FABRICATION OF NANO CLAY INTERCALATED POLYMERIC MICROBEADS FOR CONTROLLED RELEASE OF CURCUMIN

Objective: The objective of this study was to formulate and evaluate the Curcumin (CUR) encapsulated sodium alginate (SA)/badam gum (BG)/kaolin (KA) microbeads for controlled drug release studies. Methods: The fabricated microbeads were characterized by fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (X-RD), and scanning electron microscopy (SEM). Dynamic swelling studies and in vitro release kinetics were performed in simulated intestinal fluid (pH 7.4) and simulated gastric fluid (pH 1.2) at 37 °C. Results: FTIR confirms the formation of microbeads. DSC studies confirm the polymorphism of CUR in drug loaded microbeads which indicate the molecular level dispersion of the drug in the microbeads. SEM studies confirmed the microbeads are spherical in shape with wrinkled and rough surfaces. XRD studies reveal the molecular dispersion of CUR and the presence of KA in the developed microbeads. In vitro release studies and swelling studies depend on the pH of test media, which might be suitable for intestinal drug delivery. The % of drug release values fit into the Korsmeyer-Peppas equation and n values are obtained in the range of 0.577-0.664, which indicates that the developed microbeads follow the non-Fickian diffusion drug release mechanism. Conclusion: The results concluded that the CUR encapsulated microbeads are potentially good carriers for controlled drug release studies

REVIEW ON FORMULATION AND EVALUATION OF SOLID LIPID NANOPARTICLES FOR VAGINAL APPLICATION

Vaginal drug administration can improve prophylaxis and treatment of many conditions affecting the female reproductive tract, which includes fungal and bacterial infections, sexually transmitted diseases and cancer also. This is the best route for the administration of proteins, peptides, and also other therapeutic drugs like macro-molecules. For the administration of drugs like contraceptives, steroids, metronidazole, anti-retroviral, vaginal drug delivery is the most preferable route. However, achieving sufficient drug concentration in the vagina can be challenging because of its low permeability. The benefits of the vaginal drug delivery system are it increases the bioavailability, least systemic side effects; easiness of use and self-medication is possible. However vaginal drug delivery system is considered as a less effective route because of the unfortunate absorption of drugs across the vaginal epithelium. The traditional commercial preparations, such as creams, foams, gels, irrigations and tablets, are known to reside in the vaginal cavity for a relatively short period of time owing to the self-cleaning action of the vaginal tract and often require multiple daily doses to ensure the desired therapeutic effect. With the rapidly developing field of nanotechnology, the use of specifically designed carrier systems such as Nanoparticle-based drug delivery has been proven an excellent choice for vaginal application to overcome the challenges associated with the low permeability

Well-Being Programme for Caregivers of Persons with Spinal Cord Injury

Background: SCI is a high-cost chronic disability, and it is a life-changing experience for family members and societies. For families, the unpredictable nature of the injury leads some of the members into an 'unexpected career' as family caregivers, the caregiver’s have to put enormous efforts, to provide continuous full-time caregiving for the recovery of Person with Spinal cord injury, which will affect the caregiver's physical and mental health. The current study aims to develop and test the feasibility of a well-being programme for caregivers of persons with spinal cord injury.            Methods/Design: The current study adopts a Quasi-experimental study design, which have three phases; the first phase is to explore the needs of the caregivers by conducting in-depth interviews with different stakeholders. The second phase is to develop a well-being programme, and checking the feasibility of the programme is the third phase by recruiting 24 caregivers. Qualitative data will be analyzed using thematic analysis, whereas quantitative data will be analyzed using appropriate parametric or non- parametric tests upon confirming normality of data distribution. Discussion: This study would help us to understand the psycho-social issues and unique needs of the caregivers at different time periods. It also gives information about psycho-social interventions and outcome measures for the well-being of the caregivers

Cerebellar Morphology and Behavioral Profiles in Mice Lacking Heparan Sulfate Ndst Gene Function

Disruption of the Heparan sulfate (HS)-biosynthetic gene N-acetylglucosamine N-Deacetylase/N-sulfotransferase 1 (Ndst1) during nervous system development causes malformations that are composites of those caused by mutations of multiple HS binding growth factors and morphogens. However, the role of Ndst function in adult brain physiology is less explored. Therefore, we generated mice bearing a Purkinje-cell-specific deletion in Ndst1 gene function by using Cre/loxP technology under the control of the Purkinje cell protein 2 (Pcp2/L7) promotor, which results in HS undersulfation. We observed that mutant mice did not show overt changes in the density or organization of Purkinje cells in the adult cerebellum, and behavioral tests also demonstrated normal cerebellar function. This suggested that postnatal Purkinje cell development and homeostasis are independent of Ndst1 function, or that impaired HS sulfation upon deletion of Ndst1 function may be compensated for by other Purkinje cell-expressed Ndst isoforms. To test the latter possibility, we additionally deleted the second Purkinje-cell expressed Ndst family member, Ndst2. This selectively abolished reproductive capacity of compound mutant female, but not male, mice, suggesting that ovulation, gestation, or female reproductive behavior specifically depends on Ndst-dependent HS sulfation in cells types that express Cre under Pcp2/L7 promotor control

Diagnosis of Chikungunya Virus in Febrile Patients From a Malaria Holoendemic Area

Introduction: Accurate diagnosis of chikungunya (CHIK) is essential for effective disease management and surveillance. In a cohort of febrile Congolese patients, available diagnostic methods widely used in CHIK diagnosis were evaluated. In addition, plasma cytokines were quantified in CHIK patients and those coinfected with malaria compared with healthy controls. Methods: Between June and November 2019, a total of 107 febrile patients with suspected CHIK were subjected to differential diagnosis both for CHIK and malaria. Patients were screened for CHIK virus using molecular diagnosis by real-time PCR, serologic testing by IgM-specific and IgG-specific ELISAs, and lateral flow-based method with rapid diagnostic test (RDT), while malaria diagnosis was confirmed by PCR methods. Pro-inflammatory (IL-12, IL-16, IFN-γ, TNF-α) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines were quantified in patients and healthy controls by ELISA assays. Results: Molecular diagnoses revealed that 57% (61/107) were positive for CHIK by RT-PCR, while serologic testing revealed 31% (33/107) and 9% (10/107) seropositivity for anti- IgM and IgG, respectively. None of the patients were CHIK RDT-positive. Also, 27% (29/107) were PCR-positive for malaria. Among the malaria-positive patients, 14% (15/107) were co-infected with CHIK and 13% (14/107) were monoinfection. Plasma IL-12 and TNF-α levels were increased in patients with malaria and IL-13 levels were increased in patients with co-infection (p<0.05). Conclusion: Co-infection of malaria and CHIK were common in febrile Congolese patients. Real-time PCR was a better tool for detecting actual occurrences of CHIK in a malaria holoendemic area

Heparan sulfate expression in the neural crest is essential for mouse cardiogenesis

Impaired heparan sulfate (HS) synthesis in vertebrate development causes complex malformations due to the functional disruption of multiple HS-binding growth factors and morphogens. Here, we report developmental heart defects in mice bearing a targeted disruption of the HS-generating enzyme GlcNAc N-deacetylase/GlcN N-sulfotransferase 1 (NDST1), including ventricular septal defects (VSD), persistent truncus arteriosus (PTA), double outlet right ventricle (DORV), and retroesophageal right subclavian artery (RERSC). These defects closely resemble cardiac anomalies observed in mice made deficient in the cardiogenic regulator fibroblast growth factor 8 (FGF8). Consistent with this, we show that HS-dependent FGF8/FGF-receptor2C assembly and FGF8-dependent ERK-phosphorylation are strongly reduced in NDST1(-/-) embryonic cells and tissues. Moreover, WNT1-Cre/LoxP-mediated conditional targeting of NDST function in neural crest cells (NCCs) revealed that their impaired HS-dependent development contributes strongly to the observed cardiac defects. These findings raise the possibility that defects in HS biosynthesis may contribute to congenital heart defects in humans that represent the most common type of birth defect

Host genetic factors determining COVID-19 susceptibility and severity.

The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) poses an unprecedented challenge to humanity. SARS-CoV-2 infections range from asymptomatic to severe courses of COVID-19 with acute respiratory distress syndrome (ARDS), multiorgan involvement and death. Risk factors for disease severity include older age, male sex, increased BMI and pre-existing comorbidities. Ethnicity is also relevant to COVID-19 susceptibility and severity. Host genetic predisposition to COVID-19 is now increasingly recognized and whole genome and candidate gene association studies regarding COVID-19 susceptibility have been performed. Several common and rare variants in genes related to inflammation or immune responses have been identified. We summarize research on COVID-19 host genetics and compile genetic variants associated with susceptibility to COVID-19 and disease severity. We discuss candidate genes that should be investigated further to understand such associations and provide insights relevant to pathogenesis, risk classification, therapy response, precision medicine, and drug repurposing

Antimicrobial resistance preparedness in sub-Saharan African countries

Background: Antimicrobial resistance (AMR) is of growing concern globally and AMR status in sub-Saharan Africa (SSA) is undefined due to a lack of real-time data recording, surveillance and regulation. World Health Organization (WHO) Joint External Evaluation (JEE) reports are voluntary, collaborative processes to assess country capacities and preparedness to prevent, detect and rapidly respond to public health risks, including AMR. The data from SSA JEE reports were analysed to gain an overview of how SSA is working towards AMR preparedness and where strengths and weaknesses lie. Methods: SSA country JEE AMR preparedness scores were analysed. A cumulative mean of all the SSA country AMR preparedness scores was calculated and compared to the overall mean SSA JEE score. AMR preparedness indicators were analysed, and data were weighted by region. Findings: The mean SSA AMR preparedness score was 53% less than the overall mean SSA JEE score. East Africa had the highest percentage of countries reporting having AMR National Action Plans in place, as well as human and animal pathogen AMR surveillance programmes. Southern Africa reported the highest percentage of countries with training programmes and antimicrobial stewardship. Conclusions: The low mean AMR preparedness score compared to overall JEE score, along with the majority of countries lacking implemented National Action Plans, suggests that until now AMR has not been a priority for most SSA countries. By identifying regional and One Health strengths, AMR preparedness can be fortified across SSA with a multisectoral approach

Diagnosis of Chikungunya Virus in Febrile Patients From a Malaria Holoendemic Area

Accurate diagnosis of chikungunya (CHIK) is essential for effective disease management and surveillance. In a cohort of febrile Congolese patients, available diagnostic methods widely used in CHIK diagnosis were evaluated. In addition, plasma cytokines were quantified in CHIK patients and those coinfected with malaria compared with healthy controls

What do family physicians consider an error? A comparison of definitions and physician perception

BACKGROUND: Physicians are being asked to report errors from primary care, but little is known about how they apply the term "error." This study qualitatively assesses the relationship between the variety of error definitions found in the medical literature and physicians' assessments of whether an error occurred in a series of clinical scenarios. METHODS: A systematic literature review and pilot survey results were analyzed qualitatively to search for insights into what may affect the use of the term error. The National Library of Medicine was systematically searched for medical error definitions. Survey participants were a random sample of active members of the American Academy of Family Physicians (AAFP) and a selected sample of family physician patient safety "experts." A survey consisting of 5 clinical scenarios with problems (wrong test performed, abnormal result not followed-up, abnormal result overlooked, blood tube broken and missing scan results) was sent by mail to AAFP members and by e-mail to the experts. Physicians were asked to judge if an error occurred. A qualitative analysis was performed via "immersion and crystallization" of emergent insights from the collected data. RESULTS: While one definition, that originated by James Reason, predominated the literature search, we found 25 different definitions for error in the medical literature. Surveys were returned by 28.5% of 1000 AAFP members and 92% of 25 experts. Of the 5 scenarios, 100% felt overlooking an abnormal result was an error. For other scenarios there was less agreement (experts and AAFP members, respectively agreeing an error occurred): 100 and 87% when the wrong test was performed, 96 and 87% when an abnormal test was not followed up, 74 and 62% when scan results were not available during a patient visit, and 57 and 47% when a blood tube was broken. Through qualitative analysis, we found that three areas may affect how physicians make decisions about error: the process that occurred vs. the outcome that occurred, rare vs. common occurrences and system vs. individual responsibility CONCLUSION: There is a lack of consensus about what constitutes an error both in the medical literature and in decision making by family physicians. These potential areas of confusion need further study