KR158 spheres harboring slow-cycling cells recapitulate GBM features in an immunocompetent system.

Glioblastoma (GBM) poses a significant challenge in clinical oncology due to its aggressive nature, heterogeneity, and resistance to therapies. Cancer stem cells (CSCs) play a critical role in GBM, particularly in treatment-resistance and tumor relapse, emphasizing the need to comprehend the mechanisms regulating these cells. Also, their multifaceted contributions to the tumor-microenvironment (TME) underline their significance, driven by their unique properties. This study aimed to characterize glioblastoma stem cells (GSCs), specifically slow-cycling cells (SCCs), in an immunocompetent murine GBM model to explore their similarities with their human counterparts. Using the KR158 mouse model, we confirmed that SCCs isolated from this model exhibited key traits and functional properties akin to human SCCs. KR158 murine SCCs, expanded in the gliomasphere assay, demonstrated sphere forming ability, self-renewing capacity, positive tumorigenicity, enhanced stemness and resistance to chemotherapy. Together, our findings validate the KR158 murine model as a framework to investigate GSCs and SCCs in GBM-pathology, and explore specifically the SCC-immune system communications, understand their role in disease progression, and evaluate the effect of therapeutic strategies targeting these specific connections.

Evaluation of clinical trials of ethnomedicine used for the treatment of diabetes: A systematic review.

Diabetes mellitus (DM) is a widespread metabolic disorder with a yearly 6.7 million deaths worldwide. Several treatment options are available but with common side effects like weight gain, cardiovascular diseases, neurotoxicity, hepatotoxicity, and nephrotoxicity. Therefore, ethnomedicine is gaining the interest of researchers in the treatment of DM. Ethnomedicine works by preventing intestinal absorption and hepatic production of glucose as well as enhancing glucose uptake in muscles and fatty tissues and increasing insulin secretion. A variety of plants have entered clinical trials but very few have gained approval for use. This current study provides an evaluation of such clinical trials. For this purpose, an extensive literature review was performed from a database using keywords like "ethnomedicine diabetes clinical trial", "clinical trials", "clinical trial in diabetes", "diabetes", "natural products in diabetes", "ethno-pharmacological relevance of natural products in diabetes", etc. Clinical trials of 20 plants and natural products were evaluated based on eligibility criteria. Major limitations associated with these clinical trials were a lack of patient compliance, dose-response relationship, and an evaluation of biomarkers with a small sample size and treatment duration. Measures in terms of strict regulations can be considered to achieve quality clinical trials. A specific goal of this systematic review is to discuss DM treatment through ethnomedicine based on recent clinical trials of the past 7 years.

Wrist accelerometer shape feature derivation methods for assessing activities of daily living.

BACKGROUND: There has been an increasing interest in understanding the usefulness of wrist-based accelerometer data for physical activity (PA) assessment due to the ease of use and higher user compliance than other body placements. PA assessment studies have relied on machine learning methods which take accelerometer data in forms of variables, or feature vectors. METHODS: In this work, we introduce automated shape feature derivation methods to transform epochs of accelerometer data into feature vectors. As the first step, recurring patterns in the collected data are identified and placed in a codebook. Similarities between epochs of accelerometer data and codebook's patterns are the basis of feature calculations. In this paper, we demonstrate supervised and unsupervised approaches to learn codebooks. We evaluated these methods and compared them with the standard statistical measures for PA assessment. The experiments were performed on 146 participants who wore an ActiGraph GT3X+ accelerometer on the right wrist and performed 33 activities of daily living. RESULTS: Our evaluations show that the shape feature derivation methods were able to perform comparably with the standard wrist model (F1-score: 0.89) for identifying sedentary PAs (F1-scores of 0.86 and 0.85 for supervised and unsupervised methods, respectively). This was also observed for identifying locomotion activities (F1-scores: 0.87, 0.83, and 0.81 for the standard wrist, supervised, unsupervised models, respectively). All the wrist models were able to estimate energy expenditure required for PAs with low error (rMSE: 0.90, 0.93, and 0.90 for the standard wrist, supervised, and unsupervised models, respectively). CONCLUSION: The automated shape feature derivation methods offer insights into the performed activities by providing a summary of repeating patterns in the accelerometer data. Furthermore, they could be used as efficient alternatives (or additions) for manually engineered features, especially important for cases where the latter fail to provide sufficient information to machine learning methods for PA assessment.

Distribution and determinants of cytomegalovirus induced end organ disease/s among people living with HIV/AIDS in a poor resource setting: observation from India.

BACKGROUND: In India, despite well-established anti-retroviral treatment programs, Cytomegalovirus (CMV) infection-related end-organ diseases (EODs) still remain a major concern resulting in exacerbation of morbidity and mortality among HIV/AIDS patients. A prospective study was designed to understand the distribution and prognosis of CMV associated EODs and to determine a standardized cut-off value for serum CMV viral load associated with the development of EODs amongst HIV/AIDS subjects. METHODS: In a cohort of 400 late-diagnosed HAART naïve HIV/AIDS subjects attending anti-retroviral centers of Kolkata during 2008-2014, the median duration of follow-up was 560 days, and at least 3 visits subsequent to the baseline were mandatory for eligibility. HIV-1 and CMV viral load were estimated by performing Real-Time Polymerase Chain Reactions (PCR). RESULTS: Among subjects, 40.5% (162/400) had CMV EODs which were more common at lower CD4 counts. Poor prognosis and higher death rate were associated with a low CD4 count and increased HIV-1 and CMV viral loads. Subjects having higher CD4 count responded better to therapy [for CD4 = 60-100: Risk Ratio:RR = 1.48 (95% Confidence Interval: 95%CI = 1.18-1.82) and for CD4 = 30-59: RR = 1.64 (95%CI = 1.18-2.27)]. The cut off value of the serum CMV viral load (expressed as log10DNA/ml serum) associated with the development of EODs and disseminated CMV EODs was determined as 5.4 (p<0.0001) and 6.4 (p<0.0001) respectively. These cut offs were found to have satisfactorily high sensitivity, specificity, positive and negative predictive values. CONCLUSION: Prognosis of CMV EOD was poor as indicated by higher death rates among subjects with lower CD4 count, and specific cut-off values were found to have useful potential for identification and treatment of CMV infected HIV/AIDS patients in due time to avoid CMV EODs among HIV/AIDS subjects. Targeted intervention programs seemed to be required urgently to make these cut-offs operational in order to minimize the burden of CMV EOD in this vulnerable population.

Unravelling the Gordian knot: diagnostic dilemma in an HIV-positive patient with neurological involvement.

We report a case of a 40-year-old seropositive-HIV patient with a CD4 count of 120 who presented with fever, severe headache and neck stiffness. Suspecting a case of tubercular meningitis (TBM; as tuberculosis is the commonest opportunistic infection in HIV/AIDS patients in India), a lumbar puncture was performed and a cerebrospinal fluid study revealed TBM. The patient was started on combination antitubercular drug therapy from directly observed treatment, short course (DOTS) (Cat 1 regimen) along with pyridoxine 40 mg/day and adjunctive corticosteroid therapy. However, despite adequate antitubercular therapy for 4 weeks, the patient did not show any improvement in his clinical condition. On the contrary, in the process he developed cytomegalovirus (CMV) retinitis. So we question our learned readers if the coinfection of Mycobacterium tuberculosis and CMV should be implicated for the failure to respond to isolated antitubercular therapy contrary to our expectation.

Incidence of CMV-HCV coinfection in renal transplant recipient.

The authors report a case of a 47-year-old cytomegalovirus (CMV) immunoglobulin G (IgG) seropositive male patient with end stage renal disease who received a live renal transplant from a CMV IgG seropositive donor. Six months post-transplantation, the patient presented with reduced renal allograft function associated with fever, severe breathlessness, new onset jaundice and pancytopenia. His CMV DNA PCR came positive. Hepatitis C virus (HCV) RNA PCR also came positive (genotype I) though anti-HCV test performed before and after transplantation was negative. The patient was treated with oral valganciclovir and showed improvement of his clinical condition and was subsequently discharged under supervised therapy. However, the patient could not be treated for HCV because of risk of renal allograft rejection. The authors suggest oral valganciclovir for management of CMV infection and proper detection and eradication of HCV before renal transplantation to avoid future complications and prolongation of allograft survival.

Zinc and vitamin A can minimise the severity of oral submucous fibrosis.

We report a case of a 24-year-old man who presented with a complaint of reduced mouth opening and a burning sensation. On examination, he was clinically diagnosed with oral submucous fibrosis (OSF). Following routine biopsy and histopathological confirmation of OSF, the patient was supplemented with zinc acetate along with vitamin A and was followed up for 4 months. Following treatment the patient reported increased mouth opening and a reduced burning sensation. Histopathologically re-epithelialisation was evident along with the appearance of normal rete pegs. The data for mouth opening, collagen content and epithelial thickness of six other cases similarly treated are also presented, showing a significant increase in mouth opening and epithelial thickness and decrease in collagen content. We propose the use of zinc acetate and vitamin A for the management of OSF.