Dasatinib loaded mucoadhesive lecithin-chitosan hybrid nanoparticles for its augmented oral delivery, in-vitro efficacy and safety.

Dasatinib (DAS) is an oral tyrosine kinase inhibitor; however, its efficacy is significantly subsided by its low oral bioavailability. The present research aimed to improve DAS's oral delivery and efficacy in triple-negative breast cancer by fabricating its mucoadhesive lecithin-chitosan hybrid nanoparticles (DAS-L/CS-NPs). DAS-L/CS-NPs were optimized using Box-Behnken design which showed mean particle size and percent entrapment efficiency of 179.7 ± 5.42 nm and 64.65 ± 0.06 %, respectively. DAS-L/CS-NPs demonstrated sustained release profile in different release media up to 48 h and showed 10 times higher apparent permeability coefficient and flux than free DAS suspension. The binding of DAS-L/CS-NPs to the mucus layer was demonstrated via ex-vivo mucoadhesion study and change in absorbance using turbidimetry. In cell culture studies, DAS-L/CS-NPs revealed a 4.14-fold decrease in IC50, significantly higher cellular uptake and mitochondrial membrane depolarization, 3.82-fold increased reactive oxygen species generation and 2.10-fold enhanced apoptosis in MDA-MB-231 cells than free DAS. In in-vivo pharmacokinetic assessment, DAS-L/CS-NPs showed a 5.08-fold and 3.74-fold rise in AUC (0-t) and Cmax than free DAS suspension, respectively. An acute toxicity study revealed a good safety profile of DAS-L/CS-NPs. In a nutshell, proposed hybrid nanoparticles are promising carriers for improved oral delivery of poorly water-soluble drugs.

Understanding the need for developing a structured competency-based curriculum for health policy and programs among community medicine postgraduates: A grounded theory approach.

Introduction: Many plans and policy changes about health outcomes have evolved, but none of them have ever given a definite shape to the postgraduate (PG) curriculum so as to make it more intensive and integrative, which needs to be so structured and tailored that it is more patient, community centric, and less knowledge based. Objectives: The objective of this study was to identify the gap in existing curriculum in learning of health policy and program among PGs of community medicine and recommend a structured model for the same. Materials and Methods: A qualitative study (grounded theory approach) with all PGs of community medicine in one teaching institute in South India (8 PG students) was taken up. Results: PGs felt that they never had any day-to-day update. They wanted to understand the working pattern and ground reality of policy and program which was unavailable to them. People who came to postgraduation after being medical officers felt that the monitoring and evaluation done by inexperienced MD Community Medicine students was never accepted by state public health because they did not understand the implementation problems and so could not rightly critically evaluate the programmatic challenges. Conclusion: With the shift in medical education patterns and expectations of residents, it becomes important to justify the need of developing a structured based curriculum, more so for policy and programs, which will make them capable enough by polishing their managerial and financial skill set. The evaluation technique should focus more on practical aspects on field instead of their theory examination.

New cycloartane triterpenoids from Dysoxylum malabaricum and their cytotoxic evaluation.

The cytotoxic dichloromethane-methanol bark extract of Dysoxylum malabaricum was subjected to bioassay-guided fractionation, followed by systematic dereplication to focus on the identification of new compounds. From the bark of Dysoxylum malabaricum, two new cycloartane-type triterpenoids were isolated in addition to two previously known triterpenoids. The structures and absolute configurations of the isolated compounds were elucidated unambiguously via NMR, HRESIMS data, and electronic circular dichroism calculations. The isolated compounds were tested for their cytotoxic potential against the panel of breast, lung, and hypopharynx cancer cell lines and displayed notable cytotoxicity against breast cancer cell lines. Compound 3 exhibited the most potent cytotoxic effect with an IC50 14 µM against MCF-7 cell lines and induced cell cycle arrest. Through western blot and cell cycle analysis, it was revealed that compound 3 halts the G0/G1 phase of the cell cycle by inhibiting CDC20 and CDC25 enzymes.

Evaluation of Serum Testosterone Levels Following Three Months of SA3X (Spilanthes acmella) Supplementation.

INTRODUCTION:  Low testosterone is usually associated with erectile dysfunction (ED). SA3X (Spilanthes acmella) has proven to be effective in alleviating symptoms of ED, which could be due to an alteration in serum testosterone levels. This study was carried out to evaluate the change in testosterone levels in participants with ED supplemented with SA3X for three months. MATERIALS AND METHODS:  A group of 326 sexually active men aged 25-60 years was investigated from November 2021 to May 2022 in Hyderabad. The participants were subjected to supplementation with SA3X capsules for three months, and a follow-up was done at the end of six months with serum testosterone assessment in each visit. The change in testosterone level was assessed using a mixed model repeated measures analysis. RESULTS:  A significant increase was observed in the mean serum testosterone levels by the end of the second month (323.91 ± 13.76 ng/dL vs. 309.84 ± 14.11 ng/dL; p=0.03) and third month (332.27 ± 12.85 ng/dL vs. 309.84 ± 14.11 ng/dL; p<0.01) of SA3X therapy. The adjusted mean change in testosterone levels was found to be 22.43 ng/dL at the end of the three-month therapy. It was also observed that the change in testosterone levels was significantly lower in participants having diabetes mellitus, hypercholesterolemia, and a history of substance abuse. However, participants on phosphodiesterase-5 inhibitors had an increased change in testosterone levels. CONCLUSION:  Supplementation with SA3X capsules for three months increases the serum testosterone levels. However, causality cannot be ascertained owing to the longitudinal nature of the study, and further controlled trials are required for the same.

Randomized, Triple-Blinded, Placebo-Controlled Trial of SA3X (Spilanthes acmella) for the Management of Erectile Dysfunction.

Introduction Spilanthes acmella has been used as an aphrodisiac in India and other countries. However, studies concerning humans have been limited. This randomized controlled trial was carried out to evaluate the effect of SA3X capsules containing 500 mg of S. acmella on sexual function domain scores in sexually active men with symptoms of erectile dysfunction (ED) using the Men's Sexual Health Questionnaire (MSHQ). Materials and methods This triple-blind, placebo-controlled, parallel-group was conducted at two centres in Hyderabad and Secunderabad from May to December 2021. Patients were randomized 1:1 to SA3X therapy or placebo for one month along with an observational cohort. The change of MSHQ score and its subdomains from baseline to month 1 (primary endpoint) and one-month post-treatment (secondary outcome) was assessed using a mixed model repeated measures analysis. Additional secondary outcomes measured were the change in the International Index of Erectile Function (IIEF) and duration of penile erection. Safety was evaluated. Results The intention-to-treat population included 448 patients (152 - SA3X therapy; 146 - placebo; 150 - observational cohort). A significant increase was observed with SA3X therapy versus placebo on the total MSHQ score (17.24 vs 4.72; SE: 2.11, 1.98; P<0.001) along with the sub-domains at the end of one month of therapy. At one-month post-treatment, the increase in MSHQ score with SA3X therapy was significant (18.48 vs 3.78; SE 2.81, 1.39; P<0.001). The IIEF scores and duration of penile erection also increased significantly in the SA3X therapy group. Dysgeusia (3.94%) was the most common drug-related adverse effect. No serious adverse effects were noted. Conclusion SA3X was concluded to be safe and effective as a potential treatment for ED.

Effect of SA3X (Spilanthes acmella) Supplementation on Serum Testosterone Levels in Males with Erectile Dysfunction - A Parallel Double-Blind Randomized Controlled Trial.

Objectives:To determine whether SA3X (Spilanthes acmella) supplementation improves serum testosterone levels, in comparison with placebo, in participants with erectile dysfunction (ED) and low testosterone levels. Material and methods:This double-blind placebo-controlled parallel-group was conducted in Hyderabad, India, among male participants who were randomized to SA3X therapy or placebo (1:1) for three months. The change of serum testosterone levels from baseline to months 1, 2, 3 and 6 (three months after completion of the intervention) were assessed using a mixed model repeated measures analysis. Additional secondary outcomes were the change in the Male Sexual Health Questionnaire (MSHQ), International Index of Erectile Function (IIEF) and the duration of penile erection. Stratifying the effect of SA3X on testosterone levels was done to account for potential confounders and effect modifiers. Safety was evaluated. Results:The intention-to-treat population included 215 patients (105 - SA3X therapy; 110 - placebo). SA3X intervention increased the testosterone levels significantly (21.85 vs. 1.89 ng/dL; P<0.001) at the end of month 3. The elevated testosterone levels were maintained at month 6 (18.69 vs. 1.79; P<0.001) even after discontinuation of the intervention. The MSHQ scores, IIEF scores, and duration of penile erection also increased significantly in the SA3X group. Sensitivity analysis showed that the effect of SA3X on testosterone significantly differed by BMI, presence of comorbid conditions and intake of phosphodiesterase-5 inhibitors. Dysgeusia (7.61%) was the significant drug-related adverse effect. Conclusion:Supplementation with SA3X for people with ED and low testosterone is a safe option as it significantly increases testosterone levels along with erectile function.

Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barré syndrome.

Reports of Guillain-Barré syndrome (GBS) have emerged during the Coronavirus disease 2019 (COVID-19) pandemic. This epidemiological and cohort study sought to investigate any causative association between COVID-19 infection and GBS. The epidemiology of GBS cases reported to the UK National Immunoglobulin Database was studied from 2016 to 2019 and compared to cases reported during the COVID-19 pandemic. Data were stratified by hospital trust and region, with numbers of reported cases per month. UK population data for COVID-19 infection were collated from UK public health bodies. In parallel, but separately, members of the British Peripheral Nerve Society prospectively reported incident cases of GBS during the pandemic at their hospitals to a central register. The clinical features, investigation findings and outcomes of COVID-19 (definite or probable) and non-COVID-19 associated GBS cases in this cohort were compared. The incidence of GBS treated in UK hospitals from 2016 to 2019 was 1.65-1.88 per 100 000 individuals per year. GBS incidence fell between March and May 2020 compared to the same months of 2016-19. GBS and COVID-19 incidences during the pandemic also varied between regions and did not correlate with one another (r = 0.06, 95% confidence interval: -0.56 to 0.63, P = 0.86). In the independent cohort study, 47 GBS cases were reported (COVID-19 status: 13 definite, 12 probable, 22 non-COVID-19). There were no significant differences in the pattern of weakness, time to nadir, neurophysiology, CSF findings or outcome between these groups. Intubation was more frequent in the COVID-19 affected cohort (7/13, 54% versus 5/22, 23% in COVID-19-negative) attributed to COVID-19 pulmonary involvement. Although it is not possible to entirely rule out the possibility of a link, this study finds no epidemiological or phenotypic clues of SARS-CoV-2 being causative of GBS. GBS incidence has fallen during the pandemic, which may be the influence of lockdown measures reducing transmission of GBS inducing pathogens such as Campylobacter jejuni and respiratory viruses.

Evaluation of effects of Spilanthes acmella extract on muscle mass and sexual potency in males: A population-based study.

INTRODUCTION: Spilanthol, an active metabolite of the herb Spilanthes acmella, has many biological and pharmacological effects with limited studies on humans. OBJECTIVES: To determine the extent of increase/decrease in muscle mass and sexual frequency over a period of 3 weeks and 2 months in participants consuming SA3X capsules (containing 500 mg of Spilanthes acmella extract, standardized to 3.5% spilanthol delivering 17.5 mg spilanthol). MATERIALS AND METHODS: The study is longitudinal in nature and is conducted among 240 male participants consuming SA3X capsules at three points - first at recruitment, second at the end of 3 weeks, and lastly at the end of 2 months in Hyderabad and Secunderabad who were assessed for muscle gain by measuring mid upper-arm circumference (MUAC), chest circumference (CC), thigh circumference (TC), and for sexual activity by a change in frequency of sexual activity and duration of penile erection. The nutrient intake was assessed by 24-h dietary recall method at each visit along with the daily activity. RESULTS: A significant increase in the MUAC, (P = 0.050), frequency of sexual intercourse (P = 0.028), and duration of penile erection (P = 0.032) were observed at the end of 3 weeks; however, no changes were observed in CC and TC. At the end of 2 months, a significant increase in the parameters MUAC (P = 0.031), frequency of sexual intercourse (P < 0.001), duration of penile erection (P = 0.029) along with significant increase in CC; (P = 0.048) and TC; (P = 0.036) was observed. CONCLUSION: The study reflects the herb Spilanthes acmella to be a potent muscle gainer and aphrodisiac. However, further studies on humans need to be carried out to establish the temporality of the association of spilanthol with its claimed benefits.

Association between mid-upper arm circumference and body mass index in pregnant women to assess their nutritional status.

BACKGROUND: Underweight/ Undernourished is a state when the body mass index (BMI) falls below 18.5 kg/m2 and as per National Family and Health Survey-4, 22.9% of women in the reproductive age group fall into this category. Despite being considered as an important anthropometry marker, it is not measured in most of the healthcare facilities across India due to lack of basic amenities and resources. In such instances, how helpful other indicators like mid-upper arm circumference (MUAC) can be to measure the undernourished status of pregnant needs to be determined. OBJECTIVES: To estimate the prevalence of undernutrition in pregnant women (PW) based on baseline BMI and MUAC and to determine the association between them. MATERIALS AND METHODS: A cross-sectional study was conducted in Tangi Block of Odisha among 440 PW (in the first trimester) from July 2018 to November 2018 using a pre-tested, validated questionnaire and anthropometric instruments. RESULTS: PW having BMI <18.5 kg/m2 were found to be 16.6% and having MUAC <23.5 cm were 19.5%. A significant association was found between BMI and MUAC [aOR 7.91 (4.27-14.65)]. Also, a moderate correlation was established between the indicators (r = 0.57). CONCLUSION: MUAC can be used instead of BMI as it is easier to measure, cheaper, does not require any training or calculations, and insensitive to changes during the period of gestation unlike BMI. This can be beneficial to the healthcare workers at primary level who are in resource-limited settings.

Maternal Nutrition and Inadequate Gestational Weight Gain in Relation to Birth Weight: Results from a Prospective Cohort Study in India.

Inadequate/excessive gestational weight gain (GWG) can cause adverse pregnancy outcomes and only few studies have described patterns of weight gain in Indian women. Also, studies pertaining to dietary intake throughout gestation are insufficient. This prospective cohort study was conducted to evaluate GWG and nutrient intake in all trimesters of pregnancy and investigate the relationship between themselves along with that of birth weight (BW). Our study was carried out in a population-based prospective birth cohort in Odisha, India. The 418 pregnant women were followed till delivery with measurements of maternal weight, weight gain throughout gestation, and BW. Macronutrients were assessed based on a 24-hour dietary recall method in each trimester. Women characterized by under-weight pre-pregnancy body mass index (BMI) were 16.20%, and a total of 6.45% did not comply with current weight gain recommendations. Particularly, overweight and obese women gained more weight than recommended. In a multivariate analysis GWG correlated significantly with BMI (p = 0.03), total calorie intake (p < 0.001) and fat intake (p < 0.001), while BW of newborns correlated significantly with adequacy of weight gain and fat intake (p < 0.001). Though measures are taken by health workers to record the weight but nutritional counseling is not being provided regularly. A high priority should be given to increase awareness among general population regarding the importance of diet in pregnancy and how to adhere to the balanced diet for optimal growth of child.

The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings.

Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

Enhanced apoptotic effect of curcumin loaded solid lipid nanoparticles.

Curcumin is reported to show potent in vitro anticancer effects in a surfeit of human cancer cell lines and majorly in the carcinogenesis of GIT, in animals. Its poor pharmacokinetics and stability limit its vivo clinical efficacy for the other systemic cancers. We recently reported on a 32-155 times enhancement in bioavailability of curcumin when incorporated into solid lipid nanoparticles (C-SLNs). Presently we report on a 54-85% reduction in IC 50 values with developed C-SLNs in comparison to free curcumin against a panel of human cancer cell lines (HL-60, A549, and PC3). Results demonstrate mechanisms similar to those claimed for free curcumin, including induction of cellular apoptosis by activation of caspases, release of cyctochrome c, loss of membrane potential, blockade of nuclear factor kappa B (NF-κB) activation, and upregulation of TNF-R for C-SLNs. However, the extent of cell death provided by C-SLNs in all these tests was significantly higher (p < 0.001). This may be attributed to the presentation of curcumin in a dispersible/soluble form which enhanced permeability across the cell surface. The display of significantly better in vitro anticancer effect coupled with high in vivo bioavailability points toward a great potential of using C-SLNs for cancer therapeutics.