Carrier Screening for Spinal Muscular Atrophy (SMA) in 107,611 Pregnant Women during the Period 2005–2009: A Prospective Population-Based Cohort Study

BACKGROUND: Spinal muscular atrophy (SMA) is the most common neuromuscular autosomal recessive disorder. The American College of Medical Genetics has recently recommended routine carrier screening for SMA because of the high carrier frequency (1 in 25-50) as well as the severity of that genetic disease. Large studies are needed to determine the feasibility, benefits, and costs of such a program. METHODS AND FINDINGS: This is a prospective population-based cohort study of 107,611 pregnant women from 25 counties in Taiwan conducted during the period January 2005 to June 2009. A three-stage screening program was used: (1) pregnant women were tested for SMA heterozygosity; (2) if the mother was determined to be heterozygous for SMA (carrier status), the paternal partner was then tested; (3) if both partners were SMA carriers, prenatal diagnostic testing was performed. During the study period, a total of 2,262 SMA carriers with one copy of the SMN1 gene were identified among the 107,611 pregnant women that were screened. The carrier rate was approximately 1 in 48 (2.10%). The negative predictive value of DHPLC coupled with MLPA was 99.87%. The combined method could detect approximately 94% of carriers because most of the cases resulted from a common single deletion event. In addition, 2,038 spouses were determined to be SMA carriers. Among those individuals, 47 couples were determined to be at high risk for having offspring with SMA. Prenatal diagnostic testing was performed in 43 pregnant women (91.49%) and SMA was diagnosed in 12 (27.91%) fetuses. The prevalence of SMA in our population was 1 in 8,968. CONCLUSION: The main benefit of SMA carrier screening is to reduce the burden associated with giving birth to an affected child. In this study, we determined the carrier frequency and genetic risk and provided carrier couples with genetic services, knowledge, and genetic counseling

The effects of compression gloves on hand symptoms and hand function in rheumatoid arthritis and hand osteoarthritis : a systematic review

Objective: to evaluate the effects of compression gloves in adults with rheumatoid arthritis and hand osteoarthritis. Data sources: Systematic review of randomized controlled trials identified from MEDLINE, CINAHL, AMED, PEDro, OT Seeker, The Cochrane Library, ISI Web of Knowledge, Science Direct and PubMed from their inceptions to January 2015. Review methods: Methodological quality of identified trials was evaluated using the PEDro scale by three independent assessors. Effects were summarized descriptively. Results: Four trials (n=8-24; total n=74), comparing night wear of full-length finger compression gloves with placebo gloves, were assessed. Three were of moderate (PEDro score 4-5) and one low (score 3) methodological quality. Effect sizes or standardized mean differences could not be calculated to compare trials due to poor data reporting. In rheumatoid arthritis, finger joint swelling was significantly reduced, but results for pain and stiffness were inconclusive and no differences in grip strength and dexterity were identified. One study reported similar effects in pain, stiffness and finger joint swelling from both compression and thermal placebo gloves. Only one study evaluated gloves in hand osteoarthritis (n=5) with no differences. Conclusions: All the trials identified were small with a high risk of Type I and II errors. Evidence for the effectiveness of compression gloves worn at night is inconclusive in rheumatoid arthritis and hand osteoarthritis

Understanding childhood asthma in focus groups: perspectives from mothers of different ethnic backgrounds

BACKGROUND: Diagnosing childhood asthma is dependent upon parental symptom reporting but there are problems in the use of words and terms. The purpose of this study was to describe and compare understandings of childhood 'asthma' by mothers from three different ethnic backgrounds who have no personal experience of diagnosing asthma. A better understanding of parents' perceptions of an illness by clinicians should improve communication and management of the illness. METHOD: Sixty-six mothers living in east London describing their ethnic backgrounds as Bangladeshi, white English and black Caribbean were recruited to 9 focus groups. Discussion was semi-structured. Three sessions were conducted with each ethnic group. Mothers were shown a video clip of a boy with audible wheeze and cough and then addressed 6 questions. Sessions were recorded and transcribed verbatim. Responses were compared within and between ethnic groups. RESULTS: Each session, and ethnic group overall, developed a particular orientation to the discussion. Some mothers described the problem using single signs, while others imitated the sound or made comparisons to other illnesses. Hereditary factors were recognised by some, although all groups were concerned with environmental triggers. Responses about what to do included 'normal illness' strategies, use of health services and calls for complementary treatment. All groups were concerned about using medication every day. Expectations about the quality of life were varied, with recognition that restrictions may be based on parental beliefs about asthma, rather than asthma itself. CONCLUSION: Information from these focus groups suggests mothers know a great deal about childhood asthma even though they have no personal experience of it. Knowledge of how mothers from these ethnic backgrounds perceive asthma may facilitate doctor – patient communication with parents of children experiencing breathing difficulties

Characterization of lymphocyte populations in nonspecific interstitial pneumonia*

STUDY OBJECTIVES: Nonspecific interstitial pneumonia (NSIP) has been identified as a distinct entity with a more favorable prognosis and better response to immunosuppressive therapies than usual interstitial pneumonia (UIP). However the inflammatory profile of NSIP has not been characterized. DESIGN: Using immunohistochemistry techniques on open lung biopsy specimens, the infiltrate in NSIP was characterized in terms of T and B cells, and macrophages, and the T cell population further identified as either CD4 (helper) or CD8 (suppressor-cytotoxic) T cells. The extent of Th1 and Th2 cytokine producing cells was determined and compared to specimens from patients with UIP. RESULTS: In ten NSIP tissue samples 41.4 ± 4% of mononuclear cells expressed CD3, 24.7 ± 1.8% CD4, 19.1 ± 2% CD8, 27.4 ± 3.9% CD20, and 14.3 ± 1.6% had CD68 expression. Mononuclear cells expressed INFγ 21.9 ± 1.9% of the time and IL-4 in 3.0 ± 1%. In contrast, biopsies from eight patients with UIP demonstrated substantially less cellular staining for either cytokine (INFγ; 4.6 ± 1.7% and IL-4; 0.6 ± 0.3%). Significant populations of CD20 positive B-cells were also identified. CONCLUSION: The lymphocytic infiltrate in NSIP is characterized by an elevated CD4/CD8 T-cell ratio, and is predominantly of Th1 type, with additional populations rich in B-cells. Such features are consistent with the favorable clinical course observed in patients with NSIP compared to UIP

Risk of cancers of the lung, head and neck in patients hospitalized for alcoholism in Sweden

Alcoholic patients are at increased risk of cancers of the head and neck but little information is available on the magnitude of the risk for specific sites and for different histological types. We followed 182 667 patients with a hospital discharge diagnosis of alcoholism during 1965–1994, for an average of 10.2 years. We compared their incidence of site- and histological type-specific cancers of the oral cavity, pharynx, larynx and lung with that of the national population. The standardized incidence ratio (SIR) of cancer of the oral cavity and pharynx was 5.33 (95% confidence interval [CI] 5.04–5.64, based on 1207 cases). The SIRs of laryngeal and lung cancer were 4.21 (95% Cl 3.78–4.68, 347 cases) and 2.40 (2.29–2.51, 1880 cases), respectively. The SIR was highest for cancers of the hypopharynx, floor of the mouth, mesopharynx and base of the tongue. The relative excess of lung cancer was similar for squamous cell carcinoma and adenocarcinoma. Low age at first hospitalization was associated with higher SIRs for all sites under study. 25 years after first hospitalization for alcoholism, the cumulative probability of developing a lung cancer was in the order of 5%, for oral and pharyngeal cancer it was 2.5%, and for oesophageal or laryngeal cancer 1% each. Our study shows that the risk of head and neck cancer among heavy drinkers is highest for sites in direct contact with alcohol. The high risk of head and neck neoplasms may justify specific medical attention. © 2001 Cancer Research Campaign http://www.bjcancer.co

Rightward hemispheric asymmetries in auditory language cortex in children with autistic disorder: an MRI investigation

Purpose: determine if language disorder in children with autistic disorder (AD) corresponds to abnormalities in hemispheric asymmetries in auditory language cortex. Methods: MRI morphometric study in children with AD (n = 50) to assess hemispheric asymmetries in auditory language cortex. A key region of interest was the planum temporale (PT), which is larger in the left hemisphere in most healthy individuals. Results: (i) Heschl’s gyrus and planum polare showed typical hemisphere asymmetry patterns; (ii) posterior Superior Temporal Gyrus (pSTG) showed significant rightward asymmetry; and (iii) PT showed a trend for rightward asymmetry that was significant when constrained to right-handed boys (n = 30). For right-handed boys, symmetry indices for pSTG were significantly positively correlated with those for PT. PT asymmetry was age dependent, with greater rightward asymmetry with age. Conclusions: results provide evidence for rightward asymmetry in auditory association areas (pSTG and PT) known to subserve language processing. Cumulatively, our data provide evidence for a differing maturational path for PT for lower functioning children with AD, with both pre- and post-natal experience likely playing a role in PT asymmetry

Hidden expectations: Scaffolding subject specialists' genre knowledge of the assignments they set

Subject specialists’ knowledge of academic and disciplinary literacy is often tacit. We tackle the issue of how to elicit subject specialists’ tacit knowledge in order to develop their pedagogical practices and enable them to communicate this knowledge to students. Drawing on theories of genre and metacognition, a professional development activity was designed and delivered. Our aims were to (1) build participants’ genre knowledge and (2) scaffold metacognitive awareness of how genre knowledge can enhance their pedagogical practices. The findings reveal that participants built a genre-based understanding of academic literacy and that the tasks provided them with an accessible framework to articulate and reflect upon their knowledge of disciplinary literacy. Participants gained metacognitive awareness of misalignments between what they teach and what they expect from students, their assumptions about students’ prior learning and genre-based strategies to adapt their practice to students’ needs. Our approach provides a theoretically grounded professional development tool for the HE sector

Rasl11b Knock Down in Zebrafish Suppresses One-Eyed-Pinhead Mutant Phenotype

The EGF-CFC factor Oep/Cripto1/Frl1 has been implicated in embryogenesis and several human cancers. During vertebrate development, Oep/Cripto1/Frl1 has been shown to act as an essential coreceptor in the TGFβ/Nodal pathway, which is crucial for germ layer formation. Although studies in cell cultures suggest that Oep/Cripto1/Frl1 is also implicated in other pathways, in vivo it is solely regarded as a Nodal coreceptor. We have found that Rasl11b, a small GTPase belonging to a Ras subfamily of putative tumor suppressor genes, modulates Oep function in zebrafish independently of the Nodal pathway. rasl11b down regulation partially rescues endodermal and prechordal plate defects of zygotic oep−/− mutants (Zoep). Rasl11b inhibitory action was only observed in oep-deficient backgrounds, suggesting that normal oep expression prevents Rasl11b function. Surprisingly, rasl11b down regulation does not rescue mesendodermal defects in other Nodal pathway mutants, nor does it influence the phosphorylation state of the downstream effector Smad2. Thus, Rasl11b modifies the effect of Oep on mesendoderm development independently of the main known Oep output: the Nodal signaling pathway. This data suggests a new branch of Oep signaling that has implications for germ layer development, as well as for studies of Oep/Frl1/Cripto1 dysfunction, such as that found in tumors