Rifampin monotherapy for children with idiopathic infantile hypercalcemia

Idiopathic Infantile Hypercalcemia (IIH) is characterized by hypercalcemia and hypercalciuria owing to PTH-independent increases in circulating concentrations of 1,25(OH)2D. At least 3 forms of IHH can be distinguished genetically and mechanistically: infantile hypercalcemia-1 (Hypercalcemia, Infantile, 1; HCINF1) due to CYP24A1 mutations results in decreased inactivation of 1,25(OH)2D; HCINF2 due to SLC34A1 mutations results in excessive 1,25(OH)2D production; and HCINF3 in which a variety of gene variants of uncertain significance (VUS) have been identified and where the mechanism for increased 1,25 (OH)2D is unclear. Conventional management with dietary calcium and vitamin D restriction has only limited success. Induction of the P450 enzyme CYP3A4 by rifampin can provide an alternate pathway for inactivation of 1,25(OH)2D that is useful in HCINF1 and may be effective in other forms of IIH. We sought to assess the efficacy of rifampin to decrease levels of serum 1,25(OH)2D and calcium, and urinary calcium concentrations in subjects with HCINF3, and to compare the response to a control subject with HCINF1. Four subjects with HCINF3 and the control subject with HCINF1 completed the study using rifampin 5 mg/kg/day and 10 mg/kg/day each for 2 months separated by a 2-month washout period. Patients had age-appropriate intake of dietary calcium plus 200 IU vitamin D/day. Primary outcome was efficacy of rifampin to lower serum concentrations of 1,25(OH)2D. The secondary outcomes included the reduction of serum calcium, urinary calcium excretion (as random urine calcium: creatinine (ca:cr) ratio) and serum 1,25(OH)2D/PTH ratio. Rifampin was well tolerated and induced CYP3A4 at both doses in all subjects. The control subject with HCINF1 showed significant response to both rifampin doses with decreases in the serum concentration of 1,25(OH)2D and the 1,25(OH)2D/PTH ratio while the serum and urine ca:cr levels were unchanged. The four patients with HCINF3 showed reductions in 1,25(OH)2D and urinary ca:cr after 10 mg/kg/d, but hypercalcemia did not improve and there were variable responses in 1,25(OH)2D/PTH ratios. These results support further longer-term studies to clarify the usefulness of rifampin as a medical therapy for IIH

Meaning as a core principle in Social Work practice = El sentido como principio básico en la práctica del Trabajo Social

This paper explores the concept of meaning as a focus area for expanding core values and practice realities in social work. By focusing on helping clients develop a sense of meaning and purpose in their lives, social workers can help clients maximize their personal and cultural strengths in the service of meeting their developmental and social aims. A case example is used, and concepts discussed are applied in the area of finding meaning in life.En este trabajo se explora el concepto de significado como un área de interés para la expansión de los valores fundamentales y las realidades de la práctica en el trabajo social. Al centrarse en ayudar a los clientes a desarrollar un sentido de significado y propósito en sus vidas, los trabajadores sociales pueden ayudar a los clientes a maximizar sus fortalezas personales y culturales al servicio del cumplimiento de sus objetivos sociales y de desarrollo. Se utiliza un ejemplo de caso, y conceptos tratados se aplican en el ámbito de la búsqueda de sentido de la vida

Relationship between risk factors for impaired bone health and HR-pQCT in young adults with type 1 diabetes

Objective In type 1 diabetes, risk factors associated with impaired bone health contribute to increased risk of fracture. The aim of this study was to (1): compare the high-resolution peripheral quantitative computed tomography (HR-pQCT) parameters of young adults with type 1 diabetes with those of healthy controls (2), identify sex differences, and (3) evaluate the association between diabetes and bone health risk factors, with HR-pQCT. Methods This is a cross-sectional study in young Canadian adults with childhood onset type 1 diabetes. Z-scores were generated for HR-pQCT parameters using a large healthy control database. Diet, physical activity, BMI, hemoglobin A1C (A1C) and bone health measures were evaluated, and associations were analyzed using multivariate regression analysis. Results Eighty-eight participants (age 21 ± 2.2 years; 40 males, 48 females, diabetes duration 13.9 ± 3.4 years) with type 1 diabetes were studied. Low trabecular thickness and elevated cortical geometry parameters were found suggesting impaired bone quality. There were no sex differences. Significant associations were found: Vitamin D (25(OH)D) with trabecular parameters with possible synergy with A1C, parathyroid hormone with cortical parameters, BMI with cortical bone and failure load, and diabetes duration with trabecular area. Conclusions Our data suggests impairment of bone health as assessed by HR-pQCT in young adults with type 1 diabetes. Modifiable risk factors were associated with trabecular and cortical parameters. These findings imply that correction of vitamin D deficiency, prevention and treatment of secondary hyperparathyroidism, and optimization of metabolic control may reduce incident fractures

Mild Idiopathic Infantile Hypercalcemia—Part 1: Biochemical and Genetic Findings

Context: Idiopathic infantile hypercalcemia (IIH), an uncommon disorder characterized by elevated serum concentrations of 1,25 dihydroxyvitamin D (1,25(OH)2D) and low parathyroid hormone (PTH) levels, may present with mild to severe hypercalcemia during the first months of life. Biallelic variants in the CYP24A1 or SLC34A1 genes are associated with severe IIH. Little is known about milder forms. Objective: This work aims to characterize the genetic associations and biochemical profile of mild IIH. Methods: This is a cross-sectional study including children between age 6 months and 17 years with IIH who were followed in the Calcium Clinic at the Hospital for Sick Children (SickKids), Toronto, Canada. Twenty children with mild IIH on calcium-restricted diets were evaluated. We performed a dietary assessment and analyzed biochemical measures including vitamin D metabolites and performed a stepwise molecular genetic analysis. Complementary biochemical assessments and renal ultrasounds were offered to first-degree family members of positive probands. Results: The median age was 16 months. Median serum levels of calcium (2.69 mmol/L), urinary calcium:creatinine ratio (0.72 mmol/mmol), and 1,25(OH)2D (209 pmol/L) were elevated, whereas intact PTH was low normal (22.5 ng/L). Mean 1,25(OH)2D/PTH and 1,25(OH)2D/25(OH)D ratios were increased by comparison to healthy controls. Eleven individuals (55%) had renal calcification. Genetic variants were common (65%), with the majority being heterozygous variants in SLC34A1 and SLC34A3, while a minority showed variants of CYP24A1 and other genes related to hypercalciuria. Conclusion: The milder form of IIH has a distinctive vitamin D metabolite profile and is primarily associated with heterozygous SLC34A1 and SLC34A3 variants. Keywords: CYP24A1; genetic; hypercalcemia; nephrocalcinosis; nephrolithiasis; vitamin

The cellular composition of the human immune system is shaped by age and cohabitation.

Detailed population-level description of the human immune system has recently become achievable. We used a 'systems-level' approach to establish a resource of cellular immune profiles of 670 healthy individuals. We report a high level of interindividual variation, with low longitudinal variation, at the level of cellular subset composition of the immune system. Despite the profound effects of antigen exposure on individual antigen-specific clones, the cellular subset structure proved highly elastic, with transient vaccination-induced changes followed by a return to the individual's unique baseline. Notably, the largest influence on immunological variation identified was cohabitation, with 50% less immunological variation between individuals who share an environment (as parents) than between people in the wider population. These results identify local environmental conditions as a key factor in shaping the human immune system

Men at Risk: Considering Masculinity During Hospital-Based Social Work Intervention

The needs of hospitalized male patients are often unrecognized and unmet. Men occupy greater than half of all inpatient hospital beds and incur a broad array of illnesses and injuries at higher rates than women‰ÛÓyet often receive health care that pays surprisingly little attention to the concept of patient masculinity, or to masculinity\u27s influence on the male patient\u27s perspectives, behaviors, goals, interests, needs, and challenges. Little emphasis is placed on considering hospitalized male patients as men, understanding their need for patient-centered care within this context, and intervening in ways that regularly allow strengths to be adequately recognized and utilized. In this article, we explore how hospital social workers can reconsider masculinity as a vibrant and formative component of male patients\u27 lives and actively view its characteristics as comprising more than just potential challenges to medical treatment‰ÛÓbut also as untapped sources of resilience and strength

Poetry Matters: A Case for Poetry in Social Work Practice

Poetry matters: a case for poetry in social work This article seeks to contribute to an unfortunate decline in literature that explores the importance of the arts and humanities to social work practice, education and research through an exploration of the role of poetry in social work. The authors explore the metaphor of the poet/practitioner, identifying what practitioners can learn from the poet. Second, the authors explore the use of poetry in therapeutic settings, identifying the strengths of using this tool in clinical practice. Third, the authors address the use of poetry within the context of research, exploring how the research poem can be used as a tool of post-modern qualitative research to help social workers understand the lived experiences of their clients. Finally, the authors explore current and future consequences of the profession ignoring the arts and humanities. Poëzie doet ertoe: de toegevoegde waarde van poëzie in het sociaal werk In dit artikel wordt de toegevoegde waarde van kunst en de geesteswetenschappen voor praktijk, onderzoek en onderwijs op het gebied van sociaal werk onderzocht. In het bijzonder wordt er ingegaan op de rol van poëzie in het sociaal werk. De auteurs verkennen de metafoor van “de dichter/sociaal werker” en stellen vast wat de sociaal werker kan leren van de dichter. Verder onderzoeken de auteurs de rol en kracht van poëzie in therapeutische settings. Voorst wordt achterhaald hoe poëzie, in het bijzonder het onderzoeksgedicht, ingezet kan worden als vorm van kwalitatief onderzoek, met als doel het verkrijgen van inzicht in de belevingswereld van cliënten. Het artikel wordt afgesloten met een pleidooi voor het integreren van de kunsten en geesteswetenschappen in de sociaal werk professie

Poetry, Masculinities, and Disability

All persons with new disabilities must grieve and mourn aspects of their own identity, and engage in the process of re-authoring and developing new conceptions of self and living. This is particularly true for men whose identities are often anchored by traditional conceptions and traits of hegemonic masculinity, which often make seeking and receiving help difficult for many men. As an alternative to traditional methods of talk therapy, the expressive arts and expressive arts therapies have been important in helping people with disabilities increase their social inclusion and overall wellness. While poetry therapy has been frequently utilized with men, little has been written about working with men as men in poetry therapy. This research incorporates gender and masculinity studies to support the therapeutic possibility that men who have experienced disabling conditions may develop positive conceptions of themselves as men via means of self-expression that go beyond traditional therapy