therapeutic benefits in mitigating diabetes-induced lung injury. Objective: The study aimed to investigate the effects of supplementation by either NAC or glycine or their combination on reducing lung injury in rats with type 1 diabetes Materials and methods: The study used 30 adult Wistar albino rats (10 weeks old, weighing between 180 g and 380 g). Six of them were used as controls, while 24 adult rats (10 weeks old, 180-380 g) with type 1 diabetes, induced through a single intraperitoneal injection of streptozotocin (STZ) at a dose of 55 mg/kg, were randomly assigned to four experimental groups: control (CTL), diabetic (Db), NAC treatment (diabetic+NAC), glycine treatment (diabetic+glycine), and combined NAC and glycine treatment (diabetic+NAC+glycine). NAC (100 mg/kg) and glycine (250 mg/kg) were administered orally for 12 weeks. At the end of the study, lung tissues were collected for histopathological examination. Qualitative, semi-quantitative, and stereological histological analysis was used to analyze structural changes in the lung tissue. Semi-quantitative scoring was carried out to evaluate the extent of inflammation, while stereological analysis was performed to determine the volume density of alveolar spaces and septal connective tissue. The semi-quantitative scoring included scores ranging from 0 (absent), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe). Results: Qualitative histological analysis revealed pronounced inflammation and fibrosis in the lungs of untreated diabetic rats, characterized by thickened alveolar septa and immune cell infiltration. Both treatments with NAC and glycine individually reduced inflammation and fibrosis compared to untreated diabetic rats. The greatest improvement was observed in the NAC+glycine group, where the alveolar structure appeared almost normal, with minimal inflammation. Semiquantitative analysis showed statistically significant differences in peribronchial and peribrochiolar infiltrates between the diabetic group (2.16±0.47) and the control group (0.33±0.21, p=0.026). The combination of NAC and glycine significantly reduced peribronchial and peribronchiolar infiltrates (0.33±0.33, p=0.026) compared to the diabetic group. Similarly, septal inflammatory infiltrates were significantly lower in the NAC+glycine group (1±0.36) compared to diabetic rats (3.33±0.33, p=0.004). Total airway inflammatory infiltration was also significantly reduced in the NAC+glycine group (1.33±0.33, p=0.002) compared to the diabetic group (5.5±0.5). Conclusion: As the combination of NAC and glycine demonstrated protective effects against lung inflammation and fibrosis in diabetic rats, a synergistic effect of NAC and glycine in mitigating pulmonary complications associated with type 1 diabetes may be suggested. These findings warrant further exploration of the combination for managing diabetic lung disease and potentially other fibrotic conditions.

(1) Background: This study investigates the effects of curing light intensity, exposure time, and distance on the Vickers microhardness (VMH), hardness bottom-to-top ratio (HR), and temperature rise (TR) of conventional dental resin-based composite (RBC). (2) Materials and Methods: Specimens of one conventional RBC (Tetric EvoCeram, Ivoclar Vivadent) were cured with 12 different curing protocols (CPs), created with three different light intensities (Quartz Tungsten Halogen 300 mW/cm2, LED 650 mW/cm2, LED 1100 mW/cm2), two exposure times (20 and 40 s), and two distances of curing tip (0 and 8 mm). The VMH of top (VMH-T) and bottom (VMH-B) surfaces was measured. The hardness bottom-to-top ratio (HR) was calculated from VMH-B and VMH-T. The HR below 80% was rated as inadequate polymerization. The TR at the depth of 2 mm within the RBC was measured using a K-type thermocouple. Data were analyzed using Levene’s test and the multivariate analysis of variance (MANOVA). The level of significance was set at p < 0.05. (3) Results: Exposure time and distance significantly influenced VMH-B and HR. Increased distance significantly reduced VMH-B, HR, and TR. CPs 300 mW/cm2/8 mm/20 s and 650 mW/cm2/8 mm/20 s produced inadequate polymerization (HR < 80%). Prolonged exposure time produced higher values of VMH-B and HR. The TR was significantly influenced by light intensity and distance. (4) Conclusions: Suboptimal light intensity (<800 mW/cm2) can produce inadequate polymerization at the lower side of the composite layer when used from a distance. Prolonged irradiation can improve the polymerization to a certain extent. Clinicians are advised to monitor the intensity of the LCUs in order to optimize the photopolymerization process. Caution is required when polymerizing with high-intensity curing light in direct contact with the RBC with longer exposure times than recommended.

Summary Background Stillbirth is a devastating and often avoidable adverse pregnancy outcome. Monitoring stillbirth levels and trends—in a comprehensive manner that leaves no one uncounted—is imperative for continuing progress in pregnancy loss reduction. This analysis, completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, methodically accounted for different stillbirth definitions with the aim of comprehensively estimating all stillbirths at 20 weeks or longer for 204 countries and territories from 1990 to 2021. Methods We extracted data on stillbirths from 11 412 sources across 185 of 204 countries and territories, including 234 surveys, 231 published studies, 1633 vital statistics reports, and 10 585 unique location-year combinations from vital registration systems. Our final dataset comprised 11 different definitions, which were adjusted to match two gestational age thresholds: 20 weeks or longer (reference) and 28 weeks or longer (for comparisons). We modelled the ratio of stillbirth rate to neonatal mortality rate with spatiotemporal Gaussian process regression for each location and year, and then used final GBD 2021 assessments of fertility and all-cause neonatal mortality to calculate total stillbirths. Secondary analyses evaluated the number of stillbirths missed with the more restrictive gestational age definition, trends in stillbirths as a function of Socio-demographic Index, and progress in reducing stillbirths relative to neonatal deaths. Findings In 2021, the global stillbirth rate was 23·0 (95% uncertainty interval [UI] 19·7–27·2) per 1000 births (stillbirths plus livebirths) at 20 weeks' gestation or longer, compared to 16·1 (13·9–19·0) per 1000 births at 28 weeks' gestation or longer. The global neonatal mortality rate in 2021 was 17·1 (14·8–19·9) per 1000 livebirths, corresponding to 2·19 million (1·90–2·55) neonatal deaths. The estimated number of stillbirths occurring at 20 weeks' gestation or longer decreased from 5·08 million (95% UI 4·07–6·35) in 1990 to 3·04 million (2·61–3·62) in 2021, corresponding to a 39·8% (31·8–48·0) reduction, which lagged behind a global improvement in neonatal deaths of 45·6% (36·3–53·1) for the same period (down from 4·03 million [3·86–4·22] neonatal deaths in 1990). Stillbirths in south Asia and sub-Saharan Africa comprised 77·4% (2·35 million of 3·04 million) of the global total, an increase from 60·3% (3·07 million of 5·08 million) in 1990. In 2021, 0·926 million (0·792–1·10) stillbirths, corresponding to 30·5% of the global total (3·04 million), occurred between 20 weeks' gestation and 28 weeks' gestation, with substantial variation at the country level. Interpretation Despite the gradual global decline in stillbirths between 1990 and 2021, the overall number of stillbirths remains substantially high. Counting all stillbirths is paramount to progress, as nearly a third—close to 1 million in total—are left uncounted at the 28 weeks or longer threshold. Our findings draw attention to the differential progress in reducing stillbirths, with a high burden concentrated in countries with low development status. Scarce data availability and poor data quality constrain our capacity to precisely account for stillbirths in many locations. Addressing inequities in universal maternal health coverage, strengthening the quality of maternal health care, and improving the robustness of data systems are urgently needed to reduce the global burden of stillbirths. Funding Bill & Melinda Gates Foundation.

AIM Acute kidney injury (AKI) presents a high mortality complication in patients with acute myocardial infarction (AMI). Yet, its correlation with non-ST elevation myocardial infarction (NSTEMI) remains neglected in the literature. This study aims to investigate the prevalence, risk factors, clinical features, and short-term outcomes associated with AKI development in patients with acute NSTEMI. METHODS A one-year prospective observational cohort study involved 170 consecutive patients hospitalized in the Intensive Care Department of the Internal Medicine Clinic at the University Clinical Centre Tuzla diagnosed with acute NSTEMI. Patients were subsequently categorized into AKI and non-AKI groups based on AKI development within 48 hours. Demographic characteristics, laboratory findings, and short-term clinical outcomes were compared between the groups. RESULTS Of 170 patients, 31 (18.2%) developed AKI within 48 hours of acute NSTEMI. Significant age differences, blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), blood glucose level (BGL), C-reactive protein (CRP), and high sensitivity (hs) troponin were observed, making patients with lower baseline kidney function, more extensive myocardial infarction, and a heavier systemic inflammatory response following acute NSTEMI more susceptible to AKI development. In the follow-up period, mortality rates were significantly higher in the AKI group, amounting to 35.5% compared to 10.1% in the non-AKI group. Additionally, mortality increased with the severity of AKI, reaching 100% in AKI stage 2. CONCLUSION This study highlights demographic, clinical and laboratory findings in patients with acute NSTEMI, which contribute to AKI development. Early detection and tailored interventions are crucial in mitigating AKI-associated morbidity and mortality.

ABSTRACT Background: The triglyceride/high-density lipoprotein (TG/HDL) ratio emerges as a promising marker for cardiovascular risk. However, the relationship between overall serum lipid levels and hemorrhagic stroke (HS) remains uncertain. Therefore, our study aims to explore the association between this novel index and mortality in HS patients. Methods: Utilizing a retrospective-prospective framework from January 2020 to August 2023, we scrutinized data from 104 hospitalized patients diagnosed with HS, with particular attention to their medical backgrounds and lipid profiles. Results: Age (odds ratio [OR], 1.078; 95% confidence interval [CI], 1.032–1.125; P = 0.001), atrial fibrillation (OR, 0.237; 95% CI, 0.074–0.760; P = 0.015), glucose level (OR, 1.121; 95% CI, 1.007–1.247; P = 0.037), and TG/HDL index (OR, 0.368; 95% CI, 0.173–0.863; P = 0.020) emerged as independent predictors for in-hospital mortality, as determined by both univariable and multivariable logistic regression analyses. Conclusion: Our results add weight to the growing evidence backing the utility of the TG/HDL index in assessing cardiovascular risk among HS patients. They emphasize the necessity of adopting a comprehensive risk assessment and management strategy that incorporates both traditional markers and novel indicators.

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Background and Objectives: This study aimed to investigate the novel adiponectin–resistin (AR) index as a predictor of the development of metabolic syndrome (MetS) in individuals with type 2 diabetes mellitus (T2DM). MetS is common in T2DM and increases cardiovascular risk. Adiponectin and resistin, adipokines with opposing effects on insulin sensitivity and inflammation, make the AR index a potential marker for metabolic risk. Materials and Methods: This prospective observational study included 80 T2DM participants (ages 30–60) from Sarajevo, Bosnia and Herzegovina, over 24 months. The participants were divided into two groups: T2DM with MetS (n = 48) and T2DM without MetS (n = 32). Anthropometric data, biochemical analyses, and serum levels of adiponectin and resistin were measured at baseline and every six months. The AR index was calculated using the formula AR = 1 + log10(R) − 1 + log10(A), where R and A represent resistin and adiponectin concentrations. Logistic regression identified predictors of MetS. Results: T2DM patients who developed MetS showed a significant decline in adiponectin levels (40.19 to 32.49 ng/mL, p = 0.02) and a rise in resistin levels (284.50 to 315.21 pg/mL, p = 0.001). The AR index increased from 2.85 to 2.98 (p = 0.001). The AR index and resistin were independent predictors of MetS after 18 months, with the AR index showing a stronger predictive value (p = 0.007; EXP(B) = 1.265). Conclusions: The AR index is a practical marker for predicting MetS development in T2DM participants, improving metabolic risk stratification. Incorporating it into clinical assessments may enhance early detection and treatment strategies.

Cationic nanostructured lipid carriers (cNLCs) represent promising non-viral carriers for nucleic acids, such as miRNAs, forming stable self-assembled miRNA complexes due to electrostatic interactions. Prepared by high-pressure homogenization, cNLC formulations, both with and without Nile Red dye demonstrated stable particle sizes in the range of 100-120 nm and positive surface charges (> 30 mV), which are necessary for effective cellular uptake. The miRNA complexes formed at mass ratios of 1:2.5 and 1:5 showed similar stability and size, with positive zeta potentials, as well as high cell viability (> 80%) in 3T3-L1 and MCF-7 cell lines. The cellular uptake studies of miRNA:cNLC complexes in both cell lines revealed that uptake was time- and concentration-dependent, with rapid initial uptake in 30 minutes and a zig-zag pattern over 24 hours. To elucidate the endocytosis mechanism of miRNA:cNLC complexes, 3T3-L1 and MCF-7 cells were incubated with different inhibitors (chlorpromazine, 5-[N-ethyl-N-isopropyl] amiloride, dynasore, nystatin, or sodium azide with 2-deoxy-D-glucose). Results showed significant inhibition of uptake at low temperatures and with ATP depletion, suggesting endocytosis, particularly macropinocytosis, as the main uptake mechanism in 3T3-L1 cells. In MCF-7 cells, the uptake was less inhibited by the substances, indicating the need for more specific methods to fully decipher the endocytic mechanisms involved. Confocal laser scanning microscopy images revealed that the complexes are internalized in vesicles, and are primarily localized in the juxtanuclear region, suggesting trafficking through the endolysosomal system. Colocalization study with LysoTracker™ Green DND-26 showed significant colocalization of miRNA:cNLC complexes with lysosomes in 3T3-L1 cells, indicating trafficking through the endolysosomal system. In MCF-7 cells, colocalization was lower, suggesting macropinocytosis as the primary uptake mechanism. Additional studies showed partial colocalization between labeled NLCs and miRNA, indicating that about 50% of miRNA is released from NLCs within 30 minutes post-transfection.

OBJECTIVES Testicular torsion (TT) is an emergency requiring timely surgery to prevent testicular loss. There is a lack of reports on the clinical significance of the time of admission (on-hours vs. off-hours) on the long-term surgical outcome of TT. METHODS We retrospectively reviewed all consecutive patients <18 years who were admitted to the hospital and treated for TT during the ten years. Patients were classified according to their admission time: weekday (on-hours), outside working hours, and weekends (off-hours). They were also classified based on their testicular outcome: salvaged and non-salvaged testis. RESULTS Seventy-two patients were included. Their median age was 14.2 years. Thirty-three patients (46 %) were admitted during on-hours, whereas 39 patients (54 %) were admitted during off-hours. Forty-three patients (59.7 %) required orchidopexy and, out of those, during the long-term follow-up, only 27 (37.5 %) had definitive testicular salvage. Forty-five patients (62.5 %) were with no testicular salvage. On-hours vs. off-hours admission had no impact on the clinical outcome (p = 0.25). However, significant differences in the duration of symptoms (DoS) between the orchidopexy and orchidectomy groups were observed (p < 0.001). CONCLUSION Testicular torsion is a time-dependent diagnosis, and any delay in treatment could cause testicular loss. Our data suggest that the DoS before admission, rather than the admission time, influences the testicular outcome. The efficient management of emergencies regardless of the time of day is a key factor for the reduced probability that admission timing affects outcomes.