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Background and Objectives: Polydeoxyribonucleotides (PDRN), composed of DNA fragments derived from salmon DNA, is widely recognized for its regenerative properties. It has been extensively used in medical applications, such as dermatology and wound healing, due to its ability to enhance cellular metabolic activity, stimulate angiogenesis, and promote tissue regeneration. In the field of dentistry, PDRN has shown potential in promoting periodontal healing and bone regeneration. This study aims to investigate the effects of PDRN on the morphology, survival, and osteogenic differentiation of gingiva-derived stem cell spheroids, with a focus on its potential applications in tissue engineering and regenerative dentistry. Materials and Methods: Gingiva-derived mesenchymal stem cells were cultured and formed into spheroids using microwells. The cells were treated with varying concentrations of PDRN (0, 25, 50, 75, and 100 μg/mL) and cultivated in osteogenic media. Cell morphology was observed over seven days using an inverted microscope, and viability was assessed with Live/Dead Kit assays and Cell Counting Kit-8. Osteogenic differentiation was evaluated by measuring alkaline phosphatase activity and calcium deposition. The expression levels of osteogenic markers RUNX2 and COL1A1 were quantified using real-time polymerase chain reaction. RNA sequencing was performed to assess the gene expression profiles related to osteogenesis. Results: The results demonstrated that PDRN treatment had no significant effect on spheroid diameter or cellular viability during the observation period. However, a PDRN concentration of 75 μg/mL significantly enhanced calcium deposition by Day 14, suggesting increased mineralization. RUNX2 and COL1A1 mRNA expression levels varied with PDRN concentration, with the highest RUNX2 expression observed at 25 μg/mL and the highest COL1A1 expression at 75 μg/mL. RNA sequencing further confirmed the upregulation of genes involved in osteogenic differentiation, with enhanced expression of RUNX2 and COL1A1 in PDRN-treated gingiva-derived stem cell spheroids. Conclusions: In summary, PDRN did not significantly affect the viability or morphology of gingiva-derived stem cell spheroids but influenced their osteogenic differentiation and mineralization in a concentration-dependent manner. These findings suggest that PDRN may play a role in promoting osteogenic processes in tissue engineering and regenerative dentistry applications, with specific effects observed at different concentrations.

Background and Objectives: Irritable bowel syndrome (IBS), as a gastrointestinal disorder, presents with abdomen pain and alterations in the bowel habits. Its pathogenesis remains unclear. Here, we examined mitochondrial DNA copy number (mtCN) in IBS and its clinical value. Materials and Methods: mtCN was analyzed in 43 IBS patients using quantitative real-time polymerase chain reaction. Furthermore, data on the clinical characteristics of patients and symptom severity of IBS were collected, and their association with mtCN was analyzed. Results: mtCN was higher in patients with IBS (p = 0.008) and those with a drinking habit (p = 0.004). Smoking and the presence of a sleep partner showed a possible association with mtCN; however, it did not reach significance. The severity of IBS symptoms tended to positively correlate with mtCN (r = 0.279, p = 0.070). Conclusions: Overall, we demonstrated a potential association between mtCN and the clinicopathologic characteristics of patients with IBS. Further studies considering genetic and clinical factors are required.

Background and Objectives: Stroke patients often experience changes in their pelvic tilt, trunk impairments and decreased gait and balance. While various therapeutic interventions have been attempted to improve these symptoms, there is a need for interventions that are easy to apply and reduce the physical labor of physical and occupational therapists. We aimed to investigate the immediate effects of two different methods of trunk elastic taping on the pelvic inclination, trunk impairment, balance, and gait in chronic stroke patients. Materials and Methods: We performed a single-blind randomized controlled trial involving 45 patients with chronic stroke. Participants were randomly assigned to one of three groups: forward rotation with posterior pelvic tilt taping (FRPPT, n = 14), backward rotation with posterior pelvic tilt taping (BRPPT, n = 14), or placebo taping (PT = 14). This study was conducted from December 2023 to January 2024. All the measurements were performed twice: before the intervention and immediately after the intervention. The pelvic inclination was assessed using the anterior pelvic tilt angle. The trunk impairment scale (TIS) was used to measure the trunk impairment. The balance and gait were evaluated using a force plate and walkway system. Results: The pelvic inclination was significantly different in the FRPPT and BRPPT groups compared to the PT group (p < 0.05, p < 0.001). The TIS and gait were significantly increased in the FRPPT group compared to the PT group (p < 0.05). The balance significantly improved in the FRPPT and BRPPT within groups (p < 0.05). Conclusions: Two different methods of posterior pelvic tilt taping improved the anterior pelvic tilt in chronic hemiplegic stroke patients compared with PT, and the FRPPT method also improved the trunk impairment and gait. Therefore, posterior pelvic tilt taping can be used as an intervention with immediate effect.

Background and Objectives: Sarcopenia, a condition characterized by muscle mass loss, is prevalent in up to 68% of rectal cancer patients and has been described as a negative prognostic factor, impacting overall survival and tumor response. While there are extensive data on rectal cancer globally, only a handful of studies have evaluated the role of sarcopenia in locally advanced rectal cancer (LARC). Our study aimed to investigate the relationship between sarcopenia, overall response rate, and toxicity in patients who underwent total neoadjuvant treatment (TNT) for LARC. Materials and Methods: We performed a retrospective study of patients with rectal cancer treated with TNT and surgery with curative intent between 2021 and 2023 at Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj-Napoca. Sarcopenia was assessed on MRI images by measuring the psoas muscle area (PMA) at the level of the L4 vertebra before and after neoadjuvant therapy. The primary endpoints were the overall complete response rate (oCR) and acute toxicity. Results: This study included 50 patients with LARC. The oCR rate was 18% and was significantly associated with post-treatment sarcopenia (OR 0.08, p = 0.043). Patients who did not achieve a clinical or pathologic complete response had, on average, an 8% muscle loss during neoadjuvant therapy (p = 0.022). Cystitis and thrombocytopenia were significantly associated with post-treatment sarcopenia (p = 0.05 and p = 0.049). Conclusions: Sarcopenia and loss of psoas muscle during neoadjuvant therapy were negatively associated with tumor response in locally advanced rectal cancer. Thrombocytopenia and cystitis are more frequent in sarcopenic than non-sarcopenic patients undergoing neoadjuvant chemoradiation for rectal cancer.

Background and Objectives: Allergy to dust mites (HDMs) plays an important role in atopic dermatitis (AD). However, the role of this allergy in other dermatoses is little known. The aim of this study was to assess hypersensitivity to HDMs in patients with AD or hand disease using the basophil activation test. Material and Methods: A total of 52 patients with AD, 57 with hand eczema disease, and 68 healthy volunteers qualified for this study. Diagnosis was based on the Hanifin and Rajka criteria, dermatological assessment, and exclusion of other dermatoses. The participants underwent skin prick tests (SPTs), a basophil activation test (BAT) with D. pteronyssinus allergen extract, and the concentration of specific IgE (sIgE) for the same allergen in blood serum was determined. Results: Positive results in all tests (SPT, sIgE, and BAT) were obtained (24 (46.2%) patients with AD, 9 (15.8%) with hand disease, and none in the control group for p < 0.05). The results of the SPT, sIgE, and BAT correlated with each other in the AD and hand eczema groups (Spearmen correlation test, r = 0.72 or 0.85, p < 0.05). However, the BAT was positive more often than the SPT and sIgE for D. pteronyssinus. Conclusions: House dust mite hypersensitivity is common in patients with AD and eczema. The BAT may be more sensitive for assessing sensitization to house dust mites, especially in patients with hand eczema.

Background and Objectives: Dovitinib (DVB) is a pan-tyrosine kinase inhibitor (TKI) that can be administered orally. In September 2023, the FDA granted Oncoheroes approval to proceed with an Investigational New Drug (IND) application for dovitinib. This application is intended for the treatment of relapsed or advanced juvenile solid tumors, namely, osteosarcoma. Materials and Methods: The target of the present study was to develop a rapid, green, accurate, and sensitive UHPLC-MS/MS method for measuring DVB levels in human liver microsomes (HLMs). The validations of the HLMs were performed via the established UHPLC-MS/MS approach, as stated in the US FDA reported guidelines for the standards of bioanalytical method validation protocol. The StarDrop in silico software package (version 6.6), which involves the DEREK and WhichP450 in silico modules, was used to check the DVB structure for hazardous alerts and metabolic instability. The DVB and encorafenib (EFB), internal standard, and chromatographic peaks were successfully separated using a reversed phase column (an Eclipse Plus Agilent C8 column) and an isocratic mobile phase. The production of DVB parent ions was accomplished by utilizing the positive ionization mode of an ESI source. The identification and measurement of DVB daughter ions were conducted using the MRM mode. Results: The inter-day accuracy and precision exhibited a spectrum of values in the range of −0.56% to 9.33%, while the intra-day accuracy and precision showcased a range of scores between 0.28% and 7.28%. The DVB calibration curve showed a linear relationship that ranged from 1 to 3000 ng/mL. The usefulness of the currently validated UHPLC-MS/MS method was approved by the lower limit of quantification (LLOQ) of 1 ng/mL. The AGREE findings demonstrate that the UHPLC-MS/MS method had a noteworthy degree of ecological greenness. The in vitro half-life (t1/2) and intrinsic clearance (Clint) of DVB were calculated to be 15.48 min and 52.39 mL/min/kg, respectively, which aligned with the findings from the WhichP450 software (version 6.6). Conclusions: Via the usage of in silico software, it has been observed that making small changes to the structure of the aryl piperazine ring and quinolinone moieties, or replacing these groups in the drug design process, shows potential for enhancing the metabolic safety and stability of newly developed derivatives compared to DVB.

Background and Objectives: Health-seeking behavior is a critical determinant of health outcomes, particularly in countries like Indonesia. Given the increasing burden of noncommunicable diseases, understanding the factors that influence health-seeking behavior in this context is essential for developing more accessible and effective public health strategies. This study aimed to identify various factors associated with health-seeking behavior among patients with chronic diseases across Indonesia, especially in formal facilities. Materials and Methods: This study used a cross-sectional research design, utilizing Indonesian Family Life Survey (IFLS)-5 data. The inclusion criteria included respondents aged 20–74 years old with at least one chronic disease based on self-reported data. Respondents who did not receive treatment, practiced self-medication, or provided incomplete data were excluded. We used multivariate logistic regression to identify factors associated with health-seeking behavior in formal facilities. Results: The results revealed that 80.7% (n = 1993) of the 2471 respondents sought treatment in formal facilities, whereas 19.3% (n = 478) opted for informal facilities. Respondents who were Bugis (OR 9.187, 95% CI 2.182–38.683; p = 0.002), retired (OR 2.966, 95% CI 1.233–7.135; p = 0.015), did not smoke (OR 1.604, 95% CI 1.126–2.285; p = 0.009), made less than IDR 1,500,000 a month (OR 1.466, 95% CI 1.174–1.831; p = 0.000), had to travel more than 3 km to reach a treatment facility (OR 1.847, 95% CI 1.41–2.42; p = 0.000), or had more than one comorbidity (OR 1.396, 95% CI; p = 0.01) were more likely to seek treatment at formal facilities. Conclusions: These findings are expected to provide recommendations for policymakers, healthcare providers, and researchers to contribute to the development of targeted interventions that can improve healthcare access and utilization, ultimately enhancing health outcomes and equity in Indonesia.

Background and Objectives: Alopecia areata (AA) is a tissue-specific immune-mediated disorder that affects hair follicles and the nail apparatus. Due to the collapse of hair follicle immune privilege in AA, hair loss ranges in severity from small, localized patches on the scalp to the loss of entire body hair. Although AA is of uncertain etiology, the disease has a common genetic basis with a number of other autoimmune diseases. Materials and Methods: To identify candidate genes that confer susceptibility to AA in the Jordanian population and further understand the disease background, we performed DNA genotyping using case–control samples of 152 patients and 150 healthy subjects. Results: While no significant result was observed in the ten single-nucleotide polymorphisms (SNPs), CLEC4D rs4304840 variants showed significant associations with AA development within our cohort (p = 0.02). The strongest associations were for the codominant and recessive forms of rs4304840 (p = 0.023 and p = 0.0061, respectively). Conclusions: These findings suggest that CLEC4D gene variants may contribute to AA pathogenesis among Jordanians. Further advanced genetic analysis and functional investigations are required to elucidate the genetic basis of the disease.

Background and Objectives: The Coronal Plane Alignment of the Knee (CPAK) classification is a pragmatic distribution of nine phenotypes for coronal knee alignment that can be used on healthy and arthritic knees. Our study aimed to describe the CPAK distributions in a Spanish southeast osteoarthritic population and compare them to other populations’ published alignment distributions. Method and Materials: Full-leg standing X-rays of the lower limb from 528 cases originating from the so-called Vega Alta del Segura (southeast of the Iberian Peninsula) were retrospectively analysed. We measured the mechanical hip–knee–ankle, lateral distal femoral, and medial proximal tibial angles. We calculated the arithmetic hip–knee–ankle angle and the joint line obliquity to classify each case according to the criteria of the CPAK classification. Results: Based on the aHKA result, 59.1% of the cases were varus (less than −2°), 32.7% were neutral (0° ± 2°), and 8.2% were valgus (greater than +2°). Based on the JLO result, 56.7% of the cases had a distal apex (less than 177°), 39.9% had a neutral apex (180° ± 3°), and 3.4% had a proximal apex (greater than 183°). The most common CPAK distribution in our Spanish southeast osteoarthritic population was type I (30.7%), followed by type IV (25.9%), type II (21%), type V (11.2%), type III (5%), type VI (2.8%), type VII (2.4%), type VIII (0.6%), and type IX (0.4%). Conclusions: We described the distribution according to the CPAK classification in a sample of the osteoarthritic population from southeastern Spain. In our sample, more than 75% of the patients were classified as type I, II, and IV.

Background and Objectives: The deltopectoral (DP) flap represents a reconstructive option for the head and neck. It is a fasciocutaneous flap raised from the anterior chest wall below the clavicle. Its role partially declined with the arise of free flaps. However, it still remains a valid option in patients that could not undergo a reconstruction with free flaps. The aim of this retrospective study was to evaluate the role of the DP flap in head and neck reconstruction, with a focus on surgical outcomes and complications. Materials and Methods: Thirty-one patients who underwent head and neck reconstruction with DP flap were included in the study. The delayed technique was not used in any procedure to harvest the flap beyond the deltopectoral groove. The patients’ characteristics, the recipient site, the closure of the donor site, and the flap-related complications were recorded. Results: The median time to autonomization of DP flap was 23 days. Postoperative complications were observed in 10 subjects (32.3%). A partial necrosis was seen in five patients (16.1%), while a complete necrosis developed only in one case (3.2%). The diabetes mellitus was the only parameter associated with postoperative complications. In particular, the percentage of necrosis in subjects with or without diabetes was 66.7% and 8.0%, respectively. Conclusions: The DP has a wide range of applications in head and neck reconstruction, and a low complication rate can be observed. The delayed technique does not necessarily need to be applied, and the flap can be extended beyond the deltopectoral groove when necessary. However, patients with diabetes mellitus have a higher risk of postoperative necrosis of the distal portion of the flap.

Background/Objectives: Hallux valgus is a common foot deformity that requires surgical correction to restore proper alignment. Precision in the osteotomies performed during these surgeries is critical to avoid complications and improve outcomes. However, variability in surgeon experience can negatively affect precision. In this context, advances in 3D printing have enabled the development of customized surgical guides, which may enhance precision and reduce variability among surgeons with different levels of expertise. This study aims to evaluate the effectiveness of a 3D-printed surgical guide in minimally invasive hallux valgus correction, focusing on the accuracy of osteotomies performed by novice surgeons, experienced surgeons, and theoretically trained consultants. Methods: An ex vivo study was performed with 30 cadaveric feet, divided into three groups according to the level of experience of the surgeons: 3D guide group, Master’s students, professionals. All surgeons performed Akin and Reverdin-Isham osteotomies, but the experimental group (the 3D guide group) utilized a customized 3D-printed surgical guide for enhanced precision during these procedures. Radiographic measurements of osteotomy angles and alignment were taken after the interventions, and compared with the planned values. Statistical analyses were conducted to evaluate the variability in the precision of the cuts. Results: The use of the 3D-printed surgical guide significantly reduced angular variability in the experienced group, achieving higher levels of accuracy than experienced surgeons. Effect sizes, which ranged from small to large, indicated a greater impact on angle measurements (η2 = 0.46, p < 0.001); no significant differences were found between the groups in other evaluated parameters. Conclusions: The incorporation of 3D-printed surgical guides in hallux valgus surgery significantly improves osteotomy accuracy, particularly in less experienced surgeons. This suggests that these guides can help standardize procedures, reduce the learning curve, and lower intraoperative complications.

Background and Objectives: Remimazolam, an ultra-short-acting benzodiazepine, is increasingly used in procedural sedation and general anesthesia. It is characterized by rapid onset of action, inactive metabolites, no delay in recovery, and few adverse events. Its hemodynamic and respiratory stability are comparable to other anesthetics, and it is safe in high-risk and geriatric patients. Materials and Methods: This prospective, observational study enrolled 110 geriatric patients (aged 65 to 85 years) scheduled for primary total knee arthroplasty (TKA). The patients were divided into the old (65 to n = 52) and the elderly (75 to 85 years; n = 47) geriatric groups. All surgical and anesthetic methods were applied in the same manner, and TKA was performed by one surgeon. Remimazolam was infused at 6 mg/kg/h for 3 min and then at 1 mg/kg/h until the end of surgery The primary study endpoint was the requirement for flumazenil; secondary endpoints were the times to reach a bispectral index (BIS) < 60 and >80, as well as the rate of apnea occurrence. Results: Flumazenil administration was similar in both groups. There were no differences in the time to reach BIS < 60 or the rate of apnea occurrence. Recovery characteristics, including the time to reach BIS > 80 and the achievement of full consciousness, were also comparable between the groups. Conclusions: Remimazolam is well-tolerated in geriatric patients undergoing orthopedic surgery, with minimal age-related differences in response. These results suggest that remimazolam is an appropriate anesthetic for geriatric patients, even with similar dosing strategies. It provides effective anesthetic depth with no significant increases in adverse outcomes during orthopedic surgery.

Psoriasis is a common chronic inflammatory skin disease, associated with significant morbidity and a considerable negative impact on the patients’ quality of life. The complex pathogenesis of psoriasis is still incompletely understood. Genetic predisposition, environmental factors like smoking, alcohol consumption, psychological stress, consumption of certain drugs, and mechanical trauma, as well as specific immune dysfunctions, contribute to the onset of the disease. Mounting evidence indicate that skin dysbiosis plays a significant role in the development and exacerbation of psoriasis through loss of immune tolerance to commensal skin flora, an altered balance between Tregs and effector cells, and an excessive Th1 and Th17 polarization. While the implications of skin dysbiosis in psoriasis pathogenesis are only starting to be revealed, the progress in the characterization of the skin microbiome changes in psoriasis patients has opened a whole new avenue of research focusing on the modulation of the skin microbiome as an adjuvant treatment for psoriasis and as part of a long-term plan to prevent disease flares. The skin microbiome may also represent a valuable predictive marker of treatment response and may aid in the selection of the optimal personalized treatment. We present the current knowledge on the skin microbiome changes in psoriasis and the results of the studies that investigated the efficacy of the different skin microbiome modulation strategies in the management of psoriasis, and discuss the complex interaction between the host and skin commensal flora.

Implant-supported immediate loading full-arch rehabilitation has been documented in the literature. More recently, computed surgical guides have frequently been used since they facilitate planning and performing surgical treatment without the need to raise a flap, thus reducing trauma and morbidity. This case report describes an immediate full-arch, fixed rehabilitation with full loading placed on four commercially available 3D-printed implants, with a 24-month follow-up. The implants were placed with the help of a digitally planned 3D-printed surgical guide. The provisional fixed prosthesis installed immediately was replaced after 3 months. At the time, the soft and hard tissue around the implants appeared stable, without signs of inflammation. The same situation was observed at the 24-month follow-up. Three-dimensional-printed implants seem to be a promising choice in this case. However, further clinical studies with longer follow-up periods are necessary to confirm their efficacy.

Background and Objectives: Intravenous amikacin, recommended for severe or recurrent M. avium complex (MAC) infections and as initial treatment for M. abscessus lung disease, is often limited by serious adverse effects such as renal and auditory toxicities. Inhaled Amikacin Liposome Inhalation Suspension (ALIS) enhances pulmonary drug deposition while minimizing systemic adverse effects, and it has recently been introduced as an add-on therapy for refractory MAC infections or when other standard treatments are inadequate. This study aims to retrospectively describe the outcomes of Greek patients with difficult-to-treat non-tuberculous mycobacterial (NTM) lung disease following the addition of ALIS to guideline-based therapy. Materials and Methods: Seventeen consecutive patients (median age: 66 years) treated with ALIS as an add-on therapy to a standard regimen at “Sotiria” General Hospital of Chest Diseases (Athens, Greece) from 2020 to 2023 were enrolled in this study. These patients had recurrent or refractory NTM lung disease and/or limited treatment options due to prior treatment-related adverse effects. Clinical, radiological, and microbiological data on treatment response and overall outcomes after ALIS initiation were recorded for each patient. Results: By the end of 2023, 14 out of 17 patients had either successfully completed or were continuing their ALIS therapy. At 6 months, 85.7% (12/14) showed clinical, microbiological, and radiological improvement. However, 25% (3/12) of treated patients, primarily those with monomicrobial or combined M. abscessus lung disease, experienced disease relapse after therapy completion. The most frequent adverse effects related to ALIS were mild and localized to the respiratory tract, with only one patient discontinuing therapy due to hypersensitivity pneumonitis. Conclusions: Adding ALIS to standard regimens was effective and safe in a small group of Greek patients with refractory or recurrent NTM lung disease, particularly those who had discontinued intravenous aminoglycosides due to significant adverse effects, with notable responses observed in MAC lung disease. Further research is needed to validate these findings in clinical practice and to investigate ALIS’s role in NTM lung disease caused by other species.

(1) Background and Objectives: Flow assessment using cardiovascular magnetic resonance (CMR) provides important implications in determining physiologic parameters and clinically important markers. However, post-processing of CMR images remains labor- and time-intensive. This study aims to assess the validity and repeatability of fully automated segmentation of phase contrast velocity-encoded aortic root plane. (2) Materials and Methods: Aortic root images from 125 patients are segmented by artificial intelligence (AI), developed using convolutional neural networks and trained with a multicentre cohort of 160 subjects. Derived simple flow indices (forward and backward flow, systolic flow and velocity) and complex indices (aortic maximum area, systolic flow reversal ratio, flow displacement, and its angle change) were compared with those derived from manual contours. (3) Results: AI-derived simple flow indices yielded excellent repeatability compared to human segmentation (p < 0.001), with an insignificant level of bias. Complex flow indices feature good to excellent repeatability (p < 0.001), with insignificant levels of bias except flow displacement angle change and systolic retrograde flow yielding significant levels of bias (p < 0.001 and p < 0.05, respectively). (4) Conclusions: Automated flow quantification using aortic root images is comparable to human segmentation and has good to excellent repeatability. However, flow helicity and systolic retrograde flow are associated with a significant level of bias. Overall, all parameters show clinical repeatability.

Background: Diabetic retinopathy (DR) is a leading cause of blindness in patients with type 2 diabetes mellitus (T2DM). Cardiovascular risk factors, such as hypertension, obesity, and dyslipidemia, may play a crucial role in the development and progression of DR, though the evidence remains mixed. This study aimed to assess cardiovascular risk factors as independent predictors of DR and to develop a predictive model for DR progression in T2DM patients. Methods: A retrospective cross-sectional study was conducted on 377 patients with T2DM who underwent a comprehensive eye exam. Clinical data, including blood pressure, lipid profile, BMI, and smoking status, were collected. DR staging was determined through fundus photography and classified as No DR, Non-Proliferative DR (NPDR), and Mild, Moderate, Severe, or Proliferative DR (PDR). A Multivariate Logistic Regression was used to evaluate the association between cardiovascular risk factors and DR presence. Several machine learning models, including Random Forest, XGBoost, and Support Vector Machines, were applied to assess the predictive value of cardiovascular risk factors and identify key predictors. Model performance was evaluated using accuracy, precision, recall, and ROC-AUC. Results: The prevalence of DR in the cohort was 41.6%, with 34.5% having NPDR and 7.1% having PDR. A multivariate analysis identified systolic blood pressure (SBP), LDL cholesterol, and body mass index (BMI) as independent predictors of DR progression (p < 0.05). The Random Forest model showed a moderate predictive ability, with an AUC of 0.62 for distinguishing between the presence and absence of DR XGBoost showing a better performance, featuring a ROC-AUC of 0.68, while SBP, HDL cholesterol, and BMI were consistently identified as the most important predictors across models. After tuning, the XGBoost model showed a notable improvement, with an ROC-AUC of 0.72. Conclusions: Cardiovascular risk factors, particularly BP and BMI, play a significant role in the progression of DR in patients with T2DM. The predictive models, especially XGBoost, showed moderate accuracy in identifying DR stages, suggesting that integrating these risk factors into clinical practice may improve early detection and intervention strategies for DR.

Given the plethora of studies today that focus on the same topic, clinicians and other healthcare professionals increasingly rely on meta-analysis to aid in their evidence-based decision-making. This research method, which combines data from multiple studies to produce a single, more precise estimate of effect size, is invaluable for synthesizing evidence, resolving inconsistencies and guiding clinical practice and public health policies. Especially in disease prevention and control, meta-analysis has emerged as a critical tool. Meta-analysis is particularly valuable in assessing the effectiveness of preventive interventions such as vaccines, lifestyle modifications and screening programs. It provides robust evidence that supports the implementation of effective preventive measures and the discontinuation of ineffective or harmful ones. Furthermore, meta-analysis provides evidence to develop clinical practice guidelines, ensuring patients receive evidence-based treatments. In addition, public health policies aimed at disease prevention and control often rely on evidence from meta-analyses, which provide the data needed to justify and design large-scale public health initiatives. This comprehensive review delves into the role of meta-analysis in disease prevention and control, exploring its advantages, applications, challenges and overall impact on guiding clinical practice and public health policies. Through case studies and an examination of future directions, this paper underscores the pivotal role of meta-analysis in disease prevention and control.

Background and Objectives: Alzheimer’s disease is a global health concern, with a rising prevalence among the elderly. Current pharmacological treatments, including acetylcholinesterase inhibitors (AChEIs) and N-Methyl D-Aspartate (NMDA) receptor antagonists, are associated with adverse events (AEs), particularly in the context of polypharmacy. This study aimed to investigate the relationship between Alzheimer’s disease treatment combinations, the number of concomitant medications, and the occurrence of AEs. Materials and Methods: Data from the Japanese Adverse Drug Event Report database, spanning from April 2004 to June 2020, were analyzed. Patients aged 60 and older with Alzheimer’s disease treated with AChEIs (donepezil, galantamine, and rivastigmine) or the NMDA receptor antagonist memantine were included. Logistic regression models were employed to assess the association between AEs and Alzheimer’s disease drug combinations, as well as the number of concomitant medications. Results: Among 2653 patients, 47.7% were prescribed five or more drugs. The frequency of AEs was 6.4% for bradycardia, 4.6% for pneumonia, 3.6% for altered state of consciousness, 3.5% for seizures, 3.5% for decreased appetite, 3.5% for vomiting, 3.4% for loss of consciousness, 3.4% for fracture, 3.2% for cardiac failure, and 3.0% for falls. The combination of memantine with AChEIs was associated with a higher risk of bradycardia, whereas donepezil alone was linked to a reduced risk of fractures and falls. Polypharmacy was significantly correlated with an increased incidence of AEs, particularly altered state of consciousness, decreased appetite, vomiting, and falls. The adjusted odds ratios for using five or more drugs compared to no drugs was 10.45 for altered state of consciousness, 7.92 for decreased appetite, 4.74 for vomiting, and 5.95 for falls. Conclusions: In the treatment of Alzheimer’s disease, the occurrence of AEs is associated with the number of concurrent medications, independently of the known AEs of Alzheimer’s disease drugs and their combination patterns.

Background and Objectives: Urine serves as a vital diagnostic fluid, and urine cytology analysis plays a crucial role in identifying urinary system illnesses such as bladder cancer and kidney stones. The Paris System for Reporting Urinary Cytology establishes a uniform method for diagnosing urinary tract cancer. This study aimed to provide valuable insights that can inform diagnostic strategies related to kidney stones and ultimately improve patient outcomes via the early detection of the cellular changes associated with kidney stones and their relation to kidney function tests. Materials and Methods: A comparative study was conducted and comprised two groups: group 1, consisting of 50 patients diagnosed with kidney stones, and group 2, comprising 50 patients diagnosed with other kidney diseases. Renal function tests and urinalysis (via the PAP staining of urine cellular deposits to detect nuclear changes) were performed, and the results were analyzed. Results: There was a statistically significant increase in urinary red blood cells, white blood cells, and nuclear reactive atypical changes in urinary sediments of kidney stone patients compared to the patients without stones, while there was a decrease in the estimated glomerular filtration rate (eGFR). eGFR showed a 96.7% specificity in detecting cases with nuclear reactive atypia. Conclusions: eGFR emerges as a reliable diagnostic marker for the comprehensive assessment of kidney stones, particularly when associated with nuclear atypia. The significant correlation between the indicators of chronic kidney disease, such as decreased eGFR, and the presence of kidney stones emphasizes the urgent need for efficient diagnostic practices.

Background and Objectives: Acute myeloid leukemia and myelodysplastic syndrome are both clonal hematologic malignancies that primarily affect older adults. Current treatments for AML/MDS are both limited in number and efficacy. This study aims to evaluate venetoclax-based therapies in AML/MDS, focusing on overall survival and recurrence-free survival rates, and to expand real-world data on its use. Materials and Methods: Clinical and laboratory data on patients with AML/MDS aged 18≥ treated with venetoclax between January 2019 and July 2022 were included. Survival analysis was calculated based on the period from 2019 to December 2023. Results: A total of 161 AML and 40 patients with MDS were included. The median age was 63.53 ± 15.30 years for AML and 70.12 ± 10.21 years for MDS. In both groups, over 55% are male. A total of 77.6% of patients with AML and 75% of patients with MDS received treatment prior to venetoclax. Venetoclax was administered in combination with azacitidine to 84.5% of AML and 67.5% of MDS. The relapse rate in AML is approximately 15%. Overall, the 2-year survival rate is 46% and 18.73 months. The overall CR/CRi rate for patients with AML is 49.1%, while for patients with MDS, it is 50%. The 2-year survival rate for patients with MDS is 52.7%. The 2-year RFS rate was 75.5% for AML and 90.9% for MDS. The relapse rate in AML is approximately 15%. The percentage of adverse events leading to treatment discontinuation among those with grade 3–4 toxicity is low; 26.7% for AML (n = 43) and 15% for MDS (n = 6). Conclusions: Our real-world data demonstrate that venetoclax has the potential to improve overall survival rates when used in combination with HMAs and supports its use in patients with AML/MDS.

Background and Objectives: This study aimed to investigate the effect of zinc phosphate (ZnP) cement, glass ionomer cement (GIC), and nano-integrated bio-ceramic (NIB) cement on mineralization when placed in contact with bone tissue-forming cells. Materials and Methods: ZnP cement, GIC, and NIB cement were divided into direct and indirect groups. A total of 72 cement pellets (24 pellets of each test sample) of 3 × 1 mm (width × height) were prepared using polytetrafluoroethylene molds. A total of 3 sample groups were demarcated using 96- cell well culture plates. In the control group, 24 wells were filled with mineralized osteoblasts and 1 µL of gingival crevicular fluid (GCF). In test group 1, to show a direct effect, 36 samples were plated with mineralized osteoblasts and 1 µL GCF for 24 h; the cells were directly exposed to cement pellets. A total of 36 samples were immersed in GCF for 24 h; later the supernatant was transferred to the mineralized osteoblasts to demonstrate an indirect effect in test group 2. To assess the mineralization, osteoblasts were stained with alizarin red and later observed under an inverted phase-contrast microscope. Data were analyzed using the statistical package for social sciences. An independent t-test compared the direct and indirect effects of the ZnP cement, GIC, NIB cement, and control groups on the mineralization of osteoblasts derived from hDPCs. Results: A statistically significant difference was observed between the ZnP cement, GIC, and NIB cement groups (p < 0.05). ZnP cement exhibited a moderate, NIB cement the least harmful effect, and GIC showed the most harmful effect on the mineralization of osteoblast cells. Conclusions: The biocompatibility of dental luting cements is an important aspect that clinicians should consider during their selection. Nano-integrated bio-ceramic cement showed the least negative effect on the mineralization of osteoblast cells which is beneficial for the cementation of cement-retained implant prostheses. However, further studies are needed to evaluate osteoblast and osteoclast activity in vivo.

Background and Objectives: Brain imaging studies in pediatric patients with headaches often reveal inflammation of the sphenoid sinus. When we encounter patients presenting with headaches without respiratory symptoms, determining the causal relationship between isolated sphenoid sinusitis observed in brain imaging studies and headache is challenging. This study aims to evaluate the clinical characteristics of pediatric patients with headaches and isolated sphenoid sinusitis identified by brain imaging studies and to determine the effects of antibiotics on headache relief. Materials and Methods: Among patients aged Results: Brain imaging studies were performed for 1751 patients, and 205 (11.7%) and 41 (2.3%) patients demonstrated sinusitis and isolated sphenoid sinusitis, respectively. For the 41 patients with isolated sphenoid sinusitis, migraine with or without aura (58.5%) was the most frequent type of headache. Throbbing pain (34.1%) occurred most frequently, and the temporal area (51.2%) was the most common location of headache. Nausea/vomiting (56.1%) was the most common accompanying symptom, followed by ocular symptoms (34.1%). Only one (2.4%) patient complained of neurologic symptoms. Headache improved in 26 (63.4%) patients, with improvement without antibiotic therapy in 19 (46.3%) patients. The acute BS and non-BS groups demonstrated comparable characteristics, except for a higher frequency of ocular symptoms in the acute BS group than in the non-BS group (p = 0.044). Conclusions: Isolated sphenoid sinusitis was rarely identified in pediatric patients with headache examined using brain imaging studies. Considering the clinical characteristics and antibiotic effects, early intensive antibiotic therapy cannot be prioritized.

Background and Objectives: In Italy, as in the rest of the world, government restrictions aimed at containing the spread of COVID-19 primarily imposed limitations on social relationships and personal behavior. This situation significantly affected the management of chronic illnesses, including type 2 diabetes (T2D). The objective was to evaluate the perceptions of patients with T2D regarding the quality of care received during the COVID-19 pandemic and the impact on dietary and physical activity behaviors. Materials and Methods: We conducted a retrospective cross-sectional survey. Data were collected from June to July 2023 using the convenience sampling of patients with T2D, and the Patient Assessment of Chronic Illness Care (PACIC) and Medi-Lite questionnaires were administered. Results: During the research period, out of the 130 subjects who met all enrollment criteria, 103 patients were included in this study (79.23%). The results of the administered questionnaires were heterogeneous. The average scores from the PACIC Questionnaire for each question displayed significant variability, indicating a range of experiences in the quality of care. In the Medi-Lite survey, fruit, cereals, and olive oil showed the highest adherence levels, with mean scores ranging from 2.58 (SD ± 1.18) for fruit to 1.89 (SD ± 0.34) for olive oil and 1.97 (SD ± 0.17) for cereals. Patients who reported increased food intake during the lockdown attributed it to having more time to prepare meals. Physical activity levels remained unchanged for 48 patients, decreased for 45 patients, and only 9 patients managed to exercise more during the COVID-19 restrictions. Conclusions: Healthcare systems must prioritize comprehensive care plans for T2D that address not only physical health, but also emotional and social well-being. Post-pandemic, promoting healthier lifestyles and empowering patients to manage their condition is crucial. A multidisciplinary and multidimensional approach could support the care of vulnerable individuals, such as patients with T2D, especially during crises like pandemics or other dramatic events.

Background and Objectives: Remodeling and healing of the graft are crucial processes for long-term graft survival after anterior cruciate ligament reconstruction (ACLR). However, few studies have objectively evaluated the differences in graft healing between autografts and allografts. This study aimed to compare the status of the anterior cruciate ligament (ACL) grafts between hamstring tendon (HT) autografts and tibialis anterior tendon (TAT) allografts using second-look arthroscopy. Materials and Methods: The outcomes of 193 consecutive patients (153 males and 40 females, with an average age of 30.38 and BMI of 25.43 kg/m2) who underwent second-look arthroscopy following primary ACLR were retrospectively reviewed. Prior to participating in this study, all patients provided written informed consent. The patients were divided into two groups: those with HT autografts and those with TAT allografts. Confounding factors were matched between the two groups using propensity score matching (PSM). ACL graft status was assessed during second-look arthroscopy using a numeric scale system based on the degree of four parameters: graft tension, continuity, synovium coverage, and vascular marking. Clinical outcomes were assessed using the Lysholm and International Knee Documentation Committee (IKDC) scores. Graft status and clinical outcomes were compared between the two groups. Additionally, a subgroup analysis based on the timing of the second-look arthroscopy (12–24 months vs. >24 months after the initial ACLR) was conducted. Results: After PSM, 62 patients were included in each group. The second-look arthroscopy was conducted at 23.6 ± 6.6 months for the HT group and at 24.0 ± 7.9 months for the TAT group (p = 0.749). The continuity and tension of the ACL graft were not significantly different between the two groups (p = 0.146 and 0.075, respectively). However, the TAT group exhibited significantly inferior synovial coverage and vascular marking of the ACL graft compared with the HT group (p = 0.021 and 0.007, respectively). These findings were consistent regardless of the timing of the second-look arthroscopy. Clinical outcomes, according to the Lysholm and IKDC scores, significantly improved in both groups with no significant differences (p = 0.386 and 0.733, respectively). Conclusions: Although there were no differences in graft tension and continuity between HT autografts and TAT allografts, the biological healing of ACL grafts, in terms of synovialization and vascularization, was superior in HT autografts compared to TAT allografts.

Background and Objectives: Perceived health status (PHS) is associated with various health outcomes in older adults, but its relationship with resilience in the context of events with a major impact on functional status (FS), such as hip fracture, has not been explored. Our objective was to evaluate whether older adults who report good PHS before a hip fracture have a higher probability of returning to their baseline physical performance (PP) and personal independence. Materials and Methods: We analyzed data from waves 1 and 2 of the Survey of Health, Ageing and Retirement in Europe (SHARE) study, enrolling patients ≥ 65 years who experienced a hip fracture between these two waves. As study outcomes, we analyzed changes in PP and functional abilities (FAs). Results: We included 149 participants with a mean age of 75.7 years (SD: 6.5); women comprised 66%. The incidence of loss of PP was 51.7% among participants with good PHS and 59.6% among those with poor PHS. FA worsened in 40% of participants with good PHS and 58.4% in those with poor PHS. Relative risk (RR) for loss of FA in people with good PHS was 0.68 (95% CI: 0.48–0.98), which did not change after an adjustment for age, gender, baseline FA, depression, number of comorbidities, education, income, and social support, despite it not reaching statistical significance. After adjustment, the risk of worsening PP in participants with good PHS was reduced by 34% (95% CI: 0.41–1.06). Conclusions: A simple question on PHS may predict the resilience of older adults after an acute stressor. A systematic evaluation of PHS can help identify patients with a higher probability of regaining function after a hip fracture and thus provide useful information for resource allocation.

Background and Objectives: Children with disabilities face unique challenges that can affect their well-being and quality of life (QOL). This study aimed to assess the QOL and coping strategies adopted by children with disabilities and explore how socio-demographic factors influence QOL and coping strategies. Materials and Methods: This cross-sectional study, which was conducted in Saudi Arabia with children aged 6 to 18 years, used a stratified random sample to ensure representation from a variety of demographic groups. Short Form-12 (SF-12) was used to assess the QOL in the sample population. The Brief COPE Inventory was used to examine coping strategies among the children. One-way analysis of variance was applied to examine differences in the QOL, coping strategies scores, and demographic variables. Multiple regression analyses were performed to examine the role of demographic variables in predicting QOL and p value was considered statistical significance at p < 0.05. Results: The results of the study clearly revealed significant differences between the mean scores of QOL for gender, age, and type of disability, duration of disability, education qualification, family status, family occupation, and housing status. Female participants showed better QOL in physical functioning than their male counterparts. Children with intellectual disability reported better QOL in general health, vitality, social functioning, and mental health. Participants with seven to eight years of disability reported higher scores in physical functioning, vitality, and mental health. Children whose parents were working in private agencies and living in rented houses scored higher on the general health aspects of quality of life. The findings also revealed that the duration of the disability was a significant predictor of the QOL. The mean scores of different dimensions of coping strategies clearly revealed that male participants used dysfunctional coping (p < 0.01), as compared to problem-focused and emotional-focused coping while female children relied more on emotional-focused coping. Emotion-focused coping was significantly higher in participants with visual (p < 0.01), learning (p < 0.01), and intellectual disabilities (p < 0.01). Dysfunctional coping scores were higher among children with auditory disabilities (p < 0.01) and multiple disabilities (p < 0.01). Conclusions: This study highlights the significance of demographic factors in understanding and improving the well-being of a diverse population of disabled juveniles. It offers valuable insights into the subtle factors affecting quality of life. Future interventions and policies can leverage these findings to enhance the quality of life of individuals with disabilities and to foster a more supportive and inclusive approach.

Background and Objectives: Adolescent Idiopathic Scoliosis (AIS) affects individuals aged 10–18 years and is characterized by spinal deformity, three-dimensional axis deformation, and vertebral rotation. Schroth method exercises and braces have been shown to reduce the Cobb angle and halt spinal deformity progression. The aim of this study was to investigate the impact of a 12-month, supervised Schroth exercise program on scoliosis severity and quality of life in adolescents with AIS. Materials and Methods: Eighty adolescents with AIS (aged 10–17 years) were prescribed a brace and were divided into two groups. The intervention group followed a supervised Schroth exercise program three times a week for 12 months in addition to wearing a brace. The control group used only the brace. Outcomes included the Cobb angle of the main curvature and the sum of curves using radiography, the maximum angle of trunk rotation (ATR maximum, using a scoliometer), and quality of life with the Scoliosis Research Society-22 (SRS-22) questionnaire. Evaluations were conducted at baseline, after 12 months, and 6 months post-intervention. A multivariate analysis of covariance (MANCOVA) was used for statistical analysis (p-Value < 0.05). Results: The intervention group showed statistically significant improvement compared to the control group in the 12th month in Cobb angle (mean differences, 95% CI: −3.65 (−5.81, −1.53), p-Value < 0.001, Cohen’s d = 0.30), ATR maximum (mean differences, 95% CI: −3.05 (−3.86, −2.23), p-Value < 0.001, Cohen’s d = 0.74), and SRS-22 score (mean differences, 95% CI: 0.87 (0.60, 1.13), p-Value < 0.001, Cohen’s d = 0.58). Differences in ATR maximum and SRS-22 score remained significant at the 18-month measurement. No significant differences were found between groups in the sum of curves (p-Value > 0.05). Conclusions: A 12-month supervised Schroth exercise program in AIS patients undergoing brace treatment significantly improves scoliosis severity (Cobb angle and ATR maximum) and quality of life. Improvements were greater than those in shorter-duration studies, suggesting a linear dose–response relationship. Further clinical studies are needed to clarify the impact of long-term Schroth programs.

Background and Objectives: Immune checkpoint inhibitors (ICIs), which target immune checkpoints in cancer cells, are increasingly used as a mainstay in anticancer treatment. The combination of atezolizumab and bevacizumab is also a first-line treatment for hepatocellular carcinoma (HCC). However, ICIs can cause immune-related adverse events (IrAEs) which range from mild to severe, potentially leading to the need for discontinuing immunotherapy. We report a case of a pneumothorax, a rare side effect caused by IrAEs. Materials and Methods: This paper reports a case of a 78-year-old male HCC patient who developed a recurrent pneumothorax, suspected to be an adverse effect of ICIs. Results: The patient was a current smoker with a 30 pack-year smoking history. Prior to initiating ICIs, a chest CT scan showed mild emphysema and fibrosis attributable to smoking. Following ICI treatment, the patient developed a recurrent pneumothorax. Further tests revealed no underlying cause for the pneumothorax other than the ICIs and smoking, and there were no signs of intrapulmonary metastasis or pneumonitis. Conclusions: When a pneumothorax occurs in a patient undergoing immunotherapy, it is important to consider it as a potential adverse effect of the treatment. Special attention should be given to the possibility that immunotherapy may exacerbate underlying lung conditions. Patients should be advised on the importance of smoking cessation. As there are currently no guidelines for resuming immunotherapy after a pneumothorax, it is crucial to weigh the risks and benefits and consider dose reduction or discontinuation of the medication.

Background and Objectives: Developmental and epileptic encephalopathy refers to a group of conditions where patients experience abnormal development due to various causes as well as frequent epileptiform discharges that ultimately contribute, in an independent and additive fashion, to cognitive and linguistic impairments. The language and cognition outcome of these patients in adulthood has been understudied. This paper aims to present a scoping review of linguistic abilities in adults with developmental and epileptic encephalopathy to determine the extent to which language outcomes in adulthood and their relation to cognitive outcomes have been studied. Design: Two online databases were searched and the methodological framework by Arksey & O’Malley (2005) was adopted. Results: Out of the 27 selected studies, only 13 exclusively examined adults, 15 were group studies, 5 were case studies and 7 were case series. A total of 9 out of the 15 group studies provided individual results for adults. Twenty-two studies included a follow-up examination. Twenty-three studies addressed the relationship between language and cognition. The selected studies indicate the presence of language impairments, which are nevertheless differentially manifested in the syndromes under investigation, whereas individual variability is also reported. Aspects of cognition seem to correlate with linguistic abilities. Conclusions: In sum, despite variability in linguistic abilities, language deficits constitute a significant aspect of the clinical profile of many adults with developmental and epileptic encephalopathy, a finding that should be taken into account for the treatment protocols of these individuals.

The most prevalent reason for vision impairment in aging inhabitants is age-related macular degeneration (AMD), a posterior ocular disease with a poor understanding of the anatomic, genetic, and pathophysiological progression of the disease. Recently, new insights exploring the role of atrophic changes in the retinal pigment epithelium, extracellular drusen deposits, lysosomal lipofuscin, and various genes have been investigated in the progression of AMD. Hence, this review explores the incidence and risk factors for AMD, such as oxidative stress, inflammation, the complement system, and the involvement of bioactive lipids and their role in angiogenesis. In addition to intravitreal anti-vascular endothelial growth factor (VEGF) therapy and other therapeutic interventions such as oral kinase inhibitors, photodynamic, gene, and antioxidant therapy, as well as their benefits and drawbacks as AMD treatment options, strategic drug delivery methods, including drug delivery routes with a focus on intravitreal pharmacokinetics, are investigated. Further, the recent advancements in nanoformulations such as polymeric and lipid nanocarriers, liposomes, etc., intended for ocular drug delivery with pros and cons are too summarized. Therefore, the purpose of this review is to give new researchers an understanding of AMD pathophysiology, with an emphasis on angiogenesis, inflammation, the function of bioactive lipids, and therapy options. Additionally, drug delivery options that focus on the development of drug delivery system(s) via several routes of delivery can aid in the advancement of therapeutic choices.

This report describes the case of a 62-year-old male patient in Saudi Arabia who developed a diverticular pouch in his oral cavity. Diverticula are rare conditions that appear as protrusions or pouches within the digestive tract’s inner lining. The condition can occur in different parts of the digestive system, but the colon is the most affected part. As part of the patient’s symptoms, he presented with dysphagia, weight loss, and globus sensations. Multiple diagnostic tests, including ultrasound, computerized tomography (CT), and magnetic resonance imaging (MRI), did not identify the diverticula. Barium and upper gastrointestinal studies were the diagnostic tests that provided accurate diagnoses where several diverticula were discovered during the videofluoroscopic swallow study (VFSS) and fiberoptic endoscopic evaluation of swallowing (FEES). Surgical intervention was recommended by the multidisciplinary team; however, the patient rejected this treatment option. This report highlights the necessity for instrumental swallowing diagnostic evaluation in the workup of the infrequent etiologies of dysphagia and suggests a gap in the current knowledge, prompting further studies on the etiology, incidence, and optimum management of upper gastrointestinal (GI) tract diverticular disease.

Human reproduction is a captivating yet intricate field, constantly presenting new challenges and discoveries [...]

Background and Objectives: Middle East Respiratory Syndrome (MERS) is a viral respiratory illness caused by a coronavirus called Middle East respiratory syndrome. In the current study, immunoinformatics studies were applied to design an epitope-based vaccine construct against Middle East Respiratory Syndrome. Materials and Methods: In this study, epitopes base vaccine construct was designed against MERS using immunoinformatics approach. Results: In this approach, the targeted proteins were screened, and probable antigenic, non-allergenic, and good water-soluble epitopes were selected for vaccine construction. In vaccine construction, the selected epitopes were joined by GPGPG linkers, and a linear multi-epitope vaccine was constructed. The vaccine construct underwent a physiochemical property analysis. The 3D structure of the vaccine construct was predicted and subjected to refinement. After the refinement, the 3D model was subjected to a molecular docking analysis, TLRs (TLR-3 and TLR-9) were selected as receptors for vaccine construct, and the molecular docking analysis study determined that the vaccine construct has binding ability with the targeted receptor. Conclusions: The docking analysis also unveils that the vaccine construct can properly activate immune system against the target virus however experimental validation is needed to confirm the in silico findings further.

Background and Objectives: The Connexin43 (Cx43) gene is a suspected tumor suppressor gene, as re-expressed wild-type Cx43 genes reduce the malignancy potential of tumor cells. However, the role of Cx43 gene expression in human lung tumorigenesis remains unclear. Materials and Methods: Tumor tissues from 165 primary lung cancer patients were collected to study Cx43 protein expression and gene mutations using immunohistochemistry and direct DNA sequencing. In addition, Cx43 genes with or without mutations were transfected to CL-3 human lung cancer cells to confirm the function of these mutant forms of the Cx43 gene. Results: Aberrant localization of Cx43 protein in the nucleus and cytoplasm of tumor cells was detected in 14 out of 165 non-small cell lung cancer (NSCLC) patients. Mutations in the Cx43 gene were also found in patients with aberrant Cx43 localization, and transfection of these mutant genes into lung cancer cells enhanced their proliferation. Conclusions: To our knowledge, this is the first study to demonstrate Cx43 gene mutations in human lung neoplasm, supporting the hypothesis that Cx43 may function as a tumor suppressor in some lung cancer patients. Additionally, the findings suggest an association between aberrant localization of Cx43 protein expression and tumor progression.

The older segment of the global population is increasing at a rapid pace. Advancements in public health and modern medicine lengthened life expectancy and reduced the burden of disease in communities worldwide. Concurrent with this demographic change is the rise in overweight people and obesity, which is evident in all age groups. There is also an aging-related reduction in muscle mass and function, or sarcopenia, that is exacerbated by sedentary lifestyle and poor nutrition. The coexistence of muscle loss and elevated body mass index, termed “sarcopenic obesity”, has particularly deleterious consequences in older individuals. Worsening insulin resistance and a proinflammatory state operate at the pathophysiologic level and lead to adverse health outcomes such as a proclivity to cardiovascular disease, type 2 diabetes, and even cognitive dysfunction. Although the concept of sarcopenic obesity as a disease construct is being increasingly recognized, a clearer understanding is warranted in order to define its components and health impact. Research is needed at the molecular-cellular level to tie together derangements in insulin action, cytokines, myokines, and endothelial dysfunction with clinical outcomes. Lifestyle modifications as well as targeted nonpharmacologic approaches, such as supplements and antioxidants, appear to have a promising role in reducing the chronic burden of this emerging disorder. Breakthroughs in drug therapies that retard or even reverse the underlying dynamics of sarcopenia and obesity in older persons are being actively explored.

Background and Objectives: Glial fibrillary acidic protein (GFAP) is a type III intermediate filament protein primarily produced by cells in the central nervous system (CNS) and other major organs such as the kidneys. This study investigated whether serum GFAP could be used to estimate cross-sectional vasculitis activity presented via the Birmingham vasculitis activity score (BVAS) in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 74 patients with AAV. Clinical and laboratory data at diagnosis including BVAS and C-reactive protein (CRP) were reviewed. During follow-up, all-cause mortality and end-stage kidney disease (ESKD) were considered poor outcomes. Serum GFAP was measured from sera collected and stored at diagnosis. Results: The median age of the 74 patients was 63.5 years. Serum GFAP was inversely correlated with the cross-sectional BVAS (r = −0.373) and CRP (r = −0.320). It was also significantly correlated with general (r = −0.237) and renal (r = −0.335) manifestations among BVAS systemic items, and furthermore, among minor items of renal manifestation, correlating with sum scores for proteinuria (r = −0.409) and haematuria (r = −0.305). Additionally, compared with patients with serum GFAP > 194.9 pg/mL, those with serum GFAP ≤ 194.9 pg/mL showed a higher risk for progression to ESKD (relative risk 3.150) and a significantly lower cumulative ESKD-free survival rate. Conclusions: This study demonstrated the clinical potential of serum GFAP at diagnosis for predicting not only cross-sectional vasculitis activity through the anticipation of the extent of renal involvement but also future progression to ESKD in patients with AAV.

Background and Objectives: This study aims to examine the factors affecting the daily functioning of patients with obstructive sleep apnea (OSA). Materials and Methods: In addition to the polysomnography records of 361 patients, participants completed the Turkish FOSQ-10 (Functional Outcomes of Sleep-10), Medical Outcome Survey Short Form-12, Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). First, the psychometrics properties of the Turkish FOSQ-10 were evaluated. Then, factors affecting daily functioning were examined through univariate and multivariate analyses. Results: Of all participants, 68.7% (n = 248) were male, and the average age was 47.94 ± 11.08. According to the OSA category, 23% (n = 83) were mild, 22.7% (n = 82) were moderate, 45.2% (n = 163) were severe, and 9.1% (n = 33) were OSA negative. The Turkish FOSQ-10 was found to be a valid and reliable scale through validity and reliability analyses. The moderate and severe OSA patients had different FOSQ-10 Total scores compared to the negative OSA group. Daily functioning was positively associated with overall quality of life while inversely associated with depression, being anxious, and daytime sleepiness in OSA patients. In a multiple regression model, BDI, mental component summary-12, physical component summary-12, and ESS scores were significantly related to the FOSQ-10 Total score in OSA patients (p < 0.05). Conclusions: The daily functioning of moderate and severe OSA patients was worse than that of the negative OSA group. Depression, quality of life, and daytime sleepiness were simultaneously important variables associated with daily functioning in OSA patients.

Background and Objectives: Kidney disease (KD) is a common complication of diabetes mellitus (DM) associated with adverse outcomes of renal failure, cardiovascular disease, and mortality. The aim of this study was to determine the prevalence and awareness of the KD among the DM type 2 (T2DM) patients. Materials and Methods: This cross-sectional study was conducted at the University Hospital of Split between November and December of 2023 during an open call for DM patients. For each participant, blood and urine samples, along with relevant medical information, were collected, and adherence to the Mediterranean diet (MeDi) was assessed using the Mediterranean Diet Service Score (MDSS). Furthermore, blood pressure was measured, along with body composition and anthropometric parameters. Results: Of 252 T2DM patients with a median age of 67 years (IQR: 60–73), 130 (51.6%) were women. The median duration of T2DM was 10 years (IQR: 6–20). Despite the fact that 80.95% of total participants reported receiving dietary guidelines from any source, only 53.2% reported adhering to the suggested instructions, while according to the MDSS, only 7.2% adhered to the MeDi. The median body mass index was 27.6 kg/m2 (24.2–31), with 70.1% of participants overweight or obese. Only 6% of participants believed they had KD, but after blood and urine sample analysis, 31% were found to have KD. Conclusions: This study highlights a significant gap in awareness of KD, low adherence to MeDi, and a high prevalence of obesity among T2DM patients. Due to the increasing number of T2DM patients, it is crucial to improve healthy lifestyle education and make modifications within this group, as well as perform regular screening for KD and medical check-ups.

Background and Objectives: Understanding the underlying causes of implantable cardioverter-defibrillator (ICD) discharges is vital for effective management. This study aimed to evaluate the characteristics of patients admitted following ICD discharge, focusing on myocardial ischemia as a potential exacerbating factor and potential risk factors for VT recurrence. Materials and Methods: This retrospective, single-center study included 81 patients with high energy discharge from cardiac implantable electronic device admitted urgently to the cardiology department from 2015 to 2022. The exclusion criterion was ST-segment elevation acute coronary syndrome. Data were collected anonymously from electronic medical records. Patients were categorized based on coronary angiography, percutaneous angioplasty, presence of significant stenosis, recurrent ventricular tachycardia (VT), and catheter ablation. Clinical variables, including demographic data, echocardiographic parameters, and pharmacotherapy, were analyzed. The primary endpoint was the recurrence of VT during in-hospital stay. Results: Among 81 patients, predominantly male (86.4%), with a mean age of 63.6 years, 55 (67.9%) had coronary artery disease (CAD) as the primary etiology for ICD implantation. Coronary angiography was performed in 34 patients (42.0%) and showed significant stenosis (>50%) in 18 (41.8%) patients, while 8 (26.0%) individuals underwent percutaneous coronary intervention (PCI). Recurrent VT occurred in 21 subjects (26.3%), while ventricular catheter ablation was performed in 36 patients (44.0%). Referral for urgent coronary angiography was associated with presence of diabetes (p = 0.028) and hyperlipidemia (p = 0.022). Logistic regression analysis confirmed NYHA symptomatic class (OR 4.63, p = 0.04) and LVH (OR 10.59, p = 0.049) were independently associated with relapse of VT. CAD patients underwent catheter ablation more frequently (p = 0.001) than those with dilated cardiomyopathy. Conclusions: The study showed a low referral rate for coronary angiography among patients with ICD discharge. Presence of LVH and preexisting symptomatic class influence arrhythmia recurrence. Understanding these associations can guide personalized management strategies for ICD recipients.

Background and Objectives: A difficult gallbladder anatomy augments the risk of bile duct injuries (BDIs) and other complications during a laparoscopic cholecystectomy. This study compares the outcomes of a laparoscopic subtotal cholecystectomy (LSTC) and open total cholecystectomy (OTC) for difficult cholecystectomies. Materials and Methods: This retrospective analysis of gallbladder procedures (LSTC or OTC) from 2016 to 2023 examined patient demographics, surgical details, and postoperative results. The primary outcome was the incidence of a BDI. Secondary outcomes included operative duration, blood loss, and postoperative complications. Results: Seventy-one patients were included in the study. Of them, 59.2% (n = 42) underwent an LSTC and 44.6% (n = 29) underwent an OTC. The LSTC cohort was more likely to have a day-surgery case with a same-day discharge (33.3% vs. 0%, p = 0.009), less blood loss (71.4 ± 82.26 vs. 184.8 ± 234.86, p = 0.009), and a shorter operative duration (187.86 ± 68.74 vs. 258.62 ± 134.52 min, p = 0.008). Furthermore, BDI was significantly lower in the LSTC group (2.4% vs. 17.2%, p = 0.045). However, there were no significant differences between the two groups concerning intraoperative drain placement, peri-cholecystic fluid collection, bile leak, and other complications (p > 0.05). Conclusions: LSTC is a safe and effective alternative to OTC for challenging gallbladder cases. Further studies with larger sample sizes and longer follow-up periods as well as different study designs are warranted.

Septic arthritis (SA) represents an orthopedics urgency and mainly affects the knee joint. Due to its devastating effects on cartilage, immediate management is crucial. SA is characterized by an annual incidence of 2 to 10 cases per 100,000 individuals, with mortality rates fluctuating between 0.5% and 15%, with a substantially higher mortality rate observed in older people (15%) in contrast to younger cohorts (4%). The etiology of septic arthritis is multifactorial: a spectrum of Gram-positive and Gram-negative bacteria can contribute to the development of this condition, especially Staphylococcus aureus. The treatment involves urgent (arthroscopic or arthrotomic) debridement associated with adequate antibiotic therapy. Intra-articular antibiotic carriers can also be used to increase their local concentration and effectiveness. The case of a 67-year-old woman affected by knee SA from methicillin-susceptible S. aureus is presented. She was treated with an arthroscopic debridement enhanced by intra-articular antibiotic-loaded calcium sulphate beads, together with antibiotic therapy. At 2-year follow up, the infection had been eradicated and the patient fully recovered. This is the first description, to our knowledge, in the English literature, of the use of antibiotic-loaded calcium sulphate beads as an adjuvant in the surgical treatment of SA of a native knee joint.

Background and Objectives: The objective of this paper is to determine the rate and predictors of non-adherence to antiseizure medications in Saudi Arabia. Materials and Methods: A cross-sectional study which involved questionnaires and data collection from patients’ medical records was conducted at neurology clinics. The rate of non-adherence to antiseizure medications was measured using “the Medication Adherence Rating Scale” (MARS). Predictors of non-adherence to antiseizure medications were evaluated using a multidimensional questionnaire specific to epilepsy. Results: One hundred and sixty-two patients participated in the study. The mean (SD) age was 34.1 (10.4) years, and 56% were male. Epilepsy was controlled (i.e., seizure-free ≥ 1 year) in 42% of patients. The mean ± SD (range) MARS scores were 7.80 ± 1.59 (2–10). Out of 162 patients, 58 (36%) patients had MARS scores ≤ 7 out of 10. The most frequently rated predictor for non-adherence was poor seizure control, which was reported by around 36% of patients. Forgetfulness, dosing frequency, and social stigma were also among the commonest predictors of non-adherence to antiseizure medications that were rated by approximately 27%, 24%, and 22% of the patients, respectively. The impacts of several socio-demographic and clinical factors on adherence were assessed. In the regression analysis, the odds of non-adherence in a patient who experienced adverse effects were twice that of a patient who did not have adverse effects (p = 0.113). Furthermore, females, employers, and patients who had comorbidity, those with focal epilepsy, those on polytherapy of antiseizure medication, and those receiving multiple doses per day, were all more likely (but not significantly, p > 0.05) to be non-adherent compared to their counterparts. Conclusions: The significance of this study is that it reveals that adherence to antiseizure medications is suboptimal in Saudi Arabia. Poor seizure control, forgetfulness, dosing frequency, and social stigma were the primary patient-reported predictors of non-adherence in epilepsy. This emphasizes the importance of routine evaluation of adherence in practice to identify and address what individual patients perceive as a barrier to adherence with antiseizure medications.

Angiomyofibroblastoma (AMFB) is an exceedingly rare mesenchymal tumor of the lower genital tract. AMFB primarily affects the pelviperineal region, especially the vulvar in premenopausal women. Typically, AMFB is a benign disease and does not have the potential for metastasis or recurrence, requiring complete surgical excision. Its accurate differentiation from aggressive angiomyxoma is critical due to varying prognoses. A 51-year-old woman, diagnosed with mucinous carcinoma of the breast, presented with a 12 cm abdominopelvic mass identified during breast cancer staging. Imaging suggested an ovarian origin; however, surgical exploration revealed a stalk-attached cystic mass in the anterior body of the uterus. Histopathology confirmed AMFB. Immunohistochemical analysis showed positivity for estrogen and progesterone receptors and smooth muscle actin. The patient continued breast cancer treatment postoperatively without pelvic mass recurrence or complications for a postoperative follow-up period of one year. This case highlights AMFB’s potential uterine body origin, expending known tumor sites and complicating diagnosis due to overlapping features with other mesenchymal tumors. Accurate diagnosis using immunohistochemical markers and pathological features is essential to avoid unnecessary aggressive treatments. The uterine location in this case suggests a possible shared pathogenesis with uterine myomas, warranting further research into their connection. Reporting the first case of AMFB originating in the uterine body enhances understanding of this rare condition and underscores the importance of clinical awareness and precise diagnostic strategies to guide management and improve outcomes.

Background and Objectives: Millions of people worldwide suffer from diabetes. The ever-increasing number of patients poses a huge challenge to healthcare systems. The purpose of this study was to evaluate the lifestyle and self-monitoring of type 2 diabetes patients using the Healthy Lifestyle and Self-Monitoring Questionnaire. Material and Methods: The analyses conducted were based on data collected using the Polish version of the Healthy Lifestyle and Self-Control Questionnaire among 104 patients diagnosed with type 2 diabetes who were treated at the Diabetes Outpatient Clinic. The in-house study also included an analysis of the relationship between lifestyle habits and disease acceptance and chronic disease functioning. Results: Respondents scored statistically significantly higher for the Healthy Lifestyle and Self-Monitoring Questionnaire than the norms assume, and the largest differences were observed in terms of the healthy dietary choices subscale (t = 8.07; p < 0.05). Only for the subscale of organized exercise were no statistically significant differences found (t = 0.50; p = 0.620). Conclusions: Type 2 diabetes is one of the diseases in which lifestyle not only contributes to its development but is also associated with its course and treatment outcomes. Reinforcing a health-promoting lifestyle is one of the cornerstones of treating patients with type 2 diabetes.

Gerstmann syndrome, alternatively recognized as angular gyrus syndrome, epitomizes a complex cognitive impairment that has ignited substantial scholarly discourse within the realms of neurology and neuropsychology. The syndrome’s original portrayal was, however, changed. It was demonstrated that the manifestation of its symptomatic tetrad, consisting of four main neurological impairments, is not invariably complete and frequently occurs alongside additional cognitive deficits. Furthermore, the precise cerebral localization of Gerstmann syndrome was traditionally posited to be the left angular gyrus; however, studies mention the possible involvement of other eloquent cerebral areas being pathognomonic. This case report delves into the case of an 86-year-old subject who exhibited the quintessential quartet of symptoms initially delineated by Josef Gerstmann, proposing that elderly patients may manifest a predisposition towards presenting the fully characterized symptomatology initially outlined by Gerstmann.

Background and Objectives: The proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab are recently developed promising drugs used for treatment of familial hypercholesterolemia (FH). This systematic review and meta-analysis aimed to thoroughly evaluate the efficacy and safety of evolocumab and alirocumab among pediatric patients with FH. Materials and Methods: A comprehensive search was conducted in PubMed, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov from inception through July 2024 to identify primary interventional studies among pediatric patients with FH. Meta-analyses were performed if appropriate. Statistics were analyzed using Review Manager version 5.4 and Stata version 16.0. Results: Fourteen articles reporting nine unique studies were included. There were three randomized controlled trials (RCTs) assessing evolocumab or alirocumab involving a total of 320 pediatric patients, one cross-over trial and five single-arm or observational studies. Pooled results showed significant efficacy of evolocumab/alirocumab in reducing low-density lipoprotein cholesterol (LDL-C) (weighted mean difference [WMD]: −37.92%, 95% confidence interval [CI]: −43.06% to −32.78%; I2 = 0.0%, p = 0.60), apolipoprotein B (WMD: −33.67%, 95% CI: −38.12% to −29.22%; I2 = 0.0%, p = 0.71), and also lipoprotein(a) (WMD: −16.94%, 95% CI: −26.20% to −7.69%; I2 = 0.0%, p = 0.71) among pediatric patients with FH. The efficacies of evolocumab/alirocumab on LDL-C reduction within pediatric patients with heterozygous FH (HeFH) were consistent between studies, whereas in patients with homozygous FH (HoFH), it varied dramatically. Pediatric patients with the null/null variant may respond to the treatment. PCSK9 inhibitors were generally well tolerated within most pediatric patients, in line with previous studies among adult populations. Conclusions: The PCSK9 inhibitors evolocumab/alirocumab significantly reduced LDL-C and some other lipid parameters, such as apolipoprotein B, in pediatric patients with HeFH. These drugs may be appropriate as a potential therapy for pediatric patients with HoFH who cannot achieve LDL-C targets with other treatments. Evolocumab/alirocumab was generally well tolerated in the pediatric population.

Background and Objectives: Sensation of the breast skin and nipple-areolar complex (NAC) is commonly assumed to be diminished or completely absent following nipple-sparing mastectomy (NSM) with implant- or expander-based reconstruction. The purpose of this cohort study was to evaluate breast skin and NAC long-term touch pressure sensibility, from 1 month to 1 year, after NSM followed by reconstruction with an implant or expander, and patient quality of life (QoL), hypothesizing that sensibility may diminish with a small progressive return throughout the postoperative period. Materials and Methods: This was achieved by performing sensation tests using Semmes-Weinstein monofilaments (SWM) in nine predefined points of the breast and NAC, a two-point discrimination test (TPD) in the four quadrants of the breast, and QoL assessment using the BREAST-Q. We evaluated 42 patients in Pauls Stradiņš Clinical University Hospital, with a total of 66 breasts, who underwent NSM between 2021 and 2023, performing the breast sensation tests before surgery and postoperatively at 1/3/6 months and 1 year. The BREAST-Q was administered to assess patient satisfaction and well-being. Results: Our results reflect a decline in breast skin and NAC sensation in the 1-month evaluation after NSM (mean: 4.67) when compared to the assessment before surgery (mean: 2.57), with a small progressive return reflected in the 3 months (mean: 3.79), 6 months (mean: 3.68), and 1-year evaluations (mean: 3.14). The following were the mean scores obtained from the BREAST-Q: Psychosocial Well-being (mean: 66), Sexual Well-being (mean: 50), Satisfaction with Breasts Pre-OP (mean: 58), satisfaction with breast reconstruction (mean: 52), Satisfaction with Implants, Satisfaction with nipple reconstruction, Physical Well-being Chest, Adverse effects of radiation, and Satisfaction with Information. Conclusions: This study confirms that sensibility diminishes after this procedure, as observed when comparing the sensation evaluation results before the operation with the 1-month evaluation, reflecting a small progressive return in the following months.

Background and Objectives: The selection of an appropriate anesthesia method is a critical factor in the surgical treatment of proctological diseases, significantly impacting patient outcomes and comfort. Pudendal nerve block (PNB) and spinal anesthesia (SA) are commonly employed in these surgeries, yet the optimal choice between the two remains debated. This study aims to compare the efficacy and safety of PNB and SA in patients undergoing surgical treatment for various proctological conditions, with a focus on postoperative pain management, functional outcomes, and complication rates. Materials and Methods: A prospective observational study was conducted on 590 patients who underwent proctological surgery under either PNB (n = 435) or SA (n = 155). Pain levels were assessed using the Visual Analog Scale (VAS), while functional outcomes were measured using the World Health Organization Disability Assessment Schedule (WHODAS 2.0). Statistical analysis was performed to compare the outcomes between the two groups. Results: Patients in the PNB group reported significantly lower postoperative VAS scores compared to those in the SA group, particularly in hemorrhoidectomy and laser hemorrhoidoplasty procedures. The PNB group also demonstrated superior functional outcomes, with lower postoperative WHODAS 2.0 scores and a reduced incidence of urinary retention compared to the SA group. Furthermore, the duration of surgery and hospital stay were significantly shorter for patients in the PNB group. Conclusions: The findings suggest that PNB may offer advantages over SA in proctological surgeries, particularly in terms of pain management, functional recovery, and reduced complication rates. PNB should be considered a viable alternative to SA, particularly in cases where rapid recovery and minimizing complications are priorities. Exceptions to this include specific proctological surgeries, such as those for malignant tumors in the region, complex anal fistulas, proctological conditions arising from inflammatory bowel diseases, and patients on immunosuppressive therapy. Further research is needed to confirm these results and optimize anesthesia selection in this context.

Coeliac disease (CD) affects almost of 1% of the population, yet remains undiagnosed in the majority. Though the demonstration of enteropathy in duodenal biopsy was traditionally the essential criterion for the diagnosis of coeliac disease, the guidelines published by the European Society of Paediatric Gastroenterology and Nutrition (ESPGHAN) in 2012, and revised in 2020, paved the way to a no-biopsy approach to diagnosis. In a select group of children meeting certain criteria, a definitive diagnosis of CD can now be made without the need for duodenal biopsies. This is being increasingly applied in clinical practice. It is well established that untreated coeliac disease is associated with several chronic adverse health conditions. At present, a strict gluten-free diet remains the only effective treatment for CD. The advances in our understanding of the pathogenesis of CD have led to a search for alternative treatment agents. Several investigational agents are in various phases of clinical trials at present. In this review, we outline the clinical aspects of coeliac disease and summarise various investigational treatment agents.