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Benign prostatic hyperplasia (BPH) is a chronic disorder that inflicts severe symptoms on middle-aged men. The current study compared the effects of tadalafil and tamsulosin on urological parameters after 3 and 6 months of therapy. A retrospective case–control study was conducted, in which 100 patients with moderately severe BPH were divided into two groups based on their treatment: 50 patients were given tamsulosin 0.4 mg/day and group 50 patients were administered tadalafil 5 mg daily. All patients continued therapy for approximately 6 months, and their urological parameters were assessed at baseline and after 3 and 6 months. There was no significant difference in the overall effect on the International Prostate Symptom Score at the end of the study using two-way ANOVA analysis (P = 0.448). The intercourse number was significantly improved by tadalafil compared to tamsulosin (P < 0.001). The prostatic-specific antigen, postvoiding residual, and prostatic volumes were not significantly different between tadalafil and tamsulosin (P = 0.198, 0.163, and 0.183, respectively). In conclusion, tadalafil, 5 mg once daily, appears to have similar efficacy to tamsulosin, with significant improvement in the patient’s erectile function. Tadalafil can be used for 6 months for moderate-to-severe lower urinary tract symptoms.

Hydrogels have gained much focus as a gastro-retentive technology for drug delivery. The current study aimed to design an oral mucoadhesive sustained-release dosage form to lower peptic ulcer complications (PUC). Using the Box-Behnken statistical design, the preparation method was developed by incorporating pantoprazole sodium (PZS) into hydrogel microcapsules (HGMC). The PZS was incorporated into the HGMC via an ion gelation technique, with sodium alginate as the gelling agent, calcium chloride as the crosslinking agent, and chitosan as the agent for sustained release. The optimized formulation of PZS-HGMC showed a diameter of 2.506 mm, a swelling rate of 838.2%, and an encapsulation efficiency of 93.8%. Scanning electron microscopy images revealed the microcapsules’ spherical shape. The in vitro release of the PZS from the HGMC after two hours in a simulated gastric fluid was 13.2%1±0.08%, compared with the apparent solubility of the pure PZS under the same conditions (95.24%±3.2%). After 24 hours, the percent of PZS released from the optimized formula was 69.84±2.4%, which indicates a sustained release pattern. The results from the in vivo study demonstrated improved healing of the induced ulcers in rats when treated with the PZS-HGMC formulation as compared to the standard PZS therapy; therefore, the obtained mucoadhesive HGMC was considered a potential drug delivery strategy for PUC therapy.

Rectal thermometers are commonly used to assess animal health, but non-invasive methods like thermal imaging are gaining popularity for their ease. This study explores using infra-red thermography to measure eye temperatures as a proxy for body temperature in buffaloes. Among 280 adult female buffaloes, rectal temperature averaged 38.26 ± 0.38 °C, while eye temperature averaged 36.99 ± 0.47 °C. Statistical analysis showed a significant positive correlation (0.674, p

Off-grid and grid-connected photovoltaic (PV) systems with battery storage rely heavily on efficient energy transfer to maximize PV power utilization and battery lifespan. However, existing literature often overlooks the crucial role of energy transfer efficiency in these systems. This paper proposes a novel, fundamental-based PV power flow strategy that addresses this gap by employing a concept of source-load voltage matching. The proposed strategy ensures optimal voltage matching between the PV array and the battery bank. This is achieved by configuring the battery bank voltage range (between nominal and fully charged states) to closely align with the variation in PV voltage at its Maximum Power Point (MPP) across different operating temperatures. This systematic approach requires specifying the DC load voltage, configuring the battery bank, and selecting PV modules with compatible Vmp (voltage at maximum power) parameters. The system utilizes a high-current blocking diode and current limiter for safe connection between the PV array and battery bank. Additionally, the strategy protects against battery overcharge by controlling parallel fans used for PV panel cooling. Experimental results with a 1.62 kW PV system employing lead-acid batteries demonstrate improved efficiency compared to traditional methods. This innovative approach has the potential to significantly enhance energy transfer efficiency, contributing to improved energy sustainability in PV systems.

Pancreatic adenocarcinoma, a clinically challenging malignancy constitutes a significant contributor to cancer-related mortality, characterized by an inherently poor prognosis. This review aims to provide a comprehensive understanding of pancreatic adenocarcinoma by examining its multifaceted etiologies, including genetic mutations and environmental factors. The review explains the complex molecular mechanisms underlying its pathogenesis and summarizes current therapeutic strategies, including surgery, chemotherapy, and emerging modalities such as immunotherapy. Critical molecular pathways driving pancreatic cancer development, including KRAS, Notch, and Hedgehog, are discussed. Current therapeutic strategies, including surgery, chemotherapy, and radiation, are discussed, with an emphasis on their limitations, particularly in terms of postoperative relapse. Promising research areas, including liquid biopsies, personalized medicine, and gene editing, are explored, demonstrating the significant potential for enhancing diagnosis and treatment. While immunotherapy presents promising prospects, it faces challenges related to immune evasion mechanisms. Emerging research directions, encompassing liquid biopsies, personalized medicine, CRISPR/Cas9 genome editing, and computational intelligence applications, hold promise for refining diagnostic approaches and therapeutic interventions. By integrating insights from genetic, molecular, and clinical research, innovative strategies that improve patient outcomes can be developed. Ongoing research in these emerging fields holds significant promise for advancing the diagnosis and treatment of this formidable malignancy.

Background: Hospital-acquired infection (HAI) is one of the most frequent issues that hospitals are faced with in every country worldwide. Nurses are an essential part of the medical workforce that play a special role in preventing the transmission of infections within hospitals by implementation of infection prevention standard precautions. This study aimed to assess the level of nurses’ practice regarding standard precautions.Methods: 400 nurses from eight hospitals in Babil governorate are included in this cross-sectional study. To assess the knowledge and practice levels, was used an interview questionnaire. SPSS- 27 was used to analyze the data collected from September 2022 to March 2023.Results: Among 400 nurses, the mean age was 29.07 years and a large number of them (43.8%) had a diploma; while most of nurses had less than 5 years of work experience, the main result revealed that 51.5% of them had poor practice regarding standard precautions.Conclusion: The majority of nurses did not always practice these precautions, so there is a need to hold educational courses and training workshops for nurses to improve their practice of these measures.

BackgroundDiabetes mellitus (DM) is well known for related micro and macrovascular complications. Uncontrolled hyperglycemia in diabetes mellitus leads to endothelial dysfunction, inflammation, microvascular impairment, myocardial dysfunction, and skeletal muscle changes which affect multiple organ systems. This study was designed to take an extensive view of cardiorespiratory dynamics in patients with type 2 DM.MethodsOne hundred healthy controls (HC) and 100 DM patients were enrolled. We measured and compared the breathing patterns (spirometry), VO2 max levels (heart rate ratio method) and self-reported fitness level (international fitness scale) of individuals with and without diabetes. Data was analyzed in SPSS v.22 and GraphPad Prism v8.0.ResultsWe observed restrictive spirometry patterns (FVC ConclusionThis study shows decreased pulmonary functions, decreased cardiorespiratory fitness (VO2 max) and IFiS scale variables in diabetic population as compared to healthy controls which are also associated with glycemic levels and long-standing DM. Screening for pulmonary functions can aid optimum management in this population.

Traumatic brain injury (TBI) leads to brain damage, comprising both immediate primary damage and a subsequent cascade of secondary injury mechanisms. The primary injury results in localized brain damage, while the secondary damage initiates inflammatory responses, followed by the disruption of the blood-brain barrier, infiltration of peripheral blood cells, brain edema, and the release of various immune mediators, including chemotactic factors and interleukins. TBI disrupts molecular signaling, cell structures, and functions. In addition to physical tissue damage, such as axonal injuries, contusions, and haemorrhages, TBI interferes with brain functioning, impacting cognition, decision-making, memory, attention, and speech capabilities. Despite a deep understanding of the pathophysiology of TBI, an intensive effort to evaluate the underlying mechanisms with effective therapeutic interventions is imperative to manage the repercussions of TBI. Studies have commenced to explore the potential of employing natural compounds as therapeutic interventions for TBI. These compounds are characterized by their low toxicity and limited interactions with conventional drugs. Moreover, many natural compounds demonstrate the capacity to target various aspects of the secondary injury process. While our understanding of the pathophysiology of TBI, there is an urgent need for effective therapeutic interventions to mitigate its consequences. Here, we aimed to summarize the mechanism of action and the role of phytochemicals against TBI progression. This review discusses the therapeutic implications of various phytonutrients and addresses primary and secondary consequences of TBI. In addition, we highlighted the roles of emerging phytochemicals as promising candidates for therapeutic intervention of TBI. The review highlights the neuroprotective roles of phytochemicals against TBI and the mechanistic approach. Furthermore, our efforts focused on the underlying mechanisms, providing a better understanding of the therapeutic potential of phytochemicals in TBI therapeutics.

Introduction: Neonatal hyperbilirubinemia is a common physiological finding in neonates but sometimes Urinary Tract Infections (UTI) can occur in these neonates and it can be asymptomatic or may lead to complications. Many causative factors are listed out for development of neonatal jaundice but the UTI is less mentioned in previous studies. Aim: To study the prevalence of UTI and its clinical features in the neonates with hyperbilirubinemia. Materials and Methods: This cross-sectional study was conducted in Aakash Healthcare super specialty Hospital, Dwarka, New Delhi, India, between June 2019 and May 2020. Total 116 infants with neonatal hyperbilirubinemia were included in the study. The demographic features including date and time of admission, age at presentation of jaundice, mode of parturition, type of assistance for delivery (if any used), presence of cephalohaematoma, bruising or caput succedaneum, weight at birth, age at onset of jaundice (days of life), baby’s and mother’s blood group, any metabolic diseases in mother and father etc. were studied. A thorough haematological work-up was done and urine was collected in a sterile container by catheterisation. All samples were sent to the laboratory for microscopic analysis and culture. Data was statistically analysed using Mann-Whitney U-test and level of significant p-value was considered as less than 0.05. Results: A total of 116 cases of neonatal hyperbilirubinemia were included in this study. Out of the 116 cases, 66 cases (56.89%) were male neonates and infants and 50 cases (43.11%) were female neonates and infants. In this study, out of 116 neonates with hyperbilirubinemia, only 20 babies showed pus cells >5 //hpf (high power field microscope) (suggesting UTI), out of the 20 babies, 08 babies showed culture negative and pus cells >5 /hpf and remaining 12 babies showed culture positive and pus cells >5 /hpf. Out of 12 cases of culture and sensitivity, 8 cases showed culture for Escherichia coli (E.coli) and remaining four cases, organism cultured was Klebsiella pneumonia. Conclusion: Hyperbilirubinemia may be the initial sign of UTI in neonates; it may be asymptomatic in jaundiced newborns. It is recommended that, evaluation of UTI should be made in cases of asymptomatic hyperbilirubinemia cases which helps the paediatrician for early detection and treatment of these affected newborns reducing the hospital stay and long term complications.

This study aims to examine the impact of the characteristics of the board of directors (BOD), namely board independence, board size, frequency of board meetings, and board gender diversity, on firm performance. This quantitative study uses data from all firms listed in the Bahrain Bourse for 2019 and 2020. Data on BODs were taken from the companies’ governance reports, while data on firm performance, namely return on assets (ROA), return on equity (ROE), and earnings per share (EPS), were taken from annual reports. Based on the ordinary least squares (OLS) approach, the results show insignificant relationships between BOD characteristics and firm performance. Board independence, size, frequency of meetings, and gender diversity insignificantly enhance Bahraini firms’ performance. The results indicate that firms may need to effectively implement BOD mechanisms. Moreover, other factors may moderate the impact of BOD mechanisms on firm performance. Hence, the study suggests a need for more regulations and policies to increase the effectiveness of board members. This study alerts policymakers, firms’ shareholders and stakeholders, and researchers to the need to increase directors’ roles in boosting company performance, especially in developing countries, where it is complicated to force business to follow best governance practices.

We presented in this paper a new concept of sets that we launched it neutrosophic axial sets. These sets are considered as generalization of neutrosophic sets. The union relationships, intersection, union, belonging and other concepts were built on these sets , then we created two different concepts of points. Also, we studied many important properties and basic theories about axial sets theory.

Non-small cell lung carcinoma (NSCLC) is the most common malignancy worldwide. The signaling cascades are stimulated via genetic modifications in upstream signaling molecules, which affect apoptotic, proliferative, and differentiation pathways. Dysregulation of these signaling cascades causes cancer-initiating cell proliferation, cancer development, and drug resistance. Numerous efforts in the treatment of NSCLC have been undertaken in the past few decades, enhancing our understanding of the mechanisms of cancer development and moving forward to develop effective therapeutic approaches. Modifications of transcription factors and connected pathways are utilized to develop new treatment options for NSCLC. Developing designed inhibitors targeting specific cellular signaling pathways in tumor progression has been recommended for the therapeutic management of NSCLC. This comprehensive review provided deeper mechanistic insights into the molecular mechanism of action of various signaling molecules and their targeting in the clinical management of NSCLC.

Phytochemicals are abundantly occurring natural compounds extracted from plant sources. Rosmarinic acid (RA) is an abundant phytochemical of Lamiaceae species with various therapeutic implications for human health. In recent years, natural compounds have gained significant attention as adjuvant and complementary therapies to existing medications for various diseases. RA has gained popularity due to its anti-inflammatory and antioxidant properties and its roles in various life-threatening conditions, such as cancer, neurodegeneration, diabetes, etc. The present review aims to offer a comprehensive insight into the multifaceted therapeutic properties of RA, including its potential as an anticancer agent, neuroprotective effects, and antidiabetic potential. Based on the available evidences, RA could be considered a potential dietary component for treating various diseases, including cancer, diabetes and neurodegenerative disorders.

The current study intends to characterize the respiratory tract infections that have an association with gram positive bacterial pathogens, emm typing, the pattern of antibacterial resistance in isolated pathogens, phenotyping of virulence factor and molecular detection of Macrolide resistance gene. Various samples from patients with respiratory tract infections were collected and identification and antimicrobial susceptibility of clinical isolates was performed as per standard laboratory procedure. Macrolides (Eruthromycin, Clindamycin)-resistant isolates were again subjected to MIC method. Macrolide-inducible resistance to clindamycin (D test) was conducted upon Erythromycin and Clindamycin discs. Multiplex PCR was used to detect the resistance genes in all the three types of macrolide resistance strains. Serum Opacity Factor (SOF) was detected for all the isolates of GAS. Every isolate was checked to produce biofilm through micro titre plate method. Bacterial growth got registered in 156 (36.28%) samples. The most common isolate from URI samples was GAS i.e., 64 (14.9%), only to be followed by GGS 38(8.8%), GCS 29 (6.7%) and Staphylococcus aureus 18 (4.2%). Among GAS, only one isolate was recorded from blood, whereas 8.50% from sputum and the rest. All 71 GAS isolates were found to exhibit sensitivity towards Penicillin and Ceftriazone. GAS exhibited 55% Mtype of resistance whereas 40% were resistant to cMLS and 5% to iMLS. GCS showcased an equal number of cMLS and M type too. GGS portrayed 54.54% resistance to cMLS followed by 36.36% to Mtype and 9.09% to iMLS. The current study found iMLS type with least resistance. The current study identified that Streptococcus pyogenes is the most common bacteria that cause and recur the infection. The prevalence of resistance tends to change geographically and periodically. For this purpose and to achieve a sound public health outcome, periodical screening of antibiotic-resistance pattern becomes inevitable.

Solar photovoltaic (PV) microgrids have gained popularity in recent years as a way to improve the stability of intermittent renewable energy generation in systems, both off-grid and on-grid, and to meet the needs of emergency settings during natural catastrophes. Over the last several decades, researchers have been interested in improving the efficiency of photovoltaic (PV) systems. Solar-battery charge controllers based on various algorithms are continuously and intensively employed to improve energy transfer efficiency and reduce charging time. This paper presents state-of-the-art solar photovoltaic (PV) integrated battery energy storage systems (BESS). An overview of and motivations for PV-battery systems is initially introduced, followed by the survey methodology and its contributions. In addition, this study classifies residential solar PV systems and battery charge controllers with their corresponding references in the review structure, which also provides details on battery charger topologies. Subsequently, an analytical review of the PV-Battery charge controller and the failure probability of such systems is discussed to determine the system components that mostly fail and their importance in the system. Finally, recommendation amendments to the existing charge controller that potentially contribute to increasing the system efficiency, reducing the failure probabilities, and reducing the cost are presented as future design concepts for the entire system.

Article 14 Paragraph (1) letter d of Law Number 12 Year 1995 concerning Corrections. The right to health services and the right to adequate clothing are often neglected and have not been fully implemented properly. The purpose of this research is to find out and explain the fulfilment of the rights to health and clothing of female convicts at the Sigli Class IIB Correctional Facility for Women. This research method is an empirical juridical method by using a descriptive analysis approach. The results of the study showed that the fulfilment of the rights to health and clothing has not been implemented optimally pursuant to what is mandated by law, and Article 14 Paragraph (2) of Government Regulation Number 32 Year 1999 concerning Terms and Procedures for the Implementation of the Rights of Correctional Inmates. To ensure optimal health services, at least one doctor must be provided. However, in this case it is not yet available at the Sigli Class IIB Correctional Facility for Women. One of the efforts made by the correctional facility is to collaborate with the local government to check the health of correctional inmates at least 1 (one) time in 1 (one) month and it is recorded in a health card. As for clothing need, it has been given partly to female convicts, but has not been given in full due to the lack of budget given to the Sigli Correctional Facility for Women. The responsibility of the state is to finance the fulfilment of the rights that have been regulated in the law, for example in the provision of health and clothing rights in a Correctional Facility, the facility shall have at least a doctor, nurses, clinics and medicines sufficient to support health facility in the Correctional Facility or Detention Center.

Coronavirus disease 2019 (COVID-19) has emerged from China and globally affected the entire population through the human-to-human transmission of a newly emerged virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The genome of SARS-CoV-2 encodes several proteins that are essential for multiplication and pathogenesis. The main protease (Mpro or 3CLpro) of SARS-CoV-2 plays a central role in its pathogenesis and thus is considered as an attractive drug target for the drug design and development of small-molecule inhibitors. We have employed an extensive structure-based high-throughput virtual screening to discover potential natural compounds from the ZINC database which could inhibit the Mpro of SARS-CoV-2. Initially, the hits were selected on the basis of their physicochemical and drug-like properties. Subsequently, the PAINS filter, estimation of binding affinities using molecular docking, and interaction analyses were performed to find safe and potential inhibitors of SARS-CoV-2 Mpro. We have identified ZINC02123811 (1-(3-(2,5,9-trimethyl-7-oxo-3-phenyl-7H-furo[3,2-g]chromen-6-yl)propanoyl)piperidine-4-carboxamide), a natural compound bearing appreciable affinity, efficiency, and specificity towards the binding pocket of SARS-CoV-2 Mpro. The identified compound showed a set of drug-like properties and preferentially binds to the active site of SARS-CoV-2 Mpro. All-atom molecular dynamics (MD) simulations were performed to evaluate the conformational dynamics, stability and interaction mechanism of Mpro with ZINC02123811. MD simulation results indicated that Mpro with ZINC02123811 forms a stable complex throughout the trajectory of 100 ns. These findings suggest that ZINC02123811 may be further exploited as a promising scaffold for the development of potential inhibitors of SARS-CoV-2 Mpro to address COVID-19.

OBJECTIVES:. To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN:. Prospective observational study. SETTING:. One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry. PATIENTS:. Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. INTERVENTIONS:. None. RESULTS:. Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0–81.0 yr) versus 61 years (48.0–72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, –0.84, –1.34, and –0.84; p < 0.001). CONCLUSIONS:. Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.

Circadian clocks evolved to enable organisms to anticipate and prepare for periodic environmental changes driven by the day–night cycle. This internal timekeeping mechanism is built on autoregulatory transcription–translation feedback loops that control the rhythmic expression of core clock genes and their protein products. The levels of clock proteins rise and ebb throughout a 24-h period through their rhythmic synthesis and destruction. In the ubiquitin–proteasome system, the process of polyubiquitination, or the covalent attachment of a ubiquitin chain, marks a protein for degradation by the 26S proteasome. The process is regulated by E3 ubiquitin ligases, which recognize specific substrates for ubiquitination. In this review, we summarize the roles that known E3 ubiquitin ligases play in the circadian clocks of two popular model organisms: mice and fruit flies. We also discuss emerging evidence that implicates the N-degron pathway, an alternative proteolytic system, in the regulation of circadian rhythms. We conclude the review with our perspectives on the potential for the proteolytic and non-proteolytic functions of E3 ubiquitin ligases within the circadian clock system.

Aim: This study aims to evaluate the retrieval outcome of the separated endodontic instrument by endodontic board residents. Materials and Methods: Records of 450 endodontic cases with separated endodontic instruments treated by endodontic Saudi board residents were randomly selected. The evaluation was based on the tooth type, type of fractured instrument, incidence and anatomical location in the root canal and if the instrument was retrieved, bypassed, or left. Data were statistically analyzed using IBM-SPSS.22. Results: A total of 84 (19%) separated instruments were identified. Thirty-four cases (7.55%) with separated instruments out of the total evaluated cases were done by residents. The incidence between hand stainless steel and nickel-titanium instruments was statistically significant (P < 0.05). The separated instruments were found more in the mandibular molars, i.e., 44 (52.4%). They were observed more in the buccal canal of the maxillary premolars and mesiobuccal canals of mandibular and maxillary molars. Fifty-seven (67.9%) of the separated fragments were located in the apical third of the root. Thirty-six (34.3%) were retrieved, 20 (19.0%) were bypassed, and 34 (32.4%) were left while 15 (14.3%) were managed by surgery. The ultrasonic device was more active in removing the separated instruments. Conclusions: Regardless of little experience of the endodontic residents, they were successfully managed to remove or bypass most of the separated instruments. Ultrasonic device was very helpful in removing the separated instrument.

In mammals, the hypothalamic suprachiasmatic nucleus (SCN) functions as the central circadian pacemaker, orchestrating behavioral and physiological rhythms in alignment to the environmental light/dark cycle. The neurons that comprise the SCN are anatomically and functionally heterogeneous, but despite their physiological importance, little is known about the pathways that guide their specification and differentiation. Here, we report that the stem/progenitor cell transcription factor, Sex determining region Y-box 2 (Sox2), is required in the embryonic SCN to control the expression of SCN-enriched neuropeptides and transcription factors. Ablation of Sox2 in the developing SCN leads to downregulation of circadian neuropeptides as early as embryonic day (E) 15.5, followed by a decrease in the expression of two transcription factors involved in SCN development, Lhx1 and Six6, in neonates. Thymidine analog-retention assays revealed that Sox2 deficiency contributed to reduced survival of SCN neurons during the postnatal period of cell clearance, but did not affect progenitor cell proliferation or SCN specification. Our results identify SOX2 as an essential transcription factor for the proper differentiation and survival of neurons within the developing SCN.

Casein kinase-1 alpha (CK1α) is a multifunctional protein kinase that belongs to the serine/threonine kinases of the CK1α family. It is involved in various signaling pathways associated with chromosome segregation, cell metabolism, cell cycle progression, apoptosis, autophagy, etc. It has been known to involve in the progression of many diseases, including cancer, neurodegeneration, obesity, and behavioral disorders. The elevated expression of CK1α in diseased conditions facilitates its selective targeting for therapeutic management. Here, we have performed virtual screening of phytoconstituents from the IMPPAT database seeking potential inhibitors of CK1α. First, a cluster of compounds was retrieved based on physicochemical parameters following Lipinski’s rules and PAINS filter. Further, high-affinity hits against CK1α were obtained based on their binding affinity score. Furthermore, the ADMET, PAINS, and PASS evaluation was carried out to select more potent hits. Finally, following the interaction analysis, we elucidated three phytoconstituents, Semiglabrinol, Curcusone_A, and Liriodenine, posturing considerable affinity and specificity towards the CK1α binding pocket. The result was further evaluated by molecular dynamics (MD) simulations, dynamical cross-correlation matrix (DCCM), and principal components analysis (PCA), which revealed that binding of the selected compounds, especially Semiglabrinol, stabilizes CK1α and leads to fewer conformational fluctuations. The MM-PBSA analysis suggested an appreciable binding affinity of all three compounds toward CK1α.

Defects in the apoptosis mechanism stimulate cancer cell growth and survival. B cell lymphoma 2 (Bcl-2) is an anti-apoptotic molecule that plays a central role in apoptosis. Bcl-2 is the founding constituent of the Bcl-2 protein family of apoptosis controllers, the primary apoptosis regulators linked with cancer. Bcl-2 has been identified as being over-expressed in several cancers. Bcl-2 is induced by protein kinases and several signaling molecules which stimulate cancer development. Identifying the important function played by Bcl-2 in cancer progression and development, and treatment made it a target related to therapy for multiple cancers. Among the various strategies that have been proposed to block Bcl-2, BH3-mimetics have appeared as a novel group of compounds thanks to their favorable effects on many cancers within several clinical settings. Because of the fundamental function of Bcl-2 in the regulation of apoptosis, the Bcl-2 protein is a potent target for the development of novel anti-tumor treatments. Bcl-2 inhibitors have been used against several cancers and provide a pre-clinical platform for testing novel therapeutic drugs. Clinical trials of multiple investigational agents targeting Bcl-2 are ongoing. This review discusses the role of Bcl-2 in cancer development; it could be exploited as a potential target for developing novel therapeutic strategies to combat various types of cancers. We further highlight the therapeutic activity of Bcl-2 inhibitors and their implications for the therapeutic management of cancer.

Various aspects of task execution load balancing of Internet of Things (IoTs) networks can be optimised using intelligent algorithms provided by software-defined networking (SDN). These load balancing aspects include makespan, energy consumption, and execution cost. While past studies have evaluated load balancing from one or two aspects, none has explored the possibility of simultaneously optimising all aspects, namely, reliability, energy, cost, and execution time. For the purposes of load balancing, implementing multi-objective optimisation (MOO) based on meta-heuristic searching algorithms requires assurances that the solution space will be thoroughly explored. Optimising load balancing provides not only decision makers with optimised solutions but a rich set of candidate solutions to choose from. Therefore, the purposes of this study were (1) to propose a joint mathematical formulation to solve load balancing challenges in cloud computing and (2) to propose two multi-objective particle swarm optimisation (MP) models; distance angle multi-objective particle swarm optimization (DAMP) and angle multi-objective particle swarm optimization (AMP). Unlike existing models that only use crowding distance as a criterion for solution selection, our MP models probabilistically combine both crowding distance and crowding angle. More specifically, we only selected solutions that had more than a 0.5 probability of higher crowding distance and higher angular distribution. In addition, binary variants of the approaches were generated based on transfer function, and they were denoted by binary DAMP (BDAMP) and binary AMP (BAMP). After using MOO mathematical functions to compare our models, BDAMP and BAMP, with state of the standard models, BMP, BDMP and BPSO, they were tested using the proposed load balancing model. Both tests proved that our DAMP and AMP models were far superior to the state of the art standard models, MP, crowding distance multi-objective particle swarm optimisation (DMP), and PSO. Therefore, this study enables the incorporation of meta-heuristic in the management layer of cloud networks.

Poor hygiene performance and insufficient sanitary conditions assume real parts in the expanded weight of communicable diseases inside developing nations. Lack of resources such as hand washing materials, water and sanitation facilities may be essential factors why students do not wash their hands, also struggling of affordable toothpaste and absence of awareness regarding oral hygiene may be affected by improper cleaning teeth and tongue. This study was carried out to assess the knowledge, attitude and practices (KAP) of personal and oral hygiene among undergraduate university students in Sulaimani city /Iraq and evaluated the degree to which appropriate information of hygiene was related with individual hygiene character. This cross-sectional study was carried out among 1055 undergraduate students who were met via trained staff. Data comprised of cleanliness and hand washing practices, learning about sanitation, individual cleanliness qualities, nearness of gastrointestinal parasitic disease, oral and dental diseases including dental decay and bad breathes. University students with satisfactory information of legitimate personal and oral hygiene probably had clean clothes 68.8% (P value < 0.05), clean hair 72% (0.0001 P value), fingernail trimmed 139% (P value> 0.05), clean teeth 59.4% (P value

Cancer is one of the most common causes of death and affects millions of lives every year. In addition to non-infectious carcinogens, infectious agents contribute significantly to increased incidence of several cancers. Several therapeutic techniques have been used for the treatment of such cancers. Recently, nanotechnology has emerged to advance the diagnosis, imaging, and therapeutics of various cancer types. Nanomaterials have multiple advantages over other materials due to their small size and high surface area, which allow retention and controlled drug release to improve the anti-cancer property. Most cancer therapies have been known to damage healthy cells due to poor specificity, which can be avoided by using nanosized particles. Nanomaterials can be combined with various types of biomaterials to make it less toxic and improve its biocompatibility. Based on these properties, several nanomaterials have been developed which possess excellent anti-cancer efficacy potential and improved diagnosis. This review presents the latest update on novel nanomaterials used to improve the diagnostic and therapeutic of pathogen-associated and non-pathogenic cancers. We further highlighted mechanistic insights into their mode of action, improved features, and limitations.

Aging represents a significant biological process having strong associations with cancer, diabetes, and neurodegenerative and cardiovascular disorders, which leads to progressive loss of cellular functions and viability. Astonishingly, age-related disorders share several genetic and molecular mechanisms with the normal aging process. Over the last three decades, budding yeast Saccharomyces cerevisiae has emerged as a powerful yet simple model organism for aging research. Genetic approaches using yeast RLS have led to the identification of hundreds of genes impacting lifespan in higher eukaryotes. Numerous interventions to extend yeast lifespan showed an analogous outcome in multi-cellular eukaryotes like fruit flies, nematodes, rodents, and humans. We collected and analyzed a multitude of observations from published literature and provide the contribution of yeast in the understanding of aging hallmarks most applicable to humans. Here, we discuss key pathways and molecular mechanisms that underpin the evolutionarily conserved aging process and summarize the current understanding and clinical applicability of its trajectories. Gathering critical information on aging biology would pave the way for future investigation targeted at the discovery of aging interventions.

Design and development of potential pyruvate dehydrogenase kinase 3 (PDK3) inhibitors have gained attention because of their possible therapeutic uses in lung cancer therapy. In the present study, the binding affinity of naturally occurring alkaloids, hordenine, vincamine, tryptamine, cinchonine, and colcemid was measured with PDK3. The molecular docking and fluorescence binding studies suggested that all these compounds show a considerable binding affinity for PDK3. Among them, the affinity of hordenine to the PDK3 was excellent (K = 106 M−1) which was further complemented by isothermal titration calorimetric measurements. Hordenine binds in the active site pocket of PDK3 and forms a significant number of non-covalent interactions with functionally important residues. All-atom molecular dynamics (MD) simulation study suggested that the PDK3-hordenine complex is stabilized throughout the trajectory of 100ns and leads to fewer conformational changes. The enzyme inhibition studies showed that hordenine inhibits the activity of PDK3 with an IC50 value of 5.4 µM. Furthermore, hordenine showed a cytotoxic effect on human lung cancer cells (A549 and H1299) with an admirable IC50 value. However, it did not inhibit the growth of HEK293 cells up to 200 µM, indicating its non-toxicity to non-cancerous cell lines. In summary, our findings provide the basis for the therapeutic implication of hordenine and its derivatives in lung cancer and PDK3-related diseases after required in vivo validation.

Microtubule affinity-regulating kinase (MARK4) plays a key role in Alzheimer’s disease (AD) development as its overexpression is directly linked to increased tau phosphorylation. MARK4 is a potential drug target of AD and is thus its structural features are employed in the development of new therapeutic molecules. Donepezil (DP) and rivastigmine tartrate (RT) are acetylcholinesterase (AChE) inhibitors and are used to treat symptomatic patients of mild to moderate AD. In keeping with the therapeutic implications of DP and RT in AD, we performed binding studies of these drugs with the MARK4. Both DP and RT bound to MARK4 with a binding constant (K) of 107 M−1. The temperature dependency of binding parameters revealed MARK−DP complex to be guided by static mode while MARK−RT complex to be guided by both static and dynamic quenching. Both drugs inhibited MARK4 with IC50 values of 5.3 μM (DP) and 6.74 μM (RT). The evaluation of associated enthalpy change (ΔH) and entropy change (ΔS) implied the complex formation to be driven by hydrogen bonding making it seemingly strong and specific. Isothermal titration calorimetry further advocated a spontaneous binding. In vitro observations were further complemented by the calculation of binding free energy by molecular docking and interactions with the functionally-important residues of the active site pocket of MARK4. This study signifies the implications of AChE inhibitors, RT, and DP in Alzheimer’s therapy targeting MARK4.

This Research Aims To Define The Information Resources In The Libraries Of Aleppo University And Their Role Inside The Academic Community Of The University. The Research Includes The Study Of Nineteen Libraries Distributed In The Following Faculties: The Civil Engineering, The Mechanic Engineering, The Electric Engineering, Architecture, Informatics Engineering, Education, And The Institute Of The Arabic Scientific Heritage. The Research Clarifies The Image Of The Academic Community Of The University Along With The Process Of Building And Improving The Information Resources In The Libraries At Aleppo University. It Also Discusses The Procedures Related To The Policy Of Building And Improving Information Resources And The Methods, Tools Of Selection Along With Maintenance, Exclusion, Covering And Inventory Process. The Research Resulted In: - Aleppo University Heavily Lacks The Preparation Of Teaching Committee Members. - There Is No Clearly Written Policy For Building And Improving Information Resources Followed By The Libraries At The University. The Same Lack Applies To The Process Of Selection.

We have examined the effect of stearylamine (SA) in liposomes on the viability of Plasmodium falciparum in culture by studying the inhibition of incorporation of [3H]-hypoxanthine in the nucleic acid of parasites. Stearylamine in liposomes significantly inhibits the growth of the parasites depending on the phospholipids composition. The maximum inhibition was observed when SA was delivered through Soya phosphatidylcholine (SPC) liposomes. The chain length of alkyl group and density of SA in liposomes play a significant role in inhibiting the growth of the parasites. Incorporation of either cholesterol or Distearylphosphatidylethanolamine−Methoxy-Polyethylene glycol-2000 (DSPE-mPEG-2000) in Soya phosphatidylcholine-stearylamine (SPC-SA) liposomes improves the efficacy. Intraerythrocytic entry of intact SPC-SA liposomes into infected erythrocytes was visualized using fluorescent microscopy. No hemolysis was observed in uninfected erythrocytes, and slight hemolysis was noted in infected erythrocytes at high concentrations of SPC-SA liposomes. Overall, our data suggested SA in SPC-liposomes might have potential application in malaria chemotherapy.