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Context: Heart disease complicates approximately 1% of all pregnancies. Maternal cardiac disease in pregnancy has a bearing on pregnancy course and neonatal outcomes. Indian studies in this regard are sparse and moreover were undertaken mostly by obstetricians. Aims: The present study was planned looking from a paediatrician’s perspective in order to study all possible neonatal outcomes born to mothers with heart disease delivered by operative mode. Settings & Design: The data consisted of retrospective (old patient records with obstetric and cardiac details including echocardiography reports) and prospective data (monitored from the first antenatal visit to the delivery regularly by obstetricians and cardiologists) conducted in a multispeciality hospital including a tertiary care cardiac centre. Materials and Methods: Pregnant women with Congenital Heart Disease and Rheumatic Heart Disease and their newborns born by caesarean section were enrolled from 2006 - 2010. These women were treated according to their New York Heart Association (NYHA) class to improve their cardiac status. The neonatal group was followed for certain events (outcome) from delivery till discharge. These outcomes were compared between the test group (mothers with cardiac risk factors, unoperated mothers and those without drugs) and the control groups (mothers with no cardiac risk factors, operated mothers and those on drugs). Statistical Analysis used: SPSS v 17 software was used for statistical analysis. Descriptive analysis, Chi Square test and multiple logistic regression were used. Statistical level of significance was fixed at p < 0.05. Results: 55 pregnant women with heart disease and their 55 newborns were seen. Neonatal outcome was adverse in 58% babies; 47% were born to mothers with cardiac risk factors. 25 newborns (45%) had low birth weight, 15 (27%) were preterm, 20 (36%) had jaundice. 18 (33%) were small for gestational age, 8 babies (15%) had congenital anomalies (cardiac - 7; non cardiac – 3). 21% of babies with CHD were born to mothers with CHD. There were 2 neonatal deaths (4%). Statistically significant outcome was found with respect to prematurity only. 33% mothers had one or more of the 5 cardiac risk factors. There was no difference in neonatal outcomes between mothers with RHD or CHD. Conclusion: The outcome of newborns is influenced by maternal cardiac risk factors. There were no differences in neonatal outcomes born to mothers with RHD and CHD and mothers with operated and unoperated heart disease.

Objectives: To correlate prenatal and postnatal findings of urorectal septum malformation sequence and to study spectrum of malformation.Methods: Nine cases were reviewed with features suggestive of urorectal septum malformation (URSM) sequence. Associated anomalies were studied. Sex of the fetus was assigned by karyotype when available or by examination of internal genitalia.Results: Out of nine cases 5 fetuses were male and 4 were female. Gestational age ranged from 14 to 34 weeks. Six cases were complete URSM sequence and 3 were partial URSM sequence. Associated anomalies of other systems were seen in 4 cases. In one case karyotype was 47, XXY.Conclusion: Cases with severe oligohydromnios with or without distended bladder, URSM sequence should be suspected, as this condition is usually lethal. Non-visualization of bladder, presence of hydronephrosis, multicystic kidneys or distended gut loops suggests the possibility of URSM sequence. The confirmation of diagnosis is possible after autopsy. Associated malformation of other organs and deformation due to oligohydromnios are commonly present. [ABSTRACT FROM AUTHOR]

Objective: Mutation analysis in Indian children with achondroplasia.Methods: We studied 11 sporadic cases of achondroplasia. Mutation analysis was done by PCR/RFLP (Polymerase chain reaction/Restriction fragment length polymorphism) method.Results: Nine of the 11 cases had mutation G-->A at 1138 nucleotide position in transmembrane domain of fibroblast growth-factor receptor 3 (FGFR3) gene. Substitution G-->A is a common recurrent mutation reported worldwide. In two cases we could not detect any common mutation and also in entire region of transmembrane domain sequenced. There is possibility of mutation in the other regions of FGFR3 gene in these two cases.Conclusion: Further study of these two cases is needed in order to define other genotypes resulting in achondroplasia. Postnatal diagnosis of achondroplasia depends on clinical and radiological features. Mutation detection is mainly useful for prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Background and aim Diabetes is a chronic metabolic disorder characterized by elevated blood glucose levels. Although current antidiabetic drugs are highly effective, they are associated with various adverse drug reactions, including life-threatening hypoglycemia, skin rashes, and gastrointestinal intolerance, in addition to being costly. This animal-based experimental study aims to develop a herbal alternative or adjuvant to current antidiabetic drugs using  Berberis asiatica  ( BA ) and  Withania somnifera  ( WS ), which could potentially have fewer adverse drug reactions and reduce the required dose of existing antidiabetic medications. Material and methods Seventy-eight adult albino Wistar rats weighing between 150 and 250 g were used for the study. Diabetes mellitus (DM) was induced by intraperitoneal (i.p) injections of streptozotocin (STZ) (65 mg/kg) 15 minutes after nicotinamide (NIC) (110 mg/kg) administration. As the diabetes was confirmed (blood glucose level > 250 mg/dL), rats were divided into 13 different groups mentioned. The standard antidiabetic drugs (metformin [MET] and glimepiride [GLI]) and polyherbal combinations (PHC) ( BA + WS ) were administered orally, individually ( WS and BA ), and in combination ( BA + WS ). Blood samples were collected for biochemical analysis using the tail vein prick method.  The study is based on a total of 13 groups, six rats in each group. Groups 1 and 2 (normal control [NC] and diabetic control [DC]) received distilled water at a dose of 10 mL/kg orally for 28 days. Groups 3-5 ( BA  250, 500, and 1000) received dried ethanolic root extract of BA at a dose of 250, 500, and 1000 mg/kg orally, respectively, for 28 days. Groups 6-8 ( WS  250, 500, and 1000) received dried ethanolic root extract of WS at a dose of 250, 500, and 1000 mg/kg orally, respectively, for 28 days. Groups 9-11 (PHC 250, 500, and 1000) received dried ethanolic root extract of  BA + WS  at a dose of 250, 500, and 1000 mg/kg orally, respectively, for 28 days. Groups 12 and 13 (MET and GLI) received standard drugs MET and GLI at a dose of 250 and 10 mg/kg orally, respectively, for 28 days. Results The dried ethanolic root extract of medicinal herbal plants  BA  and  WS  and their combination exhibited significant antidiabetic efficacy. PHC has been shown to have a superior antidiabetic effect than individuals. PHC 500 and 1000 showed blood glucose levels similar to those of the GLI group (P < 0.05). Additionally, PHC 1000 showed blood glucose levels similar to those of the MET group (P < 0.05). Conclusion Our results indicate that both  BA  and  WS  possess hypoglycemic activity, and their combination also has a synergistic antidiabetic effect compared to the individual extract. These findings are promising in developing new safe and cost-effective herbal combinations as alternatives or additives to currently used synthetic antidiabetic drugs., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: The approval was taken from the Institutional Ethics Committee of Krishna Vishwa Vidyapeeth (Deemed to be University), Karad, India (IEC Approval no. 385/2020-2021), and the Institutional Animal Ethics Committee of Krishna Vishwa Vidyapeeth (Deemed to be University) Reg. No. 255/PO/REBi/S/2000/CPCSEA (IAEC Approval no. IAEC/KIMS/2021/16). The rats were injected, orally fed, and sacrificed according to guidelines by the Committee for Purpose of Control and Supervision of Experiments on Animals (CPCSEA) and the Indian National Science Academy Guidelines (INSA) in the Central Animal House, KIMSDU. Issued protocol number 385/2020-2021. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tiwari et al.)

Heterozygous RTN2 variants have been previously identified in a limited cohort of families affected by autosomal dominant spastic paraplegia (SPG12-OMIM:604805) with a variable age of onset. Nevertheless, the definitive validity of SPG12 remains to be confidently confirmed due to the scarcity of supporting evidence. In this study, we identified and validated seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) using exome, genome and Sanger sequencing coupled with deep-phenotyping. All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity and hyperreflexia, with onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography. Despite a slowly progressive disease course, all patients remained ambulatory over a mean disease duration of 19.71 ± 13.70 years. Characterization of Caenorhabditis elegans RTN2 homologous loss-of-function variants demonstrated morphological and behavioural differences compared with the parental strain. Treatment of the mutant with an endoplasmic/sarcoplasmic reticulum Ca2+ reuptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences, suggesting a potential therapeutic benefit for RTN2-disorder. Despite RTN2 being an endoplasmic reticulum (ER)-resident membrane shaping protein, our analysis of patient fibroblast cells did not find significant alterations in ER structure or the response to ER stress. Our findings delineate a distinct form of autosomal recessive dHMN with pyramidal features associated with RTN2 deficiency. This phenotype shares similarities with SIGMAR1-related dHMN and Silver-like syndromes, providing valuable insights into the clinical spectrum and potential therapeutic strategies for RTN2-related dHMN., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Significant progress has been achieved in understanding Duchenne muscular dystrophy (DMD) mechanisms and developing treatments to slow disease progression. This review article thoroughly assesses primary and secondary DMD therapies, focusing on innovative modalities. The primary therapy addresses the genetic abnormality causing DMD, specifically the absence or reduced expression of dystrophin. Gene replacement therapies, such as exon skipping, readthrough, and gene editing technologies, show promise in restoring dystrophin expression. Adeno-associated viruses (AAVs), a recent advancement in viral vector-based gene therapies, have shown encouraging results in preclinical and clinical studies. Secondary therapies aim to maintain muscle function and improve quality of life by mitigating DMD symptoms and complications. Glucocorticoid drugs like prednisone and deflazacort have proven effective in slowing disease progression and delaying loss of ambulation. Supportive treatments targeting calcium dysregulation, histone deacetylase, and redox imbalance are also crucial for preserving overall health and function. Additionally, the review includes a detailed table of ongoing and approved clinical trials for DMD, exploring various therapeutic approaches such as gene therapies, exon skipping drugs, utrophin modulators, anti-inflammatory agents, and novel compounds. This highlights the dynamic research field and ongoing efforts to develop effective DMD treatments.

Purpose: DISP1 encodes a transmembrane protein that regulates the secretion of the morphogen, Sonic hedgehog, a deficiency of which is a major cause of holoprosencephaly (HPE). This disorder covers a spectrum of brain and midline craniofacial malformations. The objective of the present study was to better delineate the clinical phenotypes associated with division transporter dispatched-1 (DISP1) variants., Methods: This study was based on the identification of at least 1 pathogenic variant of the DISP1 gene in individuals for whom detailed clinical data were available., Results: A total of 23 DISP1 variants were identified in heterozygous, compound heterozygous or homozygous states in 25 individuals with midline craniofacial defects. Most cases were minor forms of HPE, with craniofacial features such as orofacial cleft, solitary median maxillary central incisor, and congenital nasal pyriform aperture stenosis. These individuals had either monoallelic loss-of-function variants or biallelic missense variants in DISP1. In individuals with severe HPE, the DISP1 variants were commonly found associated with a variant in another HPE-linked gene (ie, oligogenic inheritance)., Conclusion: The genetic findings we have acquired demonstrate a significant involvement of DISP1 variants in the phenotypic spectrum of midline defects. This underlines its importance as a crucial element in the efficient secretion of Sonic hedgehog. We also demonstrated that the very rare solitary median maxillary central incisor and congenital nasal pyriform aperture stenosis combination is part of the DISP1-related phenotype. The present study highlights the clinical risks to be flagged up during genetic counseling after the discovery of a pathogenic DISP1 variant., Competing Interests: Conflict of Interest All authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The application of genomic technologies has led to unraveling of the complex genetic landscape of disorders of epilepsy, gaining insights into their underlying disease mechanisms, aiding precision medicine, and providing informed genetic counseling. We herein present the phenotypic and genotypic insights from 142 Indian families with epilepsy with or without comorbidities. Based on the electroclinical findings, epilepsy syndrome diagnosis could be made in 44% (63/142) of the families adopting the latest proposal for the classification by the ILAE task force (2022). Of these, 95% (60/63) of the families exhibited syndromes with developmental epileptic encephalopathy or progressive neurological deterioration. A definitive molecular diagnosis was achieved in 74 of 142 (52%) families. Infantile-onset epilepsy was noted in 81% of these families (61/74). Fifty-five monogenic, four chromosomal, and one imprinting disorder were identified in 74 families. The genetic variants included 65 (96%) single-nucleotide variants/small insertion-deletions, 1 (2%) copy-number variant, and 1 (2%) triplet-repeat expansion in 53 epilepsy-associated genes causing monogenic disorders. Of these, 35 (52%) variants were novel. Therapeutic implications were noted in 51% of families (38/74) with definitive diagnosis. Forty-one out of 66 families with monogenic disorders exhibited autosomal recessive and inherited autosomal dominant disorders with high risk of recurrence., (© 2024 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Rheumatoid arthritis (RA) is a chronic condition causing joint pain and inflammation that has now spurred the interest in nanotechnology-based drug delivery for more effective treatment, and in this regard, carbon nanotubes (CNTs) are being explored for their potential to deliver the drugs steadily to manage the RA. Many investigators have been investigating both single-walled carbon nanotubes (SWCNT) as well as multi-walled carbon nanotubes (MWCNT) for managing arthritis via targeted drug delivery. Moreover, functionalized CNTs show promise in delivering the drugs precisely and in a controlled manner, thereby minimizing toxicity. However, research on applications of CNTs as drug carriers for RA remains limited, thus necessitating further exploration to address the various challenges. In this present piece of writing, challenges in RA treatment and the advances in applications of CNTs for RA management are reported, consequently reflecting the CNTs as advanced drug delivery vehicles for arthritis treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

CHST3-related chondrodysplasia with congenital joint dislocations (CDCJD, #MIM 143095), is a rare genetic skeletal disorder caused by biallelic loss of function variants in CHST3. CHST3 is critical for the sulfation of chondroitin sulfate. This study delineates the clinical presentation of nine individuals featuring the key symptoms of CDCJD; congenital joint (knee and elbow) dislocations, short trunk short stature progressive vertebral anomalies, and metacarpal shortening. Additional manifestations include irregular distal femoral epiphysis, supernumerary carpal ossification centers, bifid humerus, club foot, and cardiac abnormalities. Sanger sequencing was carried out to investigate molecular etiology in eight patients and exome sequencing in one. Genetic testing revealed five homozygous variants in CHST3 (four were novel and one was previously reported). All these variants are located on sulfotransferase domain of CHST3 protein and were classified as pathogenic/ likely pathogenic. We thus report on nine individuals with CHST3-related chondrodysplasia with congenital joint dislocations from India and suggest monitoring the health of cardiac valves in this condition., (© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

The engineering of nanoscale materials has broadened the scope of nanotechnology in a restricted functional system. Today, significant priority is given to immediate health diagnosis and monitoring tools for point-of-care testing and patient care. Graphene, as a one-atom carbon compound, has the potential to detect cancer biomarkers and its derivatives. The atom-wide graphene layer specialises in physicochemical characteristics, such as improved electrical and thermal conductivity, optical transparency, and increased chemical and mechanical strength, thus making it the best material for cancer biomarker detection. The outstanding mechanical, electrical, electrochemical, and optical properties of two-dimensional graphene can fulfil the scientific goal of any biosensor development, which is to develop a more compact and portable point-of-care device for quick and early cancer diagnosis. The bio-functionalisation of recognised biomarkers can be improved by oxygenated graphene layers and their composites. The significance of graphene that gleans its missing data for its high expertise to be evaluated, including the variety in surface modification and analytical reports. This review provides critical insights into graphene to inspire research that would address the current and remaining hurdles in cancer diagnosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The contribution of de novo variants as a cause of intellectual disability (ID) is well established in several cohorts reported from the developed world. However, the genetic landscape as well as the appropriate testing strategies for identification of de novo variants of these disorders remain largely unknown in low-and middle-income countries like India. In this study, we delineate the clinical and genotypic spectrum of 54 families (55 individuals) with syndromic ID harboring rare de novo variants. We also emphasize on the effectiveness of singleton exome sequencing as a valuable tool for diagnosing these disorders in resource limited settings. Overall, 46 distinct disorders were identified encompassing 46 genes with 51 single-nucleotide variants and/or indels and two copy-number variants. Pathogenic variants were identified in CREBBP, TSC2, KMT2D, MECP2, IDS, NIPBL, NSD1, RIT1, SOX10, BRWD3, FOXG1, BCL11A, KDM6B, KDM5C, SETD5, QRICH1, DCX, SMARCD1, ASXL1, ASXL3, AKT3, FBN2, TCF12, WASF1, BRAF, SMARCA4, SMARCA2, TUBG1, KMT2A, CTNNB1, DLG4, MEIS2, GATAD2B, FBXW7, ANKRD11, ARID1B, DYNC1H1, HIVEP2, NEXMIF, ZBTB18, SETD1B, DYRK1A, SRCAP, CASK, L1CAM, and KRAS. Twenty-four of these monogenic disorders have not been previously reported in the Indian population. Notably, 39 out of 53 (74%) disease-causing variants are novel. These variants were identified in the genes mainly encoding transcriptional and chromatin regulators, serine threonine kinases, lysosomal enzymes, molecular motors, synaptic proteins, neuronal migration machinery, adhesion molecules, structural proteins and signaling molecules., (© 2023. The Author(s).)

Improving the energy share of renewable energy technologies is the only solution to reduce greenhouse gas emissions and air pollution. The high-performing green battery energy storage technologies are critical for storing energy to address the intermittent nature of renewable energy resources. In recent years, aqueous batteries, particularly Zn-ion batteries (ZIBs), have achieved and shown great potential for stationary energy storage systems owing to their low cost and safer operation. However, the practical applications of the ZIBs have significantly been impeded due to the gap between the breakthroughs achieved in academic research and industrial developments. The present review discusses the ZIB's advantages, possibilities, and shortcomings for stationary energy storage systems. The Review begins with a brief introduction to the ZIBs and their charge storage mechanisms based on the structural properties of cathode materials. The scientific and technical challenges that obstruct the commercialization of the ZIBs are discussed in detail concerning their impact on accelerating the utilization of the ZIBs for real-life applications. The final section highlights the outlook on research in this flourishing field., (© 2023 Wiley-VCH GmbH.)

We used tip-enhanced Raman spectroscopy (TERS) to examine plasmon-driven dimerization of 4-bromothiophenol (4-BTP) into thiophenol (TP) and 4,4'-biphenyldithiol (4,4'-BPDT) on Au and Ni@AuNPs. TERS revealed that cross-coupling of these molecular reactants into 4,4'-BPDT occurred primarily on Ni nano islands rather than the surrounding Au on the surface of Ni@AuNPs.

The aim of the present study was to explore Cassia fistula L. seed mucilage as a natural polymer in controlled release floating drug delivery system. First, seed mucilage was extracted and evaluated for phytochemical screening, solubility studies, swelling index, viscosity and surface tension. Then, Atenolol floating systems were prepared with and without the C. fistula L. seed mucilage by direct compression method. Phytochemical screening resulted from the presence of secondary metabolite carbohydrates, glycosides, flavonoids and phenolic compounds in good amounts. Results of hardness, friability, drug content and swelling index were satisfactory. The floating behaviour can increase the gastric residence time and eventually improve the bioavailability of the drug as evidence from in vitro buoyancy and dissolution studies. Interestingly, developed floating system showed remarkable increase in dissolution. Conclusively, the results suggest that developed Atenolol floating system with C. fistula L. seed mucilage demonstrate interesting attributes to be explored for potential pharmaceutical application.

Autosomal recessive CYP26B1 disorder is characterised by syndromic craniosynostosis of variable severity, and survival ranging from prenatal lethality to survival into adulthood. Here we report on two related individuals of Asian-Indian origin with syndromic craniosynostosis characterised by craniosynostosis, and dysplastic radial heads, caused by monoallelic CYP26B1 likely pathogenic variant NM&#95;019885.4:c.86C > A:p. (Ser29Ter). We propose the possibility of autosomal dominant phenotype of CYP26B1 variant., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Magnesium nanoparticles (MgNPs) exhibit localized surface plasmon resonances across the ultraviolet, visible, and near-infrared parts of electromagnetic spectrum and are attracting increasing interest due to their sustainability and biocompatibility. In this study, we used tip-enhanced Raman spectroscopy (TERS) to examine the photocatalytic properties of MgNP protected by a thin native oxide layer and their Au-modified bimetallic analogs produced by partial galvanic replacement, Au-MgNPs. We found no reduction of 4-nitrobenzenethiol (4-NBT) to p , p '-dimercaptoazobisbenzene (DMAB) when a Au-coated tip was placed in contact with a self-assembled monolayer of 4-NBT molecules adsorbed on MgNPs alone. However, decorating Mg with Au made these bimetallic structures catalytically active. The DMAB signal signature of photocatalytic activity was more delocalized around AuNPs attached to Mg than around AuNPs on a Si substrate, indicating coupling between the Mg core and Au decorations. This report on photocatalytic activity of a bimetallic structure including plasmonic Mg paves the way for further catalyst architectures benefiting from Mg's versatility and abundance., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Patient safety is an important step in providing high-quality health care. Every intensive care unit (ICU) is unique and its needs would be different; it is thus necessary to build a safety culture based on local and cultural characteristics. Various measures such as regular training, the use of bundles of care, and a blame-free environment can promote patient safety in ICUs. These measures are simple to implement even in resource-limiting settings and can go a long way in improving patient outcomes in our country., How to Cite This Article: Patil SJ, Ambulkar R, Kulkarni AP. Patient Safety in Intensive Care Unit: What can We Do Better? Indian J Crit Care Med 2023;27(3):163-165., Competing Interests: Source of support: Nil Conflict of interest: Dr Atul Prabhakar Kulkarni is associated as Editor-in-Chief of this journal and this manuscript was subjected to this journal's standard review procedures, with this peer review handled independently of the Editor-in-Chief and his research group., (Copyright © 2023; The Author(s).)

Background: Adapting existing health programs for synchronous remote implementation has the potential to support vulnerable youth during the COVID 19 pandemic and beyond., Methods: The Stanford Youth Diabetes Coaches Program (SYDCP), a school-based health promotion and coaching skills program, was adapted for remote implementation and offered to adolescents from low-income communities in the US: an urban site in San Jose, CA and rural sites in Lawrence County, MO, and Central Valley, CA. Participants completed online pre- and post- surveys. Analysis included paired T-tests, linear regression, and qualitative coding., Results: Of 156 enrolled students, 100 completed pre- and post-surveys. Of those: 84% female; 40% Hispanic; 37% White; 28% Asian; 3% African American; 30% other race. With T-tests and regression models, the following measures showed statistically significant improvements after program participation: health knowledge, patient activation, health understanding and communication, consumption of fruits and vegetables, psychosocial assets of self-esteem, self-efficacy, problem-solving, and ability to reduce stress. Technology barriers were frequently reported at Lawrence County site. 96% participants reported making a lifestyle change after program participation., Conclusions: Remote implementation of health promotion programs for vulnerable youth in diverse settings has potential to support adoption of healthy behaviors, enhance patient activation levels, and improve psychosocial assets.

Competing Interests: There are no conflicts of interest.

The Stanford Youth Diabetes Coaches' Program (SYDCP) trains high school students to become diabetes coaches for friends and adult family members. The objective of this study was to assess effects of SYDCP participation on youth and adults from a rural and urban underserved high school community. We used a mixed-methods approach. Patient-Reported Outcomes Measurement Information System (PROMIS) measures for Pediatric Sense of Meaning and Purpose were measured in high school students. PROMIS Adult Global Health and Self-Efficacy was measured in coached adults. Paired t tests compared pre- and postintervention and 6-month follow-up scores. Thematic analysis was used to analyze focus group discussion of adults. Twenty-five students participated, 15 students coached adults with diabetes or prediabetes. Students' sense of meaning and purpose significantly improved postintervention compared to preintervention. Diet and physical activity behaviors improved. Adolescent-adult relationships mediated participation benefits. Our study showed SYDCP improved adolescents' sense of meaning and purpose. In addition, youth and adult relatedness led to improved health behaviors. These findings have important implications, as a sense of purpose and youth-adult connectedness are associated with health behaviors and psychological well-being. Further larger studies of health education programs that engage related youth-adult dyads and assess long-term behaviors and health outcomes are needed., Competing Interests: Conflicts of Interest: None., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Biotinidase deficiency (BD) is an autosomal recessive disorder caused by bi-allelic mutation in the BTD gene. Clinical manifestations in BD mainly depends on residual biotinidase enzyme activity, although there are some exceptions. Broadly BD disorders are classified as profound BD and partial BD. Further profound BD can be early onset, late onset, and sometimes may be asymptomatic. Clinically late-onset profound BD can present with spectrum of manifestations ranging from single organ to multiple organ involvement, typically affecting function of brain, eye, ear, and skin. Here, a first-born child to consanguineous parents with late-onset profound BD presenting with hyperventilation secondary to lactic acidosis, hypotonia, evolving spasticity, and abnormal neuroimaging findings caused by novel homozygous variant, c.466-3T>G in the BTD gene is reported., (© 2021. Dr. K C Chaudhuri Foundation.)

Objective: Exome sequencing (ES)-based diagnosis of Mendelian diseases in the fetus is limited by paucity of phenotypic information. This study reports the comprehensive phenotypes of some fetuses with Mendelian disorders., Methods: Next generation technology-based sequencing of all coding regions of the genome (Exome sequencing) or targeted gene sequencing using Sanger or next generation platforms was performed in a cohort of deeply phenotyped, cytogenetically normal fetuses with morphological defects. Prenatal ultrasonographic phenotypes and postmortem details including dysmorphology, histopathology, and radiography were ascertained. Novel candidate genes, novel/unusual findings, and unusual genotypes in cases with confirmed Mendelian disorders are described., Results: Of the 102 fetuses sequenced, 45 (44%) achieved definitive diagnosis of a Mendelian disorder with 50 pathogenic/likely pathogenic variants. The majority (87%) were autosomal recessive, 69% families were consanguineous, and 54% variants were novel. Dysmorphic syndromes, skeletal dysplasias, and metabolic disorders were the commonest disease categories, ciliopathies and dystroglycanopathies, commonest molecular categories. We describe the first fetal description of six monogenic diseases, and nine cases with novel histological findings. Nineteen cases had novel/unusual findings., Conclusion: This cohort demonstrates how deep fetal phenotypes of some Mendelian disorders can show novel/unusual findings, which have important implications for prenatal diagnosis of these conditions., (© 2022 John Wiley & Sons Ltd.)

Background: Identifying individual and neighborhood-level factors associated with worsening cardiometabolic risks despite clinic-based care coordination may help identify candidates for supplementary team-based care. Methods: Secondary data analysis of data from a two-year nurse-led care coordination program cohort of Medicare, Medicaid, dual-eligible adults, Leveraging Information Technology to Guide High Tech, High Touch Care (LIGHT2), from ten Midwestern primary care clinics in the U.S. Outcome Measures: Hemoglobin A1C, low-density-lipoprotein (LDL) cholesterol, and blood pressure. Multivariable generalized linear regression models assessed individual and neighborhood-level factors associated with changes in outcome measures from before to after completion of the LIGHT2 program. Results: 6378 participants had pre-and post-intervention levels reported for at least one outcome measure. In adjusted models, higher pre-intervention cardiometabolic measures were associated with worsening of all cardiometabolic measures. Women had worsening LDL-cholesterol compared with men. Women with pre-intervention HbA1c > 6.8% and systolic blood pressure > 131 mm of Hg had worse post-intervention HbA1c and systolic blood pressure compared with men. Adding individual’s neighborhood-level risks did not change effect sizes significantly. Conclusions: Increased cardiometabolic risks and gender were associated with worsening cardiometabolic outcomes. Understanding unresolved gender-specific needs and preferences of patients with increased cardiometabolic risks may aid in tailoring clinic-community-linked care planning.

Transition metal selenides (TMSs) have enthused snowballing research and industrial attention due to their exclusive conductivity and redox activity features, holding them as great candidates for emerging electrochemical devices. However, the real-life utility of TMSs remains challenging owing to their convoluted synthesis process. Herein, a versatile in situ approach to design nanostructured TMSs for high-energy solid-state hybrid supercapacitors (HSCs) is demonstrated. Initially, the rose-nanopetal-like NiSe@Cu 2 Se (NiCuSe) positive electrode and FeSe nanoparticles negative electrode are directly anchored on Cu foam via in situ conversion reactions. The complementary potential windows of NiCuSe and FeSe electrodes in aqueous electrolytes associated with the excellent electrical conductivity results in superior electrochemical features. The solid-state HSCs cell manages to work in a high voltage range of 0-1.6 V, delivers a high specific energy density of 87.6 Wh kg -1 at a specific power density of 914.3 W kg -1 and excellent cycle lifetime (91.3% over 10 000 cycles). The innovative insights and electrode design for high conductivity holds great pledge in inspiring material synthesis strategies. This work offers a feasible route to develop high-energy battery-type electrodes for next-generation hybrid energy storage systems., (© 2022 Wiley-VCH GmbH.)

Developing highly efficient noble-metal-free electrocatalysts with a scalable and environmentally friendly synthesis approach remains a challenge in the field of electrocatalytic water splitting. To overcome this problem, self-supported fluorine-modified 2D ultrathin nickel hydroxide (F-Ni(OH) 2 ) nanosheets (NSs) for the oxygen evolution reaction (OER) and urea oxidation reaction (UOR) are prepared with a scalable and ascendant one-step synthesis route. The enhanced redox activity, electrical conductivity and a great number of exposed active sites of the heterogeneous catalysts improve charge migration for the electrocatalytic reactions. The density of states of the d orbitals of the Ni atoms significantly increases near the Fermi level, thereby indicating that the Ni atoms near the F-dopants promote electrical conduction in the Ni(OH) 2 monolayer. The F-Ni(OH) 2 electrocatalyst exhibits notable OER and UOR activity with onset potentials of 1.43 and 1.16 V versus RHE, respectively required to reach 10 mA cm -2 , which are comparable to those of commercial noble-metal-based electrocatalysts. With RuCo-OH nanospheres, the settled F-Ni(OH) 2 ||RuCo-OH cell requires merely 1.55 and 1.37 V to reach 10 mA cm -2 with superb durability for 24 h in overall water and urea electrolysis, respectively. Overall, high-quality, and efficient noble-metal-free electrocatalysts for overall water and urea electrolysis can be prepared with a simple, scalable, and reproducible preparation method., (© 2021 Wiley-VCH GmbH.)

Genetic disorders with predominant central nervous system white matter abnormalities (CNS WMAs), also called leukodystrophies, are heterogeneous entities. We ascertained 117 individuals with CNS WMAs from 104 unrelated families. Targeted genetic testing was carried out in 16 families and 13 of them received a diagnosis. Chromosomal microarray (CMA) was performed for three families and one received a diagnosis. Mendeliome sequencing was used for testing 11 families and all received a diagnosis. Whole exome sequencing (WES) was performed in 80 families and was diagnostic in 52 (65%). Singleton WES was diagnostic for 50/75 (66.67%) families. Overall, genetic diagnoses were obtained in 77 families (74.03%). Twenty-two of 47 distinct disorders observed in this cohort have not been reported in Indian individuals previously. Notably, disorders of nuclear mitochondrial pathology were most frequent (9 disorders in 20 families). Thirty-seven of 75 (49.33%) disease-causing variants are novel. To sum up, the present cohort describes the phenotypic and genotypic spectrum of genetic disorders with CNS WMAs in our population. It demonstrates WES, especially singleton WES, as an efficient tool in the diagnosis of these heterogeneous entities. It also highlights possible founder events and recurrent disease-causing variants in our population and their implications on the testing strategy., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Home blood pressure measurements have equal or even greater predictive value than clinic blood pressure measurements regarding cardiovascular outcomes. With advances in home blood pressure monitors, we face an imminent flood of home measurements, but current electronic health record systems lack the functionality to allow us to use this data to its fullest. We designed a data visualization display for blood pressure measurements to be used for shared decision making around hypertension., Methods: We used an iterative, rapid-prototyping, user-centred design approach to determine the most appropriate designs for this data display. We relied on visual cognition and human factors principles when designing our display. Feedback was provided by expert members of our multidisciplinary research team and through a series of end-user focus groups, comprised of either hypertensive patients or their healthcare providers required from eight academic, community-based practices in the Midwest of the United States., Results: A total of 40 participants were recruited to participate in patient (N = 16) and provider (N = 24) focus groups. We describe the conceptualization and development of data display for shared decision making around hypertension. We designed and received feedback from both patients and healthcare providers on a number of design elements that were reported to be helpful in understanding blood pressure measurements., Conclusions: We developed a data display for substantial amounts of blood pressure measurements that is both simple to understand for patients, but powerful enough to inform clinical decision making. The display used a line graph format for ease of understanding, a LOWESS function for smoothing data to reduce the weight users placed on outlier measurements, colored goal range bands to allow users to quickly determine if measurements were in range, a medication timeline to help link recorded blood pressure measurements with the medications a patient was taking. A data display such as this, specifically designed to encourage shared decision making between hypertensive patients and their healthcare providers, could help us overcome the clinical inertia that often results in a lack of treatment intensification, leading to better care for the 35 million Americans with uncontrolled hypertension., (© 2021. The Author(s).)

Robinow syndrome (RS) is a rare heterogeneous disorder characterized by short stature, short-limbs, craniofacial, oro-dental abnormalities, vertebral segmentation defects, and frequently genital hypoplasia. Both autosomal dominant and recessive patterns of inheritance are observed with many causative genes. Here, we present the phenotypes and genotypes of four children with RS from different Indian families. Sequence variants were identified in genes ROR2, DVL1, and DVL3. Our results expand the mutational spectrum of RS and we also highlight the radiological changes in the radius and ulna in patients with ROR2 sequence variants which are primarily characteristic for ROR2 related RS but have been reported in WNT5A related RS., (© 2021 Wiley Periodicals LLC.)

Nanofabrication of heteroatom-doped metal oxides into a well-defined architecture via a "bottom-up" approach is crucial to overcome the boundaries of the metal oxides for energy storage systems. In the present work, this issue was addressed by developing sulfur-doped bimetallic cobalt tungstate (CoWO 4 ) porous nanospheres for efficient hybrid supercapacitors via a single-step, ascendable bottom-up approach. The combined experimental and kinetics studies revealed enhanced electrical conductivity, porosity, and openness for ion migration after amendments of the CoWO 4 via sulfur doping. As a result, the sulfur-doped CoWO 4 nanospheres exhibited a specific capacity of 248.5 mA h g -1 with outstanding rate capability and cycling stability. The assembled hybrid supercapacitor cell with sulfur-doped CoWO 4 nanospheres and activated carbon electrodes could be driven reversibly in a voltage of 1.6 V and exhibited a specific capacitance of 177.25 F g -1 calculated at 1.33 A g -1 with a specific energy of 63.41 Wh kg -1 at 1000 W kg -1 specific power. In addition, the hybrid supercapacitor delivered 94.85 % initial capacitance over 10000 charge-discharge cycles. The excellent supercapacitive performance of sulfur-doped CoWO 4 nanospheres may be credited to the sulfur doping and bottom-up fabrication of the electrode materials., (© 2021 Wiley-VCH GmbH.)

Marfan syndrome and related disorders are a group of heritable connective tissue disorders and share many clinical features that involve cardiovascular, skeletal, craniofacial, ocular, and cutaneous abnormalities. The majority of affected individuals have aortopathies associated with early mortality and morbidity. Implementation of targeted gene panel next-generation sequencing in these individuals is a powerful tool to obtain a genetic diagnosis. Here, we report on clinical and genetic spectrum of 53 families from India with a total of 83 patients who had a clinical diagnosis suggestive of Marfan syndrome or related disorders. We obtained a molecular diagnosis in 45/53 (85%) index patients, in which 36/53 (68%) had rare variants in FBN1 (Marfan syndrome; 63 patients in total), seven (13.3%) in TGFBR1/TGFBR2 (Loeys-Dietz syndrome; nine patients in total) and two patients (3.7%) in SKI (Shprintzen-Goldberg syndrome). 21 of 41 rare variants (51.2%) were novel. We did not detect a disease-associated variant in 8 (15%) index patients, and none of them met the Ghent Marfan diagnostic criteria. We found the homozygous FBN1 variant p.(Arg954His) in a boy with typical features of Marfan syndrome. Our study is the first reporting on the spectrum of variants in FBN1, TGFBR1, TGFBR2, and SKI in Indian individuals.

Knobloch syndrome (KS) is an autosomal recessive disorder caused by biallelic pathogenic variants in COL18A1 . KS clinically manifests with the typical eye findings (high myopia, vitreoretinal degeneration, retinal detachment, and lens subluxation), variable neurological findings (occipital encephalocele, polymicrogyria, cerebellar malformations, epilepsy, and intellectual disability), and the other uncommon clinical manifestations. Literature review of all KS patients (source PubMed) was done with special reference to cerebellar abnormalities. Here, we report two siblings with typical KS with posterior fossa malformations and novel cerebellar midline cleft abnormality analyzed by whole exome sequencing. Known pathogenic homozygous variant c.2908C > T; (p.Arg970Ter) in exon 26 of COL18A1 was found as a cause for KS. These two siblings presented with early-onset severe ocular manifestations, facial dysmorphism, and variable central nervous system manifestations along with novel cerebellar midline cleft abnormality. The presence or absence of structural brain malformations and genotypes does not absolutely predict cognitive functions in KS patients. However, the presence of posterior fossa abnormality may be predictive for the development of ataxia in later life and needs further studies., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)