A sub-group evaluation of the multi-month dispensing strategy for differentiated HIV care: is personalization of care guidelines warranted in Haiti?

Background Differentiated care strategies are rapidly becoming the norm for HIV care delivery globally. Building upon an interest in tailoring antiretroviral therapy (ART) delivery for client-centered needs, the Ministry of Health and Population in Haiti formally endorsed multiple-month dispenses (MMD) in the 2016 national ART guidelines This study explores heterogeneity in retention in care with MMD for specific Haitian populations living with HIV and evaluates if a targeted algorithm for optimal ART prescription intervals is warranted in Haiti. Methods This study included ART-naïve individuals who started ART on or after January 1st, 2017 in Haiti. To identify subgroups in which to explore heterogeneity of retention, we implemented a double-lasso regression method to determine which individual characteristics would define the subgroups. Characteristics evaluated for potential subgroup definition included: sex, age category, WHO clinical stage, and body mass index category. We employed instrumental variable models to estimate the causal effect of increasing ART dispensing length on ART retention, by client subgroup. The outcome of interest was retention in care after one year in treatment. We then estimated the marginal effect of a 30-day increase to ART dispensing length to retention in care for each of these subgroups. Results There was evidence for heterogeneity in the effect of extending ART dispensing intervals on retention by WHO clinical stage. We observed significant improvements to retention in care at one year with a 30-day increase in ART dispense length for all subgroups defined by WHO clinical stages 1-4. The effects ranged from a 14.7% increase (95% CI: 12.4-17.0) to the likelihood of retention for people with HIV in WHO stage 1 to a 21.6% increase (95% CI: 18.7-24.5) to the likelihood of retention for those in WHO stage 3. Conclusions All the subgroups defined by WHO clinical stage experienced a benefit of extending ART intervals to retention in care at one year. Though the effect did differ slightly by WHO stage, the effects went in the same direction and were of similar magnitude. Therefore, a standardized recommendation for MMD among those living with HIV and new on ART is appropriate for Haiti treatment guidelines.

MicroRNA-625-3p improved proliferation and involved chemotherapy resistance via targeting PTEN in high grade ovarian serous carcinoma

Objective High-grade serous ovarian cancer (HGSOC) is an aggressive gynaecological malignancy and associated with poor prognosis. Here we examined the effects of miR-625-3p on proliferation, treatment, migration and invasion in HGSOC. Methods The proliferation of HGSOC cells was evaluated by MTT assay. Transwell assay was performed to examine migration and matrigel assay were used to assess invasion. The effect of miR-625-3p on cisplatin-induced apoptosis was investigated by Caspase-Glo3/7 assay. The dual-luciferase reporter assay was carried out to confirm the potential binding site. Results Overexpression of miR-625-3p promoted proliferation, and increased migration and invasion in HGSOC cells. MiR-625-3p significantly inhibited cisplatin sensitivity in HGSOC cells. Meanwhile, miR-625-3p decreased cisplatin-induced apoptosis by regulation of BAX and Bcl-2 expression. Furthermore, aberrant expression of miR-625-3p changed PTEN expression by directly binding to 3’UTR of PTEN. Further study showed miR-625-3p expression was higher in human HGSOC tissue than normal ovarian tissues and associated with higher clinical stage. Conclusions miR-625-3p promotes HGSOC growth, involves chemotherapy resistance and might serve as a potential biomarker to predict chemotherapy response and prognosis in HGSOC.

Lower GDNF Serum Level Is a Possible Risk Factor for Constipation in Patients With Parkinson Disease: A Case–Control Study

Background: Constipation is a significant symptom of Parkinson's disease (PD). Glial-derived neurotrophic factor (GDNF) is important for the morphogenesis of the enteric nervous system and plays a critical role in the preservation of mucosal integrity under enteric glia surveillance. The aim of this work was to evaluate the serum levels of GDNF in patients with PD with and without constipation.Methods: This work included 128 patients with PD. The patients were classified into three groups: those with PD but no constipation (nCons-PD) (n = 49), those with prodromal stage constipation (Cons-Pro-PD) (n = 48), and those with clinical stage constipation (Cons-Clinic-PD) (n = 31). The association between serum GDNF concentration and constipation was explored using logical regression.Results: The nCons-PD group's mean GDNF levels were 528.44 pg/ml, which was higher than the Cons-Pro-PD group's 360.72 pg/ml and the Cons-Clinic-PD group's 331.36 pg/ml. The results of binary logistic regression indicated that GDNF was a protective factor in the prevention of constipation. Cons-Clinic-PD group had a higher score of MDS-UPDRS-II, MDS-UPDRS-III, MDS-UPDRS-IV, and a higher H-Y staging as compared with nCons-PD group. Relative to the nCons-PD group, Cons-Clinic-PD had higher NMSS scores, lower MoCA and PDSS scores, and were more likely to have RBD.Conclusions: GDNF serum levels are lower in patients with PD who are constipated. A low GDNF level is a potential risk factor for constipation in patients with PD.

Incidence and predictors of anemia among adults on HIV care at South Gondar Zone Public General Hospital Northwest Ethiopia, 2020; retrospective cohort study

Background Anemia is a major public health problem worldwide which accounts 24.8% of the population. Subsequently, anemia is a leading killer of people living with human immunodeficiency virus and many of these deaths occur in developing countries including Ethiopia. Cross sectional studies have done on anemia and human immunodeficiency virus. However, there is limited study on incidence of anemia and its predictors among adults on HIV care, especially no survival study has been conducted in the study area. Objective To assess incidence and predictors of anemia among adults on Human immunodeficiency virus care. Methods An institution-based retrospective cohort study was conducted among 434 adults on HIV care from January 1st 2015 to December 30th 2019 at Debre Tabor Referral Hospital. A computer-generated simple random sampling technique was employed to select the study participants. Ethical clearance was obtained from the Institutional Review Board of Bahir Dar University, and also, we got implied consent to review charts from the concerned bodies in the hospital. Data were entered using Epi-data version 3.1 and analyzed by using STATA version 14.0. A Kaplan Meier survival curve was utilized to estimate anemia free survival time. Bivariable and Multivariable Cox proportional hazards model were fitted to identify predictors of anemia. Results The overall incidence density rate of anemia was 6.27 (95% CI: 0.051, 0.077) per 100 person years. Clinical stage III/IV (AHR = 1.04; 95% CI = 1.02, 1.06), Body Mass Index less than 18.5 kg/m2 (AHR = 3.11; 95% CI = 1.56, 6.22), serum creatinine greater than 1.1 IU/L(AHR = 2.07; 95% CI = 1.12, 3.81) and fair/poor level of adherence(AHR = 1.05; 95% CI = 1.03, 1.07) were statistically significant predictors of anemia while increased anti-retroviral treatment duration (AHR = 0.98; 95% CI = 0.97, 0.99) decrease the risk of anemia at 95% confidence level. Conclusion The overall incidence density rate of anemia was high. Patients with clinical stage III/IV, body mass index < 18.5 kg/m2, serum creatinine greater than 1.1 IU/L and fair/poor level of adherence were significant predictors of anemia while increased antiretroviral treatment duration had decreased the risk of anemia. Recommendation Even if the overall incidence rate of anemia was lower as compared to previous studies in Ethiopia, still the incidence of anemia was high. So, prevention measures should be taken beside with HIV care especially within 6-months ART initiation.

Speech- and Language-Based Classification of Alzheimer’s Disease: A Systematic Review

Background: Alzheimer’s disease (AD) has paramount importance due to its rising prevalence, the impact on the patient and society, and the related healthcare costs. However, current diagnostic techniques are not designed for frequent mass screening, delaying therapeutic intervention and worsening prognoses. To be able to detect AD at an early stage, ideally at a pre-clinical stage, speech analysis emerges as a simple low-cost non-invasive procedure. Objectives: In this work it is our objective to do a systematic review about speech-based detection and classification of Alzheimer’s Disease with the purpose of identifying the most effective algorithms and best practices. Methods: A systematic literature search was performed from Jan 2015 up to May 2020 using ScienceDirect, PubMed and DBLP. Articles were screened by title, abstract and full text as needed. A manual complementary search among the references of the included papers was also performed. Inclusion criteria and search strategies were defined a priori. Results: We were able: to identify the main resources that can support the development of decision support systems for AD, to list speech features that are correlated with the linguistic and acoustic footprint of the disease, to recognize the data models that can provide robust results and to observe the performance indicators that were reported. Discussion: A computational system with the adequate elements combination, based on the identified best-practices, can point to a whole new diagnostic approach, leading to better insights about AD symptoms and its disease patterns, creating conditions to promote a longer life span as well as an improvement in patient quality of life. The clinically relevant results that were identified can be used to establish a reference system and help to define research guidelines for future developments.

Serum exosomal miR-451a acts as a candidate marker for pancreatic cancer

Objectives The aim of this study was to explore the diagnostic efficiency of serum exosomal miR-451a as a novel biomarker for pancreatic cancer. Methods Serum samples were collected prior to treatment. First, we analyzed microRNA (miRNA) profiles in serum exosomes from eight pancreatic cancer patients and eight healthy volunteers. We then validated the usefulness of the selected exosomal miRNAs as biomarkers in another 191 pancreatic cancer patients, 95 pancreatic benign disease (PB) patients, and 90 healthy controls. Results The expression of miR-451a in serum-derived exosomes from pancreatic cancer patients was significantly upregulated compared with those from PB patients and healthy individuals. Serum exosomal miR-451a showed excellent diagnostic power in identifying pancreatic cancer patients. In addition, exosomal miR-451a showed a significant association with clinical stage and distant metastasis in pancreatic cancer, and the expression level of serum exosomal miR-451a was sensitive to therapy and relapse. Conclusions Serum exosomal miR-451a might serve as a novel diagnostic marker for pancreatic cancer.

Clinical and immunological features of psoriasis vulgaris in HIV-infected patients

Introduction. Psoriasis is an inflammatory dermatosis, which has characteristic clinical features and is closely associated with immunological changes in the skin. HIV-infected patients suffering from psoriasis have immunological features associated with the effect of HIV virus on CD4+T-lymphocytes.Aim. To identify clinical features of psoriasis in HIV-infected patients depending on the stage of HIV infection and immune status.Materials and methods. An open prospective study (2014–2018) included 143 patients with psoriasis vulgaris, of which 79 (55.2%) were infected with HIV and 64 (44.8%) were not infected with HIV. The groups were comparable in terms of age and gender. The diagnosis of psoriasis vulgaris was established with due account for its clinical presentation and histologically confirmed in 29 (20.3%) patients, of which 17 (58.6%) were infected with HIV and 12 (41.4%) were not infected with HIV. In a biopsy, tissue samples were taken from the areas of inflammatory and healthy skin in each patient. Numbers of CD4+ and CD8+T-lymphocytes in the biopsy samples obtained were calculated using immunohistochemical staining of biopsy. The severity of psoriasis progress was assessed using the psoriasis lesions severity index, taking into account the body surface area covered by lesions, the intensity of erythema, infiltration and sloughing of skin. In the course of the study, the patients had general clinical examinations performed, their HIV infection confirmed or denied, their immune status assessed, and their clinical stage of HIV infection determined.Results and discussion. Mild psoriasis was less often identified, and moderately severe and severe psoriasis was more often observed in HIV-infected patients as compared to HIV-negative patients. The psoriatic plaque CD8+T-lymphocyte counts in HIV-infected patients grew with increasing immunosuppression and clinical stage of HIV infection; these changes were not observed in HIV-negative patients.Сonclusion. HIV-infected patients often have moderately severe (39.2%) and severe (22.8%) psoriasis vulgaris. The psoriatic plaque CD8+T-lymphocyte counts in HIV-infected patients predominate over the CD4+T-lymphocyte counts, while the HIV-negative patients show the opposite test results.