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.

Precision medicine is a developing trend in oncology, and it includes the prognosis and treatment of advanced-stage ccRCC. New predictive factors and therapeutic targets for this disease are steadily needed. The aim of this study was to explore the tumor expression of inversin as a potential prognostic factor and/or therapeutic target in ccRCC. We compared the expression of inversin between primary ccRCC and normal renal tissues by using immunohistochemistry and rtPCR in our cohort, and we also analyzed publicly available data from the TCGA-KIRC cohort. We found that the expression of inversin was significantly lower in primary tumor tissue, in comparison to solid normal tissue. Data from the KIRC study confirmed that a lower INVS expression level in ccRCC was significantly related with the overall and disease-specific survival, as well as with a shorter progression-free interval (p < 0.05). Four out of ten inversin interactome partners were significantly related with the overall and disease-specific survival in ccRCC. A lower expression of ANKS6 was a negative survival predictor, while a higher expression of NPHP3, DVL1, or DVL3 was related with a lower survival. The expression of INVS and its interactome partners in ccRCC was correlated with the differentiation of the tumor and metastasis. The expression of INVS and its partners was also correlated with tumor leukocyte infiltration and the expression of immune checkpoint genes. The results of this study point to inversin and a distinguished group of its interactome partners as potential prognostic factors in ccRCC, with their predominant involvement in the modulation of the inflammatory infiltration of the tumor microenvironment and a strong relationship with the metastatic potential of the tumor.

AIM To investigate the predictors of biochemical relapse (BCR) among patients with non-metastatic prostate cancer treated with radiotherapy as the first-line therapy. METHODS The study included 91 patients diagnosed with prostate cancer at the University Clinical Centre in Tuzla, Bosnia and Herzegovina. After the radiation treatment as the first line of treatment, the patients were monitored for the next 36 months. If patients were classified in medium and high-risk groups, hormone therapy was administered. The occurrence of BCR was determined based on prostate-specific antigen (PSA) values. Potential prognostic parameters, including Gleason score (GS), PSA, tumour size (TNM), and standardised risk classification (RC), were monitored. RESULTS A total of 46 (50.5%) patients were aged 66-75, with a median PSA of 14.50 ng/mL. A Gleason score <6 was found in 72 (79.1%) of patients, and 31 (34.1%) had T2c tumours. The BCR occurred in 32 (35.2%) patients, with a median relapse time of 18 months. Significant predictors of BCR were Gleason score ≥6 (OR:4.46; p=0.006) and tumour stage >T2b (OR:3.59; p=0.021). The RC showed an Area Under Curve (AUC) of 0.634 (p=0.050), indicating its potential diagnostic accuracy. CONCLUSION Gleason score ≥6 and TNM>T2b are significant predictors of biochemical relapse in prostate cancer patients treated with radiotherapy. These results emphasize the need for additional monitoring and timely treatment of clinical disease progression in patients with Gleason score ≥6 and tumour stage >T2b.

AIM Care for the inflammatory bowel disease (IBD) patients presents unique challenges as decisions regarding therapy must consider numerous distinct characteristics of each patient. The aim of the study was to recognize patients' characteristics as predictors of success in vedolizumab treatment. METHODS In a retrospective observational study, data regarding age, gender, body mass index (BMI), length of disease, previous exposure to anti-tumour necrosis factor (TNF), drugs, and smoking status were extracted from the routine clinical practice. Patients were assessed for clinical remission and steroid-free remission after the 26-week treatment with vedolizumab. RESULTS The study included 76 patients with UC and 63 with CD. A total of 63 (out of 76; 82.9%) (Cl: 72.5-90.6% ) of UC and 54 (out of 63; 85.7%) (Cl: 74.6-93.3%) CD patients achieved clinical remission in the 26-week vedolizumab treatment. Over five years, illness was noticed in 32 (53.1%) CD patients. Clinical remission was not achieved in six (out of 13; 46.1%) UC patients aged 40-49 years and six (out of nine; 66.6%) CD patients aged 30-49 years. Among CD patients, remission was achieved in 22 (85.7%) females and 23 (63.6%) males. Remission rates were generally higher in patients with a BMI of 18.6-25 and 25.1-30. Previous exposure to anti TNF drugs and smoking status did not influence treatment outcomes. CONCLUSION The efficacy of vedolizumab is a viable treatment option for both ulcerative colitis and Crohn's disease. The exploration of individual patient characteristics holds promise in predicting a treatment outcome.

AIM To compare the impact of electrical cardioversion (ECV) and pharmacological cardioversion (PCV) on left atrial size (LA) and left ventricular ejection fraction (LVEF), as well as to identify predictors of rhythm disorder recurrence in patients with atrial fibrillation (AF) or atrial flutter (AFL). METHODS A prospective observational cohort study was conducted on 105 patients with persistent AF or AFL at the University Clinical Centre Tuzla. The patients were divided into two groups: 53 underwent ECV and 52 received PCV. Demographic and clinical data, including ECG and transthoracic echocardiography, were collected. Follow-up assessments were conducted at 7 days, 1 month, and subsequently every 3 months for a year. RESULTS Baseline characteristics were similar between the groups. Recurrence of rhythm disorder within one year was observed in 52.4% of cases, with ECV showing a slightly lower, though not significantly different, primary failure rate at 7 days compared to PCV (13.2% vs. 23.1%). Significant predictors of recurrence included longer duration of disorder (p< 0.001), hypertension (p=0.016), lack of pre-cardioversion amiodarone (p=0.027), and larger LA (p< 0.001). Both ECV and PCV significantly reduced LA over time, with no significant differences in LVEF between groups. CONCLUSION Both ECV and PCV are effective in restoring sinus rhythm, with a trend towards lower recurrence in the ECV group. Predictors such as disorder duration, hypertension, lack of pre-cardioversion amiodarone, and LA should be considered when planning cardioversion to optimize patient outcomes.

AIM To investigate clinical and morphometric characteristics of patients with lower urinary tract symptoms (LUTS) due to lumbar spinal stenosis (LSS). METHODS This study evaluated LSS patients using clinical assessments of motor, sensory, bladder, and bowel functions, and functional disability scores from the Oswestry Disability Index (ODI) and Swiss Spinal Stenosis Questionnaire (SSSQ). Morphometric analysis included MRI measurements of the anteroposterior diameter of the intervertebral disc and dural sac, and the modified Torg-Pavlov ratio (mTPR), with follow-up re-evaluations at 6 months. RESULTS Of 159 patients, 49 (30.8%) had LUTS and 110 (69.2%) were in the control group. LUTS patients had a significantly higher prevalence of neurogenic claudication (100% vs. 47.3%; p<0.001), lower back pain (93.9% vs. 77.3%; p=0.011), and lower extremity pain (57.1% vs. 34.5%; p=0.008). The LUTS group also had higher ODI (54.0 vs. 50.0; p=0.019) and SSSQ score (44.0 vs. 34.0; p<0.001). Morphometric analysis showed significantly lower mTPR in LUTS patients (median 0.31 vs. 0.45; p<0.001), with an AUC of 0.704 (95%CI 0.627-0.774). mTPR ≤0.31 predicted surgical revision within 6 months (OR:3.4, CI: 1.2-9.8), motor deficiency (OR:2.1, 95%CI: 1.4-5.2), and persistent LUTS post-surgery (OR:4.5, 95%CI: 1.1-18.9). mTPR ≤0.34 was associated with worse follow-up outcome, including increased ODI (β:3.2; 95%CI: 1.1-5.3; p=0.004) and SSSQ score (β:4.8; 95%CI:2.1-7.5). CONCLUSION LUTS patients with LSS exhibit more severe symptoms and poorer outcome, with mTPR ≤0.34 being a predictor of adverse clinical outcome and the need for surgical revision within 6 months.

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