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.

Knowledge, attitude, and practices of parents regarding the red flags of developmental milestones in children aged 0-5 years in Karachi, Pakistan: a cross-sectional study.

BACKGROUND: Developmental delays in children are assessed in four basic domains: gross motor, fine motor, social, and language. Early years of life are crucial in a child's development, so it is imperative that parents be aware of developmental milestones to facilitate early diagnosis and treatment in case of a developmental delay. This study assessed parental knowledge, attitude, and practices regarding children's developmental milestones and associated "red flags". METHODS: A cross-sectional study was conducted at the Department of Pediatrics at Liaquat National Hospital, Karachi. 390 parents, who had at least one child under 5 years of age, with no diagnosed developmental delay, were interviewed during outpatient clinic visits. The questionnaire consisted of three components to assess parental knowledge, attitude, and practices. RESULTS: 59% and 54% of parents had poor knowledge of gross and fine motor milestones respectively; In the social domain, 56% of the respondents had inadequate knowledge. 42% had inadequate knowledge of language milestones; 29% of parents strongly agreed that their pediatricians provide satisfactory information regarding red flags of developmental milestones. 60% of parents strongly agreed that their child's developmental delay would be a cause of concern for them. In the case of developmental delay, 55% of parents said they would consult a general pediatrician, 11% preferred a pediatric neurologist, 21% opted for a developmental pediatrician and 13% opted for a family physician. Residence and family systems were found to be associated with language-related milestones with significantly higher odds of knowledge among urban residents than rural ones and a significantly lower likelihood of language milestones knowledge among joint families than nuclear families. Female gender was found to be significantly associated with positive attitude. CONCLUSION: The majority of our respondents showed considerably poor knowledge regarding developmental milestones. This highlights the need to devise ways to educate parents on this subject to enable them to vigilantly monitor their child's developmental status and any associated abnormalities and ultimately facilitate the right course of action.

Ductal Stenting in Low-Resource Environments.

Duct-dependent pulmonary circulation has traditionally been addressed by the Blalock-Taussig-Thomas shunts (BTTS). Recently, catheter-based alternatives such as ductal stenting have emerged as a particularly advantageous option, especially in resource-constrained settings. This article delves into the nuances of ductal stenting within low-resource environments, highlighting its relative ease of application, reduced morbidity, and cost-effectiveness as key factors in its favor. Comparisons in mortality between the two procedures are however likely to be confounded by selection biases. Ductal stenting appears to be particularly beneficial for palliating older infants and children with cyanotic congenital heart disease and diminished pulmonary blood flow who present late. Additionally, it serves as a valuable tool for left ventricular training in late-presenting transposition with an intact ventricular septum. A meticulous pre-procedure echocardiographic assessment of anatomy plays a pivotal role in planning access and hardware, with additional imaging seldom required for this purpose. The adaptation of adult coronary hardware has significantly enhanced the technical feasibility of ductal stenting. However, challenges such as low birth weight and sepsis specifically impact the performance of ductal stenting and patient recovery in low-resource environments. There is potential for systematic application of quality improvement processes to optimize immediate and long-term outcomes of ductal stenting. There is also a need to prospectively examine the application of ductal stenting in low-resource environments through multi-center registries.

Transcatheter Closure of Perimembranous Ventricular Septal Defect Using KONAR-MF™: A Multicenter Experience.

Transcatheter closure of perimembranous ventricular septal defect (PmVSD) is an established procedure. However, the occurrence of complete heart block limits its scope. The newer KONAR-MF™ occluder has specific design characteristics that may improve the safety of PmVSD closure. The objective of the study was to describe the efficacy and mid-term follow-up of transcatheter closure of PmVSD using KONAR-MF™. The study was conducted prospectively in 3 Indian centers (January 2018-December 2022). PmVSD closure was done by both antegrade and retrograde methods, and patients were followed up at 1, 3, 6, 12 months, and annually after that. 121 out of 123 patients were included with the following characteristics: median age 4.4 (0.18-40) years; weight 15 (2.1-88) kg; mean Qp/Qs ratio 1.87 ± 0.52 and pulmonary artery mean pressure: 22 ± 6.9 mmHg. The procedure was successful in all but 3; the device was removed due to significant residual shunt (n = 2) and new development of aortic regurgitation (AR) (≥ mild) in 1. The median defect size was 5.2 (2.5-12) mm. Device sizes from 6/4 to 14/12 were deployed (median fluoroscopy time 13.3 min; range 3.6-47.8). Shunt occlusion rates were 90%-Immediate, 95%-pre-discharge, and 97%-1 month, with no instances of complete heart block after the procedure and during follow-up. Six had new onset AR (mild: 2, trivial 4), and one had increased tricuspid regurgitation. All patients were well during follow-up (median: 20 months; range: 6-46). The new KONAR-MF™ occluder appears to be a promising and safe alternative for the closure of the PmVSD; further long-term follow is merited.

Closing the gap between acceptable and ideal in catheterisation for paediatric and congenital heart disease-A global view.

In recent issues of the Journal of the Society for Cardiovascular Angiography and Interventions and the Journal of the American College of Cardiology: Cardiovascular Interventions, Holzer and colleagues presented an Expert Consensus Document titled: "PICS / AEPC / APPCS / CSANZ / SCAI / SOLACI: Expert consensus statement on cardiac catheterization for pediatric patients and adults with congenital heart disease." This Expert Consensus Document is a massively important contribution to the community of paediatric and congenital cardiac care. This document was developed as an Expert Consensus Document by the Pediatric and Congenital Interventional Cardiovascular Society, the Association for European Paediatric and Congenital Cardiology, the Asia-Pacific Pediatric Cardiac Society, the Cardiac Society of Australia and New Zealand, the Society for Cardiovascular Angiography and Interventions, and the Latin American Society of Interventional Cardiology, as well as the Congenital Cardiac Anesthesia Society and the American Association of Physicists in Medicine.As perfectly stated in the Preamble of this Expert Consensus Document, "This expert consensus document is intended to inform practitioners, payors, hospital administrators and other parties as to the opinion of the aforementioned societies about best practices for cardiac catheterisation and transcatheter management of paediatric and adult patients with congenital heart disease, with added accommodations for resource-limited environments." And, the fact that the authorship of this Expert Consensus Document includes global representation is notable, commendable, and important.This Expert Consensus Document has the potential to fill an important gap for this patient population. National guideline documents for specific aspects of interventions in patients with paediatric heart disease, including training guidelines, do exist. However, this current Expert Consensus Document authored by Holzer and colleagues provides truly globally applicable standards on cardiac catheterisation for both paediatric patients and adults with congenital heart disease (CHD).Our current Editorial provides different regional perspectives from senior physicians dedicated to paediatric and congenital cardiac care who are practicing in Europe, the Asia-Pacific region, Latin America, Australia/New Zealand, and North America. Establishing worldwide standards for cardiac catheterisation laboratories for children and adults with CHD is a significant stride towards improving the quality and consistency of care. These standards should not only reflect the current state of medical knowledge but should also be adaptable to future advancements, ultimately fostering better outcomes and enhancing the lives of individuals affected by CHD worldwide.Ensuring that these standards are accessible and adaptable across different healthcare settings globally is a critical step. Given the variability in resources and infrastructure globally, the need exists for flexibility and tailoring to implement recommendations.The potential impact of the Expert Consensus Document and its recommendations is likely significant, but heterogeneity of healthcare systems will pose continuing challenges on healthcare professionals. Indeed, this heterogeneity of healthcare systems will challenge healthcare professionals to finally close the gap between acceptable and ideal in the catheterisation of patients with paediatric and/or congenital heart disease.

Cardiology across continents: an interactive, case-based learning series.

Heart University [https://www.heartuniversity.org/] is a free educational website providing structured training curricula with knowledge-based testing and access to webinars and conference recordings for practicing and in-training providers of paediatric and congenital cardiac care. To date, there are over 15,000 registered website users from over 140 countries on Heart University, with over 2,000 training modules and/or recorded educational videos. Heart University has developed an "asynchronous" educational lecture series entitled "Pediatric and Congenital Cardiac Care in Resource-Limited Settings." This recorded lecture series is specifically focused on topics relevant to practicing paediatric and/or congenital cardiac care in low-resource settings.A relatively new initiative, "Cardiology Across Continents," supplements the existing educational resources for providers of paediatric and/or congenital cardiac care in low-income countries and lower-middle-income countries by providing an additional live, interactive, case-based forum. Sessions occur every 1-2 months and focus on challenging cases from diagnostic or management perspective with a view to promote collaboration between partnered institutions. "Cardiology Across Continents" is an expanding initiative that facilitates learning and collaboration between clinicians across varied practice settings via interactive case discussions. We welcome trainees and providers of paediatric and congenital cardiac care to join the sessions and invite any insight that can enhance learning for clinicians around the world. This manuscript describes "Cardiology Across Continents" and discusses the development, history, current status, and future plans of Heart University.

RLIM Is a Candidate Dosage-Sensitive Gene for Individuals with Varying Duplications of Xq13, Intellectual Disability, and Distinct Facial Features.

Interpretation of the significance of maternally inherited X chromosome variants in males with neurocognitive phenotypes continues to present a challenge to clinical geneticists and diagnostic laboratories. Here we report 14 males from 9 families with duplications at the Xq13.2-q13.3 locus with a common facial phenotype, intellectual disability (ID), distinctive behavioral features, and a seizure disorder in two cases. All tested carrier mothers had normal intelligence. The duplication arose de novo in three mothers where grandparental testing was possible. In one family the duplication segregated with ID across three generations. RLIM is the only gene common to our duplications. However, flanking genes duplicated in some but not all the affected individuals included the brain-expressed genes NEXMIF, SLC16A2, and the long non-coding RNA gene FTX. The contribution of the RLIM-flanking genes to the phenotypes of individuals with different size duplications has not been fully resolved. Missense variants in RLIM have recently been identified to cause X-linked ID in males, with heterozygous females typically having normal intelligence and highly skewed X chromosome inactivation. We detected consistent and significant increase of RLIM mRNA and protein levels in cells derived from seven affected males from five families with the duplication. Subsequent analysis of MDM2, one of the targets of the RLIM E3 ligase activity, showed consistent downregulation in cells from the affected males. All the carrier mothers displayed normal RLIM mRNA levels and had highly skewed X chromosome inactivation. We propose that duplications at Xq13.2-13.3 including RLIM cause a recognizable but mild neurocognitive phenotype in hemizygous males.

A sustainable approach to the degradation of dyes by fungal species isolated from industrial wastewaters: Performance, parametric optimization, kinetics and degradation mechanism.

Fungal abetted processes are among the finest approaches for the transformation or degradation and decolorization of dyes in effluents. In this piece of research; biodegradation and metabolic pathways of two toxic dyes Congo Red (CR) and Reactive black 5 (RB5) by two strains of Aspergillus sp. fungus in batch experiments has been investigated. Morphological characteristics of the isolates were observed with both light and electron microscopies. Based on molecular characterization the isolates were identified as Aspergillus flavus and Aspergillus niger. The degradation was also optimized via. operational parameters such as pH, temperature, incubation time, inoculums size, dye concentration, carbon sources and nitrogen sources. Degradation measurements revealed that the isolates effectively degraded 90% and 96% of CR and RB5 respectively. Metabolites were identified with Liquid chromatography-mass spectrometry (LCMS) and degradation pathways of the dyes were proposed. Toxicity assay Phaseolus mungo seeds showed that pure CR and RB5 dyes exhibits significant toxicity whereas fungal treated dye solution resulted in an abatement of the toxicity and cell viability was increased. The results stipulated in this article clearly showed the effectiveness of the isolates on detoxification of CR and RB5 dyes.

Charting a roadmap for heart failure research in India: Insights from a qualitative survey.

Background & objectives: Heart failure (HF) is emerging as a major health problem in India. The profile of HF in India is divergent from elsewhere in the world. While cardiologists must equip themselves with the requisite clinical management tools, scientists and health policymakers would need epidemiological data on HF and information on the resources required to meet the challenges ahead. The aim of this study was to identify the lacunae and to suggest recommendations to improve HF research. Methods: We surveyed a multidisciplinary group of HF experts using a two stage process. An email-based survey was conducted using a structured questionnaire, followed by an online discussion. The experts prioritized the major challenges in convergence research in India and inter-rater agreement values were calculated. In addition, they enlisted potential research gaps and barriers in the domains of epidemiology, diagnostics, management and technology and suggested recommendations to overcome those barriers. Results: The experts identified a paucity of data on HF burden, lack of state-of-the-art diagnostic facilities and trained personnel, overt dependence on imported devices/equipment/reagents, lack of interaction/awareness/information among stakeholders and lack of biobanks, as major barriers in HF research. Three fourths of the experts agreed that lack of interaction among stakeholders was the major challenge with the highest inter-rater agreement in both stages (19 out of 25 and 11 out of 17, respectively). The experts recommended the creation of multidisciplinary taskforces dedicated to population sciences, data sciences, technology development and patient management with short-, intermediate- and long-term strategies. Interpretation & conclusions: The study generated a wish list for advances in HF research and management, and proposed recommendations for facilitating convergence research as a way forward to reduce the burden of HF in India.

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.

Enhancing Quality of Congenital Heart Care Within Resource-Limited Settings.

Over 90% of the world's children with congenital heart disease (CHD) are born in the resources poor settings of low- to middle-income countries (LMICs). The shortfall in human and material resources and dysfunctional health systems leads to poor quality of care (QoC) which contributes substantially to suboptimal outcomes of patients with CHD in LMICs. Notwithstanding these challenges, it is possible to develop a quality improvement (QI) framework that can have a significant impact on outcomes and prevent a number of deaths. In this review, we examine the common barriers to implementing effective QI processes in LMICs. Using examples of successful QI initiatives in LMIC, we propose a broad framework that focuses on simple, yet effective measures involving cohesive efforts of all key participants guided and nurtured by a leadership that strongly values QoC.

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.

Assessment of Vitamin D Levels and Other Bone Related Biochemical Markers in Healthy Adults in Rural Population of Uttarakhand, India.

Despite being close to equator and receiving sufficient sun rays, evidences revealed that Indians have severe deficiency of vitamin D (vit D) ranging from 41 to 100% in different geographical locations. Therefore, in this study levels of 25(OH)D (physiologically measurable form) along with other bone metabolism associated biochemical markers were determined in serum sample of 300 apparently healthy study subjects (rural) from Doiwala block of Dehradun district in the state of Uttarakhand. Demographic data was also obtained based on a structured questionnaire to establish an association between 25(OH)D levels and various dietary and socio-cultural factors. Results demonstrated that of all study subjects, 197 (65%) had 25(OH)D levels below < 12 ng/mL (deficient) and 65 (21%) had 25(OH)D levels between 12 and 20 ng/mL (insufficient) with all other markers falling within respectively established reference ranges. Further, in univariate analysis, gender, occupation (indoor and outdoor), education were independently associated with vitamin D status. Additionally, parathyroid hormone associated significantly with gender and occupation, while calcium associated significantly with gender, occupation and education. Lastly, regression analysis revealed that gender and occupation independently associated with vitamin D status of subjects. In conclusion, apparently healthy subjects showed considerable vitamin D deficiency thereby generating an urgent need for formulating and implementing better government policies for enrichment of vitamin D levels among rural adults of Uttarakhand in future. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01048-6.

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.

Effective removal of Pb(II) and Ni(II) ions by Bacillus cereus and Bacillus pumilus: An experimental and mechanistic approach.

Herein, we report a bacteria-based strategy as an efficient, reasonable, benign, and promising methodology for remediating heavy metals fed waterbodies. The contemporary study deals with isolating, screening, and characterizing heavy metal resistive bacteria from metal-rich sites. The transcriptome analysis reveals the identity of the isolated species as Bacillus pumilus and Bacillus cereus. Batch studies put forth the bioremoval results in designed conditions of different pH, concentration, dose, and time. The mechanistic actions are drawn using complementary techniques such as Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The theory of surface adsorption of lead (Pb(II)) and nickel (Ni(II)) is further fostered by the application of adsorption isotherms. The conducted studies establish the bacterial morphological stratagems and multifarious biochemical approaches for countering metallic ions of Pb(II) and Ni(II). The exhibition of significant removal results by the isolated bacterial strains in simulated water samples with remarkable proliferation rates has opened up its favorability for industrial platforms.

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.

Is this as good as it gets? Implications of an asymptotic mortality decline and approaching the nadir in pediatric intensive care.

Despite advances in medicine, some children will always die; a decline in pediatric intensive care unit (PICU) mortality to zero will never be achieved. The mortality decline is correspondingly asymptotic, yet we remain preoccupied with mortality outcomes. Are we at the nadir, and are we, thus, as good as we can get? And what should we focus to benchmark our units, if not mortality? In the face of changing case-mix and rising complexity, dramatic reductions in PICU mortality have been observed globally. At the same time, survivors have increasing disability, and deaths are often characterized by intensive life-sustaining therapies preceded by prolonged admissions, emphasizing the need to consider alternate outcome measures to evaluate our successes and failures. What are the costs and implications of reaching this nadir in mortality outcomes? We highlight the failings of our fixation with survival and an imperative to consider alternative outcomes in our PICUs, including the costs for both patients that survive and die, their families, healthcare providers, and society including perspectives in low resource settings. We describe the implications for benchmarking, research, and training the next generation of providers.Conlusion: Although survival remains a highly relevant metric, as PICUs continue to strive for clinical excellence, pushing boundaries in research and innovation, with endeavors in safety, quality, and high-reliability systems, we must prioritize outcomes beyond mortality, evaluate "costs" beyond economics, and find novel ways to improve the care we provide to all of our pediatric patients and their families. What is Known: • The fall in PICU mortality is asymptotic, and a decline to zero is not achievable. Approaching the nadir, we challenge readers to consider implications of focusing on medical and technological advances with survival as the sole outcome of interest. What is New: • Our fixation with survival has costs for patients, families, staff, and society. In the changing PICU landscape, we advocate to pivot towards alternate outcome metrics. • By considering the implications for benchmarking, research, and training, we may better care for patients and families, educate trainees, and expand what it means to succeed in the PICU.

Prenatal diagnosis lowers neonatal cardiac care costs in resource-limited settings.

BACKGROUND: Prenatal diagnosis of critical CHDs and planned peripartum care is an emerging concept in resource-limited settings. OBJECTIVE: To report the impact of prenatal diagnosis and planned peripartum care on costs of neonatal cardiac care in a resource-limited setting. METHODS: Prospective study (October 2019 to October 2020). Consecutive neonates undergoing surgery or catheter-based interventions included. Patients were divided into prenatal (prenatal diagnosis) and post-natal (diagnosis after birth) groups. Costs of cardiac care (total, direct, and indirect) and health expenses to income ratio were compared between study groups; factors impacting costs were analysed. RESULTS: A total of 105 neonates were included, including 33 in prenatal group. Seventy-seven neonates (73.3%) underwent surgical procedures while the rest needed catheter-based interventions. Total costs were 16.2% lower in the prenatal group (p = 0.008). Direct costs were significantly lower in the prenatal group (18%; p = 0.02), especially in neonates undergoing surgery (20.4% lower; p = 0.001). Health expenses to income ratio was also significantly lower in the prenatal group (2.04 (1.03-2.66) versus post-natal:2.58 (1.55-5.63), p = 0.01);, particularly in patients undergoing surgery (prenatal: 1.58 (1.03-2.66) vs. post-natal: 2.99 (1.91-6.02); p = 0.002). Prenatal diagnosis emerged as the only modifiable factor impacting costs on multivariate analysis. CONCLUSION: Prenatal diagnosis and planned peripartum care of critical CHD is feasible in resource-limited settings and is associated with significantly lower costs of neonatal cardiac care. The dual benefit of improved clinical outcomes and lower costs of cardiac care should encourage policymakers in resource-limited settings towards developing more prenatal cardiac services.

Exploring the Application Sphere of the Internet of Things in Industry 4.0: A Review, Bibliometric and Content Analysis.

This paper aims to comprehensively review 891 documents in the Scopus database about Internet of Things (IoT) in Ind 4.0 to understand the historical growth, current state, and potential expansion trend. From 2014 to 2020, a systematic methodology gathered information on IoT in Ind 4.0 documents in various Scopus databases. The relevant IoT research in Ind 4.0 documents is provided, and their types, publications, citations, and predictions are discussed. The VOSviewer 1.16.6 and Biblioshiny 2.0 applications display IoT status in Ind 4.0 publications for visualization research. The citation review aims to find the most prominent and influential authors, sources, papers, countries, and organizations. For citation analysis and ranking, document selection criteria were well defined. The author keywords, index keywords, and text data content analysis were used to identify the hotspots and development trends. The yearly IoT in Ind 4.0 article publications presented a speedily increasing trend, and a curve was fitted employing an exponential function. The paper "Intelligent manufacturing in the context of Industry 4.0: a review" was rated first with 754 citations. With 1629 citations, the "International Journal of Production Research" was ranked #1 along with Wan J. The South China University of Technology in Guangzhou, China, was placed first along with the United States as the most prolific and influential country. 'Industry 4.0' appeared the first time in 2014 with an application of IoT in Ind 4.0 with an overall appearance of 528, followed by the 'internet of things' in 2015, three times with a total count of 220 up to 2020. The IoT in Ind 4.0 assessment and bibliometric analysis intended to provide intellectuals a broad perspective working in IoT in Ind 4.0. Scholars should understand the hotspots in this area as soon as possible. This is also the first paper to thoroughly use bibliometric research to examine the IoT in Ind 4.0 literature. It will assist researchers of IoT in Ind 4.0 in expanding their knowledge and quickly comprehending the development status and pattern.

Verifiable, Secure Mobile Agent Migration in Healthcare Systems Using a Polynomial-Based Threshold Secret Sharing Scheme with a Blowfish Algorithm.

A mobile agent is a software application that moves naturally among hosts in a uniform and non-uniform environment; it starts with one host and then moves onto the next in order to divide data between clients. The mobile paradigm is utilized in a wide assortment of medical care applications such as the medical information of a patient, the recovery of clinical information, the incorporation of information pertaining to their wellbeing, dynamic help, telemedicine, obtaining clinical data, patient administration, and so on. The accompanying security issues have grown in tandem with the complexity and improvements in mobile agent technologies. As mobile agents work in an insecure environment, their security is a top priority when communicating and exchanging data and information. Data integrity, data confidentiality and authentication, on-repudiation, denial of service, and access control, are all key security concerns with mobile agent migration. This paper proposes a Verifiable, Secure Mobile Agent Migration model, based on two polynomials (t, n), and an edge secret imparting plan with Blowfish encryption, to enable secure information transmission in clinical medical care.