Prevalence of cervical intraepithelial lesions and associated factors among women attending a cervical cancer clinic in Western Uganda; results based on Pap smear cytology.

Introduction: There are high incidence and mortality rates of cervical cancer among females in East Africa. This is exacerbated by limited up-to-date data on premalignant lesions and associated factors in this setting. In this study, we determined the prevalence of cervical intraepithelial lesions and associated factors among women attending the Mbarara Regional Referral Hospital cervical cancer clinic in Southwestern Uganda. Methods: In this cross-sectional study, 364 participants were recruited from among women attending the Mbarara Regional Referral Hospital cervical cancer clinic from 1 April to 30 June 2023. On consent, the study nurse collected demographic data and Pap smears, which were microscopically examined and reported by a laboratory scientist and a pathologist following the Bethesda grading system (2014). Statistical analyses were done in STATA version 17, using proportions, Chi-square, bivariate, and multivariate logistic regression analysis to determine associated factors at ⩽0.05 significance level. Results: The mean age of participants was 41.9 years. A third of all study participants (37.6%, 132/351) were contraceptive users, mostly hormonal contraceptives (87.1%, 115/132). Almost 88% (307/351) had an unknown Human Papilloma Virus status. The prevalence of cervical intraepithelial lesions among our study participants was 6.6% (23/351), of which 73.9% (17/23) were low-grade squamous intraepithelial lesions. More than half (9/17, 52.9%) of low-grade squamous intraepithelial lesions were active hormonal contraceptive users. Use of hormonal contraceptives (OR: 3.032, p: 0.0253), use of intrauterine devices (OR: 6.284, p: 0.039), and any family history of cervical cancer (OR: 4.144, p: 0.049) were significantly associated with cervical intraepithelial lesions. Conclusion: The prevalence of cervical intraepithelial lesions was 6.6%, lower than global estimates. Use of hormonal and intrauterine device contraceptives, as well as family history of cervical cancer, were significantly associated with cervical intraepithelial lesions among our study population. Prospective studies are recommended to further understand associations between different types of intrauterine devices and hormonal contraceptives, and cervical lesions.

Association between serum P16ink4A concentration and CIN and cervical cancer among women attending a cervical cancer clinic in western Uganda: A case control study.

Introduction: Tissue expression of P16ink4A is correlated with cervical lesions. In this study we determined the association between serum P16ink4A concentrations and cervical lesions among women attending the cervical cancer clinic at Mbarara Regional Hospital (MRRH) South Western Uganda. Material and Methods: We recruited 90 cervical intraepithelial neoplasia (CIN) cases, 90 cervical cancer (CC) cases before treatment and 90 controls. Clinical and demographic data were recorded. Serum P16ink4A concentrations were measured by quantitative Elisa. Cases were confirmed with cytology and/or histology. Descriptive statistics and logistic regression were done with STATA 17 and P-values of <0.05 were considered statistically significant. Results: The mean serum P16ink4A concentration among CIN cases, CC cases and controls was 1.11(+/-0.66) ng/ml, 1.45(+/-1.11) ng/ml and 1.13(+/-0.61) ng/ml respectively (p = 0.008). 50 % of CIN cases and controls as well as 60 % of CC cases had P16ink4A concentration above 0.946 ng/ml. There were increased odds of CIN for serum P16ink4A though statistically insignificant (AOR: 1.11, p-value: 0.70). There was also a statistically significant reduction in odds of CC for serum P16ink4A (AOR: 0.55, p-value: 0.01). Conclusion: Serum P16ink4A may likely be associated with cervical lesions especially CC in our study population and this may aid detection of such lesions. Diagnostic utility studies for circulating P16ink4A in detection of cervical cancer are recommended.

Development of a customized m-Health-based intervention to reduce loss to follow-up among patients undergoing treatment for cervical lesions at a rural referral Hospital, South Western Uganda.

Background: Loss to follow-up (LTFU) in individuals undergoing cervical cancer treatment is a major challenge in many low resource settings. We describe development of a customized and tailored mHealth intervention for reducing LTFU among patients undergoing cervical cancer treatment at Mbarara Regional Referral Hospital (MRRH). Methods: We interviewed all health care providers (HCPs) at the cervical cancer clinic of MRRH, between April and May 2023. Transcripts were subsequently derived, reviewed and coded to generate themes and categories using inductive content analytic approach. Four medical experts used this data to develop relevant SMS content, which was incorporated into an app. Results: HCPs had owned a phone for 13.8 ≤ years, had worked at the clinic for 5 ≤ years, and used text messages regularly. Qualitative data revealed that the main challenge to re-engagement was absence of a reminder mechanism between HCPs and patients. HCPs preferred text and or audio mode of messaging to improve health care responsiveness to LTFUs, awareness, continuity of care, and health service uptake among the majority illiterate population; though with potential constraints of costs and workload. Identified key messaging content included; the importance of attending scheduled follow-ups, follow up visit date and clinic customization and tailoring the message to the intended recipient. SMS content was uploaded onto the cc-follow-up app platform and customized according to preferred language, day, frequency and time of delivery. Conclusion: Tailoring an mHealth messaging intervention could help re-engage and reduce LTFU through improved information sharing, awareness, responsiveness, care engagement and medical compliance. A pilot study is required for our intervention in South Western Uganda.

Dyslipidemia: prevalence and association with precancerous and cancerous lesions of the cervix; a pilot study.

BACKGROUND: In Sub-Saharan Africa, the prevalence of dyslipidemia is on the rise, with studies showing dyslipidemia as a contributing factor to the progression of premalignant lesions to cervical cancer. In Uganda, cervical cancer and dyslipidemia are common health concerns, considering the increasing trends of dyslipidemia in the general population and inadequate information regarding dyslipidemia and cervical lesions. This study aimed to determine the prevalence of dyslipidemia and its association with precancerous and cancerous lesions of the cervix among women attending a cervical cancer clinic at the Uganda Cancer Institute. METHODS: This cross-sectional study was conducted from February to April 2022 among women with premalignant and malignant lesions of the cervix. Data on social demographics and health-seeking behaviours were collected using a pretested structured questionnaire after written informed consent had been obtained. Pap smear collection preceded visual inspection with acetic acid; cervical biopsies were collected appropriately from eligible participants; and cervical lesions were classified using the Bethesda system 2014. Serum lipids, total cholesterol (T.C.), high-density lipoprotein (HDLc), low-density lipoprotein (LDLc), and triglycerides (T.G.s) were analysed using the COBAS™ 6000 Clinical Chemistry Analyser. The associations were assessed using the chi-square test, and P ≤ 0.05 was considered statistically significant. RESULTS: The overall prevalence of dyslipidemia among women with cervical lesions was 118/159 (74%), and low HDLc was the most prevalent at 64.6% (95% CI 39.0-54.3). High T.C. (P = 0.05), high T.G.s (P = 0.011), and low HDL-c (P = 0.05) showed a significant association with precancerous lesions. High LDL-c (P = 0.019), high T.G.s (P = 0.02), and high T.G.s (P < 0.001) showed a statistically significant association with cancerous lesions. CONCLUSION: The prevalence of dyslipidemia was high, with high TC, T.G.s, and low HDL-c significantly associated with precancerous lesions. Also, elevated T.G.s and high LDLc were significantly associated with cancerous lesions. Women may benefit from dyslipidemia screening along with cervical cancer screening. WHAT THIS STUDY ADDS: The present study builds upon previous findings suggesting a link between dyslipidemia and cervical lesions by investigating the relationship between these two factors, specifically in women of this geographical location, where we need adequate information on these associations.

High Rate of Loss to Follow-Up Among Patients Undergoing Treatment for Premalignant Cervical Lesions at Mbarara Regional Referral Hospital, Southwestern Uganda: A Retrospective Cohort Study.

BACKGROUND: For a cervical cancer control program to be effective in reducing the incidence of the disease, there should be high compliance to treatment and follow-up of women diagnosed with precursor lesions. Screening programs in low-resource countries such as Uganda are challenged by poor adherence to follow-up following treatment for premalignant cervical lesions. This study sought to describe the burden and factors associated with loss to follow-up among women undergoing treatment for premalignant cervical lesions at a tertiary hospital in southwestern Uganda. METHODS: This was a retrospective cohort study. We reviewed the registers at the Mbarara Regional Referral Hospital (MRRH) cervical cancer clinic for a period of four years from January 2017 to December 2020. Data on age, district of residence, diagnosis, date of diagnosis, date and type of initial treatment, and date of follow-up visit were collected. We also captured data on whether patients returned on the scheduled follow-up date or within three months after the scheduled follow-up date. We defined loss to follow-up as failure to return for follow-up either on the scheduled date or within three months after the scheduled date. RESULTS: Out of the 298 patients who underwent treatment for premalignant cervical lesions in the study period, 227 (76.2%) did not return for follow-up at one year. At bivariate analysis, failure to attend the review visit at six weeks predicted the loss to follow-up at one year following treatment for premalignant lesions almost perfectly (risk ratio (RR)=2.84, 95% confidence interval (CI): 2.18-3.71, p<0.001). Negative HIV serostatus and receiving thermocoagulation slightly increased the risk of getting lost to follow-up, while being more than 45 years old reduced the odds. At multivariate analysis, treatment with thermocoagulation (adjusted risk ratio (aRR)=1.21, 95% CI: 1.07-1.36, p=0.03) was associated with loss to follow-up at one year. CONCLUSION: The proportion of women who did not return for follow-up at one year following treatment for premalignant cervical lesions at Mbarara Regional Referral Hospital is very high. There is a need to implement strategies such as telephone-aided reminders to prompt patients to return for follow-up following treatment for premalignant cervical lesions.

Prevalence, correlates and treatment needs of dental caries in patients attending a diabetic clinic in rural southwestern Uganda: a cross-sectional study.

BACKGROUND: Diabetes mellitus is a complex heterogeneous metabolic disorder known to lead to several pathogenic disorders, and has a bidirectional relationship with oral health conditions. This study aimed at estimating the prevalence, treatment needs and correlates of dental caries among adult patients attending a diabetic clinic in Uganda. METHODS: This was a cross-sectional study that used questionnaires to collect data on socio-demographic factors, diabetes history, oral health status, dental health care, dietary factors, lifestyle factors, and dental examination guided by the modified World Health Organization oral health questionnaire for adults. RESULTS: We enrolled 239 participants, prevalence of dental caries was 71.6%, treatment need was nearly 100%, and mean DMFT was 3.82 (SD = 5.46). Dental caries experience was associated with being widowed. CONCLUSION: We found a high prevalence of dental caries experience and large treatment need among our participants. We recommend integration of oral health care into routine diabetic services in rural sub Saharan Africa.

Cucumeropsis mannii seed oil ameliorates Bisphenol-A-induced adipokines dysfunctions and dyslipidemia.

This study demonstrated the therapeutic potentials of Cucumeropsis mannii seed oil (CMSO) capable of alleviating BPA-induced dyslipidemia and adipokine dysfunction. In this study, we evaluated the effects of CMSO on adipokine dysfunctions and dyslipidemia in bisphenol-A (BPA)-induced male Wistar rats. Six-week-old 36 albino rats of 100-200 g weight were assigned randomly to six groups, which received varied doses of BPA and/or CMSO. The administration of BPA and CMSO was done at the same time for 42 days by oral intubation. The adipokine levels and lipid profile were measured in adipose tissue and plasma using standard methods. BPA induced significant (p < .05) increases in triglycerides, cholesterol, leptin, LDL-C, and atherogenic and coronary risk indices in adipose tissue and plasma, as well as a decrease in adiponectin and HDL-C levels in Group II animals. BPA administration significantly (p < .05) elevated Leptin levels and reduced adiponectin levels. BPA plus CMSO reduced triglycerides, cholesterol, leptin, LDL-C, and atherogenic and coronary risk indices while increasing adiponectin levels and HDL-C in adipose tissue and plasma (p < .05). The results showed that BPA exposure increased adipose tissue as well as serum levels of the atherogenic index, triglycerides, cholesterol, coronary risk index, LDL-C, leptin, and body weight with decreased adiponectin levels and HDL-C. Treatment with CMSO reduced the toxicities caused by BPA in rats by modulating the body weight, adiponectin/leptin levels, and lipid profiles in serum and adipose tissue. This study has shown that CMSO ameliorates BPA-induced dyslipidemia and adipokine dysfunctions. We suggest for further clinical trial to establish the clinical applications.

Safety profile of colocasia esculenta tuber extracts in benign prostate hyperplasia.

INTRODUCTION: This study was motivated by the increasing global incidence of benign prostatic hyperplasia (BPH) and the promising potential of nutraceuticals as complementary therapies in ameliorating its burden. We report the safety profile of C. esculenta tuber extracts, a novel nutraceutical in benign prostate hyperplasia in a rat model. METHODS: In this study, forty-five male albino rats were randomly assigned to 9 groups of 5 rats each. Group 1 (normal control) received olive oil and normal saline. Group 2 (BPH untreated group) received 3 mg/kg of testosterone propionate (TP) and normal saline, and group 3 (positive control) received 3 mg/kg of TP and 5 mg/kg of finasteride. Treatment groups 4, 5, 6, 7, 8, and 9 received 3 mg/kg of TP and a middle dose (200 mg/kg) of LD50 of ethanol crude tuber extract of C. esculenta (ECTECE) or hexane, dichloromethane, butanone, ethyl acetate and aqueous fractions of ECTECE respectively for a period of 28 days. RESULTS: The negative controls showed a significant (p < 0.05) increase in mean relative prostate weight (approximately 5 times) as well as a reduction in relative testes weight (approximately 1.4 times less). There was no significant (p > 0.05) difference in the mean relative weights of most vital organs: liver, kidneys, and heart. This was also observed in hematological parameters: RBC, hemoglobin, HCT, MCV, MCH, MCHC, and platelets counts. In general, we note that the effects of the well-established drug finasteride on the biochemical parameters and histology of selected organs are comparable to those of C. esculenta fractions. CONCLUSION: This study demonstrates that C. esculenta tuber extracts provide potentially safe nutraceutical if applied in the management of benign prostate hyperplasia based on a rat model.

Comparison of the Nutritional Status of Swiss Albino Mice Fed on Either a Purified or Cereal-Based Diet for 15 weeks.

Background: Laboratory animals are commonly fed on cereal-based diets (CBDs) whose nutrient composition is unknown and may confound the metabolic response to study interventions. Purified diets such as AIN-93M are therefore recommended, as their nutrient composition is known. However, few studies have evaluated their use as adequate control diets. The aim of this study was to compare the nutrition status of Swiss albino mice fed on either CBD or AIN-93M for 15 weeks. Methods: Twenty Swiss albino mice aged 6-8 weeks and weighing 21.7 g ± 0.6 were fed on either CBD or AIN-93M diet for 15 weeks. Their nutritional status was evaluated using anthropometric and hematological indices, serum glucose, total protein, albumin, and total cholesterol to select an appropriate normal control diet. Results: The CBD had low-calorie content (2.57 kcal/g) and protein (11 ± 3.8 g/100 g) compared to AIN-93M (3.8 kcal/g and 14 g/100 g, respectively). The BMI of male mice fed on CBD and AIN-93M diets was significantly higher (P=0.0139 and P=0.0325, respectively) compared to that of females fed on similar diets. Animals in the CBD group had lower hemoglobin (15.1-16.9 g/dl) compared to those in the AIN-93M group (18.1-20.8 g/dl). Serum albumin levels were higher in both male (P=0.001) and female (P=3 × 10-6) mice fed on AIN-93M compared to those fed on CBD. Females in the AIN-93M group had higher cholesterol (P=0.026) than those in the CBD group. Conclusion: The AIN-93 diet of caloric value 3.85 kcal/g (total protein 14 g, total fat 4 g of soy bean oil, fibre 5 g, and total carbohydrate 42 g per 100 g) can be safely used as a normal control diet in long-term research studies using Swiss albino mice.

UCP-LF and other assay methods for schistosome circulating anodic antigen between 1978 and 2022.

Detection of circulating anodic antigen (CAA) is known for its high sensitivity in diagnosing schistosomiasis infection, even in low-prevalence settings. The Up-Converting Phosphor-Lateral Flow (UCP-LF) assay developed in 2008 presented greater sensitivity than other assay methods in use for CAA detection. Our study aims to comprehensively review all studies conducted in this area and thus generate informed conclusions on the potential for adopting the UCP-LF assay for diagnosing this important yet neglected tropical disease. Using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, we generated search criteria to capture all studies in English journals available in the Scopus and PubMed databases on 20 December 2022. A total of 219 articles were identified, and 84 that met the inclusion criteria were retrieved and eventually included in the study. Twelve different assay methods were identified with a noteworthy transition from enzyme-linked immunosorbent assay (ELISA) to the UCP-LF assay, a laboratory-based assay that may be applicable as a point-of-care (POC) diagnostic test for schistosomiasis. Reducing the time, cost, and dependence on specialized laboratory skills and equipment, especially relating to the trichloroacetic acid extraction step and centrifugation in the UCP-LF CAA assay may go a long way to aid its potential as a POC tool. We also propose the development of a CAA-specific aptamer (short protein/antigen-binding oligonucleotide) as a possible alternative to monoclonal antibodies in the assay. UCP-LF has great potential for POC application.

Association between obesity and cervical intraepithelial neoplasia: results from a case control study in south western Uganda.

BACKGROUND: Though obesity has been said to be associated with a number of malignancies including cervical cancer, its association with cervical intraepithelial neoplasia (CIN) is still a contentious issue. This study was designed to determining the prevalence and association between obesity and CIN. METHODS: This was an unmatched case control study, involving women with cervical intraepithelial neoplasia (cases) and those negative for intraepithelial lesions or malignancy (controls) at the cervical cancer clinic of Mbarara Regional Referral Hospital, in south-western Uganda, between April and November 2022. Cases and controls provided written informed consent and were recruited in a ratio of 1:1. Cases were identified by visual inspection with acetic acid (VIA) and subsequent confirmation with cytology and/or histology. Demographic information was collected using an enrolment form and height, weight and waist circumference were recorded. We calculated body mass index (BMI) and identified obese women as those with body mass index of ≥ 30 kg/m2 from both case and control groups. Central obesity was defined as waist: height ration of ≥ 0.5. Data was analysed using STATA version 17. Categorical variables were analysed using proportions, chi-square and logistic regression analysis to determine association between obesity and CIN. Our level of statistical significance was set at ≤ 0.05. RESULTS: The prevalence of general and central obesity among cases was 25.5% (24/94) and 0% (0/94) respectively while the prevalence of general and central obesity among controls was 33.3% (37/111) and 0% (0/111) respectively. There was an increased prevalence of general obesity among women with low grade squamous intraepithelial lesions (LSIL). However, there was no statistically significant association between general obesity and CIN. Factors associated with general obesity included residing in Mbarara city (AOR 2.156, 95%CI 1.085-4.282, P-value 0.028), age group of 31-45 years (AOR 2.421, 95%CI 1.577-9.705, P-value 0.003) and ≥ 46 years (AOR 1.971, 95%CI 1.022-11.157, P-value 0.046). CONCLUSION: We observed an increased prevalence of general obesity among women with LSIL. However, there was no association between obesity and CIN. Factors associated with general obesity included residing in Mbarara city, and being in the age groups of 31-40 and ≥ 46 years. This highlights the need to rethink management of CIN to control other non-communicable diseases that could arise due to general obesity.

In-vivo and in-silico studies revealed the molecular mechanisms of Colocasia esculenta phenolics as novel chemotherapy against benign prostatic hyperplasia via inhibition of 5α-reductase and α1-adrenoceptor.

Benign Prostatic Hyperplasia (BPH) is a major cause of lower urinary tract infections and erectile dysfunction thus a major contributor to lowering the quality of life among older men. In this study, we investigated the molecular mechanism of Colocasia esculenta (CE) as a novel agent for BPH chemotherapy. In vivo, we assigned 45 male Wistar albino rats about 6 weeks old into 9 experimental groups (n = 5). BPH was induced in groups 2-9 with 3 mg/kg of Testosterone Propionate (TP) subcutaneously. Group 2 (BPH) was not treated. Group 3 was treated with 5 mg/kg Finasteride (standard drug). Group 4-9 were treated each with 200 mg/kg body weight (b.w) of CE crude tuber extracts/fractions (ethanol, hexane, dichloromethane, ethyl acetate, butanol, aqueous). At the end of treatment, we sampled the rats' serum to check the level of PSA. In silico, we conducted a molecular docking of the crude extract of CE phenolics (CyP) previously reported, targeting 5α-Reductase and α1-Adrenoceptor linked to the BPH progressions. We adopted the standard inhibitors/antagonists (5α-reductase: finasteride; α1-adrenoceptor: tamsulosin) of the target proteins as controls. Furthermore, the pharmacological properties of the lead molecules were studied in terms of ADMET using swissadme and pKCSM resources, respectively. Results showed that administration of TP in male Wistar albino rats significantly (p < 0.05) elevated serum PSA levels whereas CE crude extracts/fractions significantly (p < 0.05) lowered the serum PSA level. Also, fourteen of the CyPs bind to at least one or two of the target proteins with their binding affinity of between - 9.3 to - 5.6 kcal/mol and - 6.9 to - 4.2 kcal/mol, respectively. The CyPs possess better pharmacological properties compared to the standard drugs. Therefore, they have the potentials to be enlisted for clinical trials towards the management of BPH.

The diagnostic accuracy of serum microRNAs in detection of cervical cancer: a systematic review protocol.

BACKGROUND: Cervical cancer remains a public health problem worldwide, especially in sub-Saharan Africa. There are challenges in timely screening and diagnosis for early detection and intervention. Therefore, studies on cervical cancer and cervical intraepithelial neoplasia suggest the need for new diagnostic approaches including microRNA technology. Plasma/serum levels of microRNAs are elevated or reduced compared to the normal state and their diagnostic accuracy for detection of cervical neoplasms has not been rigorously assessed more so in low-resource settings such as Uganda. The aim of this systematic review was therefore to assess the diagnostic accuracy of serum microRNAs in detecting cervical cancer. METHODS: We will perform a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. We will search for all articles in MEDLINE/PubMed, Web of Science, Embase, and CINAHL, as well as grey literature from 2012 to 2022. Our outcomes will be sensitivity, specificity, negative predictive values, positive predictive values or area under the curve (Nagamitsu et al, Mol Clin Oncol 5:189-94, 2016) for each microRNA or microRNA panel. We will use the quality assessment of diagnostic accuracy studies (Whiting et al, Ann Intern Med 155:529-36, 2011) tool to assess the risk of bias of included studies. Our results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy studies (PRISMA-DTA). We will summarise studies in a flow chart and then describe them using a structured narrative synthesis. If possible, we shall use the Lehmann model bivariate approach for the meta analysis USE OF THE REVIEW RESULTS: This systematic review will provide information on the relevance of microRNAs in cervical cancer. This information will help policy makers, planners and researchers in determining which particular microRNAs could be employed to screen or diagnose cancer of the cervix. SYSTEMATIC REVIEW REGISTRATION: This protocol has been registered in PROSPERO under registration number CRD42022313275.

TDP-43 and NEAT long non-coding RNA: Roles in neurodegenerative disease.

Understanding and ameliorating neurodegenerative diseases represents a key challenge for supporting the health span of the aging population. Diverse protein aggregates have been implicated in such neurodegenerative disorders, including amyloid-ß, α-synuclein, tau, fused in sarcoma (FUS), and transactivation response element (TAR) DNA-binding protein 43 (TDP-43). Recent years have seen significant growth in our mechanistic knowledge of relationships between these proteins and some of the membrane-less nuclear structures that fulfill key roles in the cell function. These include the nucleolus, nuclear speckles, and paraspeckles. The ability of macromolecular protein:RNA complexes to partition these nuclear condensates through biophysical processes that involve liquid-liquid phase separation (LLPS) has also gained attention recently. The paraspeckle, which is scaffolded by the architectural long-non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) plays central roles in RNA processing and metabolism and has been linked dynamically to TDP-43. In this mini-review, we outline essential early and recent insights in relation to TDP-43 proteinopathies. We then appraise the relationships between TDP-43 and NEAT1 in the context of neuronal paraspeckles and neuronal stress. We highlight key areas for investigation based on recent advances in our understanding of how TDP-43 affects neuronal function, especially in relation to messenger ribosomal nucleic acid (mRNA) splicing. Finally, we offer perspectives that should be considered for translational pipelines in order to improve health outcomes for the management of neurodegenerative diseases.

MicroRNAs in the epigenetic regulation of disease progression in Parkinson's disease.

Parkinson's disease (PD) is a multifactorial neurodegenerative condition with symptoms such as resting tremor, rigidity, bradykinesia (slowness of moment), and postural instability. Neuroinflammation plays a significant part in the onset and progression of neurodegeneration in a wide range of disorders, including PD. The loss of dopaminergic neurons in the substantia nigra (SN) is thought to be the primary cause of PD disease progression. However, other neurotransmitter systems like serotoninergic, glutamatergic, noradrenergic, adrenergic, cholinergic, tryptaminergic, and peptidergic appear to be affected as well. Epigenetic regulation of gene expression is emerging as an influencing factor in the pathophysiology of PD. In recent years, epigenetic regulation by microRNAs (miRNAs) has been discovered to play an important function in the disease progression of PD. This review explores the role of miRNAs and their signaling pathways in regulating gene expression from development through neurodegeneration and how these mechanisms are linked to the pathophysiology of PD, emphasizing potential therapeutic interventions.

Prevalence, correlates and treatment needs of dental caries among people on antiretroviral therapy in Uganda: a cross sectional study.

BACKGROUND: Oral diseases are estimated to affect half of people living with HIV in the western world, and are often marked by pain, discomfort, disfigurement and reduced quality of life. Both HIV-specific and antiretroviral therapy-associated oral diseases have been found in this population. However, the prevalence, correlates and treatment needs of dental caries among people on antiretroviral therapy has not been well studied in rural Africa where majority of people living with HIV reside. Moreover, health behaviors and access to dental care vary significantly from high-income countries in the global north. METHODS: A cross-sectional study was conducted among people living with HIV attending a high-volume HIV clinic with an enrollment of 10,000 patients in a regional referral hospital in Southwestern Uganda. The clinic is located in an urban setting with a large rural catchment area. Oral health data was collected using the modified World Health Organization oral health questionnaire for adults. Dental examinations were conducted to identify and classify dental caries using the decayed, missing, filled, teeth (DMFT) index and compute the treatment need. Logistic regression models were employed to identify correlate of dental caries. RESULTS: A total of 194 participants were included in the study. The majority were female (124/194, 63.9%) with a median age of 42 years (IQR 36-49). The prevalence of dental caries experience among study participants was 67%, (130/194, 95% CI 60-75%). The mean DMFT index score was 4 (IQR 2-6) and treatment need was 96% (192/200). A higher CD4 count was associated with the presence of dental caries (OR 0.403, 95% CI 0.175-0.932) although it was not significant in multivariate analysis. CONCLUSION: There is a high prevalence of dental caries among people living with HIV on ART in Uganda. Our data demonstrate a high oral treatment need among this population. We recommend inclusion of preventive and therapeutic oral care into HIV care in this region.

CRISPR/Cas9 and next generation sequencing in the personalized treatment of Cancer.

BACKGROUND: Cancer is caused by a combination of genetic and epigenetic abnormalities. Current cancer therapies are limited due to the complexity of their mechanism, underlining the need for alternative therapeutic approaches. Interestingly, combining the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9) system with next-generation sequencing (NGS) has the potential to speed up the identification, validation, and targeting of high-value targets. MAIN TEXT: Personalized or precision medicine combines genetic information with phenotypic and environmental characteristics to produce healthcare tailored to the individual and eliminates the constraints of "one-size-fits-all" therapy. Precision medicine is now possible thanks to cancer genome sequencing. Having advantages over limited sample requirements and the recent development of biomarkers have made the use of NGS a major leap in personalized medicine. Tumor and cell-free DNA profiling using NGS, proteome and RNA analyses, and a better understanding of immunological systems, are all helping to improve cancer treatment choices. Finally, direct targeting of tumor genes in cancer cells with CRISPR/Cas9 may be achievable, allowing for eliminating genetic changes that lead to tumor growth and metastatic capability. CONCLUSION: With NGS and CRISPR/Cas9, the goal is no longer to match the treatment for the diagnosed tumor but rather to build a treatment method that fits the tumor exactly. Hence, in this review, we have discussed the potential role of CRISPR/Cas9 and NGS in advancing personalized medicine.

In vitro antimycobacterial activity of medicinal plants Lantana camara, Cryptolepis sanguinolenta, and Zanthoxylum leprieurii.

Background: Imperative need exists to search for new anti-TB drugs that are safer, and more effective against drug-resistant strains. Medicinal plants have been the source of active ingredients for drug development. However, the slow growth and biosafety level requirements of M. tuberculosis culture are considerable challenges. M. smegmatis can be used as a surrogate for M. tuberculosis. In the current study, preliminary phytochemical screening and antimycobacterial activity evaluation of crude methanolic extracts of medicinal plants against M. smegmatis, and two M. tuberculosis strains, were conducted. Materials and Methods: Crude methanolic extracts, obtained from the leaves of L. camara, roots of C. sanguinolenta, and stem barks of Z. leprieurii, were tested for antimycobacterial activity against M. smegmatis (mc2155), pan-sensitive (H37Rv), and rifampicin-resistant (TMC-331) M. tuberculosis, using visual Resazurin Microtiter Assay (REMA) on 96 well plates. Preliminary qualitative phytochemical screening tests were performed using standard chemical methods. Results: The three methanolic extracts inhibited mycobacterial growth in vitro. They were more active against rifampicin-resistant strain with MICs of 176, 97, and 45 µg/mL for L. camara, C. sanguinolenta, and Z. leprieurii extracts, respectively. The lowest activity was observed against M. smegmatis with MICs of 574, 325, and 520 µg/mL, respectively. Against H37Rv, activity was intermediate to those of TMC-331 and mc2155. However, L. camara extract showed the same activity against H37Rv and M. smegmatis. Preliminary phytochemical analysis revealed alkaloids, flavonoids, phenolic compounds, saponins, tannins, and terpenoids. Conclusions: Leaves of L. camara, roots of C. sanguinolenta, and stem barks of Z. leprieurii exhibit antimycobacterial activity against M. smegmatis, pan-sensitive, and rifampicin-resistant M. tuberculosis. This offers the possibilities for novel therapeutic opportunities against TB including multidrug-resistant TB. Further investigations on safety and mechanisms of action are required. These studies could be done using M. smegmatis as a surrogate for the highly pathogenic M. tuberculosis.

Liquid biopsy: Exosomal microRNAs as novel diagnostic and prognostic biomarkers in cancer.

BACKGROUND: Detecting cancer at an early stage before clinical manifestation could be an effective strategy to decrease cancer mortality. Thus, identifying liquid biopsy biomarkers with high efficacy could be a promising approach for non-invasive diagnosis of cancer. MAIN TEXT: Liquid biopsies are increasingly used as a supplement to biopsy, as it enables disease progression to be detected months before clinical and radiographic confirmation. Many bodily fluids contain exosomal microRNAs (miRNAs) which could provide a new class of biomarkers for early and minimally invasive cancer diagnosis due to the stability of miRNAs in exosomes. In this review, we mainly focused on the exosomal miRNAs (liquid biopsy) as biomarkers in the diagnosis and prognosis of various cancers. CONCLUSION: Exosomal miRNAs can be used as diagnostic and prognosis biomarkers that provide unique insights and a more dynamic perspective of the progression and therapeutic responses in various malignancies. Therefore, the development of novel and more sensitive technologies that exploit exosomal miRNAs should be a priority for cancer management.

Corrigendum: TDP-43 and NEAT long non-coding RNA: Roles in neurodegenerative disease.

[This corrects the article DOI: 10.3389/fncel.2022.954912.].