The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

Problem-Based Learning in Professional Entry-Level Therapy Education: A Review of Controlled Evaluation Studies

Although there has been growing interest in Problem Based Learning (PBL) by professional entry-level therapy educators, its effectiveness is as yet unclear. Existing overviews of the field do not provide high quality evidence in terms of the effectiveness or otherwise of PBL in professional therapy education. The purposes of this article is to systematically review the current literature on PBL and determine its effectiveness when compared to other didactic approaches in physiotherapy, occupational therapy, speech-language therapy, dietetics, podiatry, orthoptics and therapeutic radiography entry-level education. Eight databases were searched for controlled evaluation studies investigating the effectiveness of PBL in the seven therapy professions. Four competencies were analysed; students’ knowledge, performance, approaches to learning and satisfaction. Data were extracted and risk of bias assessed by independent reviewers. One scoring system was used to assess the quality of the studies and another determined the level of evidence for each competency. The search yielded 3885 articles, of which six met inclusion criteria after full text review; three in physiotherapy, one each in occupational therapy, dietetics and podiatry. Three of the six studies were categorised as high quality. No study measured all four competencies. When compared to other didactic approaches, there is no evidence that PBL has a more positive effect on students’ knowledge and performance and satisfaction levels and limited evidence that it improves students’ approaches to learning. Currently available literature revealed no convincing evidence that PBL is more effective than traditional didactic education for entry level therapy professions

Evaluating Treatment Options for NAP1 Versus Non-NAP1 Strains of Clostridium Difficile Infection Among Pediatric Patients at an Academic Hospital.

Class of 2014 AbstractSpecific Aims: The incidence of Clostridium difficile (C. Diff) infections in pediatric patients has continually risen, which could be caused by the emergence of a hyper virulent strain, specifically NAP1/B1/027. The objectives of the study were to evaluate the incidence of strain type, compare treatment(s) prescribed, treatment duration, rate of infection recurrence based on strain and severity, rates of re-infection or recurrence, and treatment failures for patients less than 6 months and up to 18 years of age. Methods: A retrospective study of patients admitted to an academic medical center with detection of C. diff toxin was performed. Data analyses included descriptive and inferential statistics to examine demographics, strain type, infection severity, and treatment failure. Main Results: Fourty-five patients with C. Diff toxin detection were included in study analyses and the median age was 6.2 [0.31- 17.9 years]. Oral or intravenous metronidazole was prescribed as initial therapy in 89% of the patients. Strain type was available in 77% of patients, with NAP1/B1/027 detected in 31% of stool samples tested. Within 21 days after initial toxin detection, there was a 13% rate of clinical failure or death, although none directly associated with C. Diff. Within days 22 - 65 after initial toxin detection, there was a 16% rate of recurrence or reinfection. Initial therapy selection, therapy duration, and rate of recurrence or reinfection were not significantly associated with NAP1/B1/027 strain type. Conclusion: Despite variability in severity of infection, the majority of pediatric patients with C. Diff were treated with metronidazole and were infected with a non-B1/NAP1/027 strain.This item is part of the Pharmacy Student Research Projects collection, made available by the College of Pharmacy and the University Libraries at the University of Arizona. For more information about items in this collection, please contact Jennifer Martin, Librarian and Clinical Instructor, Pharmacy Practice and Science, [email protected]

Live births after embryo selection using morphokinetics versus conventional morphology: a retrospective analysis

The increasing corpus of clinical studies using time-lapse imaging for embryo selection demonstrates considerable variation in study protocols and only limited-sized study cohorts. Outcome measures are based on implantation or clinical pregnancy; some predict blastulation from early cleavage-stage data, and few have evaluated live birth. Erroneously, most studies treat the embryos as independent variables and do not include patient or treatment variables in the statistical analyses. In this study, cohort size was 14,793 patients and 23,762 cycles. The incidence of live birth (n = 973 deliveries) after embryo selection by objective morphokinetic algorithms was compared with conventional embryology selection parameters (n = 6948 deliveries). A 19% increase in the incidence of live birth was observed when morphokinetic data were used to select embryos for the patient cohort aged younger than 38 years (OR 1.19 with 95% CI 1.06 to 1.34) using their own eggs, and an increase of 37% for oocyte recipients aged over 37 years (OR 1.370; 95% Cl 0.763 to 2.450). This is the largest study of the prospective use of time-lapse imaging algorithms in IVF reporting on live birth outcome, although the nature of purely a closed system versus standard incubation could not be assessed

Data from: Leaf hydraulic parameters are more plastic in species that experience a wider range of leaf water potentials

1. Many plant species experience large differences in soil moisture availability within a season, potentially leading to a wide range of leaf water potentials (ΨLEAF). In order to decrease the risk of leaf dehydration, among species, there is a continuum ranging from strict control (isohydry) to little control (anisohydry) of minimum ΨLEAF. 2. In central Texas USA, species are exposed to a range of soil moisture from wet springs to hot, dry summers. There are diverging water management strategies among the four dominant woody species in this system; two of these species are more isohydric (Prosopis glandulosa, Quercus fusiformis) while two others are more anisohydric (Diospyros texana, Juniperus asheii). 3. To maintain leaf turgor and photosynthesis during periods of limited soil moisture, anisohydric species may adjust leaf hydraulic parameters more than isohydric species. To test this hypothesis, we quantified iso/anisohydry from three years of ΨLEAF predawn and midday measurements, and we measured the changes in turgor loss points (ΨTLP), osmotic potential at full hydration (Ψπ100), and resistance to leaf hydraulic dysfunction (leaf P50) throughout the spring and summer of 2016. 4. Diospyros and Juniperus experienced more negative ΨLEAF and adjusted ΨTLP and Ψπ100 in response to both drying soils during the summer also in response to rainfaill events during September. In contrast, the more isohydric species (Quercus and Prosopis) did not appear to adjust ΨTLP or Ψπ100 in response to soil moisture. The more anisohydric species also adjusted leaf P50 during periods of reduced soil moisture. 5. Our results suggest that species that experience wider ranges of ΨLEAF have a greater ability to alter leaf hydraulic properties. This provides insight on how species with different strategies for water potential regulation may modify properties to mitigate drought effects in the future