Abstract Background : Smoking plays a key role in the development of tuberculosis (TB) infection and is also a predictor of poor TB treatment prognosis and outcomes. The current study was conducted to determine the prevalence of smoking and to assess the effects of smoking on treatment outcomes among TB patients. Methods : A multi-center retrospective study design was used to collect data from TB patients in four different states of Malaysia, namely Penang, Sabah, Sarawak, and Selangor. The study included medical records of TB patients admitted to the selected hospitals in the period from January 2006 to March 2009. Medical records with incomplete data were not included. Patient demographics and clinical data were collected using a validated data collection form. Results: Of all patients with TB (9337), the prevalence of smokers was 4313 (46.2%). Among smokers, 3584 (83.1%) were associated with pulmonary TB, while 729 (16.9%) were associated with extrapulmonary TB. Male gender (OR= 1.43, 95% CI 1.30-1.58), Chinese ethnicity (OR= 1.23, 95% CI 1.02-1.49), Sarawak indigenous ethnicity (OR= 0.74, 95% CI 0.58-0.95), urban residents (OR= 1.46, 95% CI 1.33-1.61), employed individuals (OR= 1.21, 95% CI 1.09-1.34), alcoholics (OR= 4.91, 95% CI 4.04-5.96), drug abusers (OR= 7.43, 95% CI 5.70-9.60) and presence of co-morbid condition (OR= 1.27, 95% CI 1.16-1.40) all showed significant association with smoking habits. This study found that 3236 (75.0 %) patients were successfully treated in the smokers' group, while 4004 (79.7 %) patients were non-smokers. The proportion of deaths (6.6%, n=283), defaulters (6.6%, n=284) and treatment interruptions (4.7%, n=204) was higher in the smokers' group. Conclusions: Smoking has a strong influence on TB and is a major barrier towards treatment success (OR= 0.76, 95% CI 0.69-0.84, p< 0.001). Therefore, the findings indicate that smoking cessations are an effective way to decrease treatment failure and drug resistance.
Virtual screening aims to identify and rank compounds with drug/lead-like properties based on their affinity for the protein target. We developed a methodology that integrates structure- and ligand-based screening approaches to enhance hit rates against the TDP1 protein within a database of anthraquinone and chalcone derivatives, followed by evaluation of prioritized compounds through molecular simulations. This technique is particularly useful for training set imbalances. Four screening methods were used: QSAR, pharmacophore, shape similarity, and docking. Each method was individually trained to score compounds, and the scores were fused to create parallel Z-score fusion. The QSAR models exhibited satisfactory R2 values (0.84 to 0.75), whereas the pharmacophoric and shape similarity models demonstrated excellent performance (ROC:0.82-0.88). Docking enrichment analysis identified 6N0D as the optimal TDP1 crystal structure (ROC = 0.73). Remarkably, the consensus scoring method surpassed other screening methods, achieving the highest ROC value of 0.98. Docking screening prioritized compounds with binding modes resembling the co-crystallized ligands, whereas MMGBSA, consensus, and docking produced dynamic simulations that were as stable as the co-crystallized ligands. Additionally, the QSAR-selected compounds exhibited binding modes similar to those of commercially available TDP1 inhibitors. In this study, a strong correlation was found between the inhibitory concentrations and binding energy values of commercialized TDP1 inhibitors, indicating that the top-ranked compounds are expected to have potent inhibitory effects in the nano-/micromolar range. The results of this study establish that consensus scoring can be used as an adaptable mainstay virtual screening methodology, pending subsequent experimental validation for affirmation.Communicated by Ramaswamy H. Sarma.
Addressing infectious diseases poses a significant healthcare challenge due to the growing resistance of microorganisms to antibiotics. Consequently, extensive research efforts have been dedicated to identifying alternative molecules to antibiotics that can combat these infectious diseases. Notably, a wealth of bioactive compounds has been discovered in medicinal and aromatic plants, and their potential utility in the development of treatments for infectious diseases has been well-established. In this study, we employed two extraction methods, namely maceration and ultrasound-assisted extraction (UAE), and four different solvents with varying polarities to isolate bioactive compounds from Cistus ladanifer L. Subsequently, quantification of polyphenols was determined in all the extracted samples. Following this, we conducted both qualitative and quantitative assessments of the antibacterial activity of these extracts. Moreover, we delved into the mechanism of action of the most potent extract using scanning electron microscopy. The results revealed that methanol was the best solvent for extracting bioactive molecules and that UAE had a high extraction efficiency since it gave a higher yield of total polyphenols than the one acquired by maceration. Regarding the results of the disk diffusion assay, the extracts that were prepared by UAE were more effective against our bacterial strains than those extracted by maceration. Electron micrographs of damaged cells revealed that the methanolic extract obtained by UAE affected the integrity of the cell membrane. These outcomes have underscored the presence of active compounds within Cistus ladanifer L. that could serve as potential alternatives to antibiotics against some of the most pathogenic bacterial species.
With the growing importance of the healthcare sector, resilience has become a fundamental personal quality that healthcare professionals need to cultivate to cope with adverse events in daily work. Distress in the workplace cannot only impact the well-being of healthcare professionals but also negatively affect the capability to care effectively for others. This study was conducted to determine the score and level of resilience among private primary healthcare professionals and their relationships with independent variables. Sets of questionnaires on resilience based on the Connor-Davidson resilience scale-10 (CD-RISC-10) were completed by 164 general practitioners (GPs) and 87 community pharmacists (CPs). Inferential analysis was used to assess the difference, correlation, association, and predictor among dependent and independent variables. The validity and reliability of the study instrument were assessed using Modern Test Theory (MTT) and Classical Test Theory (CTT). The majority of GPs and CPs possessed the lowest resilience level. There were significant differences between CD-RISC-10 with gender, age, and years of experience in GPs as well as overall. Significant associations were found between CD-RISC-10 with all independent variables, except for the highest education level in GPs and overall. This study revealed significant correlations between independent variables with CD-RISC-10 in GPs and overall. However, there were nonsignificant differences, associations, and correlations among CPs between all independent variables and CD-RISC-10. Gender was the predictor of CD-RISC-10 in GPs, while age and years of experience were the predictors of CD-RISC-10 in GPs and overall. There was no predictor of independent variables for CPs. In multinomial logistics regression, years of experience and gender were the significant predictors of CD-RISC-10 among GPs. The CD-RISC-10 instrument had good validity and reliability. Overall, healthcare professionals showed a low level of resilience. This emphasized the need to cultivate and build resilience, as it is a desirable, important element when working in harsh and unprecedented healthcare settings.
The efficacy and safety of Momordica charantia based on relevant studies and reviews are described. M. charantia also known as bitter melon has been proposed to exert effects in lowering blood glucose levels by means of various forms and extracts from the plant. Over the years, commercially available preparations containing bitter melon are made available in the market despite limitations on available clinical trials. Clinical trial conducted demonstrates variety in findings on the effect of M. charantia on glycemic control with mostly not exhibiting statistically significant differences. Monitoring is vital in view of the reported side effects and precaution warranted for the specific individuals and unknown herbal-drug or herbal-food interaction that could possibly interrupt the overall management plan. For the meantime, findings generated from the studies only provide implication on the potential advantages that M. charantia offers in preventing and managing type 2 diabetes as well as the microvascular complications instead of a certain conclusion.
There is a paramount need for moral development for pharmacists and pharmacy students to practice the patient-centered profession. We aimed to explore the current situational judgment utilizing ethical reasoning among undergraduate pharmacy students.A set of ten ethical dilemmas, representing potential real-life situations that the students come across in the university and may face in the future as a pharmacist were developed by a team of students, academic staff, and stakeholders. These ethical dilemmas were validated, checked for accuracy, and piloted. An online questionnaire was created consisting of these ten scenarios as open-ended questions and administered to fourth year and fifth year PharmD students in a public university located at the city of Mecca, Saudi Arabia, asking them how they would react in that situation. Responses of the participants were analyzed using thematic analysis independently by four researchers and inter-rater agreement were achieved through consensus.Out of 205, 186 students completed the questionnaire with a response rate of 90.7%. Analysis and resulted in the generation of 32 codes, which were then categorized into seven overarching themes: student engagement, social and professional responsibility, academic integrity, legal obligation, moral obligation, signposting, and moral engagement and patient safety.Undergraduate pharmacy students experience complex state of mind in connection with ethical reasoning. The participants' situational judgment were driven by cultural norm, authority, and responsibility. Student engagement is also affected by the state of mind and feelings of mutual trust, perceived cultural influence and peer pressure. The students were prone to seek help from university administrators or teachers when faced with situations in which they were helpless.
To identify and assess the characteristics, risk and outcome of neonates treated with empiric antibiotics for suspected early onset sepsis (EOS).This is a retrospective study conducted at a Malaysian government hospital. Records of neonatal patients admitted within 72 h of life and prescribed with empirical antibiotic therapy for suspected EOS were reviewed.Three hundred and twenty-three cases met the inclusion criteria and were divided into gestational age (premature < 36 weeks; term ≥ 37 weeks) and birth weight (low birth weight (LBW) < 2.5 kg; normal body weight (NBW) ≥ 2.5 kg) groups. Premature (n = 197) and LBW (n = 194) neonates required significantly longer hospital stay, a higher degree of ventilator support and more surfactant (p = 0.001). More than 90.0% of premature and LBW neonates were diagnosed with respiratory distress syndrome, congenital pneumonia and presumed sepsis. Term (n = 123) and NBW (n = 129) neonates had greater maternal risk factors, especially meconium-stained amniotic fluid (MSAF) and perinatal asphyxia. The incidence of demonstrated EOS was 3.1%. Crystalline penicillin plus gentamicin was the standard therapy for all groups and was started within 24 h of life, with a mean treatment duration of ∼4 days. The treatment success rate was 89.0%, and only LBW neonates showed a higher risk of overall treatment failure (OR = 3.75; 95% CI: 1.22-11.53). Seventy-four percent of term and NBW neonates discharged well, while 42.0% of premature and LBW neonates required referral.Crystalline penicillin plus gentamicin prescribed within 24 h of life is effective in the prevention of EOS. However, low birth weight neonates have a higher risk of treatment failure.
Background: Hybrid learning combines traditional face-to-face instruction with online or digital learning components and has gained significant popularity in recent years. Objective: This study aimed to assess the satisfaction of hybrid learning among undergraduate health science students and identify the factors associated with the satisfaction level, providing further insights into improvements in hybrid learning adoption to make effective use of the learning approach. Methods: An online survey was distributed to the undergraduate health science students at Taylor’s University in Malaysia. Students’ satisfaction and the associated factors were assessed using a 5-point Likert scale using Pearson Chi-square and logistic regression analysis test where p-value < 0.05 is considered statistically significant. Results: More than half of the students (66.7%) in this study expressed positive satisfaction towards hybrid learning. Internet connection was determined as one of the students' satisfaction-related factors (p=xx). Multivariate binary logistics regression demonstrated that course structure, perceived ease of use, student-instructor interaction and students’ attitude toward hybrid learning had a statistically significant impact on students’ satisfaction with the hybrid learning approach. Conclusion: Students' satisfaction is valuable input for institutions and instructors to enhance the quality of hybrid learning in the future to optimise students' learning experience.
Cancer is one of the major leading causes of mortality globally and chemo-drug-resistant cancers pose significant challenges to cancer treatment by reducing patient survival rates and increasing treatment costs. Although the mechanisms of chemoresistance vary among different types of cancer, cancer cells are known to share several hallmarks, such as their resistance to apoptosis as well as the ability of cancer stem cells to produce metastatic daughter cells that are resistant to chemotherapy. To address the issue of chemo-drug resistance in cancer cells, a tetracistronic expression construct, Ad-MBR-GFP, encoding adenovirus-mediated expression of MOAP-1, Bax, RASSSF1A, and GFP, was generated to investigate its potential activity in reducing or inhibiting the chemo-drug resistant activity of the human breast cancer cells, MCF-7-CR and MDA-MB-231. When infected by Ad-MBR-GFP, the cancer cells exhibited round cell morphology and nuclei condensation with positive staining for annexin-V. Furthermore, our results showed that both MCF-7-CR and MDA-MB-231 cells stained positively for CD 44 and negatively for CD 24 (CD44+/CD24-) with high levels of endogenous ALDH activity whereas SNU-1581 breast cancer cells were identified as CD 44-/CD 24- cells with relatively low levels of endogenous ALDH activity and high sensitivity toward chemo-drugs, suggesting that both CD 44 and ALDH activity contribute to chemo-drug resistance. Moreover, both MCF-7-CR and MDA-MB-231 cells showed strong chemo-drug sensitivity to cisplatin when the cells were infected by Ad-MBR-GFP, leading to 9-fold and 2-fold reduction in the IC 50 values when compared to cisplatin treatment alone, respectively. The data were further supported by 3D (soft agar) and spheroid cell models of MCF-7-CR and MDA-MB-231 cells which showed a 2-fold reduction of a number of cell colonies and spheroid size when treated with both Ad-MBR-GFP and cisplatin, and compared to control. Other than chemo-sensitivity, Ad-MBR-GFP-infected cancer cells retarded cell migration. Flow cytometry analysis showed that the mechanism of action of Ad-MBR-GFP involved cell cycle arrest at the G1 phase and inhibition of cellular DNA synthesis. Taken together, our investigation showed that Ad-MBR-GFP mediated chemo-drug sensitization in the infected cancer cells involved the activation of apoptosis signaling, cell cycle arrest, and inhibition of DNA synthesis, suggesting that Ad-MBR-GFP is potentially efficacious for the treatment of chemo-drug resistant cancers.
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