Characteristics, knowledge, attitude, and practice of pharmacy personnel in supporting tuberculosis treatment: A multicenter cross-sectional study in a high-burden tuberculosis country.

BACKGROUND: Positive roles of community pharmacy in tuberculosis (TB) care have been widely reported. However, the actual practice of supporting TB treatment is not optimal yet. OBJECTIVES: We analyzed the current practice of community pharmacy personnel and its factors in supporting the successful treatment of TB patients in Indonesia, aiming to develop strategies for effective and sustainable TB practice models for the community pharmacy. METHODS: We performed a cross-sectional survey in 3 areas representing Indonesia's eastern, central, and western parts. Development and validation of the questionnaire were conducted to assess 4 domains, that is, characteristics, knowledge, attitudes, and practice of community pharmacy personnel in supporting the successful treatment of TB patients. Data were collected with purposive convenience sampling using online and offline questionnaires. Descriptive analyses were used to summarize factors in each domain, while binary logistic regression was used to analyze the associated factors of the practice. RESULTS: Thirty-five questionnaire items indicated a valid instrument, and the study successfully included 844 participants who comprised pharmacists (n = 473, 56%) and pharmacy assistants (n = 371, 44%). Although most of the knowledge items were correctly answered by more than 60% of the participants, items related to TB signs, risk groups, drug regimens, and medicine uses were still less than 60%. This was in line with exposure to updated TB training in only 51% of the participants (n = 426). Most of the participants had a positive attitude toward their professional role (n = 736, 87%), capability (n = 646, 77%), and consequences (n = 655, 78%) in supporting TB treatment. However, this was not aligned with the actual practice of supporting TB treatment, intensively performed by only 1.3% of participants (n = 11). We identified several factors associated with the practice, that is, a pharmacy assistant background (P < 0.05), short working time (P < 0.05), experience in TB training (P < 0.001), and a positive attitude (P < 0.001). CONCLUSION: This study highlighted a limited number of community pharmacy personnel intensively practicing as TB treatment supporters in Indonesia. An interventional package considering the identified factors is needed to develop effective and sustainable practices in the real world.

Correlation between the Cognitive Status (SIRT1) and the Metabolic Function in Geriatric Patients Using the Indonesian Version of the Montreal Cognitive Assessment (MoCA-INA).

A growing life expectancy may result in a chronic medical condition and multimorbidity because the aging process leads to a decrease in cognitive and physiological function. These risks may affect the quality of life of geriatrics. The present study aims to determine the correlation between cognitive status (in terms of SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent class III deacetylase) and metabolic function (in terms of the lipid profile, kidney function, and blood glucose) in geriatric patients. The differences in the parameters of metabolic function in the participants' cognitive status were determined by using the Indonesian version of the Montreal Cognitive Assessments (MoCA-Ina). The elderly participants (n = 120) were recruited at three sites in Indonesia from March to October 2022. Our study demonstrated a negative correlation between the cognitive status of geriatric patients and their metabolic function, represented by the MoCA-Ina score with a linear regression equation of y = 0.27 - 2.4 ×10-3x. Higher levels of LDL-C, cystatin C, and HbA1c were found in the Severe-Moderate Cognitive Impairment group. Determining the SIRT1 levels may be beneficial in predicting both the cognitive and metabolic status of geriatrics because this protein is among numerous metabolic sensors in the hypothalamus.

Antibacterial Potency of an Active Compound from Sansevieria trifasciata Prain: An Integrated In Vitro and In Silico Study.

Sansevieria trifasciata Prain holds great potential as a valuable asset in pharmaceutical development. In this study, our focus is to explore and assess the antibacterial activity of various components derived from this plant, including extracts, fractions, subfractions, and isolates, explicitly targeting two common bacteria: Escherichia coli and Streptococcus aureus. The isolated compound, identified as a derivative pyridone alkaloid (5-methyl-11-(2-oxopyridin-1(2H)-yl)undecaneperoxoicacid), demonstrates notable antibacterial effects. The extracts, fractions, subfractions, and isolates reveal significant bacterial growth reductions (p < 0.05). The minimum inhibitory concentration (MIC) values for Escherichia coli were 1.95 ppm, 3.9 ppm, 15.62 ppm, and 7.81 ppm, respectively, while the MIC values for Streptococcus aureus were 1.95 ppm, 1.95 ppm, 15.62 ppm, and 7.81 ppm, respectively. Computational analysis showed the isolates' interaction with key residues on the active site of ß-ketoacyl-ACP synthase from Escherichia coli and TyrRS from Streptococcus aureus. The findings indicate that the isolates exhibit a strong affinity for specific residues, including His333, Cys163, and Phe392 in ß-ketoacyl-ACP synthase, as well as Arg88, His117, Glu160, and Gln213 in TyrRS. Comparative energy calculations using MMPBSA demonstrate the isolates' favorable binding energy (-104,101 kJ/mol for ß-ketoacyl-ACP synthase and -81,060 kJ/mol for TyrRS) compared to ciprofloxacin. The elucidated antibacterial activity and molecular interactions of the isolates present valuable knowledge for future in vitro studies, facilitating the development of novel antibacterial agents targeting diverse bacterial strains.

Healthy mitochondrial DNA in balanced mitochondrial dynamics: A potential marker for neuro­aging prediction (Review).

The mitochondrial genome or mitochondrial DNA (mtDNA) is released as a response to cellular stress. In mitochondrial biogenesis, active communication between the mitochondria genome and nucleus is associated with the mtDNA profile that affects the mitochondrial quality. The present review aimed to assess the molecular mechanism and potential roles of mitochondria in neuro-aging, including the importance of evaluating the health status of mtDNA via mitochondrial dynamics. The normal condition of mitochondria, defined as mitochondrial dynamics, includes persistent changes in morphology due to fission and fusion events and autophagy-mitophagy in the mitochondrial quality control process. The calculated copy number of mtDNA in the mitochondria genome represents cellular health, which can be affected by a long-term imbalance between the production and accumulation of reactive oxygen species in the neuroendocrine system, which leads to an abnormal function of mitochondria and mtDNA damage. Mitochondria health is a new approach to discovering a potential indicator for the health status of the nervous system and several types of neurodegenerative disorders. Mitochondrial dynamics is a key contributor to predicting neuro-aging development, which affects the self-renewal and differentiation of neurons in cell metabolism. Neuro-aging is associated with uncontrolled mitochondrial dynamics, which generates age-associated diseases via various mechanisms and signaling routes that lead to the mtDNA damage that has been associated with neurodegeneration. Future studies on the strategic positioning of mtDNA health profile are needed to detect early neurodegenerative disorders.

Anti-Alopecia Activity of Alkaloids Group from Noni Fruit against Dihydrotestosterone-Induced Male Rabbits and Its Molecular Mechanism: In Vivo and In Silico Studies.

Androgenic alopecia (AA) is a condition that most commonly affects adult men and is caused by an increase in the hormone dihydrotestosterone (DHT) in the hair follicles. Anti-alopecia drugs should be discovered for hair follicles to enter the anagen growth phase. Therefore, this study evaluated the hair growth-promoting activity of Noni fruit's water, ethyl acetate, n-hexane fractions, and sub-fractions from the active fraction in the alopecia male white rabbit model. The Matias method was modified by inducing rabbits using DHT for 17 days, followed by topical application of Noni fruit solution for 21 days. Meanwhile, hair growth was evaluated by histological observation of the follicular density and the anagen/telogen (A/T) ratio in skin tissue. In the first stage, five groups of male white rabbits were studied to obtain the active fraction; DHT+Minoxidil as standard, DHT+vehicle (NaCMC 1%), DHT+FW, DHT+FEA, and DHT+FH. The FEA as the active fraction was followed by open-column chromatography separation (DCM:Methanol) with a gradient of 10% to produce sub-fractions. In the second stage, the six main sub-fraction groups of male rabbits studied were DHT+FEA-1 to DHT+FEA-6. The follicular density of groups FEA-3 was 78.00 ± 1.52 compared with 31.55 ± 1.64 and 80.12 ± 1.02 in the Vehicle and Minoxidil groups. Additionally, group FEA-3 showed large numbers of anagen follicles with an A/T ratio of 1.64/1 compared to the vehicle group of 1/1.50 and 1.39/1 for Minoxidil control. Group FEA-3 was identified by LC-MS/MS-QTOF, followed by molecular docking to the androgen receptor (PDB: 4K7A), causing alopecia. The results showed that three alkaloid compounds with skeleton piperazine and piperidine, namely (compounds 2 (−4.99 Kcal/mol), 3 (−4.60 Kcal/mol), and 4 (−4.57 Kcal/mol)) had a binding affinity similar to Minoxidil, with also has alkaloid skeleton piperidine−pyrimidine (−4.83 Kcal/mol). The dynamic behavior showed the stability of all androgen receptor compounds with good RMSD, SMSF, and SASA values after being studied with 100 ns molecular dynamics (MD) simulations. This study produced a common thread in discovering a class of alkaloid compounds as inhibitors of androgen receptors that cause alopecia.

Phytochemical Analysis and Immunomodulatory Potential on Diabetic-Infected Tuberculosis by Fruit Etlingera rubroloba A.D. Poulsen.

<b>Background and Objective:</b> <i> Etlingera rubroloba</i> (<i>E. rubroloba</i>) A.D. Poulsen is an endemic plant in South-East Sulawesi and is a newly discovered species. This plant is expected to have the potential as an immunomodulator in patients with diabetes mellitus (DM), which can prevent tuberculosis infection by increasing the phagocytic function of macrophage cells and interleukin-12 (IL-12) levels. <b>Materials and Methods:</b> Phytochemical analysis of the ethanolic extract of the fruit of <i>E. rubroloba</i> A.D. Poulsen using Liquid Chromatography-Mass Spectrometry (LC-MS/MS) was carried out. The immunomodulatory potential <i>in vivo</i> on BALB/c mice model DM was carried out by oral induction of TB antigen with extract dose, control positive, negative and normal groups. Furthermore, the phagocytic activity of macrophage cells can be seen with a microscope and the levels of IL-12 with the Elisa kit. <b>Results:</b> The results showed the ethanol extract of the fruit of <i>E. rubroloba</i> contained eight chemical compounds and had potential as immunomodulators in BALB/c DM mice induced by TB antigen by increasing the phagocytic activity of macrophage cells and levels of IL-12, which were significantly different from the negative control (p<0.05). <b>Conclusion:</b> The chemical composition of the ethanol extract of the fruit of <i>E. rubroloba</i> has the potential as an immunomodulator in TB antigen-induced DM <i>in vivo</i>.

Unrevealing the Potential of Sansevieria trifasciata Prain Fraction for the Treatment of Androgenetic Alopecia by Inhibiting Androgen Receptors Based on LC-MS/MS Analysis, and In-Silico Studies.

Androgenetic Alopecia (AGA) occurs due to over-response to androgens causing severe hair loss on the scalp, and requires the development of new and efficient drugs to treat this condition. This study explores and identifies secondary metabolites from Sansevieriatrifasciata Prain using the LC-MS/MS and in-silico method. The inhibitory activity of bioactive compounds from S. trifasciata Prain against androgen receptors (PDB ID: 4K7A) was evaluated molecularly using docking and dynamics studies by comparing their binding energies, interactions, and stability with minoxidil. The results of the LC-MS/MS analysis identified Methyl pyrophaeophorbide A (1), Oliveramine (2), (2S)-3', 4'-Methylenedioxy-5, 7-dimethoxyflavane (3), 1-Acetyl-ß-carboline (4), Digiprolactone (5), Trichosanic acid (6) and Methyl gallate (7) from the leaves subfraction of this plant. Three alkaloid compounds (compounds 1, 3, and 4), and one flavonoid (compound 2), had lower docking scores of -7.0, -5.8, -5.2, and -6.3 kcal/mol, respectively. The prediction of binding energy using the MM-PBSA approach ensured that the potency of the four compounds was better than minoxidil, with energies of -66.13, -59.36, -40.39, and -40.25 kJ/mol for compounds 1, 3, 2, and 4, respectively. The dynamics simulation shows the stability of compound 1 based on the trajectory analysis for the 100 ns simulation. This research succeeded in identifying the compound and assessing the anti-alopecia activity of Sansevieria trifasciata Prain. Seven compounds were identified as new compounds never reported in Sansevieria trifasciata Prain. Four compounds were predicted to have better anti-alopecia activity than minoxidil in inhibiting androgen receptors through an in silico approach.

Antiproliferation Activity and Apoptotic Mechanism of Soursop (Annona muricata L.) Leaves Extract and Fractions on MCF7 Breast Cancer Cells.

INTRODUCTION: Breast cancer is the second most common cancer in women globally, and the incidence rate has increased annually. Traditional medicine is frequently used as a cancer treatment, and soursop or Annona muricata L (A. muricata) is a traditional medicinal plant that has been widely used as an anticancer treatment and requires more thorough study. METHODS: In this research, we prepared ethanol extract and three solvents, ie, ethyl acetate, n-hexane and water fractions of A. muricata leaves and assessed their antiproliferation and cytotoxic activity on MCF7 breast cancer cells compared with that on CV1 normal kidney cells; observation of cell morphology by stained with mixture of propidium iodide and 4',6-diamidino-2-phenylindole indicated that this treatment induced an ongoing process of apoptotic cell death in MCF7 cells. To clarify the cell death mechanism via apoptosis, we assessed the mRNA expression in the caspase cascade of caspase-9, caspase-3, and PARP-1, and anti-apoptotic, Bcl-2 which mediated cytotoxic activity of extracts and ethyl acetate fractions of A. muricata leaves against MCF7 cells. RESULTS: The ethanol extract, ethyl acetate, n-hexane, and water fractions of A. muricata leaves had IC50 values of 5.3, 2.86, 3.08, and 48.31 µg/mL, respectively, in MCF7 cells but had no activity in CV1 cells. The high cytotoxic activity of A. muricata leaves was reflected by changes in the morphology of cancer cells that appeared after 6 h exposure to A. muricata leaf extract and ethyl acetate fraction; the membrane and nucleus of cells undergoing apoptosis were characterized by the rupture and loss of membranes and nuclei. The mechanism that mediates this cytotoxic activity in MCF7 cells was mediated through a decrease in the expression of Bcl-2 mRNA and an increase in caspase-9 and caspase-3 mRNA expression. CONCLUSION: Therefore, the leaves of the medicinal plant A. muricata contained compounds that on extraction exerted a highly effective activity as an anticancer treatment for breast cancer via induced apoptotic cell death.

Lack of Awareness of the Impact of Improperly Disposed Of Medications and Associated Factors: A Cross-Sectional Survey in Indonesian Households.

Introduction: Disposal of unused medications through environmentally unsafe routes is common in Indonesia. The lack of awareness of the impact of improperly disposed of medications is a significant contributing factor. The objectives of this study were to identify factors associated with lack of awareness of the impact of improperly disposed of unused medications and to assess the associations of awareness with medication disposal practices among the general population in Indonesia. Patients and methods: An observational cross-sectional survey was conducted using nonprobability sampling in Bandung, Indonesia, from November 2017 to January 2018 among respondents who were older than 18 years, had used any medication in the past, were literate, and had signed an informed consent document. Disposal practices and awareness regarding the impact of improperly disposed of unused medications were collected using an online- and a paper-based pre-validated questionnaire. The paper-based questionnaires were distributed to respondents in public places such as city center, markets, and religious places. Binary logistic regression was performed to assess associations of sociodemographic and other related factors with a lack of awareness. Odds ratios (ORs) with 95% confidence intervals (CIs) are reported. Results: Of 497 participating respondents, 433 and 64 respondents filled an online- or a paper-based questionnaire, respectively. Most respondents were female, aged between 18 and 30 years, and students/university students. Of 497 respondents, more than half (53.1%) were not aware that improper medication disposal could harm the environment and population health. Most respondents (79.5%) had never received information about proper medication disposal practices. The education level, the number of stored medications at home, and previous education about medication disposal practices were significantly associated with awareness of proper practices. In the multivariate analysis, only those with previous education about medication disposal practices were less likely to report a lack of awareness (OR: 0.043; 95% CI: 0.02-0.09). Respondents with a lack of awareness tended to dispose of their unused medications in the garbage or shared them with friends or relatives. Conclusion: There is a clear need to increase awareness of the importance of proper medication disposal practices, in particular among the student population of Bandung city, Indonesia. Healthcare providers can play an important role by educating this specific population on the proper disposal of unused medications.

Simultaneous Use of Herbal Medicines and Antihypertensive Drugs Among Hypertensive Patients in the Community: A Review.

In various countries, approximately 80% of patients use herbal medicine, both in single form or in combination with antihypertensive drugs, for the treatment of hypertension. Therefore, this research summarized studies on the simultaneous use of herbal medicines and antihypertensive drugs among hypertensive patients in the community. A literature search was conducted on PubMed in April 2020, and the following keywords were used: "herbal medicines" and "antihypertensive patients." In total, 15 of 263 articles were found to be eligible in the initial research. Results showed that studies were performed in different countries worldwide including America and those in Europe, Asia, and Africa between 1960 and 2020. The factors associated with the use of herbal medicines and antihypertensive drugs were age, gender, education level, income, and residence. Herbal medicines and antihypertensive drugs are simultaneously utilized primarily due to their safety and high efficacy. Herbal medicine is frequently recommended by friends or colleagues, herbalists, advertisements, and health workers. Garlic is the most common herbal medicine used along with antihypertensive drugs. The side effects of combination therapy with herbal medicines and prescription drugs for the management of antihypertension include shortness of breath and cough, ulcers, diarrhea, knee cramps, and abdominal discomfort. The lack of communication between patients and health care workers could cause an increase in the simultaneous use of herbal medicines and antihypertensive drugs. Therefore, effective communication among health care workers and appropriate care are important in preventing the side effects and other risks of combined therapy.

Measurement of the Quality of Life of Prolanis Hypertension Patients in Sixteen Primary Healthcare Centers in Pandeglang District, Banten Province, Indonesia, Using EQ-5D-5L Instrument.

INTRODUCTION: The prevalence of hypertension in Indonesia is increasing, not least in some peripheral areas, including in Pandeglang District, Banten Province. The government of Indonesia, through the Social Health Insurance Administration Body (BPJS Kesehatan) has launched a chronic disease management program (Prolanis) to achieve more optimal results in treating patients with chronic diseases, including hypertension. OBJECTIVE: This study aimed to measure the quality of life of Prolanis hypertension patients at the primary healthcare centers (PHCs) using EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) instrument and taking pharmacists' counseling intervention into account. This study was conducted in 96 Prolanis patients, consisting of 48 patients from 8 PHCs who did not receive pharmacists' counseling intervention (control group) and 48 other patients from 8 different PHCs who received 4 times intervention (intervention group). This study was conducted in a period of 3 months (June-August 2019) in 16 sub-districts of Pandeglang District. METHODS: An experimental study design was applied by considering a purposive sampling method. Patients' quality of life were measured by using EQ-5D-5L instrument and its Indonesian value set. For data analysis, we applied the Kruskal-Wallis, Mann-Whitney, Wilcoxon, and Binomial tests to investigate the differences of patients' quality of life in both groups of control and intervention. RESULTS AND CONCLUSIONS: The results showed that the average utility value of the intervention group experienced an improvement at each meeting (m1 = 51.25%; m2 = 66.25%; m3 = 84.17%; and m4 = 91.67%), while the control group experienced a lower and more fluctuative improvement than the intervention group (m1 = 65.42%; m2 = 70.42%; m3 = 80.42%; and m4 = 76.67%). The same results also occurred in the average value of visual analogue scale (VAS). There was a better improvement in the intervention group than in the control group. CLINICAL TRIAL REGISTRATION NUMBER: 62/UN6.KEP/EC/2019.

Induction of caspase cascade pathway by kaempferol-3-O-rhamnoside in LNCaP prostate cancer cell lines.

Prostate cancer has become a leading cause of mortality in humans. Previous studies have shown the potential anticancer properties of kaempferol-3-O-rhamnoside in breast cancer cell lines. In the present study, the anticancer potential of kaempferol-3-O-rhamnoside was investigated in LNCaP human prostate cancer cell lines. The inhibition of cell proliferation was investigated using MTT assays, whereas its ability to induce the caspase-cascade pathway was investigated by western blotting. The results showed that kaempferol-3-O-rhamnoside inhibits the proliferation of LNCaP cells in a dose-dependent manner by upregulating the expression of caspase-8, caspase-9, caspase-3 and poly (ADP-ribose) polymerase proteins. Although further studies are required, the results of the present study indicate the potential application of kaempferol-3-O-rhamnoside in cancer treatment.

Assessment of patient care indicators at community pharmacies in Bandung City, Indonesia.

Community pharmacies supply medications; therefore are involved in the patient care process. The objective of this study was to study the quality of patient care given by these pharmacies. We conducted a cross sectional study of 13 community pharmacies in Bandung City, Indonesia. Data collected were patient care indicators whose standard is defined by the World Health Organization (WHO). These were assessed by observing 1961 subjects who presented to the studied pharmacies to receive their medication. The average dispensing time was 62 seconds. Ninety-six percent of the prescribed medicine was dispensed correctly and 99% of the prescribed medication was sufficiently labeled. Only 88% of patients were able to repeat the correct dosage regimen of their prescribed medicines. Although the average dispensing time was greater than the recommended 60 seconds, the dispensing time ranged from 3 to 435 seconds. Greater attention should be focused on making sure the patient understands the dosage regimen correctly to ensure patient compliance with the correct regimen.

Antibiotic resistance in sepsis patients: evaluation and recommendation of antibiotic use.

BACKGROUND: The appropriate selection of empirical antibiotics based on the pattern of local antibiotic resistance can reduce the mortality rate and increase the rational use of antibiotics. AIMS: We analyze the pattern of antibiotic use and the sensitivity patterns of antibiotics to support the rational use of antibiotics in patients with sepsis. MATERIALS AND METHODS: A retrospective observational study was conducted in adult sepsis patient at one of Indonesian hospital during January-December 2011. Data were collected from the hospital medical record department. Descriptive analysis was used in the processing and interpretation of data. RESULTS: A total of 76 patients were included as research subjects. Lung infection was the highest source of infection. In the 66.3% of clinical specimens that were culture positive for microbes, Klebsiella pneumoniae, Escherichia coli, Staphylococcus hominis were detected with the highest frequency. The six most frequently used antibiotics, levofloxacin, ceftazidime, ciprofloxacin, cefotaxime, ceftriaxone, and erythromycin, showed an average resistance above 50%. CONCLUSIONS: The high use of antibiotic with a high level resistance requires a policy to support its rational use. Local microbial pattern based on site infection and pattern of antibiotics sensitivity test can be used as supporting data to optimize appropriateness of empirical antibiotics therapy in sepsis patients.

Kaempferol-3-O-rhamnoside isolated from the leaves of Schima wallichii Korth. inhibits MCF-7 breast cancer cell proliferation through activation of the caspase cascade pathway.

Plants consumed by non-human primates represent potential drug sources for human disease management. In this study, we isolated kaempferol-3-O-rhamnoside as an active compound from the leaves of Schima wallichii Korth., a plant commonly consumed by non-human primates. Its anti-cancer activities, including its ability to induce apoptotic mechanisms, were investigated in MCF-7 breast cancer cells. Results showed that in MCF-7 cells, kaempferol-3-O-rhamnoside inhibits cell proliferation in a dose-dependent manner and promotes apoptosis via the activation of the caspase signaling cascade, which includes caspase-9, caspase-3 and PARP. Our results provide a basis for further exploration of kaempferol-3-O-rhamnoside as an active compound for potential anti-cancer therapeutics.