Single-base substitutions in the CHM promoter as a cause of choroideremia

Although over 150 unique mutations affecting the coding sequence of CHM have been identified in patients with the X-linked chorioretinal disease choroideremia (CHM), no regulatory mutations have been reported, and indeed the promoter has not been defined. Here, we describe two independent families affected by CHM bearing a mutation outside the gene's coding region at position c.-98: C>A and C>T, which segregated with the disease. The male proband of family 1 was found to lack CHM mRNA and its gene product Rab escort protein 1, whereas whole-genome sequencing of an affected male in family 2 excluded the involvement of any other known retinal genes. Both mutations abrogated luciferase activity when inserted into a reporter construct, and by further employing the luciferase reporter system to assay sequences 5′ to the gene, we identified the CHM promoter as the region encompassing nucleotides c.-119 to c.-76. These findings suggest that the CHM promoter region should be examined in patients with CHM who lack coding sequence mutations, and reveals, for the first time, features of the gene's regulation

Evaluation and implications of natural product use in preoperative patients: a retrospective review

<p>Abstract</p> <p>Background</p> <p>Medication Reconciliation and Medication Safety are two themes emphasized in a variety of healthcare organizations. As a result, health care facilities have established methods for obtaining a patient's medication history. However, these methods may vary among institutions or even among the health care professionals in a single institution, and studies have shown that patients are reluctant to disclose their complementary and alternative medicine use to any health care professional. This lack of disclosure is important in surgical patients because of potential herbal interactions with medications and drugs used during the surgical procedure; and the potential for adverse reactions including effects on coagulation, blood pressure, sedation, electrolytes or diuresis. Therefore, the objectives of this study are to identify patterns of natural product use, to identify potential complications among patients scheduled for surgery, to improve existing medication reconciliation efforts, and to develop discontinuation guidelines for the use of these products prior to surgery.</p> <p>Methods</p> <p>A retrospective review of surgery patients presenting to the Anesthesia Preoperative Evaluation Clinic (APEC) at the University of Kansas Hospital was conducted to identify the prevalence of natural product use. The following data was collected: patient age; gender; allergy information; date of medication history; number of days prior to surgery; source of medication history; credentials of person obtaining the history; number and name of prescription medications, over-the-counter medications and natural products; and natural product dosage. Following the collection of data and analysis of the most common natural products used, possible complications and interactions were identified, and a protocol regarding the pre-operative use of natural products was developed and implemented.</p> <p>Results</p> <p>Approximately one-fourth of patients seen in the APEC indicated the use of natural products. Patients taking natural products were significantly older, were more likely to undergo cardiac or chest surgery, and were more likely to be taking more prescription and non-prescription medications (all p < 0.001).</p> <p>Conclusion</p> <p>Based on the results of this study, it is concluded that there is a need for established guidelines regarding discontinuation of selected natural products prior to surgery and further education is needed concerning the perioperative implications of natural products.</p

Blood lactate levels in 31 female dogs with pyometra

<p>Abstract</p> <p>Background</p> <p>Canine pyometra is a life-threatening disease common in countries where spaying of dogs is not routinely performed. The disease is associated with endotoxemia, sepsis, systemic inflammatory response syndrome (SIRS) and a 3–4% mortality rate. Blood lactate analysis is clinically valuable in predicting prognosis and survival, evaluating tissue perfusion and treatment response in human and veterinary critical care settings. The aims of the present study were to investigate 1) the blood lactate levels of female dogs with pyometra by a hand-held analyser and 2) if these levels are related with the clinical status or other biochemical or hematological disorders.</p> <p>Methods</p> <p>In total 31 female dogs with pyometra admitted for surgical ovariohysterectomy and 16 healthy female control dogs were included in the present study. A complete physical examination including SIRS-status determination was performed. Blood samples for lactate concentrations, hematological and biochemical parameters, acid-base and blood gas analysis and other laboratory parameters were collected and subsequently analysed. The diagnosis pyometra was verified with histopathological examination of the uterus and ovaries. Increased hospitalisation length and presence of SIRS were used as indicators of outcome.</p> <p>Results</p> <p>In the pyometra group the median blood lactate level was 1,6 mmol l^-1(range <0.8–2.7 mmol l^-1). In the control group the median lactate level was 1,2 mmol l^-1(range <0.8–2.1 mmol l^-1). Of the 31 bitches 19 (61%) fulfilled 2 or more criteria for SIRS at inclusion, 10 bitches (32%) fulfilled 3 of the SIRS criteria whereas none accomplished more than 3 criteria. Lactate levels did not differ significantly between the pyometra and control group, or between the SIRS positive and SIRS negative dogs with pyometra. Increased lactate concentration (>2.5 mmol l^-1) was demonstrated in one female dog with pyometra (3%), and was not associated with longer hospitalisation or presence of SIRS. Lactate measurement was not indicative of peritonitis. None of the bitches died during or within two months of the hospital stay. The measurements of temperature, heart rate, respiratory rate, percentage bandforms of neutrophilic granulocytes, α₂-globulins, creatinin, pvCO₂, TCO₂and base excess showed significant differences between the SIRS positive and the SIRS negative pyometra cases.</p> <p>Conclusion</p> <p>Increased blood lactate concentrations were demonstrated in 3% (1/31), and SIRS was present in 61% (19/31) of the female dogs with pyometra. Preoperative lactate levels were not related with presence of SIRS or prolonged hospitalisation. Lactate measurement was not indicative of peritonitis. The value of a single and repeated lactate analysis in more severely affected cases remains to be determined.</p

Associations of sedentary behavior and physical activity with psychological distress: a cross-sectional study from Singapore

Background: Emerging evidence suggests the adverse association between sedentary behavior (SB) and physical with mental health, but few studies have investigated the relationship between volume of physical activity and psychological distress. The present study examined the independent and interactive associations of daily SB and weekly level of moderate to vigorous physical activity (MVPA) with psychological distress in a multi-ethnic Asian population. Methods. De-identified data of 4,337 adults (18-79 years old) on sedentary behaviors, physical activity patterns, psychological distresses, and other relevant variables were obtained from the Singapore Ministry of Health's 2010 National Health Survey. Psychological distress was assessed using General Health Questionnaire-12 (GHQ-12), whereas total daily SB and total weekly volume (MET/minutes) of MVPA were estimated using the Global Physical Activity Questionnaire version 2 (GPAQ v2). Multivariate logistic regression analyses were carried out to estimate the odds ratios (95% confidence intervals) of the independent and interactive relationships of SB and MVPA with prevalence of psychological distress. Results: The category of high SB was positively associated with increased odds (OR = 1.29, 1.04-1.59) for psychological distress, whereas the category of active was inversely associated with lower odds (OR = 0.73, 0.62-0.86) for psychological distress. Multivariate analyses for psychological distress by combined daily SB and weekly MVPA levels showed inverse associations between middle SB and active categories (OR = 0.58, 0.45 - 0.74) along with low SB and active categories (OR = 0.61, 0.47-0.80). Conclusions: The present population-based cross-sectional study indicated that in the multi-ethnic Asian society of Singapore, a high level of SB was independently associated with psychological distress and meeting the recommended guidelines for physical activity along with ≤ 5 h/day of SB was associated with the lowest odds of psychological distress

Mutations in the small nuclear riboprotein 200 kDa gene (SNRNP200) cause 1.6% of autosomal dominant retinitis pigmentosa

Purpose: The purpose of this project was to determine the spectrum and frequency of mutations in the small nuclear riboprotein 200 kDa gene (SNRNP200) that cause autosomal dominant retinitis pigmentosa (adRP). Methods: A well-characterized adRP cohort of

Gender, turning points, and boomerangs: returning home in young adulthood in Great Britain

The idea of a generation of young adults “boomeranging” back to the parental home has gained widespread currency in the British popular press. However, there is little empirical research identifying either increasing rates of returning home or the factors associated with this trend. This article addresses this gap in the literature using data from a long-running household panel survey to examine the occurrence and determinants of returning to the parental home. We take advantage of the longitudinal design of the British Household Panel Survey (1991–2008) and situate returning home in the context of other life-course transitions. We demonstrate how turning points in an individual’s life course—such as leaving full-time education, unemployment, or partnership dissolution—are key determinants of returning home. An increasingly unpredictable labor market means that graduate employment cannot be taken for granted following university graduation, and returning home upon completion of higher education is becoming normative. We also find that gender moderates the relationship among partnership dissolution, parenthood, and returning to the parental home, reflecting the differential welfare support in Great Britain for single parents compared with nonresident fathers and childless young adults