Response to COVID-19 recommended preventive behavioral messages among Guraghe zone communities, South Ethiopia: using constructs of the Extended Parallel Process Model (EPPM).

INTRODUCTION: The World Health Organization declared COVID-19 is a pandemic disease. Countries should take standard measures and responses to battle the effects of the viruses. However, little is known in Ethiopia regarding the recommended preventive behavioral messages responses. Therefore, the study aimed to assess the response to COVID-19 recommended preventive behavioral messages. METHODS: Community-based cross-sectional study design was carried out from 1 to 20, July 2020. We recruited 634 respondents by using a systematic sampling method. Data were analyzed using Statistical Package Software for Social Sciences version 23. Association between variables were explored using a bivariable and multi variable logistic regression model. The strength of the association is presented using odds ratio and regression coefficient with 95% confidence interval. A p-value of less than 0.05 was declared statistically significant. RESULTS: Three hundred thirty-six (53.1%) of respondents had good response to recommended preventive behavioral messages. The general precise rate of the knowledge questionnaire was 92.21%. The study showed that merchant was 1.86 (p ≈ 0.01) times more likely respond to COVID-19 recommended preventive behavioral messages than government-employed. Respondents who scored one unit increase for self-efficacy and response-efficacy, the odds of responding to COVID-19 recommended preventive behavioral messages were increased by 1.22 (p < 0.001), and 1.05 times (p = 0.002) respectively. Respondents who scored one unit increase to cues to action, the odds of responding to COVID-19 recommended preventive behavioral messages were 43% (p < 0.001) less likely. CONCLUSION: Even though respondents were highly knowledgeable about COVID-19, there is a lower level of applying response to recommended preventive behavioral messages. Merchant, self-efficacy, response efficacy, and cues to action were significantly associated with response to recommended preventive behavioral messages. Like merchants, government employer should be applying preventive behavioral messages and also, participants' self and response efficacy should be strengthened to improve the response. In addition, we should be changed or modified the way how-to deliver relevant information, promoting awareness, and also using appropriate reminder systems to preventive behavioral messages.

Validation of 4ß-hydroxycholesterol and evaluation of other endogenous biomarkers for the assessment of CYP3A activity in healthy subjects.

AIMS: This study aimed to assess changes in the plasma concentrationss of 4ß-hydroxycholesterol (4ßHC) against intravenous (i.v.) and oral midazolam (MDZ) pharmacokinetics (PK) after administration of a potent CYP3A inhibitor [ketoconazole (KETO)] and inducer [rifampicin (RIF)]. METHODS: Thirty-two healthy subjects (HS) were allocated into three groups of 12 each in KETO and RIF and 10 in a placebo group (PLB). All HS were randomized to receive oral and i.v. MDZ on day 1 or 2 and on day 15 or 16 after receiving RIF (600 mg once daily), KETO (400 mg once daily) or PLB for 2 weeks. Subjects were followed until day 30. The effect of treatments on 4ßHC was assessed by analyzing % change from baseline using a linear spline mixed effects model. RESULTS: Compared with PLB, KETO decreased 4ßHC mean values up to 13% (P = 0.003) and RIF increased 4ßHC mean values up to 220% (P < 0.001). Within 14 days of stopping KETO and RIF, 4ßHC had either returned to baseline (KETO) or was still returning to baseline (RIF). Compared with baseline, mean oral MDZ AUC increased by 11-fold (90% CI ranging from 9-fold to 13-fold increase) and decreased by 92% (90% CI ranging from 90% to 95% decrease) after KETO and RIF, respectively. Similar trends were observed for 6ß-hydroxycortisol : cortisol (6ßHCL : CL) urinary ratios. CONCLUSIONS: Changes in plasma 4ßHC can be utilized as a surrogate for MDZ PK after multiple doses of potent CYP3A inducers. There is a more limited dynamic range for 4ßHC for assessment of potential CYP3A inhibitors. 4ßHC is a valuable tool for the assessment of potential CYP3A inducers in early drug development.

A review of dolutegravir-associated weight gain and secondary metabolic comorbidities.

Dolutegravir is an integrase inhibitor and is recommended by the World Health Organization as the preferred first-line and second-line human immunodeficiency virus treatment in all populations. Excessive weight gain associated with dolutegravir-based regimens is an emerging issue; however, the long-term metabolic consequences of this effect have not been fully understood. Growing evidence shows that this leads to a higher incidence of hyperglycemia, hypertension, and metabolic syndrome, along with elevated cardiovascular risk. Dolutegravir-based regimens, also associated with greater adipocyte differentiation and greater expression of markers associated with lipid storage, continue to be a problem among patients living with human immunodeficiency virus. The mechanisms by which certain antiretroviral therapy agents differentially contribute to weight gain remain unknown. Some clinical investigators speculate that dolutegravir could interfere with central nervous system appetite regulation (melanocortin-4 receptor) and insulin signaling, or may have better penetration of adipose tissue where they could exert a direct impact on adipose tissue adipogenesis, fibrosis, and insulin resistance. This review summarizes our current understanding of weight gain and fat changes associated with dolutegravir and its possible secondary metabolic comorbidities.

Health professionals' perspectives on the role of obstetric ultrasonography in maternity care in rural eastern Ethiopia: a qualitative descriptive study.

OBJECTIVE: The purpose of this exploratory study was to assess healthcare providers' perspectives on maternity care following the introduction of ultrasound services in the area. DESIGN: The qualitative descriptive study. STUDY SETTING: This study was carried out in health centres under Child Health and Mortality Prevention Surveillance (CHAMPS) pregnancy surveillance catchment areas in Kersa, Haramaya and Harar districts in eastern Ethiopia. PARTICIPANTS: The study participants were 14 midwives working in the maternity units and 14 health centre managers in the respective health facilities. Purposive sampling was used to select participants for in-depth interviews using a semistructured interview guide. Data were analysed using thematic analysis. RESULTS: We identified one overarching theme "improved perinatal care" and six subthemes. Based on the accounts of the participants, the introduction of ultrasound services has led to a remarkable transformation in the overall provision of maternity care at health centres. The participants have reported a substantial rise in the utilisation of antenatal, delivery and postnatal care services. The availability of ultrasound has enabled midwives to deliver comprehensive maternity care. CONCLUSION: Ultrasound service utilisation at health centres improves maternity care. The utilisation of ultrasound in healthcare enables providers to closely monitor the growth and development of the fetus, identify potential complications or abnormalities and administer timely interventions. This integration of ultrasound technology translates into enhanced prenatal care, early detection of issues and prompt management, ultimately leading to improved outcomes for both the mother and the baby.

Midwives' experiences of performing obstetric ultrasounds in antenatal care in eastern Ethiopia: Qualitative exploratory study.

BACKGROUND: In 2016, the World Health Organization recommended inclusion of an ultrasound scan as part of routine antenatal care to improve pregnancy outcomes. However, most rural women in Ethiopia do not have access to ultrasound scanning as part of their routine antenatal care. Recently, ultrasonography services were introduced at health centers in Harar, Kersa, and Haramaya districts in Eastern Ethiopia. This expoloratory study aimed to examine experiences of pregnancy surveillance midwives in the Child Health and Mortality Prevention Surveillance (CHAMPS) who performed ultrasonography at health centers that are in the catchment area of Health and Demographic Surveillance Systems, in Eastern Ethiopia. OBJECTIVE: To explor midwives' experiences across 14 health centers in Eastern Ethiopia, located in the Kersa, Haramaya, and Harar Health and Demographic Surveillance Systems from February to April 2022. DESIGN: Exploratory qualitative study. METHODS: The methods used were based on the Standards for Reporting Qualitative Research framework. Purposeful sampling was used to explore experiences of midwives who performed ultrasonography at selected health centers. The Midwives are recurited, trained and stationed at the health ceners to do ultrasound scanning and other activities by the Child Helath and Mortality Prevention Surveillance (CHAMPS) pregancny surveillance activities. Among 17 midwives who had undergone ultrasonography training and who were actively involved in ultrasound scanning at health centers in Kersa, Haramaya, and Harar Health and Demographic Surveillance Systems, three midwives who worked at health centers with no power or near a hospital were excluded. Using tape recordings and note-taking, data were collected through in-depth interviews based on a semi-structured interview guide. Thematic analysis used for data categorization, and the trustworthiness of data was kept throughout the procedure using credibility, dependability, confirmability, and transferability. RESULTS: In this study, we identified five main themes: Ultrasonography positively impacts midwives trained as sonographers; performing ultrasound scans enhances the skills and confidence of midwives, improving their professional development, Individual perception of self-efficacy; midwives' belief in their abilities to perform ultrasound scans effectively influences their job satisfaction and motivation, Provision of care; integrating ultrasound into antenatal care enhances the quality, therapeutic communication, and personalized nature of care provided to pregnant women, Barriers to providing ultrasonography services; challenges such as shortage of ultrasonography-trained staff and workload can hinder the delivery of ultrasound services in rural areas, Community acceptance; the level of community understanding, trust, and support towards ultrasound technology and midwives as sonographers impacts the successful implementation and sustainability of ultrasound services. CONCLUSION: Ultrasonography performed by midwives at rural health centers had a considerable impact on antenatal care services and incareased confidence of midwives.

Midwives' Experiences with Ultrasound Scans for Pregnant WomenThe World Health Organization recommends that pregnant women undergo at least four antenatal care (now eight times) visits during their pregnancy. The goal is to reduce feto-maternal complications. Recently, ultrasonography services are introduced in Harar, Kersa and Haramaya districts, Eastern Ethiopia.Midwives who performed ultrasonography at selected health centers were part of this exploaroty study. The information were generated through code, categories, and themes.Five themes were identified. Ultrasonography positively impacts midwives trained as sonographers, individual perception of self-efficacy, provision of care, barriers to providing ultrasonography services, and community acceptance.Ultrasonography performed by midwives at rural health centers had a considerable impact on antenatal care services and midwives confidence.

Serum uric acid and high-sensitivity C-reactive protein levels among people living with HIV on dolutegravir and ritonavir-boosted atazanavir-based antiretroviral therapy: a comparative cross-sectional study.

Background: After the introduction of antiretroviral therapy, the care given to people living with HIV has become complicated by the appearance of comorbidities as a result of HIV and HAART toxicities, in which cardiovascular disease got the most attention. So, this study aimed to assess serum uric acid and high-sensitivity C-reactive protein levels among people living with HIV on dolutegravir (DTG) and ritonavir-boosted atazanavir (ATV/r)-based therapy. Methods: An institutional-based comparative cross-sectional study was conducted from November 4, 2021, to January 4, 2022. An equal number of dolutegravir- and ritonavir-boosted atazanavir-treated patients (n = 86 each) were enrolled. A consecutive sampling method was used to select participants. Data were entered into Epidata version 4.6, exported to SPSS version 25.0, and analyzed using Chi-square, Student's t-test, Mann-Whitney U-test, and logistic regression. Statistical significance was set at p < 0.05. Results: The prevalence of hyperuricemia and high-sensitivity C-reactive protein levels ≥2 mg/L were 46.5% (40/86) and 24.4% (21/86) in the DTG group, and 30.2% (26/86) and 44.2 (38/86) in the ATV/r group, respectively. When compared to ATV/r, a higher mean level of uric acid was found among DTG-based regimens (5.38 mg/dL). Duration of ART (AOR = 2, 95% CI: 1.2, 4.4) and DTG-based regimen (AOR = 1.9, 95% CI: 1.04, 3.8) were significant predictors of developing hyperuricemia. ATV/r-based regimen (AOR = 3, 95% CI: 1.5, 8.3) and high waist circumference (AOR = 2.5, 95% CI: 1, 3.5) were significantly associated with increased high-sensitivity C-reactive protein levels. Conclusion: It is observed that DTG-based and ATV/r-based ART are associated with hyperuricemia and increased high-sensitivity C-reactive protein levels, respectively. Therefore, it is important to consider and evaluate serum uric acid and high-sensitivity C-reactive protein levels in patients taking DTG and ATV/r-based ART, as well as among those on HAART for years and with a higher waist circumference, so as to detect and prevent early the risk of having CVD.

Serum Lipid Profiles, Blood Glucose, and High-Sensitivity C-Reactive Protein Levels Among People Living with HIV Taking Dolutegravir and Ritonavir-Boosted Atazanavir-Based Antiretroviral Therapy at Jimma University Medical Center, Southwest Ethiopia, 2021.

Background: Long-term use of antiretroviral therapy, especially dolutegravir and boosted-atazanavir, raises concerns about cardiovascular disease. Thus, this study aimed to assess lipid profiles, blood glucose, and high-sensitivity C-reactive protein levels among people living with HIV on dolutegravir and ritonavir-boosted atazanavir-based therapy. Methods: An institutional-based comparative cross-sectional study was conducted from November 4, 2021, to January 4, 2022. An equal number of dolutegravir- and ritonavir-boosted atazanavir-treated patients (n = 64 each) was enrolled. A consecutive sampling was used to select participants. The Chi-square, Student's t-test, Mann-Whitney U-test, and logistic regression were used as appropriate statistical tests using SPSS Version 25.0. Statistical significance was set at p < 0.05. Results: Dyslipidemia was found in 67.2% (43/64) of ritonavir-boosted atazanavir group and 48.4% (31/64) of dolutegravir group. The dolutegravir group had significantly higher mean and median values of high-density lipoprotein and random blood sugar, respectively, as well as lower median triglyceride and high-sensitivity C-reactive protein levels than the ritonavir-boosted atazanavir group. Ritonavir-boosted atazanavir-based regimens (AOR=3.4, 95% CI: 1.5, 8) and age >40 years were predictors of dyslipidemia, while BMI ≥25 kg/m2 (AOR=3.7, 95% CI: 1.3, 10.8) and dolutegravir-based regimens (AOR=4.6, 95% CI: 1.5, 14) were predictors of hyperglycemia. Ritonavir-boosted atazanavir-based regimens (ARR=3, 95% CI: 1.3, 8) and BMI ≥25 kg/m2 (ARR=2.5, 95% CI: 1.1, 6) were associated with increased high-sensitivity C-reactive protein by 1-3 mg/L. The risk of increased high-sensitivity C-reactive protein by >3 mg/L was greater in those patients with a CD4 cell count of <500 cells/mm3 (ARR=5, 95% CI: 1.1, 24). Conclusion: When compared to ritonavir-boosted atazanavir-based regimens, dolutegravir had favorable lipid profiles and high-sensitivity C-reactive protein but unfavorable blood glucose levels. Therefore, baseline blood glucose, lipid profiles, and high-sensitivity C-reactive protein levels should be routinely measured in patients on these regimens.

Gut microbes as medical signature for the effectiveness of immunotherapy in patients with advanced non-small cell lung cancer.

Lung cancer (LC) is the most common cause of cancer-related death worldwide and poses a severe threat to public health. Immunotherapy with checkpoint blockers has improved the outlook for advanced non-small cell lung cancer (NSCLC) therapy. For the treatment of patients with advanced NSCLC, antibodies such as anti-programmed death 1 (anti-PD1), anti-programmed death ligand 1 (anti-PD-L1), and anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) are of paramount importance. Anti-PD-1 and anti-PD-L1 monoclonal antibody therapies are used to block the PD-1/PD-L1 pathway and identify cancerous cells to the body's defenses. Antibodies directed against CTLA-4 (anti-CTLA-4) have also been shown to improve survival rates in patients with NSCLC. Currently, other immunotherapy approaches like neoadjuvant immune checkpoint inhibitors (NAICIs) and chimeric antigen receptor T-cell (CAR-T) therapies are applied in NSCLC patients. NAICIs are used for resectable and early stage NSCLC and CAR-T is used to find more useful epitope sites for lung tumors and destroy cancer cells. A patient's gut microbiota might influence how their immune system reacts to NSCLC immunotherapy. The majority of intestinal microbes stimulate helper/cytotoxic T cells, induce natural killer (NK) cells, activate various toll-like receptors (TLR), build up cluster of differentiation 8 (CD8), increase PD-1 production, and attract chemokine receptors towards cancer cells. Thus, they serve as immune inducers in NSCLC immunotherapy. Nonetheless, certain bacteria can function as immune suppressors by inhibiting DC proliferation, stopping CD28 trafficking, restoring CD80/CD86, increasing immunological tolerance, and upsetting Th17 cells. Therefore, they are prevalent in non-responders with NSCLC immunotherapy.

Current updates on the molecular and genetic signals as diagnostic and therapeutic targets for hepatitis B virus-associated hepatic malignancy.

Liver cancer caused by the hepatitis B virus (HBV) is the third most common cancer-related cause of death worldwide. Early detection of HBV-caused hepatic tumors increases the likelihood of a successful cure. Molecular and genetic signals are becoming more and more recognized as possible indicators of HBV-associated hepatic malignancy and of how well a treatment is working. As a result, we have discussed the current literature on molecular and genetic sensors, including extracellular vesicle microRNAs (EV-miRNAs), long non-coding circulating RNAs (lncRNAs), extracellular vesicles (EVs), and cell free circulating DNA (cfDNA), for the diagnosis and forecasting of HBV-related hepatic cancer. Extracellular vesicle microRNAs such as miR-335-5p, miR-172-5p, miR-1285-5p, miR-497-5p, miR-636, miR-187-5p, miR-223-3p, miR-21, miR-324-3p, miR-210-3p, miR-718, miR-122, miR-522, miR-0308-3p, and miR-375 are essential for the posttranscriptional regulation of oncogenes in hepatic cells as well as the epigenetic modulation of many internal and external signaling pathways in HBV-induced hepatic carcinogenesis. LncRNAs like lnc01977, HULC (highly up-regulated in liver cancer), MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), and HOTAIR (hox transcript antisense intergenic RNA) have been demonstrated to control hepatic-tumors cell growth, relocation, encroachment, and cell death resiliency. They are also becoming more and more involved in immune tracking, hepatic shifting, vasculature oversight, and genomic destabilization. EVs are critical mediators involved in multiple aspects of liver-tumors like angiogenesis, immunology, tumor formation, and the dissemination of malignant hepatocytes. Furthermore, cfDNA contributes to signals associated with tumors, including mutations and abnormal epigenetic changes during HBV-related hepatic tumorigenesis.

Evaluation of antioxidant and antihyperglycemic effects Dovyalis Abyssinica (A.Rich).

Background: The leaves of Dovyalis Abyssinica have been used traditionally for the management of diabetes mellitus. Thus, this study aimed to evaluate the Antioxidant and Antihyperglycemic Effects of Dovyalis Abyssinica leaves crude extract in streptozotocin-induced diabetic mice. Methods: To Evaluate the Antihyperglycemic, and Antioxidant Effects of Dovyalis Abyssinica Leaves Extract in Streptozotocin-Induced Diabetic Mice. Male Swiss albino mice were induced into diabetes using 100 mg/kg of streptozotocin. Mice were allocated randomly into six groups, six mice per group. The body weight and FBG measurements were done on days 0, 7th, 14th and 21st of treatment. Additionally, in vitro Antioxidant Activity of the Extract was determined using a DPPH assay. The data were entered into Epi-Data version 4.6, exported to SPSS version 26.0, and analysed by using a one-way ANOVA followed by a Tukey post hoc test, and P < 0.05 was considered statistically significant. Results: Dovyalis Abyssinica leaves crude extract showed significant (P < 0.05-P< 0.001) blood-glucose-lowering activity. Moreover, the crude extract of D. abyssinica reduced the fasting blood glucose level by 45.13 %, 52.51 %, 54.85 %, and 56.38 %, respectively, for DA 100, DA 200, DA 400, and GLC 5 mg/kg on the 21st day of treatment. After diabetic mice were treated with Dovyalis Abyssinica (100, 200, and 400 mg/kg) for 21 days, there was a significant increase in body weight as compared to diabetic control. Antioxidant activities of the leaf extract was found to be comparable to ascorbic acid with an IC50 of 140.04 µg/ml. Conclusion: The present findings revealed that D. abyssinica leaves could be useful for the management of diabetes mellitus and other abnormalities related to this metabolic disorder. Thus, the present study may support the traditional use of D. abyssinica for diabetes mellitus treatment.

The role of miRNAs as biomarkers in breast cancer.

Breast cancer (BC) is the second most common cause of deaths reported in women worldwide, and therefore there is a need to identify BC patients at an early stage as timely diagnosis would help in effective management and appropriate monitoring of patients. This will allow for proper patient monitoring and effective care. However, the absence of a particular biomarker for BC early diagnosis and surveillance makes it difficult to accomplish these objectives. miRNAs have been identified as master regulators of the molecular pathways that are emphasized in various tumors and that lead to the advancement of malignancies. Small, non-coding RNA molecules known as miRNAs target particular mRNAs to control the expression of genes. miRNAs dysregulation has been linked to the start and development of a number of human malignancies, including BC, since there is compelling evidence that miRNAs can function as tumor suppressor genes or oncogenes. The current level of knowledge on the role of miRNAs in BC diagnosis, prognosis, and treatment is presented in this review. miRNAs can regulate the tumorigenesis of BC through targeting PI3K pathway and can be used as prognostic or diagnostic biomarkers for BC therapy. Some miRNAs, like miR-9, miR-10b, and miR-17-5p, are becoming known as biomarkers of BC for diagnosis, prognosis, and therapeutic outcome prediction. Other miRNAs, like miR-30c, miR-187, and miR-339-5p, play significant roles in the regulation of hallmark functions of BC, including invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability. Other miRNAs, such as miR-155 and miR-210, are circulating in bodily fluids and are therefore of interest as novel, conveniently accessible, reasonably priced, non-invasive methods for the customized care of patients with BC.

Liver function tests, CD4+ counts, and viral load among people living with HIV on dolutegravir compared to efavirenz-based cART; a comparative cross-sectional study.

Background: Recently, dolutegravir-based therapy has become the first-line treatment when compared to others. However, dolutegravir-associated side effects in the liver and levels of efficacy haven't been addressed yet in underdeveloped countries such as Ethiopia. Objective: The purpose of this study was to compare liver function tests, CD4+ counts, and viral load among people living with HIV on dolutegravir and efavirenz-based antiretroviral regimens at Debre Markos Comprehensive Specialized Hospital in Northwest Ethiopia. Methods: An institutional-based comparative cross-sectional study was carried out from May 20 to July 10, 2020. An equal number of dolutegravir and efavirenz-prescribed patients (n = 53 each) for 6 months and above were included, and a judgmental sampling technique was used. A comparison of categorical and continuous parameters was analyzed with chi-square and an independent t-test, respectively, using SPSS version 26. A multivariable logistic regression was conducted and considered statistically significant at a p-value of <0.05. Results: The magnitude of liver enzyme (AST/ALT) abnormalities was 22.4 % (12/53) and 30.2 % (16/53) among dolutegravir- and efavirenz-prescribed patients, respectively. The dolutegravir group had significantly higher mean CD4+ counts than the efavirenz group (589.40 ± 244.38 vs. 450.64 ± 203.54 cell/mm3; p = 0.002). The efavirenz group had a significantly higher mean viral load than the dolutegravir group (783.83 ± 476.82 vs. 997.98 ± 439.11 cp/ml; p = 0.032). There was a statistically insignificant difference in AST (p = 0.709) or ALT (p = 0.687) between dolutegravir and efavirenz-based regimens. The multivariable logistic regression analysis revealed that BMI ≥25 kg/m2 was associated with liver enzyme abnormalities (AOR = 6.60, 95 % CI: 1.17, 42.82). Conclusion: A dolutegravir-based regimen was more likely to result in patients achieving higher efficacy for viral suppression and a CD4+ count increase. Although the differences were statistically insignificant, the mean AST and ALT levels were marginally higher in efavirenz-treated groups than in dolutegravir-treated groups.

Nephroprotective Effect of the Leaf Extract of Ajuga remota Benth Against Gentamicin-Induced Nephrotoxicity in Swiss Albino Mice.

Background: Drug-induced kidney injury was among the most common renal damages, from which gentamicin occupies around 25% of this injury. Gentamicin-induced renal damage is caused by increased free radicals with subsequent amplified inflammation. Ajuga remota leaf extract has many phytochemicals with antioxidant activities, which may improve gentamicin-induced renal damage. Thus, we aimed to investigate the nephroprotective effect of Ajuga remota leaf methanolic extract on gentamicin-induced nephrotoxicity in Swiss Albino Mice. Methods: An experimental study design was used on 30 experimental mice randomly allocated in six groups: Group I, II, II, IV, and VI, among which mice were given only distilled water, only gentamicin, 600 mg/kg Ajuga remota leaf extract only, gentamicin along with 200 mg/kg extract, gentamicin with 400 mg/kg extract and gentamicin with 600 mg/kg extract, respectively. At the end of the experiment, the mice were sacrificed after being anaesthetized, and blood samples were collected through a cardiac puncture for renal function tests while the kidneys were removed for histopathological evaluation. The data were entered into Epidata version 4.6 and exported to SPSS version 25 for further analysis using one-way analysis of variance. Statistical significance was set at p < 0.05. Results: Group II mice had significantly higher levels of serum creatinine and blood urea levels compared to group I and III. The body weight of the mice in group V and group VI showed a significant increase compared with Group II. Serum creatinine and blood urea levels were reduced significantly in the Ajuga remota leaf extract administered group of mice compared to group II. Abnormal kidney architectural changes were seen among group II mice; however, those changes were improved after administration of Ajuga remota leaf methanolic extract. Conclusion: Methanol extract of Ajuga remota leaf provided effective protection against gentamicin-induced oxidative renal damage through its antioxidant effects.

Cynomolgus monkey as a potential model to assess drug interactions involving hepatic organic anion transporting polypeptides: in vitro, in vivo, and in vitro-to-in vivo extrapolation.

Organic anion-transporting polypeptides (OATP) 1B1, 1B3, and 2B1 can serve as the loci of drug-drug interactions (DDIs). In the present work, the cynomolgus monkey was evaluated as a potential model for studying OATP-mediated DDIs. Three cynomolgus monkey OATPs (cOATPs), with a high degree of amino acid sequence identity (91.9, 93.5, and 96.6% for OATP1B1, 1B3, and 2B1, respectively) to their human counterparts, were cloned, expressed, and characterized. The cOATPs were stably transfected in human embryonic kidney cells and were functionally similar to the corresponding human OATPs (hOATPs), as evident from the similar uptake rate of typical substrates (estradiol-17ß-d-glucuronide, cholecystokinin octapeptide, and estrone-3-sulfate). Moreover, six known hOATP inhibitors exhibited similar IC(50) values against cOATPs. To further evaluate the appropriateness of the cynomolgus monkey as a model, a known hOATP substrate [rosuvastatin (RSV)]-inhibitor [rifampicin (RIF)] pair was examined in vitro; the monkey-derived parameters (RSV K(m) and RIF IC(50)) were similar (within 3.5-fold) to those obtained with hOATPs and human primary hepatocytes. In vivo, the area under the plasma concentration-time curve of RSV (3 mg/kg, oral) given 1 hour after a single RIF dose (15 mg/kg, oral) was increased 2.9-fold in cynomolgus monkeys, consistent with the value (3.0-fold) reported in humans. A number of in vitro-in vivo extrapolation approaches, considering the fraction of the pathways affected and free versus total inhibitor concentrations, were also explored. It is concluded that the cynomolgus monkey has the potential to serve as a useful model for the assessment of OATP-mediated DDIs in a nonclinical setting.

Blood glucose level and serum lipid profiles among people living with HIV on dolutegravir-based versus efavirenz-based cART; a comparative cross-sectional study.

BACKGROUND: Antiretroviral therapy-linked metabolic abnormalities have become a growing concern among people living with HIV. There is limited data regarding the effects of dolutegravir-based treatment on blood glucose levels and serum lipid profiles in people living with HIV in Ethiopia. Thus, this study aimed to assess blood glucose levels and serum lipid profiles among people living with HIV on dolutegravir-based versus efavirenz-based therapy. METHOD AND MATERIALS: An institutional-based comparative cross-sectional study was conducted from 30 June 2021 to 30 August 2021. A total of 128 participants (64 in the dolutegravir-based group and 64 in the efavirenz-based group) were enrolled in the study. The Chi-square, independent t-test, Mann-Whitney U-test, and logistic regression were used as appropriate statistical tests using SPSS Version 26.0 for this study. A p-value of <0.05 was considered statistically significant. RESULT: The prevalence of hyperglycemia and dyslipidemia were 17.2% (11/64) and 79.7% (51/64) in the dolutegravir group, and 9.4% (6/64) and 75% (48/64) in the efavirenz group, respectively. The efavirenz group had significantly higher mean values of total cholesterol (190.73 ± 44.13 vs. 175.27 ± 37.67 mg/dl, p = 0.035) and high-density lipoprotein (47.53 ± 14.25 vs. 40.92 ± 13.17 mg/dl, p = 0.007) than the dolutegravir group. For a Kg/m2 increase in BMI and for each month's increase in the duration of HIV, the patients were 66% (AOR = 1.66, 95% CI: 1.13, 2.44), and 13% (AOR = 1.13, 95% CI: 1.03, 1.23) more likely to have hyperglycemia, respectively. In contrast, female patients were 3.04 times more likely to have dyslipidemia (AOR = 3.03, 95% CI: 1.14, 8.05) as compared to male patients, and with an increase in CD4 cell count of 1 cell/mm3, the odds of dyslipidemia increased by 0.3% (AOR = 1.003, 95% CI: 1.001, 1.006). CONCLUSION: Efavirenz-based therapy resulted in higher mean values of total cholesterol and high-density lipoprotein as compared with dolutegravir-based therapy. It is important to consider and evaluate high-density lipoprotein levels in HIV patients on dolutegravir-based therapy, and total cholesterol levels in people living with HIV on efavirenz-based therapy.

The long-term use of ART is thought to be one of the potential causes of metabolic abnormalities such as dysregulation of glucose and lipid metabolism.The burden of DTG-based cART-related metabolic abnormalities in resource-limited settings has not been well characterized.This study aimed to address these gaps by assessing blood glucose levels and serum lipid profiles among people living with HIV on DTG-based versus EFV-based regimens and identifying factors associated with hyperglycemia and dyslipidemia.

Exploring Effective Communication Strategies Employed by Physicians in Delivering Bad News in Ethiopian State Hospitals.

Introduction: Delivering Bad News (DBN) presents a highly challenging situation in physician-patient communication. This study aims to gain insight into the various communication strategies employed by physicians when DBN. Methods: This qualitative study conducted thematic analysis of in-depth interviews. Physicians from two comprehensive hospitals with large patient populations were selected purposively based on their engagement in delivering bad news to patients. Thematic analysis was made. Results: Thematic analysis of the data revealed several communication strategies physicians use when delivering bad news. These communication strategies include. Jointly Initiated Physician-Patient Communication Strategies: ((i) Discussing with patient family/caregivers, (ii) Collaborating with other physicians and specialists), Patient-Engaged/Led Communication Strategies: ((iii) Investigating with adolescents alone or without the family, (iv) Helping patients predict what the news is, (v) Identifying patients' emotions related to bad news, (vi) Assessing patients' level of understanding, (vii) Minimizing patient anxiety), Physician-Related Communication Strategies: ((viii) Making sure diagnostic results are accurate, (xi) Identifying causes for rejection, (x) deliveringbad news using clear and simple communication). Conclusion: Delivering bad news to patients can be challenging for physicians. It is important to be clear and accurate, and to prepare patients for the news. Patients may feel more comfortable and open when they are unaccompanied and with their healthcare provider. The study concluded that physicians need to be prepared to deliver bad news in a sensitive and effective manner.

Prevalence of Trachoma After Three Rounds of Antibiotic Mass Drug Administration in 13 Woredas of Gambella Region, Ethiopia.

BACKGROUND: Following baseline surveys in 2013 and 2014, trachoma elimination interventions, including three rounds of azithromycin mass drug administration (MDA), were implemented in 13 woredas (administrative districts) of Gambella Regional State, Ethiopia. We conducted impact surveys to determine if elimination thresholds have been met or if additional interventions are required. METHODS: Cross-sectional population-based surveys were conducted in 13 woredas of Gambella Regional State, combined into five evaluation units (EUs), 6─12 months after their last MDA round. A two-stage systematic (first stage) and random (second stage) sampling technique was used. WHO-recommended protocols were implemented with the support of Tropical Data. Household water, sanitation and hygiene (WASH) access was assessed. RESULTS: The age-adjusted prevalence of trachomatous inflammation - follicular (TF) in 1-9-year-olds in the five EUs ranged from 0.3-19.2%, representing a general decline in TF prevalence compared to baseline estimates. The age- and gender-adjusted prevalence of trachomatous trichiasis (TT) unknown to the health system in those aged ≥ 15 years ranged from 0.47-3.08%. Of households surveyed, 44% had access to an improved drinking water source within a 30-minute return journey of the house, but only 3% had access to an improved latrine. CONCLUSION: In two EUs, no further MDA should be delivered, and a surveillance survey should be conducted after two years without MDA. In one EU, one further round of MDA should be conducted followed by another impact survey. In two EUs, three further MDA rounds are required. Surgery, facial cleanliness and environmental improvement interventions are needed throughout the region.

Metabolic chiral inversion of brivanib and its relevance to safety and pharmacology.

Brivanib alaninate is an orally administered alanine prodrug of brivanib, a dual inhibitor of the vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) signaling pathways. It is currently in clinical trials for the treatment of hepatocellular carcinoma and colorectal cancer. Brivanib has a single asymmetric center derived from a secondary alcohol. The potential for chiral inversion was investigated in incubations with liver subcellular fractions and in animals and humans after oral doses of brivanib alaninate. Incubations of [¹4C]brivanib alaninate with liver microsomes and cytosols from rats, monkeys, and humans followed by chiral chromatography resulted in two radioactive peaks, corresponding to brivanib and its enantiomer. The percentage of the enantiomeric metabolite relative to brivanib in microsomal and cytosolic incubations of different species in the presence of NADPH ranged from 11.6 to 15.8 and 0.8 to 3.1%, respectively. The proposed mechanism of inversion involves the oxidation of brivanib to a ketone metabolite, which is subsequently reduced to brivanib and its enantiomer. After oral doses of brivanib alaninate to rats and monkeys, the enantiomeric metabolite was a prominent drug-related component in plasma, with the percentages of area under the curve (AUC) at 94.7 and 39.7%, respectively, relative to brivanib. In humans, the enantiomeric metabolite was a minor circulating component, with the AUC <3% of brivanib. Pharmacological studies indicated that brivanib and its enantiomer had similar potency toward the inhibition of VEGF receptor-2 and FGF receptor-1 kinases. Because of low plasma concentration in humans, the enantiomeric metabolite was not expected to contribute significantly to target-related pharmacology of brivanib. Moreover, adequate exposure in the toxicology species suggested no specific safety concerns with respect to exposure to the enantiomeric metabolite.

Systematic evaluation of the root cause of non-linearity in liquid chromatography/tandem mass spectrometry bioanalytical assays and strategy to predict and extend the linear standard curve range.

RATIONALE: The linear range of a liquid chromatography/tandem mass spectrometry (LC/MS/MS) bioanalytical assay is typically about three orders of magnitude. A broader standard curve range is favored since it can significantly reduce the time, labor and potential errors related to sample dilution - one of the bottlenecks in sample analysis. Using quadratic regression to fit the standard curve can, to a certain degree, extend the dynamic range. However, the use of a quadratic regression is controversial, particularly in regulated bioanalysis. METHODS: A number of compounds, with different physicochemical properties and ionization efficiencies, were evaluated to understand the cause of the non-linear behavior of the standard curve. RESULTS: The standard curve behavior is primarily associated with the absolute analyte response but not the analyte concentration, the properties of the analyte, or the nature of the matrix when a stable-isotope-labeled internal standard (SIL-IS) is used. For all the test compounds, a non-linear curve was observed when signals exceeded a certain response, which depends on the detector used in the mass spectrometer. With typical API4000 instruments used for the experiments, this critical response level was determined to be ~1 E+6 counts per second (cps) and it was successfully used to predict the linear ranges for the test compounds. By simultaneously monitoring two selective reaction monitoring (SRM) channels of different intensity and using SIL-IS, a linear range of five orders of magnitude was achieved. CONCLUSIONS: In this work, the root cause of the non-linear behavior of the standard curve when using a SIL-IS was investigated and identified. Based on the findings, an improved multiple SRM channels approach was proposed and successfully applied to obtain a linear dynamic range of five orders of magnitude for one test compound. This approach may work particularly well for LC/MS/MS bioanalytical assay of dried blood spot (DBS) samples, for which a direct dilution is cumbersome.

Attribution of the discrepancy between ELISA and LC-MS/MS assay results of a PEGylated scaffold protein in post-dose monkey plasma samples due to the presence of anti-drug antibodies.

High-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) and enzyme-linked immunosorbent assay (ELISA) methods were developed for the quantification of a PEGylated scaffold protein drug in monkey plasma samples. The LC-MS/MS method was based on the extraction of the therapeutic protein with a water-miscible organic solvent and the subsequent trypsin digestion of the extract followed by the detection of a surrogate peptide. The assay was linear over a range of 10-3,000 ng/mL. The ELISA method utilized a therapeutic target-binding format in which the recombinant target antigen was used to capture the drug in the sample, followed by detection with an anti-PEG monoclonal antibody. The assay range was 30-2,000 ng/mL. A correlation study between the two methods was performed by measuring the drug concentrations in plasma samples from a single-dose pharmacokinetic (PK) study in cynomolgus monkeys following a 5-mg/kg subcutaneous administration (n = 4). In the early time points of the PK profile, the drug concentrations obtained by the LC-MS/MS method agreed very well with those obtained by the ELISA method. However, at later time points, the drug concentrations measured by the LC-MS/MS method were consistently higher than those measured by the ELISA method. The PK parameters calculated based on the concentration data showed that the two methods gave equivalent peak exposure (C(max)) at 24-48 h. However, the LC-MS/MS results exhibited about 1.53-fold higher total exposure (AUC(tot)) than the ELISA results. The discrepancy between the LC-MS/MS and ELISA results was investigated by conducting immunogenicity testing, anti-drug antibody (ADA) epitope mapping, and Western blot analysis of the drug concentrations coupled with Protein G separation. The results demonstrated the presence of ADA specific to the engineered antigen-binding region of the scaffold protein drug that interfered with the ability of the drug to bind to the target antigen used in the ELISA method. In the presence of the ADAs, the ELISA method measured only the active circulating drug (target-binding), while the LC-MS/MS method measured the total circulating drug. The work presented here indicates that the bioanalysis of protein drugs may be complicated owing to the presence of drug-binding endogenous components or ADAs in the post-dose (incurred) samples. The clear understanding of the behavior of different bioanalytical techniques vis-à-vis the potentially interfering components found in incurred samples is critical in selecting bioanalytical strategies for measuring protein drugs.