Mechanisms of microbial resistance against cadmium - a review.

The escalating cadmium influx from industrial activities and anthropogenic sources has raised serious environmental concerns due to its toxic effects on ecosystems and human health. This review delves into the intricate mechanisms underlying microbial resistance to cadmium, shedding light on the multifaceted interplay between microorganisms and this hazardous heavy metal. Cadmium overexposure elicits severe health repercussions, including renal carcinoma, mucous membrane degradation, bone density loss, and kidney stone formation in humans. Moreover, its deleterious impact extends to animal and plant metabolism. While physico-chemical methods like reverse osmosis and ion exchange are employed to mitigate cadmium contamination, their costliness and incomplete efficacy necessitate alternative strategies. Microbes, particularly bacteria and fungi, exhibit remarkable resilience to elevated cadmium concentrations through intricate resistance mechanisms. This paper elucidates the ingenious strategies employed by these microorganisms to combat cadmium stress, encompassing metal ion sequestration, efflux pumps, and enzymatic detoxification pathways. Bioremediation emerges as a promising avenue for tackling cadmium pollution, leveraging microorganisms' ability to transform toxic cadmium forms into less hazardous derivatives. Unlike conventional methods, bioremediation offers a cost-effective, environmentally benign, and efficient approach. This review amalgamates the current understanding of microbial cadmium resistance mechanisms, highlighting their potential for sustainable remediation strategies. By unraveling the intricate interactions between microorganisms and cadmium, this study contributes to advancing our knowledge of bioremediation approaches, thereby paving the way for safer and more effective cadmium mitigation practices.

Open-heart surgery in preterm infants: A single-center experience.

Background: Open-heart surgery is challenging in preterm neonates and infants, and its feasibility in low-resource settings has not been defined. We describe our institutional experience with open-heart surgeries performed on consecutive preterm infants. Materials Methods and Results: This was a single-center retrospective cohort from a tertiary hospital in Southern India and included consecutive preterm neonates (<37 weeks) admitted for open-heart surgery. This report is limited to babies who were <3 months at the surgery. The salient features of the 15 preterm included twin gestation: 7 (46.7%); median gestational age at birth: 35 weeks (28-36 weeks); median corrected gestational age at surgery: 37 weeks (33-40 weeks); birth weight: 1.75 kg (1.0-2.6 kg); weight at surgery: 1.8 kg (1.2-2.9 kg); and small for gestational age: 12 (80%). The heart defects included transposition of the great arteries (7), total anomalous pulmonary venous return (3), large ventricular septal defect (VSD) (1), and VSD with coarctation of the aorta (4). Eleven (73%) were mechanically ventilated preoperatively and five had preoperative sepsis. The mean cardiopulmonary bypass time was 169.7 ± 61.5 min, and cross-clamp time was 99.7 ± 43.8 min. There was no inhospital mortality; one baby expired during follow-up at 1 month. Postoperative mechanical ventilation duration was 126.50 h (84.25-231.50 h), and intensive care unit stay was 13.5 days (9-20.8). The total hospital stay was 39 days (11-95 days). Two children (13.3%) had postoperative sepsis. Conclusion: Through collaborative multidisciplinary management, excellent outcomes are feasible in low-resource environments for selected preterm neonates undergoing corrective open-heart operations.

The 'Vaidya' - The Ancient Indian Family Physician: The origin of family medicine specialty in India - a call for action by the National Medical Commission (NMC).

Family medicine is the academic discipline, knowledge domain and specialty of family physicians or family doctors globally. Family medicine is rapidly developing in India amidst resistance and criticism. Many opponents identify family medicine as a western concept and argue for its non suitability for implementation in India. Family medicine or family physician is not a new concept for the Indian people. The family doctor concept originated in India from the community-based Vaidya system - an ancient old tradition of the Indian civilisation. A 'Vaidya' typically refers to a local physician engaging with the population. The Vaidya used to provide personalised care and primary medical care to individuals and families. The Vaidya remained the 'Family Physician', and this identity and profession has an unbreeched association of more than several millennia with the Indian population. It is to be noted that all the goals of Bachelor of Medicine and Bachelor of Surgery (MBBS) training in India, the aspirations, skills and competencies for trainees, as defined by the National Medical Commission (NMC), can be identified as the academic discipline and vocation of family physicians. However, family medicine has not yet been included as a distinct and mandatory subject for MBBS students by the NMC. The demand for personalised health care within the community by the family doctors has never diminished but has only been artificially restricted. Family physicians contribute significantly to the promotion of health, prevention of diseases and the management of various health conditions in the Indian context. We look forward to the integration of family physician and family doctor concepts within the mainstream medical education system. It is expected that family medicine will become part of MBBS curriculum as promulgated in the NMC Act 2019.

Proteomic analysis of the developing mammalian brain links PCDH19 to the Wnt/ß-catenin signalling pathway.

Clustering Epilepsy (CE) is a neurological disorder caused by pathogenic variants of the Protocadherin 19 (PCDH19) gene. PCDH19 encodes a protein involved in cell adhesion and Estrogen Receptor α mediated-gene regulation. To gain further insights into the molecular role of PCDH19 in the brain, we investigated the PCDH19 interactome in the developing mouse hippocampus and cortex. Combined with a meta-analysis of all reported PCDH19 interacting proteins, our results show that PCDH19 interacts with proteins involved in actin, microtubule, and gene regulation. We report CAPZA1, αN-catenin and, importantly, ß-catenin as novel PCDH19 interacting proteins. Furthermore, we show that PCDH19 is a regulator of ß-catenin transcriptional activity, and that this pathway is disrupted in CE individuals. Overall, our results support the involvement of PCDH19 in the cytoskeletal network and point to signalling pathways where PCDH19 plays critical roles.

Early and long-term outcomes of mitral valve replacement with mechanical valve in rheumatic heart disease.

Background: Rheumatic fever and rheumatic heart disease is endemic in India. Mitral valve replacement with mechanical valve is the commonest surgical procedure performed in rheumatic heart disease (RHD). However, there are no studies reporting the long-term outcomes of mechanical mitral valve replacement in rheumatic heart disease from India. Objective: The primary objective of the study was to look at the long-term survival following mechanical mitral valve replacement in RHD. The secondary objectives included follow up complications and event-free survival. Methods: For this study, 238 patients who underwent mitral valve replacement with TTK Chitra™ valve from 1st January 2006 to 31st December 2018 for RHD were included for analysis and reporting. The median follow-up period was 3371.50 days (9.3 years). Total follow-up was 2044 patient-years. Results: The mean age of the study population was 39.72 ± 10.48 years (range: 18-68 years). Out of 238 patients operated, 155 patients (65.12%) were alive and 69 patients (28.99%) were dead, and 14 patients (5.88%) were lost to follow-up. The operative mortality was 6 (2.52%) and the follow-up mortality was 63 (26.47%). The reasons for follow-up mortality were cardiac complications in 22 (34.9%) patients, valve-related complications in 18 (28.5%) patients, sudden unexplained death in 13 (20.6%) patients, and non-valve/ non-cardiac death in 10patients (15.8%). The one-year survival was 94.0%, five-year survival was 83.6%, ten-year survival was 70.6% and 15-year survival was 62.9%. During follow-up, valve-related events occurred in 123(52%) patients. The 15-year event-free survival was 33.0%. Conclusions: The long term outcome of mechanical valve replacement of the mitral valve in RHD patients was less than favorable. Both cardiac complications and mechanical valve related complications reduced their survival.

2023 World Heart Federation guidelines for the echocardiographic diagnosis of rheumatic heart disease.

Rheumatic heart disease (RHD) is an important and preventable cause of morbidity and mortality among children and young adults in low-income and middle-income countries, as well as among certain at-risk populations living in high-income countries. The 2012 World Heart Federation echocardiographic criteria provided a standardized approach for the identification of RHD and facilitated an improvement in early case detection. The 2012 criteria were used to define disease burden in numerous epidemiological studies, but researchers and clinicians have since highlighted limitations that have prompted a revision. In this updated version of the guidelines, we incorporate evidence from a scoping review, an expert panel and end-user feedback and present an approach for active case finding for RHD, including the use of screening and confirmatory criteria. These guidelines also introduce a new stage-based classification for RHD to identify the risk of disease progression. They describe the latest evidence and recommendations on population-based echocardiographic active case finding and risk stratification. Secondary antibiotic prophylaxis, echocardiography equipment and task sharing for RHD active case finding are also discussed. These World Heart Federation 2023 guidelines provide a concise and updated resource for clinical and research applications in RHD-endemic regions.

Recent advances and mechanisms of microbial bioremediation of nickel from wastewater.

The global concern over emerging pollutants, characterized by their low concentrations and high toxicity, necessitates effective remediation strategies. Among these pollutants, pharmaceutical and personal care products, pesticides, surfactants, and persistent organic pollutants have gained significant attention. These contaminants are extensively distributed within aquatic ecosystems, posing threats to both human and aquatic physiological systems. Nickel, a valuable metal renowned for its corrosion-resistant properties, is widely utilized in various industrial processes, leading to the generation of nickel-containing waste streams, including batteries, catalysts, wastewater, and electrolyte bleed-off. Contamination of soil, water, or air by these waste materials can have adverse effects on the environment and human health. This review article focuses on the recent advancements in environmental and economic implications associated with the removal of nickel from diverse waste sources. Physicochemical technologies employed for treating different nickel-containing effluents and wastewater are discussed, alongside bioremediation techniques and the underlying mechanisms by which microorganisms facilitate nickel removal. The recovery of nickel from waste materials holds paramount importance not only from an economic standpoint but also to mitigate environmental impacts.

Simultaneous Double Balloon Dilatation for Supravalvar Pulmonary Obstruction After Arterial Switch Operation.

The optimal approach for supravalvar right ventricular outflow tract obstruction(RVOTO) after arterial switch operation(ASO) is unclear. The results of percutaneous balloon dilatation have been variable. We report the results of simultaneous double balloon dilation for RVOTO after ASO. Sixteen patients (1.3(0.7-3.8) years; 9.8(8.1-15.1) kgs underwent the procedure at 14(8-44.5) months after ASO. Salient technical features included placement of balloons over stiff guide-wires positioned in both branch pulmonary arteries to enable dilation of the distal-most main pulmonary artery (MPA) with high inflation pressures (~ 12-14 atmospheres) and short inflation-deflation cycles. Effective balloon size was based on the PA annulus or MPA distal to the narrowing. The final balloon: narrowest segment diameter ratio was 2.7. Following dilation, the right ventricle to systemic systolic pressure ratio decreased from 0.9 ± 0.18 to 0.52 ± 0.16 (p < 0.001) and mean RVOT gradient from 78 ± 18 to 34 ± 13.9 mmHg (p < 0.001). Narrowest diameter improved from 5.4 ± 2.2 to 9.2 ± 2.2 mm. There were no major complications. Two patients with inadequate relief (final RV-systemic ratios: 1.03 and 0.7) were referred for surgery. At median follow up of 9 months, IQR 7-22, range 5-73, others are free of re interventions with median RVOT gradient of 42, IQR 27-49, range 21-55 mmHg. The immediate and short-term follow up results of double balloon dilatation for supravalvar RVOTO is encouraging and may avoid the need for repeat surgery in the majority of patients. Further follow up is needed to determine the long-term durability of the results.

Advocacy at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.

Is it "the conflict of interest" that is influencing our efforts on Climate change, tobacco control and primary care?

What seems to work against making climate change relevant, tobacco control necessary or primary care a felt need despite the efforts being claimed to the contrary? Emerging evidence points to a conflict of interest with academic institutions and academics fighting on both sides with clear support from the industry and others.

Recommendations for developing effective and safe paediatric and congenital heart disease services in low-income and middle-income countries: a public health framework.

The global burden of paediatric and congenital heart disease (PCHD) is substantial. We propose a novel public health framework with recommendations for developing effective and safe PCHD services in low-income and middle-income countries (LMICs). This framework was created by the Global Initiative for Children's Surgery Cardiac Surgery working group in collaboration with a group of international rexperts in providing paediatric and congenital cardiac care to patients with CHD and rheumatic heart disease (RHD) in LMICs. Effective and safe PCHD care is inaccessible to many, and there is no consensus on the best approaches to provide meaningful access in resource-limited settings, where it is often needed the most. Considering the high inequity in access to care for CHD and RHD, we aimed to create an actionable framework for health practitioners, policy makers and patients that supports treatment and prevention. It was formulated based on rigorous evaluation of available guidelines and standards of care and builds on a consensus process about the competencies needed at each step of the care continuum. We recommend a tier-based framework for PCHD care integrated within existing health systems. Each level of care is expected to meet minimum benchmarks and ensure high-quality and family centred care. We propose that cardiac surgery capabilities should only be developed at the more advanced levels on hospitals that have an established foundation of cardiology and cardiac surgery services, including screening, diagnostics, inpatient and outpatient care, postoperative care and cardiac catheterisation. This approach requires a quality control system and close collaboration between the different levels of care to facilitate the journey and care of every child with heart disease. This effort was designed to guide readers and leaders in taking action, strengthening capacity, evaluating impact, advancing policy and engaging in partnerships to guide facilities providing PCHD care in LMICs.

Secondary findings in a large Pakistani cohort tested with whole genome sequencing.

Studies on genomic secondary findings (SFs) are diverse in participants' characteristics, sequencing methods, and versions of the ACMG SF list. Based on whole genome sequencing and the version 3.1 of the ACMG SF list, we studied SFs in 863 individuals from five different regions in Pakistan. We identified 24 ACMG SFs in 23 (2.7%) of 863 individuals: 18 of 24 were related to cardiovascular disease and four to cancer syndromes. In addition to ACMG SFs, we identified 16 (1.9%) participants with pathogenic and likely pathogenic variants in genes that were not related to the participants' clinical conditions but with clear medical actionability (non-ACMG SFs): 4 of 16 were related to eye diseases, two to metabolic disorders, and two to urinary system disorders. By testing a large Pakistani cohort with whole genome sequencing, we concluded that in countries such as Pakistan, the ACMG SF list could be expanded, and our non-ACMG SF list is one example.

Arthrospira platensis (Spirulina) fortified functional foods ameliorate iron and protein malnutrition by improving growth and modulating oxidative stress and gut microbiota in rats.

The present study was aimed at developing Arthrospira platensis (Spirulina) fortified traditional foods of the Indian subcontinent, namely sattu (multigrain beverage mix) and chikki (peanut bar) and evaluating their ability to promote recovery from protein and iron deficiency anaemia (IDA) using albino Wistar rats. Addition of Spirulina (at 4% w/w Spirulina inclusion levels) enriched the protein content by 20.33% in sattu and 15.65% in chikki while the iron content was enhanced by 45% in sattu and 29.6% in chikki. In addition, the total carotenoid and polyphenol content and antioxidant capacity of the food products improved after Spirulina incorporation. Supplementation of 100 g of Spirulina fortified food products meets more than 50% of recommended dietary allowances (RDA) of protein, dietary fiber, iron and zinc for the age group 3 to 10 years of children. Spirulina contributed between 11% and 22% of RDA for protein and iron, respectively; however it contributed very negligibly to RDA of dietary fibre with respect to the nutrient requirements for the target age group. Supplementation of Spirulina fortified foods individually promoted bodyweight gain in malnourished rats and restored haemoglobin, serum protein, albumin, serum iron, and hepcidin levels and reduced the iron binding capacity indicating recovery from IDA. Spirulina supplementation ameliorated malnutrition induced oxidative stress in the liver, spleen and kidneys by reducing the lipid peroxidation and enhancing superoxide dismutase and glutathione activities. Histopathological analysis revealed that supplementation of Spirulina fortified foods reversed pathological changes such as fatty changes in the liver cells, thinning of cardiac muscle fibers and degeneration of intestinal villi. Fe-protein deficiency significantly altered the gut microflora by reducing the abundance of beneficial microbes. However, supplementation of Spirulina fortified foods improved the levels of beneficial gut microbes such as Lactobacillus reuteri and Akkermansia muciniphila while reducing the abundance of Helicobacteraceae, Enterobacteria and Clostridia. In summary, supplementation of Spirulina fortified foods promoted recovery from protein and iron deficiency indicating the bioavailability of nutrients (iron and protein) from Spirulina at par with casein and ferrous ascorbate.

Evaluation of TTK Chitra heart valve prosthesis in pediatric patients.

This report highlights the outcome of valve replacement using TTK Chitra heart mechanical valve in a subgroup of pediatric patients This cohort of 27 pediatric patients with implantations during January 2006 to December 2018 was followed up prospectively. The cohort consisted of 12 aortic valve replacement (AVR), 14 mitral valve replacement (MVR), and 1 double valve replacement (DVR) patients. Total follow-up was 254 patient-years (AVR = 107, MVR = 136, DVR = 11) being 90% complete. The results show that the survival rates and event-free rates were satisfactory. Despite many reservations due to the high risk involved, the long-term benefits of having a durable valve replacement seem to outweigh the risks and offer acceptable long-term survival.

Rescue right ventricular outflow tract stenting for refractory hypoxic spells.

BACKGROUND: While right ventricular outflow tract stenting (RVOTS) has become an acceptable alternative to palliative surgery in Tetralogy of Fallot (TOF) and similar physiologies, its utility for relief of refractory hypoxic spells is unclear. METHODS: Patients who underwent RVOTS for emergency relief of refractory hypoxic spells were identified. Specific modifications to enable expeditious RVOTS included use of stent delivery systems (guiding catheter or long sheath) upfront to minimize catheter exchanges; using coronary wires to cross RVOT initially; stabilizing the catheter with a wire in the aorta while crossing RVOT with a second wire. RESULTS: From 2015 to 2022, 11 patients underwent RVOTS for hypoxic spells refractory to medical management. Their median age was 27 days (IQR 8.5-442.5); weight 3.27 kg (2.7-8.96); 9 males. Median pulmonary annulus Z score was -4.13 (IQR-4.85 to -0.86). Thirteen stents with median diameter 5 (4-6.5) mm and length 19 (16-19.75) mm were implanted, fluoroscopy time:13.6 (11-26.3) min; procedure time (60, 30-70 min). All were ventilated. Oxygen saturations improved from 45% (40-60) to 90% (84-92); (p < 0.0001) with no major complications. Postprocedure ventilation was needed for 21 (20-49) hours and 4 required diuretic infusion for pulmonary over-circulation. Four needed re-stenting 13 days to 5 months later. At median follow-up of 7 (4-17) months; 2 died from unrelated causes, 3 underwent surgery (two correction and one aorto-pulmonary shunt) and 6 await surgery. CONCLUSION: RVOTS enables safe, expeditious and effective short-term palliation for refractory hypoxic spells. Specific technical modifications facilitate safety, ease and swiftness.

In-vitro cytotoxicity of nickel oxide nanoparticles against L-6 cell-lines: MMP, MTT and ROS studies.

In the present work we synthesize nickel oxide nanoparticles (NiO NPs) using Rhododendron arboretum (flower) (RNi), Tinospora cordifolia (stems) (GNi), Corylus jacquemontii (seeds) (CNi), and Nardostachys jatamansi (roots) (NNi) extracts by co-precipitation method. The synthesized NiO NPs were characterized in detail in terms of their morphological, crystalline nature, structural and antiproliferative activity against rat skeletal myoblast (L-6) cell lines. Morphological studies confirmed the formation of nanoparticles, while the structural and compositional characterization revealed the well-crystallinity and high purity of the synthesized nanoparticles. For biological applications and cytotoxicity examinations of the synthesized NPs, the rat skeletal myoblast (L-6) cell lines were subjected to study. By detailed cytotoxic investigations, it was observed that among the four kinds of NiO NPs prepared through different plant extracts, the Tinospora cordifolia (stems) showed strong antiproliferative activity against rat skeletal myoblast (L-6) cell lines and the calculated IC50 was 1.671 mg/mL. The observed antiproliferative activity towards different NiO NPs were in the order of GNi > NNi > RNi > CNi. The present studies demonstrate that simply synthesized NiO can efficiently be used as antiproliferative agents.

Oral haemangiomas- Series of two case reports and review of management.

Haemangiomas are one of the most common of all human birth defects and are based on vascular tissues. These lesions are mainly identified into two groups which are named as (a) capillary and (b) cavernous haemangioma. Capillary haemangioma consists of small capillary vessels which show lobules formation. Cavernous haemangioma consists of large dilated vessels and they can reach to large sizes. Many treatment modalities are evaluated in which some modalities are successful and some are quite disappointing. Surgical excision, irradiation, CO2 freezing, sclerosing agents, cauterization, steroid therapy and watchful waiting are among the treatment methods evaluated. The treatment plan established for Haemangiomas must consider aspects such as size, location, lesion hemodynamics, patient's age and viability of the technique to be used. In the present series of two case reports, the management of haemangioma was done using two different modalities depending on their presentation so that major complications can be avoided and more attention should be paid to more conservative treatment modalities.