Spectroscopic and nonlinear optical investigations of biscinnamyl-sulfone derivatives: Computational and experimental insights.

Novel geometrically asymmetric biscinnamyl-sulfone compounds (6a-c) with donor-π-conjugated spacer-acceptor functionality were successfully synthesized. This was achieved by coupling cinnamaldehyde precursors with 3,3'-diaminodiphenyl sulfone in dry organic solvents, resulting in high yields. Several spectroscopic techniques were employed to identify the derivatives. The absorption spectra of these compounds exhibited broad bands that spanned up to 120 nm, which can be attributed to their extended conjugation systems. In order to explore the electronic transitions of these materials, Time-Dependent Density-Functional Theory (TD-DFT) with EIFPCM solvation mode was utilized. We computationally investigated the static nonlinear optical (NLO) parameters, including dipole moments (µ), polarizability (α), anisotropic polarizability (Δα), first-order hyperpolarization (ß), and second-order hyperpolarization (γ). Although the new structures possess different functional groups, they displayed similar electronic potentials when their molecular electrostatic potentials were plotted. These potentials are crucial in stabilizing the molecules in crystal systems through noncovalent forces such as C-H⋯π stacking and hydrogen bonding. They also provide insights into the electronic assessments and energetics of these individual forces. By estimating the frontier orbitals, we gained an understanding of the intramolecular charge transfer in the compounds. Energy gap values were determined using the orbitals of density of states method and experimentally via the Tauc method. The computational and experimental results were in good agreement. Lastly, we examined the influence of different protic and aprotic solvents on the absorption bands of compound 6b, as an example. This compound showed a significant bathochromic shift of 41 nm upon changing the solvent from acetic acid to dimethyl sulfoxide.

Exploring Through-Space Charge Transfer-Mediated Optoelectrochemical Properties of Dual-State Luminescent Aliphatic Polymers and Optoelectronic Responses toward Metal Ions.

Herein, natural-synthetic hybrid dual-state luminescent conducting polymers (DLCPs/DLCP1-DLCP8) possessing significant optoelectrochemical properties are strategically developed by the polymerization of prop-2-enamide, cis-butenedioic acid, 2-acrylamido-2-methylpropane-1-sulfonic acid, and in situ-generated 2-(3-acrylamidopropanamido)-2-methylpropane-1-sulfonic acid alongside the grafting of gum tragacanth. The spectroscopic data of aliphatic DLCPs affirm DLCP7 as the most stable supramolecular assembly endowing optoelectronic properties. Computational calculations identified -C(═O)NH-, -C(═O)OH, -OH, and -SO3H as subluminophores. The absorption spectra, excitation wavelength-/solvent-polarity-/concentration-dependent luminescence, solid state luminescence, aggregation-induced enhanced luminescence, and time-correlated single photon count (TCSPC) studies confirm the occurrence of aggregation-mediated intramolecular through-space charge transfer (ITSCT) in the excited state of DLCP7. Mulliken charge, natural bond orbital, dipole moments, and electronic potential surface analyses confirm the charge donor-acceptor system in DLCP7. Furthermore, the selective optoelectronic response of DLCP7 toward Ca2+/Cu(II) at 438/574 nm is explored using ultraviolet-visible spectra, TCSPC analyses, a dynamic light scattering study, and computational investigations. The chelation-enhanced luminescence and ITSCT inhibition are responsible for turn-on and turn-off detections of Ca2+ and Cu(II), respectively. Cu(II) → Cu(I) reduction in a DLCP7 solution is inferred from electrochemical and spectroscopic analyses. The conductivities of 9.65 × 10-5 S cm-1 (solid state) and 44.35 × 10-5 S cm-1 (solution) in DLCP7 are validated by current-voltage and electrochemical impedance measurements. Again, strong electronic conductivities of 43.89 × 10-5 S cm-1 (solid state)/53.34 × 10-5 S cm-1 (solution) and 45.42 × 10-5 S cm-1 (solid state)/64.81 × 10-5 S cm-1 (solution) are observed in Ca2+-DLCP7 and Cu(II)-DLCP7, respectively.

Early Esophageal Perforation Following Anterior Cervical Discectomy and Fusion Treated With Controlled Esophageal Fistula and TachoSil® Coverage: A Case Report.

Anterior cervical discectomy and fusion (ACDF) is a commonly performed procedure. One of its most feared complications is esophageal injury (EI). There is no standard approach on how to treat these injuries. TachoSil® (Corza Medical GmbH, Düsseldorf, Germany) is a fibrinogen-containing patch that has been used in various surgical areas. Here, we present a 68-year-old male patient who was diagnosed with an EI with secondary surgical site infection following a three-level ACDF (C4/5, C5/6, and C6/7). Initially, the patient underwent incision and drainage (I&D) of the surgical site abscess, primary repair of the esophageal tear, and esophageal catheter placement to create a controlled esophagocutaneous fistula. Postoperatively, he was diagnosed with a leak and underwent a second I&D procedure. The primary repair of the EI was augmented with a TachoSil patch, and the patient was started on glycopyrrolate. The site of EI was well-sealed with no re-leaks, and the patient was discharged after he had completed a course of intravenous (IV) antibiotics and had been on parenteral nutrition for a total of 40 days. This case shows that the use of TachoSil to augment the repair of ACDF-associated EI, and glycopyrrolate to decrease salivation could decrease the risk of leak and enhance the healing process. This is an observation that needs to be scrutinized in future studies.

Clinicopathological Characteristics, Prognostic Factors, and Treatment Outcomes of Patients with Oral Tongue Squamous Cell Carcinoma Treated with Glossectomy: A Tertiary Oncology Center Experience.

Oral tongue squamous cell cancer (OTSCC) is one of the most prevalent cancers worldwide and incidence increases with age. An alarming increase in the incidence of OTSCC in the younger age group. This study aimed to explore clinical and histopathological characteristics, survival, and other post-surgical outcomes in patients with OTSCC treated with glossectomy through the Department of Otolaryngology-Head & Neck Surgery at the Ministry of National Guard Health Affairs (MNGHA) within our study period. This is a retrospective study carried out through the collection and analysis of data from medical charts of 56 patients with oral tongue cancer who were treated by glossectomy. Treatment was initiated from January 2010 to December 2021. Patient characteristics, tumor characteristics, treatment modality, failure patterns, and survival rates were collected and analyzed. At diagnosis, 62.5% were tobacco smokers, 46.8% had poor dental hygiene, and 76.8% had ulcerative lesions. Furthermore, 33 cases presented with early-stage clinical disease and 23 cases with advanced stage. The median follow-up was 54 months, 28 patients (50%) were free for 3-5 years. Patients who were free on 5-year follow-up had a significantly higher percentage of negative lymphovascular and perineural invasion (p < 0.05). Additionally, 12 patients (21.4%) had developed recurrence. Mortality in all cases was 30.3, but mortality-related cancer was 19.6%. Locoregional failure remains the main cause of treatment failure in resectable OTSCC. Pathological T-stage, N-stage, LVI, PNI, ECE, and LNR are all considered strong prognostic factors.

A Rare Case of Gastric Phytobezoar (Diospyrobezoar) in a Healthy Adult.

Phytobezoars are solid masses of indigestible plant material and are a common type of gastrointestinal bezoar, with varying incidences globally. These bezoars typically form from the ingestion of high-fiber fruits and vegetables and are associated with factors such as decreased gastric acid production and delayed gastric emptying. We present a case of a 35-year-old healthy man with recurrent upper abdominal pain, nausea, a rolling ball sensation in the abdominal region, and a history of consuming unripe persimmons. Imaging revealed the presence of phytobezoars in the stomach, leading to unsuccessful endoscopic attempts at removal. Laparoscopic extraction was eventually performed successfully after failed conservative management. The case highlights the rarity of diospyrobezoars, a subtype of phytobezoars formed from persimmon ingestion, and the challenges in their management. Surgical intervention, particularly laparoscopic extraction, can be effective but carries risks such as surgical site infections. Comprehensive care involving diagnostic imaging, non-surgical interventions, and surgical techniques is crucial for the successful management of phytobezoars. Phytobezoars, though relatively common, present unique diagnostic and management challenges, especially when formed from specific dietary factors such as persimmons. Understanding their epidemiology, clinical manifestations, and treatment options, including the role of laparoscopic surgery, is essential for optimizing patient outcomes and minimizing complications such as surgical site infections.

Electrical impedance tomography image reconstruction for lung monitoring based on ensemble learning algorithms.

Electrical impedance tomography (EIT) is a promising non-invasive imaging technique that visualizes the electrical conductivity of an anatomic structure to form based on measured boundary voltages. However, the EIT inverse problem for the image reconstruction is nonlinear and highly ill-posed. Therefore, in this work, a simulated dataset that mimics the human thorax was generated with boundary voltages based on given conductivity distributions. To overcome the challenges of image reconstruction, an ensemble learning method was proposed. The ensemble method combines several convolutional neural network models, which are the simple Convolutional Neural Network (CNN) model, AlexNet, AlexNet with residual block, and the modified AlexNet model. The ensemble models' weights selection was based on average technique giving the best coefficient of determination (R2 score). The reconstruction quality is quantitatively evaluated by calculating the root mean square error (RMSE), the coefficient of determination (R2 score), and the image correlation coefficient (ICC). The proposed method's best performance is an RMSE of 0.09404, an R2 score of 0.926186, and an ICC of 0.95783 using an ensemble model. The proposed method is promising as it can construct valuable images for clinical EIT applications and measurements compared to previous studies.

Combination diuretic therapies in heart failure: Insights from GUIDE-IT.

Introduction: Diuretics are the mainstay of maintaining and restoring euvolemia in the management of heart failure. Loop diuretics are often preferred, however, combination diuretic therapy (CDT) with a thiazide diuretic is often used to overcome diuretic resistance and increase diuretic effect. We performed an analysis of the GUIDE-IT study to assess all-cause mortality and time to first hospitalizations in patients necessitating CDT. Methods: Patients from the GUIDE-IT dataset were stratified by their requirement for CDT with a thiazide to achieve euvolemia. A total of 894 patients were analyzed, 733 of which were treated with loop diuretics alone vs 161 used either chlorothiazide or metolazone in addition to loop diuretics. Kaplan-Meir curves were derived with log-rank p-values to evaluate for differences between the groups. Results: There was no significant difference in all-cause mortality regardless of CDT utilization status (mean survival of 612.704 days vs 603.326 days, p = 0.083). On subgroup analysis, there was no significant difference in all-cause mortality amongst those using loop diuretics compared to CDT in the BNP-guided therapy group, (mean survival time 576.385 days vs 620.585 days, p = 0.0523), nor the control group (614.1 days vs 588.9 days; p = 0.5728). Time to first hospitalization was reduced in all using CDT compared to loop diuretics alone (280.5 days vs 407.2 days, p < 0.0001). On subgroup analysis, both the BNP-guided group as well as the control group had reduced time to first hospitalization in the CDT group compared to those who did not require CDT (BNP group: 287.503 days vs 402.475 days, p ≤0.0001; control group 248.698 days vs 399.035 days, p = 0.0009). Conclusion: Use of CDT is associated with earlier time to hospitalization, though no association was identified with increased all-cause mortality. Further prospective studies are likely needed to determine the true risk and benefits of combination diuretic therapy.

Natural recovery of cardiac allograft diastolic function, a retrospective longitudinal report.

Cardiac allografts suffer diastolic dysfunction early post-heart transplantation (HTx) due to ischemic injury, however the natural course of diastology recovery post HTx remains unknown (Tallaj et al., 2007 [1]). We retrospectively reviewed 60 adult HTx patients between 2015 and 2021 at a single site. Invasive hemodynamics and echocardiograms were obtained at 2 weeks and 1, 3, 6, and 12 months post-HTx. RA strain by 2D feature tracking was compared to intracardiac pressure measurements. In all patients, we observed normalization of RV and RA filling pressures by post-operative week 12 and recovery of diastolic dysfunction by month 6. There was an inverse correlation between RV end-diastolic pressure and RA contractile (r = -0.192, p < 0.05) and reservoir (r = -0.128, p < 0.05) functions in the allograft. As the post-transplant care paradigm shifts away from invasive procedures, right atrial indices should be included in imaging-based allograft surveillance studies.

A Case of Acute Migraine Without Aura Treated With a New FDA-Approved Medication Ubrogepant.

Ubrogepant is the first medication that blocks calcitonin gene-related peptide (CGRP), a protein released during a migraine attack, from binding to its receptors. Ubrogepant has shown positive safety, efficacy, and tolerability results for the treatment of acute migraine in phase 3 randomized trials. At this time, there are very few case reports on ubrogepant. Herein, we describe a complex patient with treatment-resistant migraine who showed substantial improvement in migraine severity, duration, and overall disability after using ubrogepant. A 46-year-old woman with a 25-year history of migraine presented with an improvement in headache severity, duration, and disability after using a new FDA-approved medication, ubrogepant, for less than five months. Before commencing ubrogepant,her headache duration hours ranged from 36 to 60 hours, headache severity was rated 7.5/10, and mean headache days ranged from 10 to 12 days. After taking ubrogepant, her headache duration was less than 12 hours, headache severity was 3/10, and mean headache days was five. Previously, she had been prescribed a combination of first-line medications with little improvement in headache severity. Her Migraine Disability Assessment (MIDAS) score showed moderate disability resulting in missed work and lower quality of life. To date, there have been no case reports showing the efficacy of the new FDA-approved medication, ubrogepant, showing a greater than 50% decrease in headache duration.

Prevalence and characterization of sleep quality and insomnia in security guards working on the day and night shift in Delhi-NCR.

BACKGROUND: In today's modern world, shift working has become an important part of society and industrial work; prolonged wakefulness is a widespread phenomenon due to which the sleep patterns of individuals are getting disturbed, and many sleep disorders are arising. PURPOSE: This study compared the sleep quality and insomnia of the security guards working the day and night shifts. METHODS: This observational study comprised 100 security guards from Delhi and the NCR region. Self-administered questionnaires, i.e., the Pittsburgh sleep quality index (PSQI) and the Athens Insomnia Scale (AIS), were used to assess sleep quality and insomnia. Fifty questionnaires were filled out by the day shift security guards, and the night shift security guards filled out 50. The data underwent analysis, and a comparison was conducted between security workers on night and day shifts using a Mann-Whitney U test, with a significance level set at p < 0.05. RESULTS: The result revealed a significant difference (95% CI; p < 0.05) for the variables, sleep quality and insomnia when compared between night and day shift working security guards. Among night shift workers, 74% reported issues with sleep quality and 48% experienced insomnia. In comparison, among day shift workers, 58% reported concerns about sleep quality, while 32% reported experiencing insomnia. CONCLUSION: The study concluded that night-shift working security guards had poorer sleep quality and a higher prevalence of insomnia compared to their day-shift counterparts. These differences are highly significant, highlighting the potential adverse effects of night shift work on sleep health, urging the need for interventions to improve sleep quality and manage insomnia among night shift workers.

Satisfaction-Behavior Paradox in Lifestyle Choices: A Cross-Sectional Study of Health Behaviors and Satisfaction Levels in Jazan, Saudi Arabia.

BACKGROUND: Lifestyle choices significantly affect health outcomes in Saudi Arabia, but the relationship between health behaviors and satisfaction is unclear. This study aimed to assess lifestyle choices and associated satisfaction levels among residents in the Jazan region of Saudi Arabia. METHODS: A cross-sectional study was conducted in Jazan, Saudi Arabia, with 3411 participants. Sociodemographic, lifestyle, and satisfaction data were collected using a questionnaire that was completed during interviews. Logistic regression analyses were implemented to examine the relationships between the study variables and factors related to weight, physical activity, and eating satisfaction. RESULTS: The study found that 38.3% of participants were inactive and 77% rarely ate fruits and vegetables. A total of 47.6% were overweight or obese. Weight (71.12%) and eating (71.59%) satisfaction were high despite these health concerns. The satisfaction-behavior paradox was especially evident in diet. Higher income, physical activity, and healthy eating habits were significantly associated with higher satisfaction (OR = 1.49, 95% CI: 1.15-1.93, p = 0.003 for weight satisfaction, OR = 34.74, 95% CI: 25.42-48.35, p < 0.001 for physical activity satisfaction, and OR = 2.08, 95% CI: 1.67-2.61, p < 0.001 for fruit and vegetable consumption). CONCLUSIONS: Lifestyle behaviors and satisfaction in Jazan, Saudi Arabia, are complex. The satisfaction-behavior paradox, especially in diet, reveals a major gap between perceived and actual health. These findings highlight the need for targeted, culturally sensitive interventions that address behavioral change and perception alignment to improve regional public health.

Graphene-Liquid Crystal Synergy: Advancing Sensor Technologies across Multiple Domains.

This review explores the integration of graphene and liquid crystals to advance sensor technologies across multiple domains, with a focus on recent developments in thermal and infrared sensing, flexible actuators, chemical and biological detection, and environmental monitoring systems. The synergy between graphene's exceptional electrical, optical, and thermal properties and the dynamic behavior of liquid crystals leads to sensors with significantly enhanced sensitivity, selectivity, and versatility. Notable contributions of this review include highlighting key advancements such as graphene-doped liquid crystal IR detectors, shape-memory polymers for flexible actuators, and composite hydrogels for environmental pollutant detection. Additionally, this review addresses ongoing challenges in scalability and integration, providing insights into current research efforts aimed at overcoming these obstacles. The potential for multi-modal sensing, self-powered devices, and AI integration is discussed, suggesting a transformative impact of these composite sensors on various sectors, including health, environmental monitoring, and technology. This review demonstrates how the fusion of graphene and liquid crystals is pushing the boundaries of sensor technology, offering more sensitive, adaptable, and innovative solutions to global challenges.

Determinants of Patient Satisfaction with Discharge Pharmacy Services at a Tertiary Care Center in Jeddah, KSA.

Purpose: Patient satisfaction with pharmacy services, particularly in outpatient and discharge pharmacy settings, has become a vital metric for assessing medical quality. However, there's limited research on patient satisfaction in discharge pharmacy services in the Kingdom of Saudi Arabia (KSA). This study aims to systematically investigate and delineate the various patient-related and non-patient-related factors that significantly impact patient satisfaction in the realm of discharge pharmacy services. Patients and Methods: This cross-sectional study was conducted over three months at King Abdulaziz Medical City in Jeddah (KAMC-J). The sample size was determined using a single population proportion formula, which resulted in a required sample size of 384 patients. A validated questionnaire with a five-point Likert scale evaluated satisfaction from "Strongly Dissatisfied" (1 point) to "Very Satisfied" (5 points) has been used. Data collectors underwent training and obtained written consent from participants, with questionnaire completion taking 5-10 minutes face to face. Results: The study encompassed 437 participants, primarily male (59%) with a college education (45.3%), residing mostly in Jeddah (67.3%). Notably, 84.4% were not healthcare providers, and most visited the pharmacy every six months (44.6%). The patient satisfaction survey revealed high scores for counseling understanding, pharmacist courtesy, and the way the pharmacist answered questions (4.94±0.31, 4.94±0.27, 4.94±0.32; respectively), but lower for understanding possible side effects (4.30±1.30) and pharmacy location (4.57±0.99). In logistic regression, visits lasting 10-15 minutes, and less than 10 minutes were significantly (p<0.05) associated with increased odds of patient satisfaction (OR=6.39, OR=9.45; respectively) Moreover, the medium length hospital stay was associated with decreased odds of patient satisfaction (OR=0.31, p=0.026). Conclusion: In conclusion, the study determined a significant proportion of patients are satisfied with discharge pharmacy services at KAMC-J, with the length of consultation and hospital stay being pivotal to their satisfaction. Addressing these factors, alongside optimizing pharmacist-patient communication and pharmacy service efficiency, can substantially elevate the quality of pharmaceutical care and patient experience.

Incidence of Acute Kidney Injury and Mortality Post Successful Cardiac Surgery in a Kashmiri Cohort: A Prospective Comparison of the RIFLE and KDIGO Criteria.

Background and objectives In critically ill patients, acute kidney injury (AKI) influences mortality and morbidity. Few studies have looked at mortality and the frequency of AKI following successful heart and thoracic operations. The current study investigates the association between AKI and mortality rates among patients undergoing post-cardiac surgery care within the Cardiology & Cardio Vascular Thoracic Surgery (CVTS) Intensive Care Unit (ICU). Methodology In this prospective research, 124 patients who underwent successful cardiovascular and thoracic procedures between June 2022 and June 2023 were admitted to the CVTS ICU. To determine mortality, we contrasted the two scoring methods, Kidney Disease-Improving Global Outcomes (KDIGO) and Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE). Results Based on the KDIGO criteria, AKI was identified in 37.90% (n = 47) of the patients, and it was identified in 15.32% (n = 19) of the patients utilizing RIFLE. Notably, patients diagnosed with AKI using either the RIFLE criteria or KDIGO criteria exhibited considerably higher mortality rates (p< 0.001). Receiver operating characteristic (ROC) analysis demonstrated the effectiveness of both scoring systems in identifying mortality (area under the ROC curve for RIFLE = 0.224 and KDIGO = 0.150). Conclusion Post-cardiac surgery, AKI escalates both mortality and morbidity rates. Despite KDIGO detecting more severe renal injury and mortality, both scoring systems exhibit comparable sensitivity and specificity in predicting death among patients undergoing various cardiovascular and thoracic procedures.

The Effect of Pan-Retinal Photocoagulation on Central Macular Thickness in a Sample of Iraqi Patients With Proliferative Diabetic Retinopathy.

OBJECTIVE: To evaluate the effect of pan-retinal photocoagulation (PRP) on central macular thickness (CMT) in a sample of Iraqi patients with proliferative diabetic retinopathy (PDR). METHODS: This prospective study was conducted at Ghazi Al-Hariri for Surgical Specialties Hospital, Baghdad, from March 2024 to May 2024. A total of 24 eyes from 18 treatment-naive PDR patients with no previous diabetic macular edema (DME) were enrolled. Each eye received PRP in two sessions, one week apart, using the Nidek GYC 500 laser system. CMT was measured at baseline and four weeks after the second PRP session using the Topcon DRI Triton Plus optical coherence tomography (OCT). Statistical analyses, including paired t-tests and Shapiro-Wilk tests for normality, were performed to evaluate changes in CMT. RESULTS: The mean CMT increased from 258.4 ± 30.7 microns at baseline to 269.9 ± 36.8 microns post PRP, with a mean increase of 11.5 ± 26.3 microns. This increase was statistically significant (p = 0.042). The Shapiro-Wilk test confirmed that the data were approximately normally distributed both before (W = 0.960, p = 0.445) and after (W = 0.931, p = 0.103) PRP treatment. CONCLUSION: PRP significantly increases CMT in PDR patients, although no additional treatment for macular edema was necessary. These findings align with previous studies, suggesting that PRP-induced macular thickening is a common outcome. Further research is recommended to explore long-term effects and potential mitigation strategies.

Exploring the impact of physiotherapy on health outcomes in older adults with chronic diseases: a cross-sectional analysis.

Objective: This study evaluates the impact of physiotherapy interventions on health outcomes and explores the correlation between physiotherapy session characteristics and improvements in health among older individuals. Methods: In a cross-sectional design, 384 older adults with chronic conditions such as arthritis, osteoporosis, Chronic Obstructive Pulmonary Disease (COPD), diabetes, and hypertension were recruited. Results: The proportion of arthritis (39.1%) and hypertension (45.8%) was notably high. Participants receiving physiotherapy showed significant improvements in pain levels (mean reduction from 5.09 to 2.95), mobility scores (improvement from 3.0 to 3.96), and functional independence. A positive correlation was identified between the frequency of physiotherapy sessions and pain reduction (r = 0.26, p = 0.035), and a stronger correlation between session duration and both pain reduction (r = 0.38, p = 0.002) and mobility improvement (r = 0.43, p = 0.001). High satisfaction rates with physiotherapy were reported, and age was found to be a significant negative predictor of health outcomes (Coef. = -0.3402, p = 0.0009). Conclusion: Physiotherapy interventions significantly improve health outcomes in older adults with chronic diseases.

Chemical Profiling and Antioxidant, Anti-Inflammatory, Cytotoxic, Analgesic, and Antidiarrheal Activities from the Seeds of Commonly Available Red Grape (Vitis vinifera L.).

Objectives: The current study aimed to conduct a phytochemical screening of commonly known fruit red grape (Vitis vinifera L.) seed methanolic extract through gas chromatography and mass spectrometry (GC-MS) to identify the bioactive compounds responsible for its health benefits and evaluate the pharmacological potentialities of the extract and its fractions against oxidation, inflammation, pain, and diarrhea. Methods: The in vitro antioxidant, anti-inflammatory, and cytotoxic characteristics of methanolic extracts and various solvent fractions of V. vinifera were evaluated using the DPPH free radical scavenging assay, membrane stabilizing, and brine shrimp lethality bioassay. Furthermore, the study assessed the effects of crude extracts (200, 400, and 600 mg/kg of body weight) on pain relief and reduction of diarrhea in animals using methods such as tail immersion, the acetic acid-induced writhing technique, and a diarrheal mouse model induced with castor oil. Results: A total of 73 phytoconstituents were predominantly found in the seed extract based on the GC-MS analysis. Among the identified compounds, 9-octadecenamide (13.7%), and (9E,11E)-octadeca-9,11-dienoate (11.07%) are most abundant. Several notable constituents, such as gamma-sitosterol, stigmasterol, paromomycin, 4,6-cholestadienol, gamma-tocotrienol, 24-Propylidenecholest-5-en-3beta-ol, and alpha-tocopherol acetate, are also present. The methanolic extract of V. vinifera seed and its different solvent fractions showed promising antioxidant properties (IC50 = 1.19-17.42 µg/mL) compared to the standard antioxidant butylated hydroxytoluene (IC50 = 20.46 µg/mL). Aqueous soluble fraction exerted inhibition of nearly 50% heat-induced hemolysis compared to the standard acetylsalicylic acid (42%). Besides, all the tested doses (200, 400, and 600 mg/kg bw) of the crude extract showed significant (P < .05) analgesic and antidiarrheal effects. Conclusion: The current findings endorsed the health benefits of V. vinifera by revealing potent antioxidant, anti-inflammatory, analgesic, and antidiarrheal effects. Nevertheless, further in-depth analysis of the plant's chemical constituents and pharmacological effects on health is warranted for novel drug discovery from V. vinifera.

Single Sperm RNA signatures reveal MicroRNA biomarkers for male subfertility.

PURPOSE: To investigate small RNA profiles in sperm, identify stable miRNA patterns unique to sperm, and assess the behavior of consistently expressed miRNAs in sperm from subfertile men compared to fertile controls. METHODS: The small RNA profiles of single sperm from four proven fertile men were analyzed using Small RNA next-generation sequencing (NGS). Subsequently, a specific set of miRNAs was validated using RT-qPCR on additional sperm samples from 65 subfertile men from an infertility clinic and 30 proven fertile men. RESULTS: Small RNA sequencing revealed a diverse range of sperm small RNA biotypes, including miRNAs. The mapped read percentage ranged from 22.19% for single sperm to 83.29% for enriched sperm samples used at different RNA concentrations. In single sperm, a smaller proportion of sequences were attributed to piRNAs (2.79%), miRNA (0.94%), tRNA (0.82%), and rRNA (0.47%) compared to enriched sperm samples, where piRNA (41.68%), tRNA (20.31%), miRNA (11.11%), and rRNA (6.54%) were observed. Distinct detection rates and a higher number of detected miRNAs were noted with enriched sperm samples compared to single sperm obtained using either a micromanipulator or microdissection systems. Among the identified miRNAs, 110 were consistently present in all samples. RT-qPCR revealed 15 miRNAs with increased expression and 5 miRNAs with decreased expression in sperm samples from subfertile men compared to proven fertile men. These differentially validated miRNAs were significantly correlated, either positively or negatively, with sperm count, motility, and morphology. CONCLUSION: The study extensively examines small RNAs in single sperm, identifying sperm-specific miRNAs that could serve as molecular markers to distinguish between subfertile and fertile men in clinical settings.

Histamine H3 receptor antagonist/nitric oxide donors as novel promising therapeutic hybrid-tools for glaucoma and retinal neuroprotection.

Glaucoma is a degenerative optic neuropathy in which the degeneration of optic nerve and blindness occur. The main cause is a malfunction of ciliary processes (protrusions of the ciliary bodies) resulting in increased intraocular pressure (IOP). Ocular hypertension (OHT) causes ischemic events leading to retinal ganglion cell (RGC) depletion and blindness. Histaminergic and nitrergic systems are involved in the regulation of IOP. Therefore, we developed novel hybrid compounds that target histamine H3 receptor (H3R) with nitric oxide (NO) releasing features (ST-1989 and ST-2130). After H3R binding was proven in vitro, we investigated their effects in two OHT models in New Zealand White rabbits. Compound ST-1989 showed the highest NO elevation, together with antioxidative and anti-inflammatory features partly superior to the co-administered H3R antagonist (ciproxifan) and NO donor (molsidomine). This hybrid compound demonstrated IOP reduction in both OHT models induced by intravitreal injection of hypertonic saline and carbomer into the anterior chamber of the eye, respectively. Ocular perfusion and photoreceptor neuroprotection were evaluated in a model of ischemia/reperfusion (I/R) of the ophthalmic artery induced by repeated sub-tenon injections of endothelin-1 (ET-1), twice a week for six weeks. Compound ST-1989 counteracts retinal degeneration reducing ophthalmic artery resistance index and increasing photoreceptor responses, thus rescuing RGCs. Our results indicate that compound ST-1989 is a promising molecule with long-lasting hypotensive effects and good effectiveness in reducing inflammation, oxidative stress, and RGCs apoptosis. In conclusion, these hybrid compounds could be a novel strategy to combat glaucomatous blindness and RGC depletion for ocular diseases involving retinal damage.

The effect of vitamin D3 and omega-3 combination, taken orally, on triglycerides, lining of intestine, and the biodiversity of gut microbiota in healthy rats.

AIM: The gut microbiota plays a key role in host health. An intake of omega-3 and vitamin D3 in a separate manner is vital for maintaining good health of gut microbiota and controlling some illness manifestations. The aim of this study is to investigate the potential change in biodiversity of the gut microbiome in healthy rats supplemented with vitamin D3, omega-3 alone and their combination and to reflect onto the triglyceride levels in serum and fecal samples. METHODS AND RESULTS: Using the 16S rRNA gene Miseq Illumina NGS, and monitoring triglyceride levels in serum and fecal samples coupled with several clinical parameters, we examined the effect of orally taken combination of omega-3 and vitamin D3 alongside the separate intake of supplements on gut microbiota in 24 healthy white Wistar rats for six weeks. The study findings showed that combination treatment encouraged the growth of opportunistic Clostridia class during day 21 and 42 of treatment by 7.7 and 7.4 folds, respectively, exhibited incomplete absorption levels for both supplements when used concomitantly, demonstrated a damaging effect on the gut intestinal lining wall thickness (126 µm) when compared to control group (158 µm), increasing lumen diameter (400 µm), and showed higher triglyceride level in fecal samples. CONCLUSIONS: These findings indicate that omega-3 and vitamin D3 supplements as combination intake reveal unfavorable effects, thus, it is advised to conduct further in-depth studies to clarify the presence or absence of any chemical interaction between both supplements' molecules and to investigate based on human model to attain a superior perspective.