Linagliptin mitigates cisplatin-induced kidney impairment via mitophagy regulation in rats, with emphasis on SIRT-3/PGC-1α, PINK-1 and Parkin-2.

Cisplatin (CDDP) often leads to kidney impairment, limiting its effectiveness in cancer treatment. The lack of mitophagy in proximal tubules exacerbates this issue. Hence, targeting SIRT-3 and PGC1-α shows promise in mitigating CDDP-induced kidney damage. The potential renoprotective effects of linagliptin, however, remain poorly understood. This study represents the first exploration of linagliptin's impact on CDDP-induced kidney impairment in rats, emphasizing its potential role in mitophagic pathways. The experiment involved four rat groups: Group (I) received saline only, Group (II) received a single intraperitoneal injection of CDDP at 6 mg/kg. Groups (III) and (IV) received linagliptin at 6 and 10 mg/kg p.o., respectively, seven days before CDDP administration, continuing for an additional four days. Various parameters, including renal function tests, oxidative stress, TNF-α, IL-1ß, IL-6, PGC-1α, FOXO-3a, p-ERK1, and the gene expression of SIRT-3 and P62 in renal tissue, were assessed. Linagliptin improved renal function, increased antioxidant enzyme activity, and decreased IL-1ß, TNF-α, and IL-6 expression. Additionally, linagliptin significantly upregulated PGC-1α and PINK-1/Parkin-2 expression while downregulating P62 expression. Moreover, linagliptin activated FOXO-3a and SIRT-3, suggesting a potential enhancement of mitophagy. Linagliptin demonstrated a positive impact on various factors related to kidney health in the context of CDDP-induced impairment. These findings suggest a potential role for linagliptin in improving cancer treatment outcomes. Clinical trials are warranted to further investigate and validate its efficacy in a clinical setting.

Caffeine intake and its association with nutrition, sleep, and physical activity among schoolchildren in the United Arab Emirates: a national cross-sectional study.

PURPOSE: Recent surveys indicate a significant increase in total caffeine intake among schoolchildren. Limited research has been published concerning the total intake of caffeine among schoolchildren in the Middle East and Gulf Cooperation Council (GCC) countries, including the UAE. METHODS: This cross-sectional survey estimated the total caffeine intake from foods and beverages among 10,275 schoolchildren in the UAE. Caffeine intakes were related to the European Food Safety Authority's level of no safety concern (3.0 mg/kg BW) and level of effects on sleep (1.4 mg/kg BW). RESULTS: More than half (56.2%) of the students consumed more than 100 mg (the upper limit allowed) of caffeine from dietary sources. High intake of caffeine (> 100 mg/day) was significantly associated (p = 0.001) with reduced sleep duration, difficulty falling asleep, infrequent exercising, using smart devices for more than 2 h a day, getting a lower GPA, skipping breakfast, eating fewer servings of vegetables than recommended, frequent consumption of fast food and more frequent snack consumption. CONCLUSION: Excessive intake of caffeine from different dietary sources coexists with unhealthy dietary and lifestyle behaviors and sleep problems. Tailoring educational programs and intervention strategies is warranted to correct the unhealthy intake of caffeine and the associated unhealthy dietary and lifestyle behaviors among schoolchildren in the UAE.

Adherence patterns to medications and their association with subsequent hospitalization in adult Egyptian patients with systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to evaluate the adherence pattern to medications and the influence of non-adherence on hospitalization rate among Egyptian patients who were diagnosed with systemic lupus erythematosus (SLE). METHODS: This cross-sectional interview-based study was conducted in an Egyptian rheumatology outpatient clinic. Individuals with SLE who were prescribed oral medications were included in the study. The 19-item Compliance Questionnaire of Rheumatology (CQR) was employed to evaluate drug adherence. Patients were classified as non-adherent and adherent group based on their CQR score Sociodemographic variables, clinical and therapeutic data, and the frequency of outpatient visits and hospitalization were collected and compared between the two groups. RESULTS: In total, there were 161 SLE patients who participated in the study with mean age 30.70 ± 9.62 years, 129 females and 32 males (F:M 5.4:1). Of them, 93 patients were assigned to the non-adherent group, whereas 68 patients were assigned to the adherent group. There was a statistically significant difference in terms of marital status (p = 0.009), employment (p = 0.032), and the frequency of physical activity (p = 0.045) between the two groups. The adherents had a higher rate of administration of antimalarials (88.2% vs 75.3%, p = 0.039). The frequency of recurrent fever was lower in adherents (23.5% vs 38.7%, p = 0.042), lymphadenopathy (11.8% vs 31.2%, p = 0.004), recurring oral ulcers (25% vs 50.5%, p = 0.001), and substantial hair loss (87.1% vs 98.5%, p = 0.009) in comparison to non-adherents. The number of yearly outpatient visits was considerably greater in adherents (p = 0.007), while the number of prior hospitalizations was higher in non-adherents (p < 0.001). Non-adherents believed that taking medicines disrupt patients' daily routine (p < 0.001) and were more afraid of the occurrence of an adverse drug reaction (p < 0.001). CONCLUSIONS: Egyptian SLE patients have an alarmingly high percentage of medication non-adherence. There is a strong association between medication non-adherence and frequency of hospitalization and cumulative clinical manifestations.

Screening of attention deficit hyperactivity disorder among preschool children Gharbia Governorate, Egypt.

BACKGROUND: Children who experience mental health issues, such as attention deficit hyperactivity disorder (ADHD), experience significant distress and impairment at home, at school, and in the community. Without adequate care or prevention, this frequently results in adulthood-long distress and impairment at large societal costs. Determining the prevalence of ADHD cases among preschoolers as well as some associated maternal and child risk factors was the aim of this study. METHODS: An analytical cross-sectional study including 1048 preschool children aged 3-6 years was carried out in Tanta City, Gharbia Governorate. From March to April 2022, a proportionate stratified cluster random sample of them was picked. Data were gathered using a predesigned instrument that included sociodemographic information, family history, maternal and child risk factors, and the Arabic version of the ADHD Rating Scale IV questionnaire. RESULTS: The prevalence of ADHD among preschoolers was 10.5%. The inattention type was the most common (5.3%), followed by the hyperactivity type (3.4%). There were statistically significant associations regarding positive family history of psychological and neurological symptoms (17.9% positive vs. 9.7% negative), family history of ADHD symptoms (24.5% positive vs. 9.4% negative), active smoking by the mother (21.1% positive vs. 5.3% negative), cesarean section delivery (66.4% positive vs. 53.9% negative), elevated blood pressure during pregnancy (19.1% positive vs. 12.4% negative), and history of taking drugs during pregnancy (43.6% positive vs. 31.7% negative). Significant child risk factors were: exposure to any source containing lead that causes slow poisoning (25.5% positive vs. 12.3% negative), children with cardiac health problems (38.2% positive vs. 16.6% negative), and hours spent by a child in front of the TV or mobile phone (any screens) per day (60.0% of those with positive screening spent more than 2 h/day vs. 45.7% negative). CONCLUSION: In the Gharbia governorate, 10.5% of preschoolers suffer from ADHD. Significant maternal risk factors for ADHD included a positive family history of psychiatric and neurological symptoms, a family history of ADHD symptoms, active maternal smoking, caesarean section delivery, increased blood pressure during pregnancy, and a history of drug use during pregnancy. Youngsters who had cardiac health issues and who spent more time each day watching TV or using a mobile device (screen use) were at substantial risk.

Predictors of depression among school adolescents in Northwest, Ethiopia, 2022: institutional based cross-sectional.

BACKGROUND: Adolescent depression is a serious mental disorder that makes family problems, learning challenges, drug addiction, and increases absenteeism from school. It also has a major impact on a person's ability to manage his or her daily tasks. In the end, the condition may result in self-destruction. Research is scarce among high schools in the study setting. Therefore, this study aimed to assess the prevalence and its associated factors of depression among high school adolescent students in Bahirdar City, Northwest Ethiopia in 2022. METHODS: An institutional-based cross-sectional study was done from June 18 to July 16, 2022, among public and private high school adolescent students in Bahir Dar City, Amhara region, Ethiopia. A two-stage sampling technique was utilized. First, stratification by school type was made and schools were selected 30-40% by using a simple random sampling technique. Finally, an updated sampling frame was taken from each school director to select a sample of 584 study participants after proportional allocation by simple random sampling from six high schools. Patient Health Questionnaires were used to assess depression in high school students. The independent variables, like substance-related factors, were assessed by yes-or-no questions, and the academic stressor by academic stress in secondary education, was assessed by structured questionnaires. Binary and multivariate logistic regressions were used to identify factors associated with depression. Statistical significance was declared at a 95% confidence interval when the value of p was less than or equal to 0.05. RESULTS: The response rate of the participants was 96.9%. The overall magnitude of adolescent depression was found to be 22.1% (95%CI 18.7, 25.7%). Being female (AOR: 3.43; 95%CI 2.11, 5.56), small family size (AOR: 3.01; 95%CI 1.47, 6.15); ever alcohol use (AOR: 2.40; 95%CI 1.51, 3.81); attending a public school (AOR: 3.01; 95%CI 1.68, 5.40), and having a history of abuse (AOR: 1.92; 95%CI 2.2, 3.08) were associated with depression. CONCLUSION: In this study, the magnitude of depression among high school students in Bahir Dar City was higher than the national threshold. There was a significant association between sex, family size of parents, ever alcohol use, public schools, and having a history of abuse with depression among adolescents. Hence, it is better for schools to screen and provide intervention for depression in public high school students and offer therapies, especially in females and those with a history of abuse, small family size, or alcohol use.

Toward safe dental service: risk perception and practice modification among Egyptian dental students during the COVID-19 pandemic.

BACKGROUND: COVID-19 was declared a major public health crisis and a challenge to healthcare systems especially dental services where dentists working close to patients face a greater risk of infection. This cross-sectional study aimed to assess the risk perception and practice modifications of undergraduate dental students at Tanta University to ensure safe dental practice during the COVID-19 pandemic. METHODS: A convenience sample of 450 dental students from practical academic years at Tanta University, Egypt responded to a self-administered pre-designed validated and pretested questionnaire from the 11th of February 2022 to the end of April 2022 to assess some sociodemographic data, risk perception, and their practice during the COVID-19 pandemic. RESULTS: Females reported significantly higher levels of fear than males concerning; contracting COVID-19 infection from patients (97.3% vs. 93%) (P = 0.028, 95% CI = 95.6(93.2-97.3), anxiety while treating symptomatic patients (95.1% vs. 90.3%) (P = 0.050, 95% CI = 93.1(90.4-95.3), and fear of infecting their families (94.7% vs. 89.8%) (P = 0.049, 95% CI = 92.7(89.9-94.9). More than half of the students (53.7%) had good practice scores, followed by 44% with average practice and 2.2% with poor practice. A good practice score was significantly associated with the age and academic year (P = 0.044, P = 0.044). Significant predictors of a good practice score in the logistic regression analysis were; updating knowledge with current guidelines for cross-infection regarding COVID-19 (P = 0.001, 95% CI = 53.20, 2.733), asking every patient's travel history before performing treatment (P = 0.021, 95% CI = 21.149, 1.286), deferring patients showing suspicious symptoms (P = 0.042, 95% CI = 20.688, 1.054), following routine universal precautions of infection for every patient (P = 0.016, 95% CI = 36.469, 1.438), using high-volume suction for every patient (P = 0.025, 95% CI = 20.826, 1.226) and using safety glasses or visor (P = 0.036, 95% CI = 21.673, 1.106). CONCLUSION: The dental students exhibited anxiety and fear while caring for patients during the COVID-19 pandemic. Additionally, considerable changes in dental practices based on the standard guidelines were observed among the students. It is strongly advised that all dental schools have student counselors who are accessible for in-person and online counseling sessions. Peer support is a great approach to spot problems with stress and anxiety in pupils and start solving them.

Simultaneous Administration of Bevacizumab with Bee-Pollen Extract-Loaded Hybrid Protein Hydrogel NPs Is a Promising Targeted Strategy against Cancer Cells.

Bevacizumab (Bev) a humanized monoclonal antibody that fights vascular endothelial growth factor A (VEGF-A). It was the first specifically considered angiogenesis inhibitor and it has now become the normative first-line therapy for advanced non-small-cell lung cancer (NSCLC). In the current study, polyphenolic compounds were isolated from bee pollen (PCIBP) and encapsulated (EPCIBP) inside moieties of hybrid peptide-protein hydrogel nanoparticles in which bovine serum albumin (BSA) was combined with protamine-free sulfate and targeted with folic acid (FA). The apoptotic effects of PCIBP and its encapsulation (EPCIBP) were further investigated using A549 and MCF-7 cell lines, providing significant upregulation of Bax and caspase 3 genes and downregulation of Bcl2, HRAS, and MAPK as well. This effect was synergistically improved in combination with Bev. Our findings may contribute to the use of EPCIBP simultaneously with chemotherapy to strengthen the effectiveness and minimize the required dose.

Post-Cardiac arrest targeted temperature management in a parturient with severe COVID-19 disease.

Background and Objective: Targeted temperature management (TTM) may improve neurological outcomes and mortality after cardiac arrest. We present a targeted mild hypothermia treatment in a postpartum patient with COVID-19 after successful cardiopulmonary resuscitation (CPR). Case presentation: A 23 year old, 26-week pregnant patient with the diagnosis of COVID-19. The patient developed respiratory arrest followed by cardiac arrest and underwent CPR for six minutes. The patient underwent an emergency cesarean section after CPR in intensive care unit. After the resuscitation, 72-hours hypothermia protocol was initiated. We extubated the patient 13 days after the hypothermia procedure. The patient was conscious and cooperative. Respiratory distress worsened in the following days; the patient was re-intubated 18 days after the TTM. The benefit of targeted hypothermia was improved neurologic outcome in our patient. However, severe infectious complications led to multi-organ failure and the patient died on the 45th ICU admission day.

Trends and Burden of Firearm-Related Injuries Among Children and Adolescents: A National Perspective.

INTRODUCTION: Firearm-related injuries in America have been under increasing scrutiny over the last several years. Few studies have examined the burden of these injuries in the pediatric population. The objective of this study was to describe the incidence of firearm-related injuries in hospitalized pediatric patients in the United States and identify the risk factors associated with readmission in this young population. METHODS: The Nationwide Readmission Database was examined from 2010 to 2017. Pediatric patients (aged ≤18 y) who survived their index hospitalization for any firearm injury were analyzed to determine incidence rate, case fatality rate, risk factors for 30-d readmission, and financial health care burden. RESULTS: There were 35,753 pediatric firearm injuries (86.8% male) with an overall incidence rate of 10.49 (95% confidence interval [CI]: 9.26-11.71) per 100,000 pediatric hospitalizations. Adolescents aged >12 y had the highest incidence rate (60.51, 95% CI: 55.19-65.84). In-hospital mortality occurred in 1948 cases (5.5%), with higher case fatality rates in males. There were 1616 (5.7%) unplanned 30-d readmissions. Multivariate analysis showed abdominal firearm injuries (hazard ratio: 1.13, 95% CI: 1.03-1.24; P = 0.006) and longer length of stay (hazard ratio: 1.27, 95% CI: 1.04-1.55; P = 0.016) were associated with a greater risk of 30-d readmission. The median health care cost for firearm-related injuries was $36,535 (interquartile range: $19,802-$66,443), 22% of which was due to readmissions. Cost associated with 30-d readmissions was $7978 (interquartile range: $4305-$15,202). CONCLUSIONS: Firearm-related injury is a major contributor to pediatric morbidity, mortality, and health care costs. Males are disproportionately affected by firearm injury, but females are more likely to require unplanned 30-d readmissions. Interventions should target female sex, injuries of suicidal intent, psychiatric comorbidities, prolonged index hospitalization, and abdominal injuries.

Association of Rs231775 Genetic Variant of Cytotoxic T-lymphocyte Associated Protein 4 with Alopecia Areata Disease in Males: A Case-Control Study.

BACKGROUND: Alopecia Areata (AA) is a common inflammatory immune-mediated non-scarring hair loss; however, the exact genetic susceptibility remains to be clarified. Cytotoxic T-lymphocyte Associated Protein 4 (CTLA4) has emerged as a central and critically important modulator of immune responses and is believed to play a crucial rule in AA pathogenesis. OBJECTIVES: To investigate the association of CTLA4 variant (rs231775) within codon 17 with AA risk and outcomes. METHODS: Genetic analyses of the rs231775 SNP of CTLA4 gene were performed in 186 males (93 AA patients and 93 controls). RESULTS: The rs231775 CTLA4 variant was significantly higher in AA patients in comparison with control subjects especially among heterozygous and dominant model. This association varied significantly with disease severity. CONCLUSIONS: Individuals with homozygosity of rs231775 CTLA4 variant represented AA disease risk and increased severity than their counterparts.Abbreviations: AA: Alopecia areata; CTLA4: Cytotoxic T-lymphocyte Associated Protein 4; SNP: Single nucleotide polymorphism; LADA: Latent autoimmune diabetes in adults; SLE: Systemic lupus erythematosus; SCU: Suez Canal University; SALT: Severity of Alopecia Tool; DNA: Deoxyribonucleic acid; RT-PCR: Real-time polymerase chain reaction, HWE: Hardy-Weinberg equation; RA: rheumatoid arthritis.

Cancer and COVID-19: analysis of patient outcomes.

Background: We sought to investigate the outcomes associated with COVID-19 disease in cancer patients. Methods: We conducted a retrospective cohort study of laboratory-confirmed COVID-19 patients. Results: Of the 206 patients included, 57 had at least one preexisting malignancy. Cancer patients were older than noncancer patients. Of the 185 discharged cases, cancer patients had a significantly higher frequency of unplanned reintubation (7.1% vs 0.9%, p < 0.049), and required longer hospital stay (8.58 ± 6.50 days versus 12.83 ± 11.44 days, p < 0.002). Regression analysis revealed that obesity and active smoking were associated with an increased risk of mortality. Conclusion: Outcomes in COVID-19 appear to be driven by obesity as well as active smoking, with no difference in mortality between cancer and noncancer patients.

In this study, we aimed to investigate how COVID-19 affected cancer patients and whether this altered their survival outcomes. To do this, we examined data from a database of patients who have passed through our institution ­ a retrospective cohort analysis. Of the 206 patients we included in the study from this database, 57 had at least one preexisting cancer. Cancer patients tended to be older than noncancer patients. Of the 185 discharged patients, cancer patients required longer hospital stays, but there was no difference in mortality. Disease complications and intensive care unit admission with obesity and active smoking put patients in our cohort at increased risk of death. To conclude, outcomes in COVID-19 patients appear to be driven by obesity as well as active smoking, with no difference in mortality between cancer and noncancer patients.

Maternal and Neonatal Outcomes of Critically Ill Pregnant and Puerperal Patients Diagnosed with COVID-19 Disease: Retrospective Comparative Study.

BACKGROUND: We assessed maternal and neonatal outcomes of critically ill pregnant and puerperal patients in the clinical course of coronavirus disease 2019 (COVID-19). METHODS: Records of pregnant and puerperal women with polymerase chain reaction positive COVID-19 virus who were admitted to our intensive care unit (ICU) from March 2020 to August 2021 were investigated. Demographic, clinical and laboratory data, pharmacotherapy, and neonatal outcomes were analyzed. These outcomes were compared between patients that were discharged from ICU and patients who died in ICU. RESULTS: Nineteen women were included in this study. Additional oxygen was required in all cases (100%). Eight patients (42%) were intubated and mechanically ventilated. All patients that were mechanically ventilated have died. Increased levels of C-reactive protein (CRP) was seen in all patients (100%). D-dimer values increased in 15 patients (78.9%); interleukin-6 (IL-6) increased in 16 cases (84.2%). Sixteen patients used antiviral drugs. Eleven patients were discharged from the ICU and eight patients have died due to complications of COVID-19 showing an ICU mortality rate of 42.1%. Mean number of hospitalized days in ICU was significantly lower in patients that were discharged (P = 0.037). Seventeen patients underwent cesarean-section (C/S) (89.4%). Mean birth week was significantly lower in patients who died in ICU (P = 0.024). Eleven preterm (57.8%) and eight term deliveries (42.1%) occurred. CONCLUSION: High mortality rate was detected among critically ill pregnant/parturient patients followed in the ICU. Main predictors of mortality were the need of invasive mechanical ventilation and higher number of days hospitalized in ICU. Rate of C/S operations and preterm delivery were high. Pleasingly, the rate of neonatal death was low and no neonatal COVID-19 occurred.

The interrelation between body mass index and post-dural puncture headache in parturient women.

BACKGROUND AND AIMS: Post-dural puncture headache is seen more frequently in pregnant women due to stress, dehydration, intra-abdominal pressure, and insufficient fluid replacement after delivery. Obesity protects against post-dural puncture headache in pregnant women; increased intra-abdominal fat tissue reduced cerebrospinal fluid leakage by increasing the pressure in the epidural space. Therefore, this study investigated the influence of body mass index on post-dural puncture headache in elective cesarean section patients in whom 27G spinal needles were used. MATERIAL AND METHODS: The study included 464 women who underwent elective cesarean section under spinal anesthesia. Dural puncture performed with a 27G Quincke spinal needle at the L3-4 or L4-5 intervertebral space and given 12.5 mg hyperbaric bupivacaine intrathecally. The patients were questioned regarding headache and low back pain 6, 12, 24, and 48 h after the procedure, and by phone calls on days 3 and 7. RESULTS: Post-dural puncture headache developed in 38 (8.2%) patients. Of the patients who developed post-dural puncture headache, 23 (60.5%) had a body mass index <30 and 15 (39.5%) had a body mass index ≥30. Of the patients who did not develop post-dural puncture headache, 258 (60, 6%) had a body mass index <30 and 168 (39, 4%) had a body mass index ≥30. CONCLUSION: This prospective study found the body mass index values did not affect post-dural puncture headache in the elective cesarean section performed under spinal anesthesia.

A Novel Combination Technique: Three Points of Epiduroscopic Laser Neural Decompression and Percutaneous Laser Disc Decompression With the Ho:YAG Laser in an MSU Classification 3AB Herniated Disc.

AIM: The aim of this study was to examine the effects of simultaneous epiduroscopic laser neural disc decompression (ELND) and percutaneous laser disc decompression (PLDD) applications using a holmium:yttrium-aluminum-garnet (Ho:YAG) laser in Michigan State University (MSU) classification 3AB herniated discs on VAS and Oswestry Disability Index (ODI) scores. METHODS: In this prospective observational study, ELND and PLDD procedures performed between January 2016 and December 2017 were examined. Preoperative, postoperative week 2, postoperative month 2, and postoperative month 6 ODI and VAS scores were obtained from patient files, and postoperative month 12 ODI and VAS scores were obtained from face-to-face interviews with patients and recorded. RESULTS: The data of 41 patients treated with simultaneous ELND and PLDD using a Ho:YAG laser were included in this study. Postoperative VAS scores of the patients were compared with preoperative values, and it was found that postoperative week 2, postoperative month 2, postoperative month 6, and postoperative month 12 VAS and ODI scores were significantly different compared to preoperative scores (P = 0.001; P < 0.01). 17.1% (n = 7) of the patients had a history of postoperative open surgery. Although dural puncture occurred in 7 patients (17%), only 1 patient had headache. CONCLUSION: We believe that the new combined technique of ELND and PLDD using a Ho:YAG laser is a reliable method in patients with MSU classification 3AB herniated discs, with an acceptable success rate and a low complication rate within 12 months after treatment. We think that randomized controlled studies are required for this method to be included in treatment algorithms.

Design, synthesis, anticancer evaluation, molecular docking and cell cycle analysis of 3-methyl-4,7-dihydropyrazolo[1,5-a]pyrimidine derivatives as potent histone lysine demethylases (KDM) inhibitors and apoptosis inducers.

A novel series of pyrazolo[1,5-a]pyrimidines were synthesized and proved by their spectral and elemental analysis, some elected of the newly synthesized compounds were examined for their cytotoxic activity employing MTT assay on two cancer cell lines (Breast and Hela cancers). Compounds 5, 7e and 7i showed the higher cytotoxicity against two cancer cell lines with (IC50 = 13.91 ±â€¯1.4 and 22.37 ±â€¯1.8 µM/L), (IC50 = 6.56 ±â€¯0.5 and 8.72 ±â€¯0.9 µM/L) and (IC50 = 4.17 ±â€¯0.2 and 5.57 ±â€¯0.4 µM/L) for two cancer cell lines breast and hela respectively, using doxorubicin as a reference drug. The most potent cytotoxic active compounds 5, 7e and 7i presented inhibitory activity against KDM (histone lysine demethylases) with IC50 = 4.05, 1.91 and 2.31 µM, respectively. The most potent KDM inhibitor 7e (IC50 = 1.91 µM) showed to cause cell cycle arrest at G2/M phase by 4 folds than control and induce total apoptotic effect by 10 folds more than control. In silico studies performed on the more potent cytotoxic active compounds 5, 7e and 7i included lipinisk's rule of five. Moreover, molecular docking study was utilized to explore the binding mode of the most active compounds to the target enzyme (PDB-ID: 5IVE). Also, some bioinformatics studies were carried out for compounds 7e and 7i using Swiss ADME (Swiss Institute of bioinformatics 2018).

Assessment of patient safety culture: a nationwide survey of community pharmacists in Kuwait.

BACKGROUND: Medication errors have been the largest component of medical errors threatening patient safety worldwide. Several international health bodies advocate measuring safety culture within healthcare organizations as an effective strategy for sustainable safety improvement. To the best of our knowledge, this is the first study conducted in a Middle Eastern country at the level of community pharmacy, to examine safety culture and to evaluate the extent to which patient safety is a strategic priority. METHODS: A descriptive cross-sectional study was conducted. The Pharmacy Survey on Patient Safety Culture (PSOPSC), developed by the Agency for Healthcare Research and Quality (AHRQ), was used to collect data. PSOPSC is a self-administered questionnaire which was previously tested for validity and reliability. The questionnaire was distributed among pharmacists who work in community pharmacies from the five governorates of Kuwait (Capital, Hawalli, Farwaniya, Jahra, and Ahmadi). The Statistical Package for Social Science (SPSS) software, version 24 was used for analysing data. RESULTS: A total of 255 community pharmacists from the five governorates were approached to participate in the study, of whom 253 returned a completed questionnaire, with the response rate of 99%. Results from the study showed that patient safety is a strategic priority in many aspects of patient safety standards at the level of community pharmacies. This was reflected by the high positive response rate (PRR) measures demonstrated in the domains of "Teamwork" (96.8%), "Organizational Learning-Continuous Improvement" (93.2%) and "Patient Counselling" (90.9%). On the other hand, the lowest PRR was given to the "Staffing, Work Pressure, and Pace" domain which scored 49.7%. CONCLUSIONS: Understanding community pharmacists' perspectives of patient safety culture within their organization is critical. It can help identify areas of strength and those that require improvement, which can help support decision about actions to improve patient safety. The current study showed that urgent attention should be given to the areas of weakness, mainly in the dimension of "Staffing, Work Pressure and Pace." The pharmacists pointed the need for adequate breaks between shifts and less distractible work environment to perform their jobs accurately.

MicroRNA-target cross-talks: Key players in glioblastoma multiforme.

The role of microRNAs in brain cancer is still naive. Some act as oncogene and others as tumor suppressors. Discovery of efficient biomarkers is mandatory to debate that aggressive disease. Bioinformatically selected microRNAs and their targets were investigated to evaluate their putative signature as diagnostic and prognostic biomarkers in primary glioblastoma multiforme. Expression of a panel of seven microRNAs (hsa-miR-34a, hsa-miR-16, hsa-miR-17, hsa-miR-21, hsa-miR-221, hsa-miR-326, and hsa-miR-375) and seven target genes ( E2F3, PI3KCA, TOM34, WNT5A, PDCD4, DFFA, and EGFR) in 43 glioblastoma multiforme specimens were profiled compared to non-cancer tissues via quantitative reverse transcription-polymerase chain reaction. Immunohistochemistry staining for three proteins (VEGFA, BAX, and BCL2) was performed. Gene enrichment analysis identified the biological regulatory functions of the gene panel in glioma pathway. MGMT ( O-6-methylguanine-DNA methyltransferase) promoter methylation was analyzed for molecular subtyping of tumor specimens. Our data demonstrated a significant upregulation of five microRNAs (hsa-miR-16, hsa-miR-17, hsa-miR-21, hsa-miR-221, and hsa-miR-375), three genes ( E2F3, PI3KCA, and Wnt5a), two proteins (VEGFA and BCL2), and downregulation of hsa-miR-34a and three other genes ( DFFA, PDCD4, and EGFR) in brain cancer tissues. Receiver operating characteristic analysis revealed that miR-34a (area under the curve = 0.927) and miR-17 (area under the curve = 0.900) had the highest diagnostic performance, followed by miR-221 (area under the curve = 0.845), miR-21 (area under the curve = 0.836), WNT5A (area under the curve = 0.809), PDCD4 (area under the curve = 0.809), and PI3KCA (area under the curve = 0.800). MGMT promoter methylation status was associated with high miR-221 levels. Moreover, patients with VEGFA overexpression and downregulation of TOM34 and BAX had poor overall survival. Nevertheless, miR-17, miR-221, and miR-326 downregulation were significantly associated with high recurrence rate. Multivariate analysis by hierarchical clustering classified patients into four distinct groups based on gene panel signature. In conclusion, the explored microRNA-target dysregulation could pave the road toward developing potential therapeutic strategies for glioblastoma multiforme. Future translational and functional studies are highly recommended to better understand the complex bio-molecular signature of this difficult-to-treat tumor.

Influences of copolymers (Copovidone, Eudragit RL PO and Kollicoat MAE 30 DP) on stability and bioactivity of spray-dried and freeze-dried lysozyme.

Protein stability is the most crucial factor in protein pharmaceutical preparations. Various techniques were applied for producing stable protein formulations such as spray-drying and freeze-drying. However, heating and freezing stresses are disadvantages for proteins using these methods, respectively. Accordingly, excipients have been used to preserve therapeutic effects of proteins during processing and for long period of time. Therefore, influences of Copovidone, Eudragit® RL-PO and Kollicoat® MAE-30 DP (as excipients) on stability and integrity of lysozyme (as a model protein) in spray-dried and freeze-dried forms were investigated. Protein formulations in both dried forms were prepared without and with the addition of mentioned excipients at different concentrations. Protein formulations were characterized for yield determination, morphology using scanning electron microscopic (SEM), thermal analysis by Differential Scanning Calorimetry (DSC), secondary structure stability using Fourier transform infrared (FT-IR) spectroscopy and biological activity. All protein formulations were subjected to a stability study as solid protein formulations for 3 weeks at 24 °C/76% relative humidity and aqueous protein samples were stored at 50 °C for 30 min in a water bath. Results showed that Copovidone successfully preserved integrity and biological activity of lysozyme before and after storage in both spray-dried and freeze-dried forms with more advantage for using higher concentration of the same excipient. Smooth spheres of spray-dried lysozyme formulations with Copovidone were smaller than spray-dried lysozyme without and with Kollicoat® MAE-30 DP, which affected %yield produced. Copovidone has demonstrated valuable protection ability for lysozyme.