Comparison of Informational and Educational Resource Provision for Individuals Living With Traumatic Brain Injury Based on Language, Nativity, and Neighborhood.

OBJECTIVE: To examine a resource provision program for individuals living with moderate-to-severe traumatic brain injury (TBI), using a comparison of the resources provided across social differences of language, nativity, and neighborhood. SETTING: The Rusk Rehabilitation TBI Model System (RRTBIMS) collects data longitudinally on individuals from their associated private and public hospitals, located in New York City. PARTICIPANTS: A total of 143 individuals with TBI or their family members. DESIGN: An observational study of relative frequency of resource provision across variables of language, nativity, and neighborhood, using related-samples nonparametric analyses via Cochran's Q test. MAIN MEASURES: Variables examined were language, place of birth, residence classification as medically underserved area/population (MUA), and resource categories. RESULTS: Results indicate that US-born persons with TBI and those living in medically underserved communities are provided more resources than those who are born outside the United States or reside in communities identified as adequately medically served. Language was not found to be a factor. CONCLUSION: Lessons learned from this research support the development of this resource provision program, as well as guide future programs addressing the gaps in health information resources for groups negatively impacted by social determinants of health (SDoH). An approach with immigrant participants should take steps to elicit questions and requests, or offer resources explicitly. We recommend research looking at what interpreter strategies are most effective and research on SDoH in relation to the dynamic interaction of variables in the neighborhood setting.

Family screening for hypertrophic cardiomyopathy: Is it time to change practice guidelines?

AIMS: Current guidelines recommend initiating family screening for hypertrophic cardiomyopathy (HCM) after age 10 or 12 years unless early screening criteria are met. The aim was to evaluate if current screening guidelines miss early onset disease. METHODS AND RESULTS: Children who underwent family screening for HCM before age 18 years were analysed. Major cardiac events (MaCEs) were defined as death, sudden cardiac death (SCD), or need for major cardiac interventions (myectomy, implantable cardioverter-defibrillator insertion, transplantation). Of 524 children screened, 331 were under 10 years of age, 9.9% had echocardiographic evidence of HCM, and 1.1% were symptomatic at first screening. The median (interquartile range) age at HCM onset was 8.9 (4.7-13.4) years, and at MaCE was 10.9 (8.5-14.3) years with a median time to MaCE from HCM onset of 1.5 (0.5-4.1) years. About 52.5% phenotype-positive children and 41% with MaCEs were <10 years old. Only 69% children with early HCM met early screening criteria. Cox regression identified male gender, family history of SCD, and pathogenic variants in MYH7/MYBPC3 as a predictor of early onset HCM and MaCEs. CONCLUSION: A third of children not eligible for early screening by current guidelines had phenotype-positive HCM. MYH7 and MYBC3 mutation-positive patients were at highest risk for developing early HCM and experiencing an event or requiring a major intervention. Our findings suggest that younger family members should be considered for early clinical and genetic screening to identify the subset in need of closer monitoring and interventions.

Contaminated fingers: a potential cause of Chlamydia trachomatis-positive urine specimens.

OBJECTIVES: The detection of an STI agent in a urogenital tract (UGT) specimen from a young child is regarded as being indicative of sexual abuse. However, the probabilities of contamination events that could conceivably lead to STI positive specimens in the absence of sexual contact are unclear. The objective was to estimate the potential for fingers that have come in contact with Chlamydia trachomatis-positive urine to detectably contaminate C. trachomatis-negative urine. METHODS: The study design was based on self-experimentation. Dilutions of C. trachomatis elementary bodies (EBs) were prepared. A participant contacted an EB dilution then a urine surrogate specimen. The experiment was performed by three participants using three C. trachomatis isolates, of genotype E, F and B. Two surrogate urine contact methods were used to mimic contamination of a carer assisting with a child's urine collection. All EB dilutions and urine surrogate specimens were subjected to C. trachomatis assay and quantification in a real-time PCR-based diagnostic system. RESULTS: The amplimer crossing point (Cq) for EB dilutions was 10.0±1.6 less than for corresponding finger contacted urine specimens, which corresponds to ~10 µL of EB suspension transferred. This was largely independent of participant identity, C. trachomatis strain or EB dilution. Hand decontamination led to large reductions in EBs transferred, but transfer remained consistently detectable. Recent Cq data from C. trachomatis-positive clinical urine specimens were collated, and 20% clearly contained sufficient C. trachomatis to detectably contaminate another specimen by finger-mediated transfer, as in this experiment. CONCLUSIONS: This study directly demonstrated the potential for urine contaminated fingers to convert a C. trachomatis-negative urine specimen to C. trachomatis positive as a result of contact. Accordingly, procedures for urine specimen collection, particularly from children, need to be designed to prevent contamination.

Does stress increase risk of breast cancer? A 15-year prospective study.

OBJECTIVE: The possible impact of stress on cancer incidence remains controversial. We prospectively evaluated associations between life event stressors, social support, personality characteristics (optimism, anger control, antiemotionality), and risk of developing primary breast cancer (BCa), in women at increased familial risk of BCa. METHODS: A prospective cohort, repeated measures design was used. Recruitment was through the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, which collects genetic, epidemiological, and clinical data from Australasian families with multiple BCa cases. Acute and chronic stressors for the prior 3 years and psychosocial, clinical, and epidemiological variables were measured at cohort entry and at 3-yearly intervals. Cox proportional hazard regression analysis controlling for BCa risk factors and familial clustering was undertaken. The primary outcome was histopathologically confirmed BCa (invasive or ductal carcinoma in situ, including occult cases diagnosed during risk-reducing mastectomy). RESULTS: Of 3595 consecutive women invited to participate, 3054 (85.0%) consented. Of these, 2739 (89.7%) from 990 families (range 1-16 per family) completed at least 1 assessment point. During the study, 103 women were diagnosed with BCa. No stressor or psychosocial variable or interaction between them was significantly associated with BCa in unadjusted or adjusted models (total acute stressors HR = 1.03 [0.99-1.08], P = .19; total chronic stressors HR = 1.0 [0.90-1.11], P = .98). CONCLUSIONS: This study did not demonstrate an association between acute and chronic stressors, social support, optimism, antiemotionality or anger control, and BCa risk. Women should focus on proven methods of BCa risk reduction.

Effect of High-Risk Human Papillomavirus but Normal Cytology at Test of Cure on Achieving Colposcopy Standards.

OBJECTIVE: In United Kingdom., test of cure after treatment of any grade of cervical intraepithelial neoplasia (CIN) incorporates high-risk human papillomavirus (Hr-HPV) test and cytology at 6-month follow-up. The aims of the study were to determine the rate of recurrent CIN in women who are Hr-HPV positive and cytology negative and to explore possible associated risk factors. METHODS: A retrospective observational cohort study was performed in women treated for any grade CIN between 2010 and 2015 from a regional population, who were Hr-HPV positive and cytology negative at first follow-up. RESULTS: A total of 2729 women were identified as treated for any grade CIN, and 213 (7.8%) were re-referred to colposcopy having Hr-HPV-positive test and negative cytology at test of cure. Their mean age was 31.56 years (range = 19-62 years). The mean time of follow-up per woman was 30.50 months (range = 2-63 months). At colposcopy, 171 (80.3%) had colposcopy examination only and 42 women (19.7%) had a biopsy. Twenty-four cases (11.3%) of CIN were identified of which 4 (1.9%) were CIN 2/3. Eleven women (5.2%) in total had a repeat treatment. Five women (2.3%) had biopsy-proven CIN 2/3 within 12-months after treatment. No cases of CIN 3+ after negative colposcopy were identified during the follow-up period. CONCLUSIONS: The incorporation of Hr-HPV testing yielded a very small number of women with residual CIN within 12 months of treatment. Our results suggest that women who are Hr-HPV positive and cytology negative after treatment of CIN with normal and adequate colposcopy could be discharged to routine recall if confirmed by larger national data.

High burden of complicated skin and soft tissue infections in the Indigenous population of Central Australia due to dominant Panton Valentine leucocidin clones ST93-MRSA and CC121-MSSA.

BACKGROUND: Superficial skin and soft tissue infections (SSTIs) are common among the Indigenous population of the desert regions of Central Australia. However, the overall burden of disease and molecular epidemiology of Staphylococcus aureus complicated SSTIs has yet to be described in this unique population. METHODS: Alice Springs Hospital (ASH) admission data was interrogated to establish the population incidence of SSTIs. A prospective observational study was conducted on a subset of S. aureus complicated SSTIs (carbuncles and furuncles requiring surgical intervention) presenting during a one month period to further characterize the clinical and molecular epidemiology. High resolution melting analysis was used for clonal complex discrimination. Real-time polymerase chain reaction identifying the lukF component of the Panton Valentine leucocidin (pvl) gene determined pvl status. Clinical and outcome data was obtained from the ASH medical and Northern Territory shared electronic health records. RESULTS: SSTIs represented 2.1% of ASH admissions during 2014. 82.6% occurred in Indigenous patients (n = 382) with an estimated incidence of 18.9 per 1, 000 people years compared to the non-Indigenous population of 2.9 per 1000, with an incident rate ratio of 6.6 (95% confidence interval 5.1-8.5). Clinical and molecular analysis was performed on 50 isolates from 47 patients. Community-associated methicillin-resistant S. aureus (CA-MRSA) predominated (57% of isolates). The high burden of SSTIs is partly explained by the prevalence of pvl positive strains of S. aureus (90% isolates) for both CA-MRSA and methicillin-susceptible S. aureus (MSSA). ST93-MRSA and CC121-MSSA were the most prevalent clones. SSTIs due to ST93-MRSA were more likely to require further debridement (p = 0.039), however they also more frequently received inactive antimicrobial therapy (p < 0.001). CONCLUSIONS: ST93-MRSA and CC121-MSSA are the dominant causes of carbuncles and furuncles in Central Australia. Both of these virulent clones harbor pvl but the impact on clinical outcomes remains uncertain. The high prevalence of CA-MRSA supports empiric vancomycin use in this population when antimicrobial therapy is indicated. Prompt surgical intervention remains the cornerstone of treatment.

Pregnant women's awareness, knowledge and beliefs about pelvic floor muscles: a cross-sectional survey.

INTRODUCTION AND HYPOTHESIS: Pregnant women benefit from completing pelvic floor muscle exercises (PFMEs). The aims of the study were to evaluate pregnant women's levels of awareness, knowledge, and beliefs about the pelvic floor muscles (PFMs) and PFMEs. METHODS: A cross-sectional survey was conducted. Respondents were pregnant women over the age of 18 years who attended antenatal clinics in Western Australia (WA). Questionnaire items measured awareness and knowledge about PFMs, confidence and beliefs about engaging in PFMEs, and attendance at antenatal education (ANE) classes. Chi-squared tests examined potential associations between questionnaire items and respondent characteristics. RESULTS: Mean gestation of respondents (n = 633 out of 850; 74% response rate) was 28.7 (+7.8) weeks and 50% were giving birth for the first time. Although 76% of respondents knew that PFMs can prevent urinary incontinence, only 27% knew that they prevented faecal incontinence and 41% thought it was normal to leak urine when pregnant. Only n = 72 (11%) were practicing PFMEs. Respondents who had attended ANE (28%) were significantly more knowledgeable about pelvic floor function (p < .001) and significantly less likely to believe that leaking urine during pregnancy was normal (p = 0.02), compared with those who had not attended ANE. Respondents who did not speak English at home (18%) were significantly less knowledgeable about PFMs and PFMEs, and significantly less likely to have attended, or planned to attend, ANE classes. CONCLUSION: Pregnant women require more health education regarding PFMs. Education should be provided using diverse modes, especially for women from migrant backgrounds and women who do not plan to attend formal ANE classes.

Differential Expression of Innate and Adaptive Immune Genes during Acute Physical Exercise in American Quarter Horses.

Overtraining syndrome (OTS) is the reduction in performance due to excess training and lack of proper recovery, which can lead to a chronic deprivation of energy and reduction in the repair of damage that can accumulate over time. Here, the effect of acute, intense physical exercise on the expression of innate and adaptive immune genes in 12 racing-bred American Quarter Horses, after resting for 3 days and immediately after intense exercise for 1.8 miles were compared. The expression of 84 genes related to innate and adaptive immune responses was analyzed. Significant variation among individuals and between sexes was observed. The analysis showed that five genes were differentially expressed in both females and males, three only in females, and two in males. The upregulated genes were IL13 (male only), CCR4 (female only), TLR6, TLR9 (female only), NFKBIA, CXCR3, and TLR4, while the downregulated genes were IL6 (female only), CD4 (male only), and MYD88. The three main pathways containing genes that were affected by acute, intense physical exercise were Th1 and Th2 cell differentiation, and the NF-kappa B and chemokine signaling pathways, suggesting the activation of the proinflammatory responses as a result of the stress from the acute exercise. Gene expression could be used to assess indications of OTS.

Assessment of the individual and compounding effects of marginalization factors on injury severity, discharge location, recovery, and employment outcomes at 1 year after traumatic brain injury.

Objective: The aim of this study is to examine the effect of eight distinct marginalized group memberships and explore their compounding effect on injury severity, recovery, discharge location, and employment outcomes 1-year after traumatic brain injury (TBI). Methods: Individuals with medically confirmed, complicated mild-severe TBI (N = 300) requiring inpatient rehabilitation care between the ages of 18 and 65 were recruited at two urban (public and private) health systems between 2013 and 2019. Data were collected from self-report and medical record abstraction. Marginalized group membership (MGM) includes racial and ethnic minority status, less than a high school diploma/GED, limited English proficiency, substance abuse, homelessness, psychiatric hospitalizations, psychiatric disorders, and incarceration history. Membership in four or more of these groups signifies high MGM. In addition, these factors were explored individually. Unadjusted and adjusted linear and logistic regressions and Kruskal-Wallis tests were used to assess the associations of interest in RStudio. Results: After adjusting for age, sex, and cause of injury, compared to TBI patients with low MGM, those with high MGM experience significantly longer post-traumatic amnesia (95% CI = 2.70, 16.50; p = 0.007) and are significantly more likely to have a severe TBI (per the Glasgow-Coma Scale) (95% CI = 1.70, 6.10; p ≤ 0.001) than a complicated mild-moderate injury. Individuals with high MGM also are significantly less likely to be engaged in competitive paid employment 1 year after injury (95% CI = 2.40, 23.40; p = 0.001). Patients with high MGM are less likely to be discharged to the community compared to patients with low MGM, but this association was not significant (95% CI = 0.36, 1.16; p = 0.141). However, when assessing MGMs in isolation, certain associations were not significant in unadjusted or adjusted models. Conclusion: This exploratory study's findings reveal that when four or more marginalization factors intersect, there is a compounding negative association with TBI severity, recovery, and employment outcomes. No significant association was found between high MGM and discharge location. When studied separately, individual MGMs had varying effects. Studying marginalization factors affecting individuals with TBI has critical clinical and social implications. These findings underline the importance of addressing multidimensional factors concurrent with TBI recovery, as the long-term effects of TBI can place additional burdens on individuals and their economic stability.

Setting up a Pediatric Intensive Care Unit in a Community/Rural Setting.

Community pediatric intensive care units (PICUs) play a crucial role in providing high-quality care to critically ill children in the rural setting. Setting one up requires meticulous planning and allocation of limited resources. The design and layout of PICUs vary widely but need to meet the required minimum standards and follow local and federal policies and regulatory standards. The building block is investing in the education and training of health care providers. Collaboration with tertiary facilities and community organizations helps provide care closer to home. Care coordination necessitates partnering with the families and the community and including telemedicine to increase accessibility.

Longitudinal whole-genome based comparison of carriage and infection associated Staphylococcus aureus in northern Australian dialysis clinics.

BACKGROUND: The study objective was to reveal reservoirs potentially leading to Staphylococcus aureus infections in haemodialysis clinic clients in the tropical north of the Australian Northern Territory (NT). This client population are primarily Aboriginal Australians who have a greater burden of ill health than other Australians. Reservoir identification will enhance infection control in this client group, including informing potential S. aureus decolonisation strategies. METHODS AND FINDINGS: The study participants were 83 clients of four haemodialysis clinics in the Darwin region of the NT, and 46 clinical staff and researchers who had contact with the clinic clients. The study design was longitudinal, encompassing swabbing of anatomical sites at two month intervals to yield carriage isolates, and also progressive collection of infection isolates. Swab sampling was performed for all participants, and infection isolates collected for dialysis clients only. Analysis was based on the comparison of 139 carriage isolates and 27 infection isolates using whole genome sequencing. Genome comparisons were based on of 20,651 genome-wide orthologous SNPs, presence/absence of the mecA and pvl genes, and inferred multilocus sequence type and clonal complex. Pairs of genomes meeting the definition of "not discriminated" were classed as defining potential transmission events. The primary outcome was instances of potential transmission between a carriage site other than a skin lesion and an infection site, in the same individual. Three such instances were identified. Two involved ST762 (CC1) PVL- MRSA, and one instance ST121 PVL+ MSSA. Three additional instances were identified where the carriage strains were derived from skin lesions. Also identified were six instances of potential transmission of a carriage strains between participants, including transmission of strains between dialysis clients and staff/researchers, and one potential transmission of a clinical strain between participants. There were frequent occurrences of longitudinal persistence of carriage strains in individual participants, and two examples of the same strain causing infection in the same participants at different times. Strains associated with infections and skin lesions were enriched for PVL and mecA in comparison to strains associated with long term carriage. CONCLUSIONS: This study indicated that strains differ with respect to propensity to stably colonise sites such as the nose, and cause skin infections. PVL+ strains were associated with infection and skin lesions and were almost absent from the carriage sites. PVL- MRSA (mainly CC1) strains were associated with infection and also with potential transmission events involving carriage sites, while PVL- MSSA were frequently observed to stably colonise individuals without causing infection, and to be rarely transmitted. Current clinical guidelines for dialysis patients suggest MRSA decolonisation. Implementation in this client group may impact infections by PVL- MRSA, but may have little effect on infection by PVL+ strains. In this study, the PVL+ strains were predominant causes of infection but rarely colonised typical carriage sites such as the nose, and in the case of ST121, were MSSA. The important reservoirs for infection by PVL+ strains appeared to be prior infections.

Failure to censor forbidden clones of CD4 T cells in autoimmune diabetes.

Type 1 diabetes and other organ-specific autoimmune diseases often cluster together in human families and in congenic strains of NOD (nonobese diabetic) mice, but the inherited immunoregulatory defects responsible for these diseases are unknown. Here we track the fate of high avidity CD4 T cells recognizing a self-antigen expressed in pancreatic islet beta cells using a transgenic mouse model. T cells of identical specificity, recognizing a dominant peptide from the same islet antigen and major histocompatibility complex (MHC)-presenting molecule, were followed on autoimmune susceptible and resistant genetic backgrounds. We show that non-MHC genes from the NOD strain cause a failure to delete these high avidity autoreactive T cells during their development in the thymus, with subsequent spontaneous breakdown of CD4 cell tolerance to the islet antigen, formation of intra-islet germinal centers, and high titre immunoglobulin G1 autoantibody production. In mixed bone marrow chimeric animals, defective thymic deletion was intrinsic to T cells carrying diabetes susceptibility genes. These results demonstrate a primary failure to censor forbidden clones of self-reactive T cells in inherited susceptibility to organ-specific autoimmune disease, and highlight the importance of thymic mechanisms of tolerance in organ-specific tolerance.

Gene dosage--limiting role of Aire in thymic expression, clonal deletion, and organ-specific autoimmunity.

Inactivation of the autoimmune regulator (Aire) gene causes a rare recessive disorder, autoimmune polyendocrine syndrome 1 (APS1), but it is not known if Aire-dependent tolerance mechanisms are susceptible to the quantitative genetic changes thought to underlie more common autoimmune diseases. In mice with a targeted mutation, complete loss of Aire abolished expression of an insulin promoter transgene in thymic epithelium, but had no effect in pancreatic islets or the testes. Loss of one copy of Aire diminished thymic expression of the endogenous insulin gene and the transgene, resulting in a 300% increase in islet-reactive CD4 T cells escaping thymic deletion in T cell receptor transgenic mice, and dramatically increased progression to diabetes. Thymic deletion induced by antigen under control of the thyroglobulin promoter was abolished in Aire homozygotes and less efficient in heterozygotes, providing an explanation for thyroid autoimmunity in APS1. In contrast, Aire deficiency had no effect on thymic deletion to antigen controlled by a systemic H-2K promoter. The sensitivity of Aire-dependent thymic deletion to small reductions in function makes this pathway a prime candidate for more subtle autoimmune quantitative trait loci, and suggests that methods to increase Aire activity would be a potent strategy to lower the incidence of organ-specific autoimmunity.

Differential Expression of IGF1, IGFBP5, MSTN, and MYH1 Across Different Age Classes in American Quarter Horses.

The objective of this study was to determine the influence of age on expression of insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein (IGFBP5), myostatin (MSTN), and myosin (MYH1) genes which are related to growth and muscle development in the American Quarter Horse. Thus, horses (n = 10) from weanling, yearling, 2-, 3-, and 10-year-old age classes were sampled and gene expression was assessed by RT-qPCR. ΔCT was calculated using the hypoxanthine-guanine phosphoribosyltransferase gene as an internal normalizer. The generalized linear model was used to determine differentially expressed genes, by pairwise comparison between ages. Among technical replicates, the coefficient of variation ranged from 1.0 to 5.2% and was lower than the variation observed between biological replicates (2.1-12.9%). IGF1 demonstrated significantly lower expression in the 3-year-old age class than in weanlings and yearlings, but the 10-year-old age class displayed a significantly higher level than 2- and 3-year-old age classes. Expression of IGFBP5 was highest in weanlings compared with all other age classes. Expression of MSTN was significantly higher in weanlings than in other age classes, whereas 10-year-old horses had an intermediate level of expression, but significantly different from yearlings, 2- and 3-year-old fillies. Finally, expression of MYH1 was lower in 2- and 10-year-old horses than in weanlings and yearlings, whereas 3-year-old fillies demonstrated an intermediate level of expression. Differential expression patterns observed in this preliminary study provide insight into the physiological changes occurring throughout the life span of horses. These patterns could also help explain the variation in performance and endurance between individuals at different developmental stages.

CtGEM typing: Discrimination of Chlamydia trachomatis ocular and urogenital strains and major evolutionary lineages by high resolution melting analysis of two amplified DNA fragments.

Chlamydia trachomatis infects the urogenital tract (UGT) and eyes. Anatomical tropism is correlated with variation in the major outer membrane protein encoded by ompA. Strains possessing the ocular ompA variants A, B, Ba and C are typically found within the phylogenetically coherent "classical ocular lineage". However, variants B, Ba and C have also been found within three distinct strains in Australia, all associated with ocular disease in children and outside the classical ocular lineage. CtGEM genotyping is a method for detecting and discriminating ocular strains and also the major phylogenetic lineages. The rationale was facilitation of surveillance to inform responses to C. trachomatis detection in UGT specimens from young children. CtGEM typing is based on high resolution melting analysis (HRMA) of two PCR amplified fragments with high combinatorial resolving power, as defined by computerised comparison of 65 whole genomes. One fragment is from the hypothetical gene defined by Jali-1891 in the C. trachomatis B_Jali20 genome, while the other is from ompA. Twenty combinatorial CtGEM types have been shown to exist, and these encompass unique genotypes for all known ocular strains, and also delineate the TI and T2 major phylogenetic lineages, identify LGV strains and provide additional resolution beyond this. CtGEM typing and Sanger sequencing were compared with 42 C. trachomatis positive clinical specimens, and there were no disjunctions. CtGEM typing is a highly efficient method designed and tested using large scale comparative genomics. It divides C. trachomatis into clinically and biologically meaningful groups, and may have broad application in surveillance.

Impact of Mobility Device Use on Quality of Life in Children With Friedreich Ataxia.

OBJECTIVE: To determine how mobility device use impacts quality of life in children with Friedreich ataxia. STUDY DESIGN: Data from 111 pediatric patients with genetically confirmed Friedreich ataxia were collected from a prospective natural history study utilizing standardized clinical evaluations, including health-related quality of life using the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Module. RESULTS: Mobility device use was associated with worse mean PedsQL total, physical, emotional, social, and academic subscores, after adjusting for gender, age of disease onset, and Friedreich Ataxia Rating Scale score. The magnitude of the difference was greatest for the physical subscore (-19.5 points, 95% CI = -30.00, -8.99, P < .001) and least for the emotional subscore (-10.61 points, 95% CI = -20.21, -1.02, P = .03). Transition to or between mobility devices trended toward worse physical subscore (-16.20 points, 95% CI = -32.07, -0.33, P = .05). CONCLUSIONS: Mobility device use is associated with significant worsening of all domains of quality of life in children with Friedreich ataxia.

Aplasia cutis congenita, terminal limb defects and falciform retinal folds: confirmation of a distinct syndrome of vascular disruption.

We describe a son of consanguineous parents with congenital scalp defects, transverse limb abnormalities, hypoplasia of the corpus callosum and bilateral falciform retinal folds. Aplasia cutis congenita with transverse limb defects are features of Adams-Oliver syndrome, which is usually inherited as an autosomal dominant condition. The association of bilateral retinal folds and brain abnormalities with scalp defects and terminal limb defects has only once been previously described. It is possible that these cases represent a severe variant of Adams-Oliver syndrome. We, however, suggest that they may characterize a new, distinct, autosomal recessive syndrome, involving vascular disruption.

Development and validation of the Core Beliefs Questionnaire in a sample of individuals with social anxiety disorder.

BACKGROUND: Prominent cognitive models of social anxiety have consistently emphasised the importance of beliefs about the self in the aetiology and maintenance of social anxiety. The present study sought to develop and validate a new measure of core beliefs about the self for SAD, the Core Beliefs Questionnaire (CBQ). METHODS: Three versions of the CBQ were developed: a Trait version (fundamental absolute statements about the self), a Contingent version (statements about the self related to a specific social-evaluative situation), and an Other version (statements about how others view the self in social-evaluative situations generally). The psychometric features of the scales were examined in clinical (n=269) and non-clinical (n=67) samples. RESULTS: Exploratory factor analysis yielded a one factor model for all three versions of the questionnaire. Total scores differentiated individuals with SAD from individuals without a psychiatric condition, and demonstrated excellent internal consistency. The three CBQ versions had positive associations with social anxiety while controlling for depression, although zero-order correlations indicated the Trait version was more strongly related to depression than social anxiety, the Contingent version was similarly related to depression and social anxiety, and the Other version was more strongly related to social anxiety than depression. Scores on all three versions of the CBQ reduced from pre- to post-treatment and this change predicted treatment outcome. LIMITATIONS: This is the first validation study of the CBQ. CONCLUSIONS: This study provides initial support for the reliability and validity of the CBQ.

Self-concept certainty in social phobia.

Two studies are reported which examined the content of beliefs about self-attributes in social phobia, and the level of certainty with which these beliefs are held. The results of both studies indicated that individuals with social phobia held less positive beliefs about their personality characteristics in comparison to non-anxious individuals. In addition, social anxiety was associated with reduced subjective confidence in self-descriptiveness ratings for personality attributes (Study 1), as well as longer reaction times in making self-descriptiveness decisions relative to general decisions about trait adjectives (Study 2). The association between social anxiety and reduced certainty in negative attribute ratings was evident after controlling for depression, general anxiety, stress, and the extent to which negative attributes were endorsed as being self-descriptive. Results are discussed in terms of the potential role that reduced self-concept certainty may play in social phobia.

Angiotensin-Converting Enzyme Inhibitor Initiation and Dose Uptitration in Children With Cardiovascular Disease: A Retrospective Review of Standard Clinical Practice and a Prospective Randomized Clinical Trial.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) are a mainstay of medical management in pediatric cardiology. However, there are no data defining how best to initiate and uptitrate the dose of these medications in children. METHODS AND RESULTS: Retrospective chart review revealed only 24% of our pediatric cardiology inpatients were discharged on predefined optimal doses of ACEIs and few underwent further dose uptitration in the 8 weeks after hospital discharge. Therefore, 2 alternative protocols for initiation of captopril were compared in a prospective randomized clinical trial. A "rapid uptitration" protocol reached an optimal dose on day 3, whereas the alternative, "prolonged uptitration" protocol, reached an optimal dose on day 9. Forty-6 patients (54% male) were recruited to the trial, with a median age of 0.7 year (IQR 0.5-2.3 years). Captopril was initiated while in intensive care in 39% of patients and on the cardiology ward in 61%. There were no differences between the protocols in episodes of hypotension, symptomatic hypotension, or indices of renal function. Patients following the rapid protocol reached higher doses of captopril (0.93±0.24 versus 0.57±0.38 mg/kg per dose, P<0.0001) and were more likely to have achieved the predefined target (88% versus 43%, P=0.002) and optimal ACEI doses (80% versus 29%, P=0.001) before discharge. CONCLUSIONS: A protocol of rapid ACEI dose uptitration for infants and children with cardiovascular disease can be introduced safely, even in patients receiving intensive care therapy. Compared with standard clinical practice or with a more prolonged protocol, rapid ACEI dose uptitration achieves a higher dosage in this population with no evident disadvantages. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00742040.