Dissolving microneedles for long-term storage and transdermal delivery of extracellular vesicles.

Extracellular vesicles (EVs) have shown great potential in disease diagnosis and treatment; however, their clinical applications remain challenging due to their unsatisfactory long-term stability and the lack of effective delivery strategies. In this study, we prepared human adipose stem cell-derived EV (hASC-EV)-loaded hyaluronic acid dissolving microneedles (EV@MN) to investigate the feasibility of EVs for their clinical applications. The biological activities of the EVs in this formulation were maintained for more than six months under mild storage conditions, especially at temperatures lower than 4 °C. Moreover, the EV@MN enabled precise and convenient intradermal delivery for sustained release of EVs in the dermis layer. Therefore, EV@MN significantly improved the biological functions of hASC-EVs on dermal fibroblasts by promoting syntheses of proteins for the extracellular matrix such as collagen and elastin, enhancing fibroblast proliferation, and regulating the phenotype of fibroblast, compared with other administration methods. This research revealed a possible and feasible formulation for the clinical application of EVs.

A pilot randomized controlled trial to compare the effectiveness of two 14-day primaquine regimens for the radical cure of vivax malaria in South India.

BACKGROUND: Radical cure of Plasmodium vivax malaria requires treatment with a blood schizonticide and a hypnozoitocide (primaquine) to eradicate the dormant liver stages. There has been uncertainty about the operational effectiveness and optimum dosing of the currently recommended 14-day primaquine (PQ) course. METHODS: A two centre, randomized, open-label, two arm study was conducted in South India. Patients were randomized to receive either high dose (0.5 mg base/kg body weight) or conventional dose (0.25 mg/kg) PQ for 14 days. Plasma concentrations of PQ and carboxyprimaquine (CPQ) on the 7th day of treatment were measured by reverse phase high performance liquid chromatography. Study subjects were followed up for 6 months. Recurrent infections were genotyped using capillary fragment length polymorphism of two PCR-amplified microsatellite markers (MS07 and MS 10). RESULTS: Fifty patients were enrolled. Baseline characteristics and laboratory features did not differ significantly between the groups. Mean age of the study population was 42 ± 16.0 years. Recurrences 80-105 days later occurred in 4 (8%) patients, two in each the groups. All recurrences had the same microsatellite genotype as that causing the index infection suggesting all were relapses. One relapse was associated with low CPQ concentrations suggesting poor adherence. CONCLUSIONS: This small pilot trial supports the effectiveness of the currently recommended lower dose (0.25 mg/kg/day) 14 day PQ regimen for the radical cure of vivax malaria in South India. Trial registration Clinical Trials Registry-India, CTRI/2017/03/007999. Registered 3 March 2017, http://ctri.nic.in/Clinicaltrials/regtrial.php?modid=1&compid=19&EncHid=82755.86366 .

Prevalence of diabetes mellitus amongst hospitalized tuberculosis patients at an Indian tertiary care center: A descriptive analysis.

BACKGROUND: India has a high prevalence of tuberculosis (TB) as well as diabetes mellitus (DM). DM is a chronic disease caused by deficiency of insulin production by the pancreas. The risk of TB amongst DM patients is three times higher than those without. The estimated national prevalence of DM is 7.3%. Despite the growing burden of DM, there are limited studies describing the prevalence of TB-DM in India. OBJECTIVE: Our study estimated the prevalence of DM amongst adult hospitalized TB patients at Kasturba Hospital, Manipal and determined factors associated with the likelihood of DM-TB co-prevalence. METHODS: We conducted a retrospective cohort study at Kasturba Hospital, Manipal Academy of Higher Education. All hospitalized adult patients diagnosed with pulmonary TB (PTB) and extrapulmonary TB (EPTB) between June 1st 2015 and June 30th 2016 were eligible for inclusion. Pediatric and pregnant TB patients were excluded from our study. Data were extracted from medical charts. Descriptive and multivariate analyses were performed in R. Multivariate analysis adjusted for age, gender, type of TB, history of TB, and nutrition (body mass index (BMI)) status. RESULTS: A total of 728 patients met the eligibility criteria, 517 (71%) were male, 210 (29%) female, 406 (56%) had PTB and 322 (44%) had EPTB. Amongst those with a nutritional status, 36 (30%) patients were underweight (BMI <18.4 kg/m2), 73 (40%) had a normal BMI (18.5kg/m2-24.9 kg/m2), 15 (8%) were overweight (BMI 25.0 kg/m2-29.9 kg/m2) and 9 (5%) were obese (BMI >30.0 kg/m2). A total of 720 (98.9%) of TB patients had at least one blood sugar test result. The overall prevalence of DM (n = 184) amongst TB patients was 25.3% (95% CI 22.2%, 28.6%). When stratified, it was 35.0% (30.4%, 39.9%) and 13.0% (9.7%, 17.3%) amongst PTB and EPTB patients respectively. TB patients aged 41-60 years had 3.51 times higher odds (aOR 3.51 (2.08, 6.07)) of having DM than patients 40 years or younger. Patients aged 60 years or older had 2.49 times higher odds (aOR 2.49 (1.28, 4.85)) of having DM than younger patients (<40 years). Females had lower odds (aOR 0.80 (0.46, 1.37)) of developing DM than male TB patients and patients with a history of TB had lower odds (aOR 0.73 (0.39, 1.32)) than newly diagnosed TB patients. Additionally, EPTB patients had significantly lower odds (aOR 0.26 (0.15, 0.43)) compared to PTB patients. Underweight patients also had significantly lower odds (aOR 0.25 (0.14, 0.42)) of having DM than normal weight patients. CONCLUSION: Our study found a higher prevalence of TB-DM than the national average. TB-DM co-prevalence was significantly associated with age, type of TB and undernutrition. As India's DM prevalence is expected to rise, TB-DM will become an increasingly important part of the TB epidemic requiring specialized study and care.