Congenital Portosystemic Shunts: Variable Clinical Presentations Requiring a Tailored Endovascular or Surgical Approach.

Congenital portosystemic shunts (CPSS) are rare developmental anomalies resulting in diversion of portal flow to the systemic circulation. These shunts allow intestinal blood to reach the systemic circulation directly, and if persistent or large, may lead to long-term complications. CPSS can have a variety of clinical presentations that depend on the substrate that is bypassing hepatic metabolism or the degree of hypoperfusion of the liver. Many intrahepatic shunts spontaneously close by 1 year of age, but extrahepatic and persistent intrahepatic shunts require intervention by a single session or staged closure with a multidisciplinary approach. Early detection and appropriate management are important for a good prognosis. The aim of this case series is to describe the varied clinical presentations, treatment approaches, and outcomes of 5 children with CPSS at our institution. Management of these patients should involve a multidisciplinary team, including interventional radiology, surgery, hepatology, and other medical services as the patient's clinical presentation warrants. Regardless of clinical presentation, if a CPSS persists past 1-2 years of age, closure is recommended.

A novel GNAS variant presents with disorders of GNAS inactivation and cardiomyopathy.

The GNAS gene (OMIM#139320), located on chromosome 20q13.2, encodes for the alpha-subunit of the stimulatory signaling protein, Gsα protein. GNAS variants with inactivating properties are associated with Albright's hereditary osteodystrophy (AHO) and when maternally inherited, pseudohypoparathyroidism 1a (OMIM#103580), which includes multiple hormone resistance. In this clinical report we describe a novel GNAS variant, c.159A>G, p.K53N, in an individual with features consistent with AHO and pseudohypoparathyroidism 1a and its segregation through multiple maternal relatives, including two genotype positive maternal first cousins who also display features classic for AHO. The proband developed unique features including cardiomyopathy which required a heart transplant at 5 years old and immune dysregulation resulting in multisystem organ failure and ultimately, death at the age of 18 years. Additional investigations exploring alternative explanations for the proband's presentation were pursued including whole genome sequencing which was negative. We postulate that the atypical features seen in the proband may have resulted from dysregulated Gsα signaling in cardiac tissue. Future studies are needed to explore the properties of the K53N GNAS variant and this proposed mechanism.

Tailoring the approach to radioactive iodine treatment in thyroid cancer.

The treatment of differentiated thyroid cancer continues to move away from a 'one size fits all' approach to a process of tailored therapeutic decision-making that incorporates disease-specific factors and individual patient preferences. Management options range from active surveillance to thyroid lobectomy to total thyroidectomy with or without the use of postoperative radioactive iodine (RAI). RAI may be administered for one or more reasons: Thyroid remnant ablation, adjuvant therapy, or therapy for persistent structural disease. It is important to be cognizant of the therapeutic intent of RAI and weigh the risks and benefits of treatment for each individual patient. Risk stratification should be used to identify those patients who are most likely to benefit from RAI and guide therapeutic choices. Available data suggest that RAI can be safely deferred for most patients considered at low risk for structural recurrence, while adjuvant RAI is associated with improved disease-free survival in patients with higher-risk disease. Although progress has been made, many areas of uncertainty related to the use of RAI remain. These include: (1) The appropriate selection of intermediate-risk patients to receive adjuvant RAI, (2) the superiority or inferiority of different RAI dosing activities, (3) the optimal approach to the use of RAI in special populations, including patients with end-stage renal disease and children, and (4) the management of patients with RAI-refractory disease.

Health-related quality of life of preschool caregivers in Hong Kong.

The aim of this study was to explore the health-related quality of life (HRQOL) of preschool caregivers in Hong Kong with a view to informing policy-makers about health promotion within this population. The following research questions were addressed: (i) What was the HRQOL of young children's caregivers in Hong Kong? (ii) Were there differences between these caregivers' health and the general Hong Kong population's health? (iii) What demographic factors were related to these caregivers' quality of life? Mixed methods research, including quantitative and qualitative tools, was utilized. Data from a study consisted of a survey of 834 preschool caregivers along with 3 in-depth interviews with employees of kindergarten-cum-childcare centres from different socio-economic groups within the city of Hong Kong. An HRQOL questionnaire (the SF-36 v. 1), together with demographic characteristics and illness/disease incidence data, were collected. The results suggested that the Hong Kong preschool caregivers had a substantially poorer HRQOL than Hong Kong's general population. The analysis found that young caregivers and caregivers with young families had a significantly lower HRQOL than more senior caregivers. They tended to feel tired, lacked energy and failed to perform vigorous activities. Significant differences were also found according to the caregivers' socio-economic status. Health and education policy-makers should note that young children's caregivers are in a serious state of ill health. Further health education and promotion efforts should target this population.

Chinese parental perceptions of weight and associated health risks of young children.

A mixed method was employed to determine how caregivers view preschool children's body size and associated health risks. A survey of 505 caregivers was nested in 10 in-depth case studies of mothers. Based on the International Obesity Task Force calculation of children's weight status, the caregivers who had underweight children overestimated their children's weight status but the caregivers who had overweight/obese children underestimated their children's weight status. Their estimates were substantially different from those of the caregivers of normal weight children. The mothers' thoughts revealed the complexity of beliefs and sociocultural experiences about weight preferences and affirmed the quantitative findings.

Targeted inhibition of Src kinase with dasatinib blocks thyroid cancer growth and metastasis.

PURPOSE: There are no effective therapies for patients with poorly differentiated papillary thyroid cancer (PTC) or anaplastic thyroid cancer (ATC), and metastasis to the bone represents a significantly worse prognosis. Src family kinases (SFKs) are overexpressed and activated in numerous tumor types and have emerged as a promising therapeutic target, especially in relation to metastasis. We recently showed that Src is overexpressed and activated in thyroid cancer. We therefore tested whether inhibition of Src with dasatinib (BMS-354825) blocks thyroid cancer growth and metastasis. EXPERIMENTAL DESIGN: The effects of dasatinib on thyroid cancer growth, signaling, cell cycle, and apoptosis were evaluated in vitro. The therapeutic efficacy of dasatinib was further tested in vivo using an orthotopic and a novel experimental metastasis model. Expression and activation of SFKs in thyroid cancer cells was characterized, and selectivity of dasatinib was determined using an Src gatekeeper mutant. RESULTS: Dasatinib treatment inhibited Src signaling, decreased growth, and induced cell-cycle arrest and apoptosis in a subset of thyroid cancer cells. Immunoblotting showed that c-Src and Lyn are expressed in thyroid cancer cells and that c-Src is the predominant SFK activated. Treatment with dasatinib blocked PTC tumor growth in an orthotopic model by more than 90% (P = 0.0014). Adjuvant and posttreatment approaches with dasatinib significantly inhibited metastasis (P = 0.016 and P = 0.004, respectively). CONCLUSION: These data provide the first evidence that Src is a central mediator of thyroid cancer growth and metastasis, indicating that Src inhibitors may have a higher therapeutic efficacy in thyroid cancer, as both antitumor and antimetastatic agents.

Obesity in Hong Kong Chinese preschool children: where are all the nurses?

We report an ethnographic study of 10 preschool children aged 2-6 years recruited from kindergartens in Hong Kong, 6 of whom were overweight or obese. Each was followed for 12-18 months. We confirmed previously described risk factors and showed how these interacted to produce obesity in some but not all at-risk children. Despite much rhetoric in the literature about holistic care of the preschool child, we were struck by the lack of coordinated professional input to the needs of children at risk of obesity and by the absence of nursing input in particular. We argue that a "whole-systems" nursing role, based in the community and with remit that includes clinical care, education, and policy, is urgently needed, as well as review examples of such roles from other countries.

Exploratory factor analysis: health perceptions of Chinese early childhood educators in Hong Kong.

The aim of this study was to explore health perceptions of preschool teachers, with a view to inform early childhood practices and teacher education. Pre-service student-teachers and in-service teachers (n = 200) who were voluntarily recruited completed a 24-item health attitude questionnaire. Factor analysis identified four dimensions of health attitudes, reflecting physical, psychosocial, mental and emotional domains. Inter-correlations among the factors suggested that early childhood educators in Hong Kong embrace a holistic view of health, although they consider physical and emotional health as more salient than the psychosocial and mental health dimensions. In comparisons of the perceptions of in-service teachers and student-teachers, students placed less emphasis on psychosocial health, but teachers placed more emphasis on physical health. The findings are discussed in terms of their implications for designing health education programmes for preschool teacher education.