Consensus Statement of the IAP - Neurodevelopmental Chapter On Neurodevelopmental Disorders Habilitation Process: Strategic Plan for Prevention, Early Detection and Early Intervention.

JUSTIFICATION: Neurodevelopmental disorders, as per DSM-V, are described as a group of conditions with onset in the development period of childhood. There is a need to distinguish the process of habilitation and rehabilitation, especially in a developing country like India, and define the roles of all stakeholders to reduce the burden of neurodevelopmental disorders. PROCESS: Subject experts and members of Indian Academy of Pediatrics (IAP) Chapter of Neurodevelopmental Pediatrics, who reviewed the literature on the topic, developed key questions and prepared the first draft on guidelines. The guidelines were then discussed by the whole group through online meetings, and the contentious issues were discussed until a general consensus was arrived at. Following this, the final guidelines were drafted by the writing group and approved by all contributors. OBJECTIVES: These guidelines aim to provide practical clinical guidelines for pediatricians on the prevention, early diagnosis and management of neurodevelopmental disorders (NDDs) in the Indian settings. It also defines the roles of developmental pediatricians and development nurse counselor. STATEMENT: There is a need for nationwide studies with representative sampling on epidemiology of babies with early NDD in the first 1000 days in India. Specific learning disability (SLD) has been documented as the most common NDD after 6 years in India, and special efforts should be made to establish the epidemiology of infants and toddlers at risk for SLD, where ever measures are available. Preconception counseling as part of focusing on first 1000 days; Promoting efforts to organize systematic training programs in Newborn Resuscitation Program (NRP); Lactation management; Developmental follow-up and Early stimulation for SNCU/ NICU graduates; Risk stratification of NICU graduates, Newborn Screening; Counseling parents; Screening for developmental delay by trained professionals using simple validated Indian screening tools at 4, 8, 12, 18 and 24 months; Holistic assessment of 10 NDDs at child developmental clinics (CDCs) / district early intervention centre (DEICs) by multidisciplinary team members; Confirmation of diagnosis by developmental pediatrician/developmental neurologist/child psychiatrist using clinical/diagnostic tools; Providing parent guided low intensity multimodal therapies before 3 years age as a center-based or home-based or community-based rehabilitation; Developmental pediatrician to seek guidance of pediatric neurologist, geneticist, child psychiatrist, physiatrist, and other specialists, when necessary; and Need to promote ongoing academic programs in clinical child development for capacity building of community based therapies, are the chief recommendations.

Therapeutic thoracic duct drainage: A systematic review of the Eastern European experience and future potential.

Thoracic duct drainage (TDD) is gaining renewed interest, largely due to accumulation of evidence supporting the gut-lymph model, where toxic mesenteric lymph from the intestine contributes to development of multi-organ failure in acute and critical illness (ACI). Advances in minimally invasive TDD have added to this growing interest. The English TDD literature has been previously reviewed, but the more extensive Eastern European literature has not been available to English readers. Therefore, we undertook a systematic search of Eastern European human TDD studies using Scopus and PubMed databases and Russian language websites. Indications for TDD, clinical outcomes, and complications were reviewed. 113 studies, published between 1965 and 2015, were reviewed. The most common indications for TDD were hepatic failure, acute pancreatitis, and peritonitis. It was often used late and when other treatment options had been exhausted. Human TDD appeared safe and probably effective, especially when combined with lymphosorption. The benefit appeared to correlate with the volume of lymph drained. A randomized controlled trial (and some case-control studies) showed reduced mortality in patients with ACI with TDD. Other benefits included rapid normalization of blood parameters and decreased organ edema. This review provides further support for the gut-lymph model and justification for high quality randomized controlled trials of TDD in ACI. It also highlights other potential indications for TDD, such as bridging patients with liver failure to surgery or transplant.

Aqueously altered igneous rocks sampled on the floor of Jezero crater, Mars.

The Perseverance rover landed in Jezero crater, Mars, to investigate ancient lake and river deposits. We report observations of the crater floor, below the crater's sedimentary delta, finding that the floor consists of igneous rocks altered by water. The lowest exposed unit, informally named Séítah, is a coarsely crystalline olivine-rich rock, which accumulated at the base of a magma body. Magnesium-iron carbonates along grain boundaries indicate reactions with carbon dioxide-rich water under water-poor conditions. Overlying Séítah is a unit informally named Máaz, which we interpret as lava flows or the chemical complement to Séítah in a layered igneous body. Voids in these rocks contain sulfates and perchlorates, likely introduced by later near-surface brine evaporation. Core samples of these rocks have been stored aboard Perseverance for potential return to Earth.

Fluorescent Tracers for In Vivo Imaging of Lymphatic Targets.

The lymphatic system continues to gain importance in a range of conditions, and therefore, imaging of lymphatic vessels is becoming more widespread for research, diagnosis, and treatment. Fluorescent lymphatic imaging offers advantages over other methods in that it is affordable, has higher resolution, and does not require radiation exposure. However, because the lymphatic system is a one-way drainage system, the successful delivery of fluorescent tracers to lymphatic vessels represents a unique challenge. Each fluorescent tracer used for lymphatic imaging has distinct characteristics, including size, shape, charge, weight, conjugates, excitation/emission wavelength, stability, and quantum yield. These characteristics in combination with the properties of the target tissue affect the uptake of the dye into lymphatic vessels and the fluorescence quality. Here, we review the characteristics of visible wavelength and near-infrared fluorescent tracers used for in vivo lymphatic imaging and describe the various techniques used to specifically target them to lymphatic vessels for high-quality lymphatic imaging in both clinical and pre-clinical applications. We also discuss potential areas of future research to improve the lymphatic fluorescent tracer design.

The Effects of Terrain Properties Upon the Small Crater Population Distribution at Giordano Bruno: Implications for Lunar Chronology.

The distribution of impact craters on the ejecta of Giordano Bruno, a recent (<10 Ma) 22-km diameter crater within the lunar highlands, exhibits substantial variations. We surveyed craters D ≥ 10 m across a 1,323 km2 area of Giordano Bruno's ejecta and compared the distribution of craters with variations in thermophysical properties derived from the Lunar Reconnaissance Orbiter Diviner instrument. We used Diviner-derived rock abundance and nighttime regolith temperatures along with thermal model-predicted surface temperatures for a diversity of terrains to identify and isolate areas of the ejecta based on thermophysical properties such as bulk density and thermal conductivity. We found that thermophysical properties of the ejecta vary considerably both laterally and vertically, and consistently differ from typical regolith, indicating the presence of higher thermal inertia materials. Crater-size frequencies are significantly lower in areas with terrain properties exhibiting higher: rock abundance, nighttime temperatures, and/or modeled thermal inertia. This discrepancy in crater distribution increases for craters smaller than ∼25 m. These thermophysical variations indicate changes in the mechanical properties of the target materials. We suggest that these variations-specifically, terrain-dependent crater scaling variations and impactor-scale heterogeneities in material properties such as the presence or absence of large boulders-may influence crater diameters or inhibit crater production altogether in Giordano Bruno's ejecta; furthermore, these factors are size-dependent.

Depletion of foxp3(+) T cells abrogates tolerance of skin and heart allografts in murine mixed chimeras without the loss of mixed chimerism.

The relative contribution of central and peripheral mechanisms to the generation and maintenance of allograft tolerance is of considerable interest. Here, we present new evidence that regulatory T cells (Foxp3(+) ) maintain skin and heart allograft tolerance in mixed hematopoietic chimeric mice. Transient depletion of both donor- and recipient-derived Foxp3(+) cells was necessary and sufficient to induce decisive rejection of long-accepted skin and heart allografts. In contrast, stable hematopoietic chimerism remained, and there was no detectable induction of donor-specific reactivity to hematopoietic cells. Foxp3(+) cell depletion did not result in the rejection of skin grafts of only MHC-disparate donors (B6.C-H2(d) /bByJ), indicating that MHC antigens were not the target in the graft. We conclude that two different mechanisms of tolerance are present in mixed chimeras. Hematopoietic chimerism, resistant to Foxp3(+) depletion, is probably due to deletional tolerance to MHC antigens, as supported by previous studies. In contrast, regulatory tolerance mechanisms involving Foxp3(+) cells are required to control reactivity against non-MHC antigens not present on hematopoietic lineages.

Development and normative validation of Developmental Assessment Tool for Anganwadis for 3- to 4-year-old children (DATA-II).

OBJECTIVE: To develop, standardize, and validate a developmental scale for children, 3-4 years old, attending Anganwadis (Integrated Child Development Scheme) in India, as a follow-up assessment, using a normative approach. STUDY DESIGN AND SETTING: After the development of the 12-item Developmental Assessment Tool for Anganwadis (DATA-II), its internal consistency as well as face, content, and construct validities were studied in 100 children in Anganwadis and were found to be appropriate. A total of 385 children with a mean (standard deviation) age of 43.05 (5.02) months from randomly selected 36 Anganwadis were recruited for its standardization. Raw scores were converted to standardized T scores. Scoring pattern for domains and aggregate developmental scores were formulated. RESULTS: Except for four items in the original scale, all the items were endorsed by parents suggesting a good content validity, and Kuder-Richardson Formula 20 coefficient of 0.80 suggested a high internal consistency. Factor analysis replicated the six-factor structure explaining 76.5% of variance. An aggregated developmental score based on the standardized T scores demonstrated that a DATA-II score between 29 and 33 suggested "at risk" for developing developmental delays. A score of 28 or less suggested already delayed milestones. A score of 19-28 suggested a "mild delay," 8-18 suggested a "moderate delay," and 7 or less suggested a "severe delay" in development. CONCLUSION: The DATA-II is a measure for use in Anganwadis for identifying children at risk or with developmental delays during the first follow-up assessment, in India, for appropriate referrals and interventions.

Development and validation of language evaluation scale Trivandrum for children aged 0-3 years--LEST (0-3).

OBJECTIVE: To develop and validate a simple screening tool which can be used in the Community to identify delay in language development among children of 0-3 years of age. METHODS: The normal range for the 33 items of Language Evaluation Scale Trivandrum for 0-3years LEST(0-3) were carefully selected from various existing language development charts and scales, by experts keeping in mind the face validity and content validity. The criterion validity was assessed using a community sample of 643 children of 0 to 3 years of age, including 340 (52.9%) boys. LEST (0-3) was validated against Receptive Expressive Energent Language Scale, for screening delay in language development among children of 0-3 years. RESULTS: When one item delay was taken as LEST delay (test positive), the sensitivity and specificity of LEST(0-3), was found to be 95.85% and 77.5%, respectively with a negative predictive value of 99.8% and LR (negative) of 0.05.When two item delay was taken as LEST delay(test positive), the sensitivity and specificity of LEST(0-3), was found to be 66.7% and 94.8% respectively with a negative predictive value of 98.7% and LR (negative) of 0.35. The test-retest and inter-rater reliability were good and acceptable (Inter-class correlation of 0.69 for test-retest and 0.94 for inter-rater). CONCLUSIONS: LEST (0-3) is a simple, reliable and valid screening tool for use in the community to identify children between 0-3 years with delay in language development, enabling early intervention practices.

A novel pathway of chronic allograft rejection mediated by NK cells and alloantibody.

Chronic allograft vasculopathy (CAV) in murine heart allografts can be elicited by adoptive transfer of donor specific antibody (DSA) to class I MHC antigens and is independent of complement. Here we address the mechanism by which DSA causes CAV. B6.RAG1(-/-) or B6.RAG1(-/-)C3(-/-) (H-2(b)) mice received B10.BR (H-2(k)) heart allografts and repeated doses of IgG2a, IgG1 or F(ab')(2) fragments of IgG2a DSA (anti-H-2(k)). Intact DSA regularly elicited markedly stenotic CAV in recipients over 28 days. In contrast, depletion of NK cells with anti-NK1.1 reduced significantly DSA-induced CAV, as judged morphometrically. Recipients genetically deficient in mature NK cells (γ-chain knock out) also showed decreased severity of DSA-induced CAV. Direct NK reactivity to the graft was not necessary. F(ab')(2) DSA fragments, even at doses twofold higher than intact DSA, were inactive. Graft microvascular endothelial cells responded to DSA in vivo by increased expression of phospho-extracellular signal-regulated kinase (pERK), a response not elicited by F(ab')(2) DSA. We conclude that antibody mediates CAV through NK cells, by an Fc dependent manner. This new pathway adds to the possible mechanisms of chronic rejection and may relate to the recently described C4d-negative chronic antibody-mediated rejection in humans.

Comparison of a self-rated and a clinician-rated measure for identifying depression among adolescents in a primary-care setting.

OBJECTIVE: To compare the diagnostic accuracy of a self-rated and a clinician rated measure of depression for primary care use in school setting by pediatricians. METHODS: Two tools for screening depression were administered to early adolescents in three schools. These included the self-rated Beck Depression Inventory (BDI), pediatrician rated Children's Depression Rating Scale-Revised (CDRS-R), and ICD-10 clinical interview by a psychiatrist as reference standard. These tools were compared for their overall performance using Areas Under the Curve (AUC) of Receiver Operating Characteristic (ROC) curves. The optimal screening threshold score for both tools were identified from their sensitivity and specificity plotted for all threshold scores. For the optimal cut-off scores, the diagnostic accuracy parameters like sensitivity, specificity, predictive values, likelihood ratio and diagnostic odds ratio were calculated using contingency table. RESULTS: The area under the curve for BDI was 0.67 and CDRS was 0.50 suggesting that BDI as a screening tool has better diagnostic accuracy. The optimal screening threshold score for BDI was 18 with a sensitivity of 63 and specificity of 70. For the CDRS-R cut-off score of 59, the sensitivity was 36 and specificity was 82 respectively. Using both tools concurrently improved the diagnostic accuracy. CONCLUSIONS: Using the ROC characteristics and various validity indices, the authors showed that BDI has better sensitivity and CDRS-R a better specificity. It might be prudent to use both these instrument simultaneously to improve the identification of depression in primary care settings like school health clinic.

Adolescent health care in India: progressive, regressive or at the cross-roads?

India has a sizeable adolescent population. Adolescents constitute a vulnerable population for both mental and physical illnesses, and yet their health-care needs and delivery systems are neither well defined nor developed. Many of the mental, reproductive and nutritional health needs of this population are required to be addressed and can be addressed in the primary-care pediatric setting itself if the current system of health-care can be re-organized. This restructuring will be more effective for this population if adolescent friendly approaches, public-private partnership and policy as well as sectoral linkage between the NRHM and other national programs are achieved. The health program for this age group should have promotive and preventive as well as remedial and curative components. Also, improving the availability of trained personnel in these areas of health, culturally sensitive evidence based approaches and capacity building in the primary-care approach is essential to ensure the viability of adolescent health-care in this country.

Psychopathology, traumatic life events, and coping skills among patients attending a primary-care adolescent clinic.

OBJECTIVE: To compare the type of life events experienced and coping styles used by adolescents with and without psychopathology, attending a primary-care adolescent clinic. METHODS: One hundred adolescents with and without psychopathology attending a drop-in adolescent clinic in a tertiary-care teaching hospital were recruited. Face-to-face interview used Child Behaviour Checklist, Life Event Scale, Coddington's life event scale, Impact of Event Scale and Modified Jalowiec coping scale as measures after getting written, informed consent from the primary care-giver and verbal assent from the adolescents. Bivariate and multivariate comparisons were done between the groups appropriately. RESULTS: Adolescents with psychopathology had experienced more parental fights, increased arguments with parents, increased arguments between parents, serious illness requiring hospitalization of the adolescent. The intrusive symptoms of PTSD were noted more than avoidant symptoms among those adolescents with life events. Confrontative, emotive and optimistic coping styles were most often used in adolescent with psychopathology. CONCLUSIONS: In India, adolescents with psychopathology attending a primary care clinic have significant life events and different coping styles. Therefore, adolescents with psychopathology in this setting should be screened for life events as well as dysfunctional coping styles and given appropriate intervention.

School based adolescent care services: a district model.

OBJECTIVE: To study the perceived problems of higher secondary school students in a district and to document the effect of a family life and life skill education package. METHODS: A survey was conducted among 11501 adolescents belonging to 103 higher secondary schools in Thiruvananthapuram district, using Teenage Screening Questionnaire-Trivandrum (TSQ-T). Family life and life skill education package was given to class XI students and post intervention evaluation of improvement in knowledge level was assessed after 6 months by a structured pre-tested self-administered questionnaire. RESULTS: 61.2% adolescents reported scholastic problem, 22.1% family related problems, 31.9% personal problems and 15.2% adjustment problems, with boys reporting higher percentage. 65.8% reported body image related problems, 26.4% had dental, 21.3% ENT and 16.2% had dermatological complaints. Among girls 50.2% reported menstrual problems. 506 adolescents volunteered for medical check-up and 1247 for detailed psychological assessment. Family life and life skill education package showed consistent improvement in knowledge even after a gap of 6 months. CONCLUSIONS: The study results showed that a school based adolescent care service programme is effective and feasible.

Attitude of parents and teachers towards adolescent reproductive and sexual health education.

OBJECTIVE: To assess parents' and teachers' attitude towards Adolescent Reproductive Sexual Health Education (ARSHE). METHODS: The study group consisted of a random sample of 795 parents and 115 teachers belonging to three urban schools (one boys only, one girls only and one co-education) and one co-education rural school at Thiruvananthapuram district, Kerala, where an ICMR supported ARSHE intervention programme was done subsequently. A self-administered questionnaire for parents and teachers developed by an ICMR taskforce for ARSHE programme was used to assess their opinion on the need, content and the appropriate person to provide adolescent reproductive sexual health education in a school setting. RESULTS: 65.2% of parents and 40.9% teachers have not discussed growth and development issues with their adolescents. Only 5.2% teachers and 1.1% parents discussed sexual aspects with adolescents. 44% of parents agreed that information on HIV/AIDS/STD should be provided. More than 50% of parents were not sure whether information on topics like masturbation, dating, safe sex, contraceptives, pregnancy, abortion and childcare should be provided to adolescents. CONCLUSIONS: Results pointed out the need for introducing reproductive and sexual education in the school setting. Only 1.1% of parents and 5.2% teachers actually discussed sexual aspects with adolescents which highlights the need for parent and teacher awareness programs before ARSHE is introduced in the schools.

A primary care approach for adolescent care and counseling services.

OBJECTIVE: Adolescents can have mental, emotional, and behavior problems that are a source of stress for the child as well as the family, school and community. These may disrupt the adolescent's ability to function normally. Adolescents also have reproductive concerns especially at menarche. Considering the extent of problems of adolescents and the lack of adolescent care and counseling services, it was felt that community adolescent care counseling services should be made available. This article describes the steps involved in the setting up of Taluk model of adolescent care and counseling services. METHODS: Following steps were involved in setting up a Taluk model of adolescent care counseling service delivery system. Step I: Focus Group Discussions (FGDs) among Stakeholders. Step II: Conceptualization and Strategy planning for service delivery. III: Finalization of service delivery model Step IV: Workshops for finalization of TSQ-T 2008 version the tool to be used for assessing the adolescents in the ARSH clinics. Step V: Training Programme for Medical/Paramedical health staff. Step VI: Awareness programs for mothers of adolescents. Step VII: Setting up of ACS/ARSH clinics at Taluk hospitals. Step VIII: Evaluation of the utilization of services at Taluk hospitals. The clinic has been well utilized with 1,588 adolescents being seen in 2 years. RESULTS: Medical and Reproductive problems among adolescent girls were anemia, underweight, dysmenorrhoea, menstrual irregularities and symptoms of Polycystic Ovarian Syndrome, whereas among boys problems were mostly related to concerns about masturbation and its perceived ill effects. The psychosocial problems ranged from minor anxieties, sadness and adjustment problems to psychiatric disorders. Scholastic problems included poor concentration, poor study habits and low intelligence quotient. CONCLUSIONS: The success of the clinics in these five hospitals can be replicated in other parts of the state as well as the country. These will go a long way to ameliorate the morbidity of adolescents.

Effectiveness of a reproductive sexual health education package among school going adolescents.

OBJECTIVE: To assess the effectiveness of a school based "Adolescent Reproductive Sexual Health Education (ARSHE) Package" in improving students' knowledge on reproductive sexual health matters. METHODS: An ARSHE package originally developed at Child Development Centre, Kerala, modified and approved by ICMR taskforce group was administered in three urban schools (One boys only, one girls only and one co-education) and one co-education rural school at Thiruvananthapuram district, Kerala. The study sample consisted of 1,586 adolescents including 996 boys and 560 girls of class IX and XI. Pre and post intervention knowledge regarding reproductive sexual health matters was assessed using a self-administered questionnaire. RESULTS: In the pre-intervention period, it was observed that majority of adolescents were poorly informed about reproductive sexual health matters, particularly about contraceptives. As compared to boys, girls had much poorer knowledge about prevention of pregnancy and after intervention; there was a statistically significant increase in the knowledge in both boys and girls. Among girls percentage of poor knowledge had reduced significantly from 64.1% to 8.3% and among boys from 37.7% to 3.5%. Similarly, increase in knowledge level was also observed in various other aspects of reproductive and sexual health including, STI, HIV/AIDS and perceptions about premarital sex. CONCLUSIONS: The study results revealed the feasibility and effectiveness of school based reproductive and sexual health education intervention programs for adolescents.

Priority mental health disorders of children and adolescents in primary-care pediatric settings in India 4: training and capacity building.

Training in the primary-care child and adolescent mental health should take into consideration the local milieu, national health care education and development. It should aim to improve the mental health knowledge, competency as well as develop professional relationships between various primary, secondary and tertiary-care mental health providers to enhance outcomes. The collaborative training between the various stakeholders in the Child and Adolescent Mental Health (CAMH) should be enhanced. Currently, the favoured methods, to augment the training for practicing Primary-care Physicians, like CME and short training programs with their specific goals, settings and methodology are well documented. However, to improve the skills in CAMH for medical trainees at undergraduate and postgraduate levels, restructuring of the curriculum is essential.

Priority mental health disorders of children and adolescents in primary-care pediatric settings in India 3: psychotherapy and other non-pharmacological interventions.

The pediatrician is a primary column of support for children and adolescents with a myriad of mental health problems in low-mental health care resource countries like India. While majority of mental health consultations happen in primary-care, and only 10% are referred successfully for specialised help, there is a clear role for pediatrician psychotherapists in primary care. The primary-care pediatricians should be aware of the indications for psychotherapy, the various approaches that could be used in primary-care settings, the structure and the process of the psychotherapeutic technique involved, the suggested specific techniques for the Priority Mental Health Disorders and the evidence available to support their use as well as the developmental modifications that are required based on the cognitive development of the child or adolescent.

Priority mental health disorders of children and adolescents in primary-care pediatric settings in India 2: diagnosis, pharmacological treatment and referral.

The advent of pediatric psychopharmacology has enormously improved psychiatric care of children and adolescents. Nonetheless, our practice of diagnosis, treatment and referral in primary-care pediatric settings is not optimum as current evidence based knowledge is not regularly applied in the actual clinical circumstances. To help primary-care pediatricians minimise this in research-clinical practice, pharmacological treatment and referral in their clinical practice, they need to follow a two-tier diagnostic and multi axial treatment approach. The two-tier diagnostic approach of using a screening measure followed by confirmation of the screen positive cases with reference standard clinical criterion, improves the sensitivity and specificity. The multiaxial treatment has the advantage of offering a holistic approach to the intervention and improve prognosis from the interacting axes. The primary-care physician should be aware of the medications of choice for the Priority Mental Health Disorders and their drug interactions. Finally, referral of cases with atypical presentations, multiple comorbidities and poor response to the first-line of treatment needs referral to the next tier in the system.