Ruthenium-Catalyzed Self-Coupling of Secondary Alcohols.

A simple catalytic method for self-coupling of secondary alcohols leading to the synthesis of ß-branched ketones under mild conditions is reported. Well-defined ruthenium pincer complex catalyzed the reactions. Optimization studies revealed that sodium tert-butoxide is an appropriate base for this transformation. Functionalized aryl methanols, heteroaryl methanols, and linear and branched aliphatic secondary alcohols underwent facile catalytic self-coupling reactions. Mechanistic studies revealed that both catalyst and base are crucial to achieve dehydrogenation of secondary alcohols to ketones, their subsequent controlled aldol condensation, and further hydrogenation of α,ß-unsaturated intermediates, leading to the selective formation of ß-branched ketone products. Notably, the noninnocent PNP ligand which displays amine-amide metal-ligand cooperation operative in a catalyst played a key role in facilitating this catalytic self-coupling of secondary alcohols. Liberated molecular hydrogen and water are the only byproducts.

Direct Synthesis of Aldoximes: Ruthenium-Catalyzed Coupling of Alcohols and Hydroxylamine Hydrochloride.

A catalytic method for the direct synthesis of oximes from alcohols and hydroxyl amine hydrochloride salt is reported. The reaction is catalyzed by a ruthenium pincer catalyst, which oxidizes alcohols involving amine-amide metal-ligand cooperation, and the in situ formed aldehydes condense with hydroxyl amine to deliver the oximes. Notably, the reaction requires only a catalyst and base; water and liberated hydrogen are the only byproducts, making this protocol attractive and environmentally benign.

The beneficial effect of early and prolonged kangaroo mother care on long-term neuro-developmental outcomes in low birth neonates - A cohort study.

AIM: Kangaroo mother care (KMC) has immense short-term benefits, but data on long-term outcomes are scarce. Hence, this study aimed to compare the neurodevelopmental outcomes at 12 months of corrected age (CA) in infants <2000 g receiving early and prolonged KMC to a control group. METHODS: This was a cohort study that was conducted from January 2017 to November 2018. All neonates<2000 g were eligible for the study. Neonates that received early initiation (<72 h of life) and prolonged KMC comprised the intervention group and were compared to neonates without the intervention. Bayley Scales of Infant and Toddler Development, Third edition (BSID-III) was done at 12 months of CA, and this was analysed using t-test and multi-linear regression analysis. RESULTS: There were 75 neonates in the intervention and 69 in the control group. Baseline characteristics were comparable. We found higher composite scores for cognition (110.38 ± 9.89 vs. 105.44 ± 8.77, p value = 0.023), language (107.51 ± 10.72 vs. 101.05 ± 12.06, p value = 0.014) and adaptive behaviour (87.97 ± 9.97 vs. 80 ± 9.1, p value<0.001) in the early and prolonged KMC group in comparison to the control group. CONCLUSION: Infants with early and prolonged KMC have better neurodevelopmental outcomes in terms of cognition, language and adaptive behaviour at 12 months of CA.

Ruthenium-catalysed α-prenylation of ketones using prenol.

Prenol and isoprenoids are common structural motifs in biological systems and possess diverse applications. An unprecedented direct catalytic prenylation of ketones using prenol is attained. This C-C bond formation reaction requires only a ruthenium pincer catalyst and a base, and H2O is the only byproduct.

A Boron-Nitrogen Double Transborylation Strategy for Borane-Catalyzed Hydroboration of Nitriles.

Organoborane-catalyzed hydroboration of nitriles provides N,N-diborylamines, which act as efficient synthons for the synthesis of primary amines and secondary amides. Known nitrile hydroboration methods are dominated by metal catalysis. Simple and metal-free hydroboration of nitriles using diborane [H-B-9-BBN]2 as a catalyst and pinacolborane as a turnover reagent is reported. The reaction of monomeric H-B-9-BBN with nitriles leads to the hydrido-bridged diborylimine intermediate; a subsequent sequential double hydroboration-transborylation pathway involving B-N/B-H σ bond metathesis is proposed.

46 XY disorder of sex development (DSD) due to 5 alpha (SRD5A2) deficiency - Experience from a multidisciplinary Pediatric Gender Clinic.

BACKGROUND: SRD5A2 deficiency leads to incomplete masculinization of individuals with a 46 XY karyotype. A definitive diagnosis in early infancy facilitates decisions concerning choice of sex of rearing and management. AIM: To review the clinical presentation, diagnosis, treatment and outcome of children with 46 XY DSD due to SRD5A2 deficiency at a Paediatric Gender Clinic. STUDY DESIGN AND METHODS: Retrospective review of cases of SRD5A2 deficiency (2000-15) managed with a standard protocol at a multidisciplinary clinic. Demographic data, clinical presentation, physical findings, investigations (hormonal profile, imaging, genitoscopy), psychological evaluation (child, family), medical and surgical management, outcome and follow up were collated and analyzed. RESULTS: There were 12 cases aged 3 days-14 years at presentation, 3 had parental consanguinity. Eight were reared as males and 4 as females. Specialist referral was sought for hypospadias (5), atypical genitalia (5) or incongruent pubertal masculinization (2). All had chordee, symmetrical inguinoscrotal gonads, rugose labioscrotum and proximal hypospadias (perineoscrotal -9, perineal -3). Both pubertal cases had significant masculinization and no gynecomastia. The median testosterone/dihydrotestosterone ratio was 22.1(IQR-8.6-55.7). Despite a classical phenotype, four (2 prepubertal, 2 pubertal) had a ratio <10. Genitoscopy showed urogenital sinus remnant (4) and hypoplastic verumontanum (5). Sex reassignment was done in 4. Surgical management was staged and completed by 4 years in those with infantile presentation. Besides correction of chordee and urethroplasty in 11, other procedures included orchidopexy (5), excision of a urogenital sinus remnant (4) and correction of penoscrotal transposition (4). The urethroplasty was single staged in 3. All operated cases were followed up (mean age at last follow up - 10.63 years, mean follow up period - 7.25 years). The overall cosmetic result was satisfactory, but the phallic structure remained relatively small across prepubertal period. Uroflowmetry curves were normal in 9. All showed penile tumescence/erection and two peripubertal cases had typical secondary sexual characters. All cases, including those with sex reassignment, have a well-adjusted male psyche. DISCUSSION AND CONCLUSION: The diagnosis, management and longitudinal follow up of cases of SRD5A2 deficiency at a multidisciplinary gender clinic is presented. Diagnostic dilemmas with low T/DHT ratios remained in a third of cases. Most were diagnosed in infancy and assigned a male sex of rearing, all underwent staged masculinizing genitoplasty. Those with sex reassignment also fared well with comprehensive management after family counseling.

Psychological aspects in children and parents of children with chronic kidney disease and their families.

Pediatric chronic kidney disease (CKD) is a chronic illness that affects the overall quality of life of patients during childhood. This article highlights the psychological and social burden of CKD in patients and their families. Patients with CKD and their families require comprehensive treatment for psychosocial problems. Therefore, it is crucial for pediatricians to screen for these issues and refer patients and their families for therapy. Tools that are short, easy to administer, and easy to score, such as the Pediatric Quality of Life Inventory or the Childhood Depression Inventory, can be utilized during routine clinical appointments. Reducing the negative impact of CKD on the family will improve the well-being and coping skills of patients and their families.

Parenting Style, Parental Personality, and Child Temperament in Children with Anxiety Disorders-A Clinical Study from India.

BACKGROUND: Anxiety disorders are common in children and contribute to adverse developmental outcomes. Although etiological models of child anxiety have identified various environmental factors, very few studies in India have examined these factors in children presenting with anxiety disorders. Therefore, the present study was designed to examine parenting styles, parental personality, and child temperament in children with anxiety disorders in an Indian outpatient setting. METHODS: In total, 42 children with anxiety disorders and 42 typically developing children, matched on age and gender, were screened using Child Behavior Checklist, Color Progressive Matrices, and Screen for Child Anxiety Related Emotional Disorders Parent version. Their parents were screened using Mini International Neuropsychiatric Interview 5.0, following which they filled the questionnaires for parenting styles, parent personality, and child temperament. RESULTS: There were significant differences between the two groups on parenting style, parent personality, and child temperament. Anxiety disorder was positively associated with the father's permissiveness and negatively with the mother's authoritativeness and child's sociability. A combination of parenting styles and child temperament explained 69% of the variances in child anxiety disorders. There were significant associations between parental personality, child temperament, and parenting style. Parent and child characteristics explained 14%-46% of the variances in parenting styles. CONCLUSION: Results of this study are generally consistent with Western studies outlining the influence of child temperament and parenting styles on child outcome and have important implications for clinical management of anxiety disorders.

Clinicians' Perspectives on Diagnostic Markers for Depression Among Adolescents in India: An Embedded Mixed-Methods Study.

Limited research has investigated whether clinicians around the world find diagnostic criteria for depression that were originally developed in the West are useful with diverse populations. Using an embedded mixed-methods design in India, we examined (a) clinicians' and trainees' (n = 143) ratings of the usefulness of the criteria for Major Depressive Disorder (MDD) outlined in two major diagnostic systems (Diagnostic and Statistical Manual of Mental Disorders-5; DSM-5 and International Classification of Mental and Behavioral Disorders-Tenth Edition; ICD-10), and (b) narrative descriptions of clinical cases of adolescent depression and usefulness of diagnostic and screening instruments in day-to-day practice using semi-structured interviews in a subsample of clinicians (n = 24). Qualitative findings demonstrated that Indian clinicians identified markers of depression that were consistent with the current diagnostic manuals (affective, cognitive, somatic symptoms), and the numeric ratings suggested that clinicians found a majority of DSM-5 and ICD-10 criteria for MDD to be useful. However, Indian clinicians also identified additional markers of adolescent depression (i.e., interpersonal conflicts and issues, impairment in school-related functioning, anger-based symptoms, anxiety-based symptoms, additional somatic complaints not included in DSM-5 or ICD-10), highlighting the need to modify existing diagnostic criteria to be more inclusive. The findings suggest the need for culturally informed diagnostic practices that consider a wide range of clinical presentations of depression among adolescents worldwide.

Fear of Childbirth among Pregnant Women Availing Antenatal Services in a Maternity Hospital in Rural Karnataka.

BACKGROUND: Pregnancy, though joyful, may be a time of fear and anxiety. Twenty percent of pregnant women in developed nations report a fear of childbirth, and 6%-10% describe a severe fear that is crippling. This could lead to adverse maternal and fetal outcomes. Data on fear of childbirth among pregnant women are lacking in India and would help in incorporating measures to enhance routine antenatal care. METHODOLOGY: With the objective of documenting fear of childbirth and associated factors, a cross-sectional study was conducted in rural Karnataka among women availing antenatal care services, using a face-validated 30 item questionnaire developed by the authors which was then scored to determine fear of childbirth. RESULTS: Of 388 women studied, 45.4% (176) had a fear of childbirth. The commonest fears documented were: not feeling confident about childbirth, being afraid or tense about the process of childbirth, fear of labor pains, and fear of cesarean section. Teenage pregnancy, nulliparity, primigravida status, and having no living child were significantly associated with fear of childbirth. CONCLUSION: Overall, 45.4% (176) of women had a fear of childbirth. It is important to identify and address the various fears of childbirth that women may have, as revealed by this study, with a view to providing information and reassurance to the mother, with the aim of improved maternal and fetal outcomes.

Psychosocial Issues in Children With Thalassemia: From Identification to a Model for Management in a Developing Country.

INTRODUCTION: Children with chronic disorders like ß thalassemia major (TM) and their care givers are known to face various psychosocial problems. This study used screening tests to detect these psychosocial issues so that prompt referral for counseling is possible. METHODS: A semistructured demographic questionnaire, Pediatric Symptom Checklist (PSC-17) and the Strengths and Difficulties Questionnaire (SDQ) were administered to 30 children with TM, on regular treatment at a tertiary care hospital. The same questionnaires were administered to age-matched and sex-matched controls. Parents were administered the General Health Questionnaire (GHQ). Children with TM scored higher on both PSC-17 (9.93 vs. 4.87; P<0.001) and SDQ (14.9 vs. 10.9; P=0.008). The parents of children with TM scored higher on the GHQ (10.3 vs. 8.0; P=0.027). RESULTS: Psychosocial morbidity was higher in children with TM and their care-givers. Screening tools help detect children and care givers in need of formal counseling. CONCLUSIONS: The study makes a case for management of these issues by the pediatrician in tandem with mental health professionals. Some strategies that can be used in managing these children and their families are presented. In addition, issues in management with particular focus on a developing country context are highlighted and discussed.

Development of norms for executive functions in typically-developing Indian urban preschool children and its association with nutritional status.

Executive functions (EFs) are essential and important for achieving success in children's everyday lives and play a fundamental role in children's cognitive, academic, social, emotional and behavioral functioning. A cross-sectional study was carried out to develop age- and sex-specific norms for EFs using the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P) among 2- to 5-year-olds from urban Bangalore, India. In addition, the association between EFs and anthropometric measures, a marker of nutritional status, is also examined. Primary caregivers of 412 children, equally distributed by age and sex, participated. Raw scores for each domain and indices were converted to standard t-scores and percentiles were computed. A t-score at or above 63 corresponding to the 90th percentile was considered as the cutoff for executive dysfunction in this sample. The prevalence of executive dysfunction is 10% based on the Global Executive Composite score of the BRIEF-P. The cutoff score for identifying executive dysfunction using existing United States (US) norms is higher compared to the cutoff score obtained in the current study. Therefore, using US norms for Indian children could result in the prevalence of executive dysfunction been underestimated. Multiple linear regression analysis revealed that stunted and underweight children have significantly elevated EF scores after adjusting for age, sex and socioeconomic status (SES; p < .01). A greater understanding of EFs in preschool children is important for the early identification of executive dysfunction and implementing interventions to improve their future prospects. This study also shows that undernourished children are more likely to have executive dysfunction.

Norms for developmental milestones using VABS-II and association with anthropometric measures among apparently healthy urban Indian preschool children.

Assessment of developmental milestones based on locally developed norms is critical for accurate estimate of overall development of a child's cognitive, behavioral, social, and emotional development. A cross-sectional study was done to develop age specific norms for developmental milestones using Vineland Adaptive Behavior Scales (VABS-II) (Sparrow, Cicchetti, & Balla, 2005) for apparently healthy children from 2 to 5 years from urban Bangalore, India, and to examine its association with anthropometric measures. Mothers (or caregivers) of 412 children participated in the study. Age-specific norms using inferential norming method and adaptive levels for all domains and subdomains were derived. Low adaptive level, also called delayed developmental milestone, was observed in 2.3% of the children, specifically 2.7% in motor and daily living skills and 2.4% in communication skills. When these children were assessed on the existing U.S. norms, there was a significant overestimation of delayed development in socialization and motor skills, whereas delay in communication and daily living skills were underestimated (all p < .01). Multiple linear regression revealed that stunted and underweight children had significantly lower developmental scores for communication and motor skills compared with normal children (ß coefficient ranges from 2.6-5.3; all p < .01). In the absence of Indian normative data for VABS-II in preschool children, the prevalence of developmental delay could either be under- or overestimated using Western norms. Thus, locally referenced norms are critical for reliable assessments of development in children. Stunted and underweight children are more likely to have poorer developmental scores compared with healthy children. (PsycINFO Database Record

Practical Counseling Skills for the Pediatrician in the Indian Context.

Primary care pediatricians are often faced with children and families who need more than just a consultation. Pediatricians are also the first point of contact for many children and families in distress. Hence, the decision of whether to reassure and follow them up or refer them for an evaluation and management to a mental health professional is something all pediatricians find difficult to make. In order to serve their clients well, it is necessary that pediatricians are trained to identify and manage common child psychological/psychiatric problems. They may also be called upon to break bad news, motivate families to seek treatment and motivate children to accept offered treatment. Most training courses in Pediatrics do not offer skills training in counseling, making the transition to real life practice a difficult proposition. This paper focuses on what is counseling, what situations make it necessary for pediatricians to offer counseling, the methods that can be useful and some tips to improve communication, with an emphasis on unique issues in the Indian context. Some techniques that are simple, brief and can be used by pediatricians are discussed in this paper.

Issues related to obtaining intelligence quotient-matched controls in autism research.

BACKGROUND: Intelligence Quotient (IQ) is considered to be an index of global cognitive functioning and has traditionally been used as a fulcral measure in case-control studies in neuro-developmental disorders such as autism. AIM: The aim is to highlight the issues of "matching for IQ" with controls in autism research. MATERIALS AND METHODS: Percentile scores on the Coloured Progressive Matrices of 20 children with autism in the age range of 5 to 12 years have been graphically compared with 21 age matched typically developing children. RESULTS AND CONCLUSIONS: The percentile scores of the so-called high functioning children with autism from special schools were well below that of typically developing children. There are many challenges when using IQ in case-control studies of autism. Alternative approaches need to be considered.

IQ in Autism: Is there an Alternative Global Cognitive Index?

BACKGROUND: Intelligence quotient (IQ) but not the core symptoms have been known to predict outcomes in autism. Besides resource issues in India, assessing IQ in presence of autistic symptoms is challenging in general. MATERIALS AND METHODS: In a pilot study, we explored different global indices of development in 30 children with confirmed autism. These included Wechsler intelligence scale for children or Wechsler preprimary scale of intelligence-revised (n = 10), Raven's progressive matrices (RPM) (n = 10), Vineland adaptive behavior scales II, parent report version (VABS) (n = 30) and teacher's estimate of mental age (TIQ) (n = 30). Three subgroups (Group A) with Wechsler's scales derived IQ (WISIQ), (Group B) with RPM derived IQ and (Group C) those without a formal IQ measure were compared. RESULTS: All groups were comparable on age and their scores on Childhood Autism Rating Scale and Indian Scale for Assessment of Autism Adaptive behavior composite scores (Ad Bh composite) derived from VABS and WISIQ showed significant correlations with each other in Group A; TIQ significantly correlated with Ad Bh composite scores, but not with the WISIQ, although the latter two scores themselves did not significantly differ from each other. RPM consistently overestimated children's performance compared to Ad Bh composite or TIQ in Group B, but the Ad Bh composite and TIQ were themselves significantly correlated. In Group C, there were poor correlations between Ad Bh composite and TIQ. The Ad Bh composite score in this group was significantly different from the other two groups. CONCLUSION: There is a need to fine tune the assessment for global cognitive measures in autism and explore their real world importance.

Children of men with alcohol dependence: Psychopathology, neurodevelopment and family environment.

BACKGROUND: Children of people with alcohol dependence (COAs) are at high risk for behavioral and cognitive problems. AIM: Aim of this study was to compare the nature and extent of these problems in children of men with and without alcohol dependence. MATERIALS AND METHODS: 32 children (17 in study group and 15 controls) were evaluated for psychopathology, neurodevelopment, cognitive functioning and family environment. Tools used were: Socio-demographic data sheet, Malin's Intelligence Scale for Indian Children (MISIC), Child Behavior Checklist, Trail Making Test, Neurodevelopment Scale and the Family Environment Scale. RESULTS: Children of men with alcohol dependence had higher externalizing than internalizing scores. Children of alcohol-dependent fathers had higher scores on the neurodevelopment scale and lower scores on the performance scale of the MISIC than the children in control group. These children also made more errors on the Trail Making Test. The family environment of COAs was characterized by lack of independence for its members, greater perceived control and lack of adequate cultural and intellectual activities. CONCLUSION: Our findings suggest that children of men with alcohol dependence have difficulties with frontal lobe functions and neurodevelopmental tasks. There are also difficulties in the family, which are related to alcohol consumption by the father.

Effect of methanol-induced oxidative stress on the neuroimmune system of experimental rats.

It is well known that the nervous system has increased susceptibility to methanol intoxication. The present study reveals the effect of methanol intoxication on antioxidant status, lipid peroxidation and DNA integrity in hypothalamic-pituitary-adrenal (HPA) axis organs and spleen. Non-specific and specific immune functions were analyzed. In addition, open field behavior, plasma corticosterone level and blood methanol level were estimated. Male Wistar albino rats were intoxicated with methanol (2.37 g/kg b.wt., i.p.) for 1 day, 15 and 30 days. Administration of methanol showed significant increase in enzymatic (superoxide dismutase, catalase, glutathione peroxidase), non-enzymatic (reduced glutathione and Vitamin C) antioxidants and lipid peroxidation (LPO) in hypothalamus and adrenal gland of day 1 group. However, decrease in enzymatic and non-enzymatic antioxidants with concomitant increase in LPO level were observed in 15 and 30 days groups. Plasma corticosterone level was significantly increased in day 1 and 15 days groups whereas, 30 days methanol intoxication group showed considerable decrease in corticosterone level compared with control animals. Cell-mediated immune response of footpad thickness was significantly decreased with an increased leukocyte migration inhibition. Humoral immune response of antibody titers was elevated in methanol-intoxicated groups. Neutrophil functions, adherence and phagocytic index (PI) were found to be significantly decreases. Furthermore, significant increase in the avidity index and nitro blue tetrozolium reduction was observed in the methanol exposed animals. Day 1 methanol exposed group showed increased PI compared to the control ones. Methanol exposure for 30 days showed an increased DNA fragmentation in the hypothalamus, adrenal glands, and spleen. In conclusion, exposure to methanol-induced oxidative stress disturbs the HPA-axis function altering the level of corticosterone, which lead to varied non-specific and specific immune response in experimental rats.