Vitamin D receptor gene polymorphisms and bone mass indices in post-menarchal Indian adolescent girls

To study the association between vitamin D receptor (VDR) gene polymorphisms and bone mass indices in adolescent girls, a cross-sectional study was conducted in 120 post-menarchal girls aged 15–18 years in Pune city, India. Serum levels of ionised calcium, inorganic phosphorous, parathyroid hormone and 25-hydroxy vitamin-D were measured. Bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) were measured at total body (TB), lumbar spine (LS) and left femoral neck (FN) using dual energy X-ray absorptiometry. Polymorphisms of the VDR gene at the Fok1 and Bsm1 loci were detected using SYBR Green quantitative polymerase chain reaction. The overall distribution of genotypes at the Bsm1 locus in this study was 33.3 % Bb, 29.2 % bb and 37.5 % BB while that for the Fok1 locus was 44.2 % Ff, 7.5 % ff and 48.3 % FF. There were no significant differences in the blood parameters when classified according to Bsm1 or Fok1 genotypes. Subjects with BB genotype have significantly higher mean TBBMC, TBBA, TBBMD and LSBMD than Bb and bb (p < 0.05) and showed a tendency for association with LSBMC and LSBA (p < 0.1). Subjects with Ff genotype showed a tendency for association with left FNBMC and FNBA (p < 0.1). Bsm1 genotype did not show an association with FN bone indices whereas Fok1 genotype did not show association with TB or LS bone indices. In conclusion, the present study demonstrates VDR gene polymorphism, defined by Bsm1 genotype, has an influence on total body and lumbar spine bone mass indices in post-menarchal Indian girls.     

Bone Health Status in Indian Overweight/Obese Children

This cross-sectional study, to assess bone health in Indian overweight, obese children in comparison with healthy controls was conducted in 245 (126 girls) children and adolescents aged 6–17 y in Pune, India. It was found that total body bone mineral content, bone area and bone mineral density adjusted for Tanner stage and weight were significantly lower in obese children as compared to overweight children, which in turn, was significantly lower than normal weight children (p?<?0.05). Thus, overweight and obesity is negatively related to bone health in children and adolescents. Interventions need to be planned to increase peak bone mass accrual in overweight and obese children to reduce future risk of fracture and osteoporosis.     

Pharmacological evaluation of the efficacy of <Emphasis Type="Italic">Dysoxylum binectariferum</Emphasis> stem bark and its active constituent rohitukine in regulation of dyslipidemia in rats

The antidyslipidemic effect of the ethanolic extract of Dysoxylum binectariferum stem bark and its major active constituent rohitukine was evaluated in a high fat diet (HFD)-fed dyslipidemic rat model. Chronic feeding of ethanolic extract (200 mg/kg) in HFD-fed rats showed significant lipid lowering activity. The bioassay guided fractionation of ethanolic extract resulted in the identification of known alkaloid rohitukine as major active constituent. Rohitukine (50 mg/kg) significantly decreased the plasma levels of total cholesterol (24 %), phospholipids (25 %), triglycerides (27 %), very low density lipoprotein (27 %) and low density lipoprotein (32 %) accompanied with an increase in high density lipoprotein (21 %). The present study demonstrated that ethanolic extract of Dysoxylum binectariferum stem bark and its major constituent rohitukine both have antidyslipidemic as well as antioxidant potentials. The antidyslipidemic activity of rohitukine can be correlated to its effect on enzymes involved in lipid metabolism.     

Childhood and adolescent depression

Major depression affects 3 to 5 percent of children and adolescents. Depression negatively impacts growth and development, school performance, and peer or family relationships and may lead to suicide. Biomedical and psychosocial risk factors include a family history of depression, female sex, childhood abuse or neglect, stressful life events, and chronic illness. Diagnostic criteria for depression in children and adolescents are essentially the same as those for adults; however, symptom expression may vary with developmental stage, and some children and adolescents may have difficulty identifying and describing internal mood states. Safe and effective treatment requires accurate diagnosis, suicide risk assessment, and use of evidence-based therapies. Current literature supports use of cognitive behavior therapy for mild to moderate childhood depression. If cognitive behavior therapy is unavailable, an antidepressant may be considered. Antidepressants, preferably in conjunction with cognitive behavior therapy, may be considered for severe depression. Tricyclic antidepressants generally are ineffective and may have serious adverse effects. Evidence for the effectiveness of selective serotonin reuptake inhibitors is limited. Fluoxetine is approved for the treatment of depression in children eight to 17 years of age. All antidepressants have a black box warning because of the risk of suicidal behavior. If an antidepressant is warranted, the risk/benefit ratio should be evaluated, the parent or guardian should be educated about the risks, and the patient should be monitored closely (i.e., weekly for the first month and every other week during the second month) for treatment-emergent suicidality. Before an antidepressant is initiated, a safety plan should be in place. This includes an agreement with the patient and the family that the patient will be kept safe and will contact a responsible adult if suicidal urges are too strong, and assurance of the availability of the treating physician or proxy 24 hours a day to manage emergencies.     

Tailored use of belatacept in adolescent kidney transplantation

Adolescent transplant recipients are at risk for nonadherence, development of de novo donor‐specific antibody (dnDSA), and allograft loss. Belatacept, a selective T cell costimulatory blocker, is associated with reduced dnDSA, improved renal function, and prolonged allograft survival when compared to calcineurin inhibitor‐based regimens in adults; however, its use in children is scant. Three adolescents were initiated on belatacept between August 2017 and September 2018 at the time of kidney transplantation. Selection criteria included age ≥ 14 and EBV IgG + serostatus. Intraoperative alemtuzumab and methylprednisolone were given as induction therapy. Tailored maintenance therapy included steroid‐free belatacept and sirolimus for two patients. One patient was initially maintained steroid‐free on belatacept and belimumab, an inhibitor of B cell activating factor to treat concurrent systemic lupus erythematous; steroids were added subsequently. Renal function, biopsy‐proven rejection, dnDSA, allograft survival, infection, nonadherence, and proteinuria were monitored. Renal function was 86, 73, 52 mL/min/1.73 m² at 20, 20, and 8 months, respectively. There was 100% adherence to therapy and no development of dnDSA. All patients had treatable infections. One developed steroid‐responsive acute cellular rejection. Belatacept‐based regimens can be tailored for adolescent recipients with good short‐term clinical outcomes.     

Tuberculosis of the hip in children: A retrospective analysis of 27 patients

Background:

We retrospectively evaluated the pretreatment radiological presentation and the clinicoradiological outcome at the completion of 1 year chemotherapy in osteoarticular tuberculosis of hip in children to prognosticate correlation between them.

Materials and Methods:

We retrospectively analyzed the clinical and plain radiographic findings in 27 patients with an age of 12 years or younger in whom hip tuberculosis was diagnosed and treated between 2006 and 2010. The diagnosis was based on histopathology in 14 and clinicoradiological basis in 13 patients. The pre and post treatment plain radiographs were evaluated according to Shanmugasundaram radiological classification and our observations regarding unclassified cases which were not fit in this classification were suggested. The functional outcome at the completion of chemotherapy was assessed using modified Moon''s criteria.

Results:

The male female ratio was 11:16. The left hip was involved more frequently than the right (17:10). The average age was 7.37 years (range, 2-12 years). In the pretreatment radiographs, 9 hips were normal, 6 traveling, 4 dislocating, 1 protrusio acetabuli, 3 atrophic and 4 unclassified types (3 triradiate; 1 pseudarthrosis coxae). There were no Perthes and mortar pestle at the initial presentation. Posttreatment, the types changed to 9 normal, 3 Perthes, 1 protrusio acetabuli, 1 atrophic, 4 mortar pestle and 9 unclassified types (3 triradiate, 3 pseudarthrosis coxae and 3 ankylosed). There were 37% excellent, 18.5% good, 26% fair and 18.5% poor results. The prognosis was best with initial “triradiate” and normal types and worst with posttreatment atrophic and “ankylosed” types.

Conclusions:

The Shanmugasundaram radiological types accurately predict prognosis only in normal types and “triradiate” pattern. The functional outcome is independent of radiological morphology of the hip in smaller children.     

Differential developmental trajectories of magnetic susceptibility in human brain gray and white matter over the lifespan

As indicated by several recent studies, magnetic susceptibility of the brain is influenced mainly by myelin in the white matter and by iron deposits in the deep nuclei. Myelination and iron deposition in the brain evolve both spatially and temporally. This evolution reflects an important characteristic of normal brain development and ageing. In this study, we assessed the changes of regional susceptibility in the human brain in vivo by examining the developmental and ageing process from 1 to 83 years of age. The evolution of magnetic susceptibility over this lifespan was found to display differential trajectories between the gray and the white matter. In both cortical and subcortical white matter, an initial decrease followed by a subsequent increase in magnetic susceptibility was observed, which could be fitted by a Poisson curve. In the gray matter, including the cortical gray matter and the iron‐rich deep nuclei, magnetic susceptibility displayed a monotonic increase that can be described by an exponential growth. The rate of change varied according to functional and anatomical regions of the brain. For the brain nuclei, the age‐related changes of susceptibility were in good agreement with the findings from R2^* measurement. Our results suggest that magnetic susceptibility may provide valuable information regarding the spatial and temporal patterns of brain myelination and iron deposition during brain maturation and ageing. Hum Brain Mapp 35:2698–2713, 2014. © 2013 Wiley Periodicals, Inc .     

Obstructive Thebesian valve: anatomical study and implications for invasive cardiologic procedures

Thebesian valve is the embryological remnant of the right sinoatrial valve, guarding the coronary sinus (CS) ostium. Advanced invasive and interventional cardiac diagnostic and management tools involve cannulation of the CS ostium. The presence of obstructive Thebesian valves has been reported to lead to unsuccessful cannulation of the CS. We studied the morphology of the Thebesian valve and CS ostium to assess the possible impact of these structures on invasive cardiological procedures. One hundred fifty randomly selected human cadaveric heart specimens fixed in 10 % formalin were dissected in the customary routine manner. The Thebesian valves were classified according to their shape as semilunar/fenestrated/biconcave band like and according to their composition as membranous/fibromuscular/fibrous/muscular, and the extent to which the valve covered the CS ostium was also noted. An obstructive Thebesian valve that could interfere with the cannulation of the CS was defined as non-fenestrated (semilunar/biconcave band like) and non-membranous (fibromuscular/fibrous/muscular) valves covering >75 % of the CS ostium. Thebesian valves were present in 118 (79 %) heart specimens, of which 27 (18 %) met the criteria of being obstructive. Semilunar was the most common type of Thebesian valve in terms of shape and was observed in 65 (65/118; 55 %) hearts. This type was associated with the least mean craniocaudal (7.9 ± 0.6 mm) and mean transverse (6.25 ± 0.6 mm) diameters of the CS ostium. The mean craniocaudal diameter of the CS ostium (9.4 ± 2.1 mm) was significantly larger (p = 0.004) than the mean transverse diameter (7.15 ± 1.5 mm) in specimens with Thebesian valves, and the cranial margin of the CS ostium was free from any attachment of the Thebesian valve in all the types observed (in terms of shape). Hence, attempts to direct the tip of the catheter toward the cranial margin of the CS ostium under direct vision may lead to successful cannulation of the same when conventional techniques have been unsuccessful because of the presence of an obstructive Thebesian valve.