Disturbance of parathyroid hormone-related protein signaling in the nitrofen-induced hypoplastic lung

Purpose

Despite remarkable progress in resuscitation and intensive care, the morbidity and mortality rates in congenital diaphragmatic hernia (CDH) remain high due to severe pulmonary hypoplasia. The pathogenesis of pulmonary hypoplasia associated with CDH is still not clearly understood. Pulmonary parathyroid hormone-related protein (PTHrP) is expressed in the type II epithelial cells and stimulates surfactant production by a paracrine feedback loop regulated by PTHrP receptor (PTHrP-R), which is expressed in the mesenchyme, during terminal airway differentiation. It has been reported that PTHrP knockout and PTHrP-R null mice both exhibit pulmonary hypoplasia, disrupting alveolar maturation before birth. We designed this study to test the hypothesis that gene expression of PTHrP and PTHrP-R is downregulated in the late stages of lung morphogenesis in the nitrofen-induced hypoplastic lung.

Methods

Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs were harvested on D15, 18, and 21 and divided into three groups: control, nitrofen without CDH [CDH(?)], and nitrofen with CDH [CDH(+)] (n = 8 at each time point for each group, respectively). Total mRNA was extracted from fetal lungs and mRNA expression of PTHrP and PTHrP-R was analyzed by real-time RT-PCR and the significant differences between the groups were accepted at P < 0.05 by statistical analysis. Immunohistochemical studies were also performed to evaluate PTHrP and PTHrP-R protein expression at each time point.

Results

Pulmonary mRNA expression of PTHrP-R was significantly decreased in both nitrofen groups [CDH(?) and CDH(+)] compared to controls at D18 and 21. The mRNA level of PTHrP was significantly decreased at D21 in both nitrofen groups compared to controls. Immunoreactivity of PTHrP and PTHrP-R at D18 and 21 was diminished in the distal epithelium and in the mesenchyme, respectively, in the nitrofen-induced hypoplastic lung compared to control lungs. There were no significant differences in both gene/protein expression of PTHrP and PTHrP-R on D15.

Conclusion

Downregulation of PTHrP and PTHrP-R gene expression during late lung morphogenesis may cause pulmonary hypoplasia in the nitrofen CDH model, disrupting alveolar maturation and surfactant production by interfering with mesenchymal–epithelial interactions.     

Parental involvement and mental well-being of Indian adolescents

This study examined the association between parental involvement and mental well-being among the 6721 school-going adolescents aged 13 to 15 years who participated in India??s nationally-representative Global School-based Student Health Survey (GSHS) in 2007. Parental involvement (homework checking, parental understanding of their children??s problems, and parental knowledge of their children??s free-time activities) was reported by students to decrease with age, while poor mental health (loneliness, insomnia due to anxiety, and sadness and hopelessness) increased with age. Age adjusted Logistic regression models showed that high levels of reported parental involvement were significantly associated with a decreased likelihood of poor mental health.     

Indian Children with Developmental Disabilities: Early versus Late Referral for Intervention

Objective

To study the age at referral, of children with neurodevelopmental disabilities to Child Development and Early Intervention Clinic and compare the neuromorbidity and socio-economic profile of the early and late presenters.

Methods

This retrospective observational study was conducted at Child Development and Early Intervention Clinic (CDEIC) located in Northern India. Case records of children enroled at CDEIC in last 5 y; with neurodevelopmental disabilities namely Mental Retardation/Global Developmental Delay, Cerebral Palsy, hearing and vision impairment were separated and studied.

Results

Two thousand and twenty cases were included in this study. 62.8 % presented before 3 y of age (early presenters) and 37.1 % presented at 3 y or more (late presenters). There was no difference in the overall rates and severity of mental retardation in early and late presenters. The proportion of children with quadriparetic cerebral palsy, hearing impairment, vision impairment and multiple disabilities was significantly more in early presenters. The early presenters had better parental education status, less number of siblings, better immunization status and more were delivered at a hospital and residing in urban areas.

Conclusions

Large numbers of children with neurodevelopmental disabilities are referred late for intervention services, leading to loss of opportunity for early intervention. Children with purely mental disability are the ones, most likely to be referred late. Socio-economic differences are significantly contributing to these delayed referrals.     

Rhabdoid tumor of the kidney with humoral hypercalcemia and parathyroid hormone-related protein production

This is a report of a 7-month-old infant with malignant rhabdoid tumor of the kidney (RTK). The patient (pt) demonstrated clinical and biochemical evidence of humoral hypercalcemia of malignancy (HHM). The hypercalcemia responded promptly to calcitonin treatment and tumor removal. Despite aggressive surgery and chemotherapy, the patient expired four months after diagnosis. The primary tumor displayed adenylate cyclase-stimulating activity (ACSA) indicating the production of parathyroid hormone-related protein (PTHrP) by the primary tumor. This is the first report of ACSA documented in a pt with RTK. © 1995 Wiley-Liss, Inc.     

Prenatal treatment with retinoic acid activates parathyroid hormone-related protein signaling in the nitrofen-induced hypoplastic lung

Purpose  

Prenatal treatment with retinoic acid (RA) has been reported to stimulate alveologenesis in hypoplastic lungs (HL) in the nitrofen model of congenital diaphragmatic hernia (CDH). Parathyroid hormone-related protein (PTHrP) promotes alveolar maturation by stimulating surfactant production, regulated by PTHrP receptor (PTHrP-R). PTHrP knockout and PTHrP-R null mice both exhibit pulmonary hypoplasia. We have recently reported that nitrofen inhibits PTHrP signaling in the nitrofen-induced HL. Because both PTHrP and PTHrP-R genes have RA-inducible element, we hypothesized that prenatal administration of RA upregulates pulmonary gene expression of PTHrP and PTHrP-R in the nitrofen-induced HL.     

Pitfalls in diagnosis: pediatric musculoskeletal tumors

In general, the 5-year survival for patients with most types of sarcomas has doubled since the 1970s; improved chemotherapy, surgery, radiographic, and pathologic techniques all have contributed to this accomplishment. The 5-year survival for patients with osteosarcoma, like most sarcomas, is approximately 60% when the disease is treated with appropriate chemotherapy, surgery or radiation therapy. The details of treatment are complex and many controversies remain. The initial workup, biopsy, chemotherapy, and surgery should be delivered by a center with experience in the treatment of sarcomas.     

Extensive central nervous system involvement in optic pathway gliomas in neurofibromatosis type 1

Optic pathway gliomas (OPG) in neurofibromatosis type 1 (NF1) usually remain localized to the anterior visual pathway. However, a small number can demonstrate widespread dissemination. We describe three children with NF1 OPGs and extensive central nervous system involvement. In one case, a postmortem examination revealed tumor cells extending continuously from the optic nerves to the conus medullaris. This is the most widespread NF1 OPG reported in the literature. We suggest that rapid visual deterioration in the absence of radiographic changes or increased intracranial pressure can be caused by increasing tumor infiltration within the central nervous system.     

The involvement of musculoskeletal system and its influence on postural stability in children and young adults with cystic fibrosis

Background

Cystic fibrosis (CF) affects the musculoskeletal system via a multifactorial pathway that includes vitamin D deficiency and involvement of respiratory muscles such as intercostals due to recurrent upper and lower respiratory tract infections. Eventual result is the deterioration of musculoskeletal health and posture in CF patients. Postural stability is directly affected by posture and can be compromised in every musculoskeletal problem. The aim of this study is to evaluate musculoskeletal system and postural stability in patients with CF.

Methods

Patients with CF over six years of age and age and sex-matched control groups were included in the study. Cobb angle and thoracic kyphosis angles were measured on the spine radiographs. Both patients and control group were examined with pediatric gait, arms, legs and spine scale (pGALS). They also were evaluated with a NeuroCom Balance Master for their postural stability.

Results

Fifty-one patients with CF and 94 healthy controls participated in the study. In results of the pGALS examination, CF group had significantly more pathological findings than the control group in lower extremity appearance and movement (p?=?0.006 and p?=?0.01) and spine appearance and movement (p?=?0.001 and p?=?0.022) domains. The tandem walking speed was significantly higher in controls with a mean of 24.45?±?7.79 while it was 20.47?±?6.95 in the CF group (p?=?0.03). Various limits of stability parameters also showed significant differences. Medium correlations were found between musculoskeletal examination and postural stability parameters.

Conclusion

In patients with CF, a systematic but simple musculoskeletal examination can detect pathologies, which are more frequent than the normal population. These pathologies show a medium correlation with the involvement of postural stability.

     

Amebiasis in children: the Indian experience

The clinical features including complications, diagnosis and treatment of amebiasis in children have been described with the focus on the experience in India.     

Expression of peptide fragments from proADM and involvement of mitogen‐activated protein kinase signaling pathways in pulmonary remodeling induced by high pulmonary blood flow

Pulmonary arterial hypertension (PAH) is a life‐threatening disease characterized by progressive pulmonary arterial remodeling and right ventricular failure. Despite recent advances in pathophysiological mechanism exploration and new therapeutic approaches, PAH remains a challenging condition. In this study, we investigated the roles of the peptide fragments from proadrenomedullin (proADM) such as adrenomedullin (ADM), adrenotensin (ADT), and proadrenomedullin N‐terminal 20 peptide (PAMP) during pulmonary remodeling caused by high pulmonary blood flow, and probed the possible involvement of mitogen‐activated protein kinase (MAPK) signal transduction pathways. Sixteen rat models of PAH were artificially established by surgically connecting the left common carotid artery to the external jugular vein. We subcutaneously injected an extracellular signal‐regulated protein kinase (ERK1/2) inhibitor, PD98059, in eight rats, treated another eight rats with an equal volume of saline. Eight rats without connections served as the control group. We observed that mRNA expression levels of ADM, stress‐activated protein kinase (SAPK), and ERK1/2 were significantly elevated in the shunted rats; furthermore, ERK1/2 levels were significantly inhibited by PD98059. Protein levels of ADM, PAMP, p‐SAPK, and p‐ERK1/2 were significantly higher ADT was lower, and p‐p38 remained unchanged in the rat models compared with the controls. However, the protein expression of both ADM and p‐ERK1/2 was significantly inhibited by PD98059. Our results suggest that levels of ADM, ADT, and PAMP respond to pulmonary remodeling, and that activation of the SAPK and ERK1/2 signaling pathways is involved in pulmonary hypertension and artery remodeling caused by high pulmonary blood flow.     

Lysosomal storage disorders: A review of the musculoskeletal features

The lysosomal storage disorders are a collection of progressive, multisystem disorders that frequently present in childhood. Their timely diagnosis is paramount as they are becoming increasingly treatable. Musculoskeletal manifestations often occur early in the disease course, hence are useful as diagnostics clues. Non‐inflammatory joint stiffness or pain, carpal tunnel syndrome, trigger fingers, unexplained pain crises and short stature should all prompt consideration of a lysosomal storage disorder. Recurrent ENT infections, hepatosplenomegaly, recurrent hernias and visual/hearing impairment – especially when clustered together – are important extra‐skeletal features. As diagnostic and therapeutic options continue to evolve, children with lysosomal storage disorders and their families are facing more sophisticated options for screening and treatment. The aim of this article is to highlight the paediatric presentations of lysosomal storage disorders, with an emphasis on the musculoskeletal features.     

Youth Developmental Assets in Global Perspective: Results from International Adaptations of the Developmental Assets Profile

The Developmental Assets Profile (DAP) measures young people’s reported experience of eight categories of developmental assets known to be linked to numerous indicators of well-being, including Support, Empowerment, Boundaries and Expectations, Constructive Use of Time, Commitment to Learning, Positive Values, Social Competencies, and Positive Identity. The DAP scales were found to have acceptable to good alpha reliabilities, stability reliabilities, and validity in U.S. sample field testing. DAP data have been or are currently being collected in more than a dozen countries. This paper reports on DAP data from five countries whose DAP samples were sufficiently large—Albania, Bangladesh, Japan, Lebanon, and the Philippines—to warrant an initial summary of how well the DAP appears to work in a range of diverse cultural settings, and how the youth asset profiles observed in those studies compare to U.S. levels found in the development of the DAP. Most of the DAP subscales had acceptable internal consistency reliabilities, and some had acceptable stability reliabilities, in these international samples. Where validity was examined, findings were similar to results found for U.S. samples. These results suggest that the DAP can be effectively adapted and used to study positive youth development in other cultural settings, including, with some qualifications, use in youth program monitoring, evaluation, and improvement. Across all countries, including the U.S., the least well-experienced asset scale was Constructive Use of Time, and the least asset-rich context was Community. These results help illuminate those aspects of youths’ developmental experience that appear to be important and similarly-experienced parts of adolescent development regardless of the adolescent's cultural context. The study thus has potentially important contributions to make in the realms of cross-cultural psychology, developmental psychology, community psychology, and applied developmental science.     

Reye syndrome: the Indian experience

All articles reporting cases of Reye syndrome in India were studied. The total number of reported cases is 71. Of these 54 are well-described and have been analysed with reference to their epidemiological, clinical and investigative features. The seasonal prevalence is early summer to the monsoon. Clinical and investigative features were similar to cases reported elsewhere. Mortality is high (87%). None of the patients had taken aspirin. The importance of Reye syndrome as a health problem and the need for wider surveillance of outbreaks of certain viral illnesses is dicussed.     

A longitudinal study on protein calorie malnutrition in North Indian pre-school children

Summary Eighty-one cases with marasmic kwashiorkor were found during a longitudinal study of 7493 pre-school children in an urban community at Delhi. It was observed that the major casuative factors for the variation in the clinical features of protein calorie malnutrition between South and North Indian preschool children were the types of weaning diets differing in protein and caloric content. The relationship between malnutrition and infections and infestations is enumerated. The relationship between malnutrition and somatic growth is elucidated. An extensive nutrition education programme for the prevention and control of protein calorie malnutrition among pre-school children with a liaison between the survey teams, M.C.H. clinics and hospitals is discussed. From the Longitudinal Morbidity and Mortality Survey of Children's Unit in Delhi under the Indian Council of Medical Research. Postal Address: Flat 32 Shankar Market, New Delhi-1.     

Developmental care in the UK: a developing initiative

Aim:  To review developmental care over time in the UK.
Methods:  Longitudinal study comprising two prospective observational studies of unit organization and developmental care activity collected in 2005 and 2008 in all UK neonatal units. Indices related to developmental care and an aggregated score are reported corresponding to year and level of care.
Results:  In 2008, over 90% units had open visiting for parents and modified lighting and 80% modified noise, showing no change since 2005. Incubator cover usage increased from 75% to 95%. Rates of parental tube feeding dropped from 76% to 64% and kangaroo care increased from 50% to 80%. Proportions of units with developmental care personnel and staff trained in developmental care have almost doubled to 64% and 57%. Aggregated scores, reflecting eight basic indices of developmental care, were unchanged: the 2005 mean was 5.7 (SD = 1.5) and 6.2 (SD = 1.5) in 2008. Scores were significantly higher in larger units and in those with developmental care personnel or developmentally trained staff.
Conclusion:  Despite a significant increase in developmental care skills and infrastructure, variable approaches persist, with limited improvements over time. These findings reflect a UK culture that is ambivalent towards developmental care, and enable comparison with other countries where developmental care is more fully supported.