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Charcot-Marie-Tooth Disease Type 4J (CMT4J) is an ultra-rare, autosomal recessively inherited peripheral neuropathy, first described in 2007 and caused by mutations in the Fig4 Gene. FIG4 is a PIP2 phosphatase, and its loss leads to lysosomal abnormalities and “spongiform-like” vacuolization in neurons. Clinically, CMT4J is characterized by motor developmental delay, slow nerve conduction velocities, rapidly progressive paralysis, quadriplegia, resulting respiratory complications and premature death. Later-onset patients have a more variable disease course, with some experiencing mild symptoms. There are currently no approved therapies for CMT4J patients. Gene therapy represents a reasonable and promising approach to provide a meaningful and long term therapeutic benefit for this patient population. To explore this, we conducted preclinical studies in the pale tremor mouse model, which lacks Fig4 expression. These preclinical studies used a codon optimized human FIG4 gene, delivered by AAV9. Administering this vector directly to the nervous system by either intracerebroventricular (ICV) in early neonates or later, after the onset of symptoms by intrathecal (IT) injection produced benefit, as indicated by improved survival, improved gross motor function including grip strength, improved peripheral motor nerve conduction, and improved histopathological outcomes in spinal cord and dorsal root ganglia, as well as other parts of the central nervous system. Importantly, these results indicate that the benefit is greatest the earlier the FIG4-AAV9 is delivered. Preclinical study results also indicate a clear dose-response of the treatment up to the maximum feasible dose in mice, justifying the maximum feasible dose to provide the most effective treatment. Importantly, there were no observable adverse effects, even when Fig4 was overexpressed in WT mice. Overall, our results predict a benefit of this treatment to pediatric subjects, with no obvious toxicity expected, and support the further exploration of clinical trials for CMT4J patients.

Growth is an important indicator of child health; however, measurements are frequently inaccurate and unreliable. This article reviews the literature on linear growth measurement error and describes methods used to develop and evaluate an evidence-based clinical practice guideline on the measurement of recumbent length and stature of infants, children, and adolescents. Systematic methods were used to identify evidence to answer clinical questions about growth measurement. A multidisciplinary team critically appraised and synthesized the evidence to develop clinical practice recommendations using an evidence-based practice rating scheme. The guideline was prospectively evaluated through internal and external reviews and a pilot study to ensure its validity and reliability. Adoption of the clinical practice guideline can improve the accuracy and reliability of growth measurement data.

“Youth cannot just be seen as cultural dupes but as the active creators of their own lives” (131). This quote, hidden halfway through Youthscapes and written by Susan Shepler in her discussion of c...

This study examines the experiences of ten first-year English teachers in various school contexts in two Northeastern states. Through a phenomenological approach to in-depth interviewing, teachers were interviewed at the end of their first year of teaching. Commonalities in teachers' experiences include former teachers' influences on their teacher personae, negotiating their authoritative role in the classroom, understanding how and why to set boundaries with students, and demonstrating resilience and resolve in the face of multiple challenges. Implications for teacher education and induction programs are to address the disequilibrium of the self in early teaching experiences and to model habits of mind that promote “productive disequilibrium.”

* ALT: : alanine aminotransferase AST: : aspartate aminotransferase BUN: : blood urea nitrogen CBC: : complete blood count CNS: : central nervous system CSF: : cerebrospinal fluid CT: : computed tomography ECG: : electrocardiography ED: : emergency department EEG: : electroencephalography ESR: : erythrocyte sedimentation rate GI: : gastrointestinal GU: : genitourinary Hct: : hematocrit Hgb: : hemoglobin MRI: : magnetic resonance imaging WBC: : white blood cell A 14-year-old boy is transferred from a local hospital. He was playing football and was struck in the abdomen by the head of another player who was wearing a helmet. He then fell on his abdomen. He immediately complained of left upper quadrant pain, and nausea. He was taken to a local ED and hospitalized. On admission, he was alert and oriented but experienced episodic hypotension. On examination, he looked pale and was found to have significant left upper quadrant abdominal tenderness. His initial Hct was 37%. Abdominal CT showed a 12×10×11 cm lobular enhancing mass over the left kidney, with questionable involvement of the colon and perinephric hematoma (Fig. 1). There was no free air. He was transfused with 1 unit of packed red blood cells and received 1 L of normal saline. His pain was controlled with morphine and he was transported to this institution. Figure 1. A CT scan of the abdomen shows a lobular enhancing mass over the left kidney. On arrival, he appears to be well developed and is in no acute distress, having a heart rate of 86 beats/min, respiratory rate of 20 breaths/min, blood pressure of 120/84 mm Hg, and oxygen saturation of 100% in room air. His abdomen is nondistended and has normal bowel sounds. However, he has left upper quadrant and left flank tenderness. Laboratory evaluations show Hct of 31.6%, normal coagulation studies and liver enzymes, lactose dehydrogenase concentration of 258 U/L (normal, 150 to 300 U/L), and urinalysis positive for blood and protein. Chest radiograph shows normal heart and lung fields. Additional investigation leads to the diagnosis. A 9-year-old girl presents with a 4-week history of a drooping right eyelid and occasional double vision. She does not complain of easy fatigability, and she is able to ride her bike long distances without …

In this article, we describe an approach to teaching first-year composition that is built on a qualitative design for undergraduate research and writing. As writing instructors at a state teaching college, we see the need to move our students beyond the boundaries of expressivism, personal narrative, and argument and into the murkier, messier, and more critical territory of considering subjectivities, interpreting cultural texts and contexts, and, ultimately, coming to see the dynamic and dialogic nature of rhetorical situations and knowledge production. We have discovered that asking undergraduates to do field work as a way to enter the academic conversation allows them to shift from high school writing to college-level writing. Inviting them to delve into a primary research project of their own design grants them permission to construct their ownership, authority, and intellectual engagement of ideas. Case studies of the experiences of five student research writers illustrate the process through which, as ethnographers, students become actors in their own learning process.

Subcutaneous fat necrosis of the newborn is an uncommon disorder that occurs during the first few weeks of life as firm subcutaneous nodules on the cheeks, buttocks, back, arms, and thighs. This disorder, which initially was described by Harrison and McNee in 1926,1 typically affects full-term newborns who have experienced perinatal distress. Subcutaneous fat necrosis of the newborn usually resolves over a period of months, but may result in death due to its association with hypercalcemia. The association between subcutaneous fat necrosis of the newborn and hypercalcemia was first reported by Clay in 19562; however, the mechanism that results in hypercalcemia remains incompletely understood.3-7

We report three novel activating mutations in the calcium-sensing receptor (CASR) that are responsible for autosomal dominant hypocalcemia (ADH) in three unrelated families. Each mutation involves a missense substitution resulting in a nonconservative amino acid alteration, P221L, E228Q, and Q245R. These mutations were observed in affected family members, but not in unaffected family members or in unrelated control samples. All three mutations are clustered in the extracellular domain of the CASR in a region dominated by negatively charged amino acids. Each mutant and wild-type receptor was expressed in Cos-1 cells. A luciferase reporter gene assay was utilized to detect the level of receptor activity by utilizing a protein kinase C-activated promoter to drive the production of luciferin, the reporter gene product. All three mutant receptors exhibited an increased sensitivity to calcium at all concentrations tested when compared to the wild-type receptor, supporting the hypothesis that these are activating mutations and are responsible for the ADH phenotype in these families. The data presented in this study suggest the importance of this highly negatively charged region of the extracellular domain in normal CASR function.

Valproic acid has previously been demonstrated to decrease the secretion of multiple pituitary hormones; however, clinical symptoms associated with decreased hormone secretion have not been described. A girl is reported with complex partial seizures who was treated with valproic acid from age 10 years, 7 months to 12 years, 1 month and during this time had an arrest of both growth and secondary sexual development. Two months after discontinuing valproic acid she had resumption of both pubertal growth and maturation. A prospective controlled study is needed to determine more precisely the effects of valproic acid on growth and development.

The lack of chemical maturity, subsequent to normal growth and maturation, complicates the assessment of body composition in children. Even though known to overpredict percent body fat (%BF), the use of adult prediction equations is widespread in the pediatric literature. Many sex- and age-specific modified equations have been proposed. This study reports a cross-validation analysis of selected laboratory-based criterion methods in an attempt to identify the most appropriate reference which could be used in future validation studies of the more practical field/clinical testing methods. Subjects were 48 (24 boys and 24 girls) peripubertal children evenly distributed according to stage of maturation. Criterion measurements included body density (Db) by hydrostatic weighing, total body water (TBW) by deuterium oxide dilution, and total body mineral content (TMC) by dual energy x-ray absorptiometry. Five different prediction models were evaluated. Test-retest reliabilty was high (ICC = .970 to .999). Of the prediction models tested, the four-component model was considered the most accurate laboratory-based criterion model since it involves measurement of the primary constituents of fat-free mass. Based on high r2 (≥.942) values, low standard errors of estimate (SEE = 1.8 %BF males, 1.1 %BF females); and low total prediction errors (TE = 1.9 %BF males, 2.0 %BF females), the Lohman age-adjusted prediction equation showed the best agreement with the four component model. If multiple testing facilities are unavailable, the Lohman two-component (Db) model would be the criterion method of choice. © 1993 Wiley-Liss, Inc.

The purpose of this study was to evaluate the validity and reliability of the Futrex 5000A near infrared (NIR) spectrophotometer for the assessment of body composition in children and adolescents. Forty-eight subjects (24 boys and 24 girls) with a mean age of 12.7 +/- 2.7 yr underwent three methods of body composition testing: NIR, densitometry by hydrostatic weighing (HYDRO), and skinfold anthropometry (SKF). Percent body fat (%BF) and fat free mass (FFM) derived from the Lohman's age-adjusted Siri equation served as the criterion. Within session test-retest reliability was determined for the NIR device for all subjects and between-week reliability was evaluated for all test methods in 14 subjects. Based on the excellent within- and between-session reliability (ICC ranged from 0.907-0.999), the system offers the potential of obtaining longitudinal data in growth and development studies. However, the significant mean differences, moderate correlations with the criterion (r = 0.62-0.71) and inflated standard errors of estimate (SEE = 4.9-5.5% BF, 2.2-2.9 kg FFM) and total prediction errors (TE = 5.5-8.0% BF, 2.7-3.7 kg FFM) indicate that refinement of prediction equations is needed to establish the measurement validity. Continued research with expanded populations is needed to further demonstrate and evaluate the utility of this device.

Prior to sexual maturation, children and adolescents have more water and less bone mineral content than adults, resulting in less dense fat-free body mass (FFM). This suggests that previously established adult skinfold/density equations are inappropriate for use with children and adolescents for the prediction of body fatness (%BF) and FFM. To overcome this problem, Slaughter and colleagues have introduced new skinfold (SKF) equations that take into account the changing density of FFM in children and adolescents as they mature. The purpose of our study was to cross-validate a select set of the Slaughter SKF equations by comparing them with a criterion measurement (Lohman's Siri age-adjusted body density equation) in 122 subjects ranging in sexual maturation from pre- to post-pubescent and ranging in age from 8-17. Our cross-validation found very high intraclass (reliability) correlations (ICCs = 0.98-0.99) and high validity correlations (rs = 0.79-0.99). The standard errors of the estimate for %BF ranged from 3.5-4.6% and total errors for %BF ranged from 3.6-4.6%. The Slaughter equation using tricep and calf SKF for females was significantly different (P < 0.05) from the criterion measure in its prediction of %BF. In males, there was an interaction between the SKF equation and subject maturation level. The data indicate that the Slaughter SKF equations hold promise for estimating body composition in children and adolescents but are still in need of refinement.

• Background and Design.— Increases in sebaceous gland activity are often the earliest sign of the approach of puberty in children. These increases have been attributed to increases in the secretion of adrenal androgens, but the supporting data are sparse and are based on measurements of urinary, rather than serum, androgen concentrations. In this study, we examined sebum composition, serum levels of dehydroepiandrosterone sulfate, and pubertal stage in 111 boys and girls, aged 2 to 15 years. Sebum composition was evaluated by measuring the ratio of wax esters/(cholesterol + cholesterol esters), a ratio known to increase with increasing sebaceous gland activity. Results.— Both wax esters/(cholesterol + cholesterol esters) ratios and serum dehydroepiandrosterone sulfate levels began to increase in children 7 to 10 years old. These changes occurred in many children before the appearance of any physical signs of puberty. Wax esters/(cholesterol + cholesterol esters) ratios were correlated with dehydroepiandrosterone sulfate levels in both boys and girls. In prepubertal children, the regression lines passed through the origin. In subjects who were in early or late puberty, the y intercepts of the regression lines had positive values. Conclusion.— Adrenal androgens appear to be the major determinants of sebaceous gland activity during the prepubertal period and to be additive to another hormone or hormones during puberty. ( Arch Dermatol. 1992;128:1345-1348)