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Fulltext Supplementing hand washing with proper use of alcoholic hand rub in a special neonatal care unit in a large academic public health institute at Jabalpur, Madhya Pradesh, India

Singh M, Agrawal A, Sisodia D, Kasar PK, Kaur A, Datta V, et al.

BMJ Open Qual, 2021 11;10(4).
PMID: 34759034 DOI: 10.1136/bmjoq-2020-001131

OBJECTIVE: The purpose was to increase use of alcoholic hand rub (AHR) in specialised newborn care unit (SNCU) to improve hand hygiene in order to reduce neonatal sepsis and mortality at Netaji Subhash Chandra Bose Medical College and Hospital, Jabalpur.
DESIGN: A prospective interventional and observational study.
METHODOLOGY: We formed a quality improvement (QI) team in our SNCU consisting of doctors, nurses, auxiliary staff and parents (a floating member) to improve proper use of AHR. To identify the barriers to the problem, we used fishbone analysis tool. The barriers which were not allowing the health providers to use AHR properly identified were amount of AHR in millilitres to be used per day per baby, how much and when the amount of AHR to be indented from the main store and what is the proper site to place the bottle. We used plan-do-study-act cycles to test and adapt solutions to these problems. Within 5-6 weeks of starting our project, AHR use increased from 44 mL to 92 mL per baby per day and this is sustained around 100 mL per baby per day for over 2 years now.
RESULTS: Significant decrease in neonatal mortality was observed (reduced from median of 41.0 between August 2016 and April 2018 to 24.0 between May 2018 and December 2019). The neonates discharged alive improved from 41.2 to 52.3 as a median percentage value. The percentage of babies who were referred out and went Left Against Medical Advice (LAMA) deceased too.
CONCLUSION: Multiple factors can lead to neonatal deaths, but the important factors are always contextual to facilities. QI methodology provides health workers with the skills to identify the major factors contributing to mortality and develop strategies to deal with them. Improving processes of care can lead to improved hand hygiene and saves lives.
Fulltext Implications of Down's syndrome on oral health status in patients: A prevalence-based study

Goud EVSS, Gulati S, Agrawal A, Pani P, Nishant K, Pattnaik SJ, et al.

J Family Med Prim Care, 2021 Nov;10(11):4247-4252.
PMID: 35136797 DOI: 10.4103/jfmpc.jfmpc_885_21

BACKGROUND: Down syndrome which is also known as "trisomy 21" is the commonest chromosomal defect that has been associated with intellectual disability or impairment. Clinically, it has been characterized by the generalized presence of hypotonic musculature, variety of neurobiological alterations, numerous respiratory diseases, and significantly higher risk of developing infection along with various dental abnormalities and oro-facial dysmorphological changes. Periodontal diseases are the most prominent oral health issue among individuals diagnosed with Down Syndrome.
AIM: The objective of the present prevalence analysis was to study the implications of Down's syndrome on oral health status among patients.
MATERIALS AND METHODS: This was a descriptive and cross-sectional prevalence analysis conducted within a duration of 1 year. A total of 100 children diagnosed with Down syndrome (aged between 5 and 16 years) were selected as the study sample. Inclusion criteria were (a) cytogenetic positive trisomy 21, (b) cooperative behavior, and (c) written informed consent obtained from the legal care-takers. Exclusion criteria were (a) any debilitating form of systemic diseases, (b) any other disability, and (c) extremely uncooperative children. The gingival health status was assessed using gingival index (GI) [Loe and Silness], calculus index (CI) [Ramfjord], and plaque index (PI) [Silness and Loe]. Information involving the practice of oral hygiene maintenance, diet plans, and parental educational status was derived from each parent. Based upon their intelligence quotient (I. Q.) values, the subjects were classified into three groups: a) mild (I. Q. level = 50 to 70), b) moderate (I. Q. level = 35 to 50), and c) severe (I. Q. level ≤35). Statistical analysis was performed using the statistical software tool Statistical Package for Social Sciences (SPSS) version 20.0. Qualitative data were recorded as frequencies, and percentages and quantitative data were recorded as mean and standard deviation values. All categorical outcomes were analyzed by means of the Chi-square test. The quantitative outcomes of Calculus Index, Gingival Index, and Plaque Index were analyzed by either student's t-test or one-way analysis of variance (ANOVA). Significance was set at a cut-off value of P < 0.05.
RESULTS: Down syndromic children between 12 and 16 years were reported to have statistically significant higher Calculus Index, Gingival Index, and Plaque Index values in comparison with younger age syndromic children (P < 0.01). Those with severe mental retardation had significantly higher Plaque Index (P < 0.001) and Gingival Index (P < 0.04) values when compared with those with mild and moderate mental retardation. No significant difference in comparing Calculus Index was noted.
CONCLUSION: Higher age group children with Down syndrome require close monitoring by parents for assisting in maintaining oral hygiene practices just as in younger age group children.
Embracing robotic surgery in low- and middle-income countries: Potential benefits, challenges, and scope in the future

Mehta A, Cheng Ng J, Andrew Awuah W, Huang H, Kalmanovich J, Agrawal A, et al.

Ann Med Surg (Lond), 2022 Dec;84:104803.
PMID: 36582867 DOI: 10.1016/j.amsu.2022.104803

Robotic surgery has applications in many medical specialties, including urology, general surgery, and surgical oncology. In the context of a widespread resource and personnel shortage in Low- and Middle-Income Countries (LMICs), the use of robotics in surgery may help to reduce physician burnout, surgical site infections, and hospital stays. However, a lack of haptic feedback and potential socioeconomic factors such as high implementation costs and a lack of trained personnel may limit its accessibility and application. Specific improvements focused on improved financial and technical support to LMICs can help improve access and have the potential to transform the surgical experience for both surgeons and patients in LMICs. This review focuses on the evolution of robotic surgery, with an emphasis on challenges and recommendations to facilitate wider implementation and improved patient outcomes.
Fulltext Engineering a stable CHO cell line for the expression of a MERS-coronavirus vaccine antigen

Nyon MP, Du L, Tseng CK, Seid CA, Pollet J, Naceanceno KS, et al.

Vaccine, 2018 03 27;36(14):1853-1862.
PMID: 29496347 DOI: 10.1016/j.vaccine.2018.02.065

Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 2040 patients and caused 712 deaths since its first appearance in 2012, yet neither pathogen-specific therapeutics nor approved vaccines are available. To address this need, we are developing a subunit recombinant protein vaccine comprising residues 377-588 of the MERS-CoV spike protein receptor-binding domain (RBD), which, when formulated with the AddaVax adjuvant, it induces a significant neutralizing antibody response and protection against MERS-CoV challenge in vaccinated animals. To prepare for the manufacture and first-in-human testing of the vaccine, we have developed a process to stably produce the recombinant MERS S377-588 protein in Chinese hamster ovary (CHO) cells. To accomplish this, we transfected an adherent dihydrofolate reductase-deficient CHO cell line (adCHO) with a plasmid encoding S377-588 fused with the human IgG Fc fragment (S377-588-Fc). We then demonstrated the interleukin-2 signal peptide-directed secretion of the recombinant protein into extracellular milieu. Using a gradually increasing methotrexate (MTX) concentration to 5 μM, we increased protein yield by a factor of 40. The adCHO-expressed S377-588-Fc recombinant protein demonstrated functionality and binding specificity identical to those of the protein from transiently transfected HEK293T cells. In addition, hCD26/dipeptidyl peptidase-4 (DPP4) transgenic mice vaccinated with AddaVax-adjuvanted S377-588-Fc could produce neutralizing antibodies against MERS-CoV and survived for at least 21 days after challenge with live MERS-CoV with no evidence of immunological toxicity or eosinophilic immune enhancement. To prepare for large scale-manufacture of the vaccine antigen, we have further developed a high-yield monoclonal suspension CHO cell line.
Fulltext Reactive oxygen species mediated apoptotic death of colon cancer cells: therapeutic potential of plant derived alkaloids

Nelson VK, Nuli MV, Mastanaiah J, Saleem T S M, Birudala G, Jamous YF, et al.

Front Endocrinol (Lausanne), 2023;14:1201198.
PMID: 37560308 DOI: 10.3389/fendo.2023.1201198

Colorectal cancer (CRC) is one of the most deaths causing diseases worldwide. Several risk factors including hormones like insulin and insulin like growth factors (e.g., IGF-1) have been considered responsible for growth and progression of colon cancer. Though there is a huge advancement in the available screening as well as treatment techniques for CRC. There is no significant decrease in the mortality of cancer patients. Moreover, the current treatment approaches for CRC are associated with serious challenges like drug resistance and cancer re-growth. Given the severity of the disease, there is an urgent need for novel therapeutic agents with ideal characteristics. Several pieces of evidence suggested that natural products, specifically medicinal plants, and derived phytochemicals may serve as potential sources for novel drug discovery for various diseases including cancer. On the other hand, cancer cells like colon cancer require a high basal level of reactive oxygen species (ROS) to maintain its own cellular functions. However, excess production of intracellular ROS leads to cancer cell death via disturbing cellular redox homeostasis. Therefore, medicinal plants and derived phytocompounds that can enhance the intracellular ROS and induce apoptotic cell death in cancer cells via modulating various molecular targets including IGF-1 could be potential therapeutic agents. Alkaloids form a major class of such phytoconstituents that can play a key role in cancer prevention. Moreover, several preclinical and clinical studies have also evidenced that these compounds show potent anti-colon cancer effects and exhibit negligible toxicity towards the normal cells. Hence, the present evidence-based study aimed to provide an update on various alkaloids that have been reported to induce ROS-mediated apoptosis in colon cancer cells via targeting various cellular components including hormones and growth factors, which play a role in metastasis, angiogenesis, proliferation, and invasion. This study also provides an individual account on each such alkaloid that underwent clinical trials either alone or in combination with other clinical drugs. In addition, various classes of phytochemicals that induce ROS-mediated cell death in different kinds of cancers including colon cancer are discussed.
2021 Asia-Pacific Graves' Disease Consortium Survey of Clinical Practice Patterns in the Management of Graves' Disease

Parameswaran R, de Jong MC, Kit JLW, Sek K, Nam TQ, Thang TV, et al.

Endocrine, 2023 Jan;79(1):135-142.
PMID: 36129592 DOI: 10.1007/s12020-022-03193-7

AIM: Although Graves' disease (GD) is common in endocrine practices worldwide, global differences in diagnosis and management remain. We sought to assess the current practices for GD in countries across Asia and the Pacific (APAC), and to compare these with previously published surveys from North America and Europe.
METHODS: A web-based survey on GD management was conducted on practicing clinicians. Responses from 542 clinicians were received and subsequently analysed and compared to outcomes from similar surveys from other regions.
RESULTS: A total of 542 respondents participated in the survey, 515 (95%) of whom completed all sections. Of these, 86% were medical specialists, 11% surgeons, and 3% nuclear medicine physicians. In addition to serum thyroid-stimulating hormone (TSH) and free thyroxine assays, most respondents would request TSH-receptor autoantibody (TRAb) measurement (68%) during initial work-up. Thyroid ultrasound is requested by about half of respondents (53%), while the use of nuclear medicine scans is limited. The preferred first-line treatment is anti-thyroid drug (ATD) therapy (79%) with methimazole (MMI) or carbimazole (CBZ), followed by radioiodine (RAI; 19%) and surgery (2%). In case of surgery, one-third of respondents would opt for a subtotal rather than a total thyroidectomy. In case of mild Graves orbitopathy (GO), ATDs (67%) remains the preferred treatment, but a larger proportion of clinicians prefer surgery (20%). For a patient with intention to conceive, the preferred treatment pattern remained unchanged, although propylthiouracil (PTU) became the preferred ATD-agent during the first trimester. In comparison to European and American practices, marked differences were noted in the relatively infrequent usage of nuclear medicine scans and the overall higher use of a ATDs and β-blockers and adjunctive ATD-treatment during RAI in the APAC-group.
CONCLUSION: Although regional differences regarding the diagnosis and management of GD are apparent in this first pan-Asia-Pacific survey, this study reveals the overall approach to the management of this disease in Asia-Pacific generally tends to fall between the trends appreciated in the American and European cohorts.
Fulltext Integrated genomic view of SARS-CoV-2 in India

Kumar P, Pandey R, Sharma P, Dhar MS, A V, Uppili B, et al.

Wellcome Open Res, 2020;5:184.
PMID: 32995557 DOI: 10.12688/wellcomeopenres.16119.1

Background: India first detected SARS-CoV-2, causal agent of COVID-19 in late January 2020, imported from Wuhan, China. From March 2020 onwards, the importation of cases from countries in the rest of the world followed by seeding of local transmission triggered further outbreaks in India. Methods: We used ARTIC protocol-based tiling amplicon sequencing of SARS-CoV-2 (n=104) from different states of India using a combination of MinION and MinIT sequencing from Oxford Nanopore Technology to understand how introduction and local transmission occurred. Results: The analyses revealed multiple introductions of SARS-CoV-2 genomes, including the A2a cluster from Europe and the USA, A3 cluster from Middle East and A4 cluster (haplotype redefined) from Southeast Asia (Indonesia, Thailand and Malaysia) and Central Asia (Kyrgyzstan). The local transmission and persistence of genomes A4, A2a and A3 was also observed in the studied locations. The most prevalent genomes with patterns of variance (confined in a cluster) remain unclassified, and are here proposed as A4-clade based on its divergence within the A cluster. Conclusions: The viral haplotypes may link their persistence to geo-climatic conditions and host response. Multipronged strategies including molecular surveillance based on real-time viral genomic data is of paramount importance for a timely management of the pandemic.