ProtocadherinX/Y, a Candidate Gene-Pair for Schizophrenia and Schizoaffective Disorder: A DHPLC Investigation of Gonomic Sequence

Protocadherin X and Protocadherin Y (PCDHX and PCDHY) are cell-surface adhesion molecules expressed predominantly in the brain. The PCDHX/Y gene-pair was generated by an X-Y translocation approximately 3 million years ago (MYA) that gave rise to the Homo sapiens-specific region of Xq21.3 and Yp11.2 homology. Genes within this region are expected to code for sexually dimorphic human characteristics, including, for example, cerebral asymmetry a dimension of variation that has been suggested is relevant to psychosis. We examined differences in patients with schizophrenic or schizoaffective psychosis in the genomic sequence of PCDHX and PCDHY in coding and adjacent intronic sequences using denaturing high performance liquid chromatography (DHPLC). Three coding variants were detected in PCDHX and two in PCDHY. However, neither the coding variants nor the intronic polymorphisms could be related to psychosis within families. Low sequence variation suggests selective pressure against sequence change in modern humans in contrast to the structural chromosomal and sequence changes including fixed X-Y differences that occurred in this region earlier in hominid evolution. Our findings exclude sequence variation in PCDHX/Y as relevant to the aetiology of psychosis. However, we note the unusual status of this region with respect to X-inactivation. Further investigation of the epigenetic control of PCDHX/Y in relation to psychosis is warran

Utilizing Digital Health to Collect Electronic Patient-Reported Outcomes in Prostate Cancer: Single-Arm Pilot Trial

Background: Measuring patient-reported outcomes (PROs) requires an individual’s perspective on their symptoms, functional status, and quality of life. Digital health enables remote electronic PRO (ePRO) assessments as a clinical decision support tool to facilitate meaningful provider interactions and personalized treatment. Objective: This study explored the feasibility and acceptability of collecting ePROs using validated health-related quality of life (HRQoL) questionnaires for prostate cancer. Methods: Using Apple ResearchKit software, the Strength Through Insight app was created with content from validated HRQoL tools 26-item Expanded Prostate Cancer Index Composite (EPIC) or EPIC for Clinical Practice and 8-item Functional Assessment of Cancer Therapy Advanced Prostate Symptom Index. In a single-arm pilot study with patients receiving prostate cancer treatment at Thomas Jefferson University Hospital and affiliates, participants were recruited, and instructed to download Strength Through Insight and complete ePROs once a week over 12 weeks. A mixed methods approach, including qualitative pre- and poststudy interviews, was used to evaluate the feasibility and acceptability of Strength Through Insight for the collection and care management of cancer treatment. Results: Thirty patients consented to the study; 1 patient failed to complete any of the questionnaires and was left out of the analysis of the intervention. Moreover, 86% (25/29) reached satisfactory questionnaire completion (defined as completion of 60% of weekly questions over 12 weeks). The lower bound of the exact one-sided 95% CI was 71%, exceeding the 70% feasibility threshold. Most participants self-identified with having a high digital literacy level (defined as the ability to use, understand, evaluate, and analyze information from multiple formats from a variety of digital sources), and only a few participants identified with having a low digital literacy level (defined as only having the ability to gather information on the Web). Interviews were thematically analyzed to reveal the following: (1) value of emotional support and wellness in cancer treatment, (2) rise of social patient advocacy in online patient communities and networks, (3) patient concerns over privacy, and (4) desire for personalized engagement tools. Conclusions: Strength Through Insight was demonstrated as a feasible and acceptable method of data collection for ePROs. A high compliance rate confirmed the app as a reliable tool for patients with localized and advanced prostate cancer. Nearly all participants reported that using the smartphone app is easier than or equivalent to the traditional paper-and-pen approach, providing evidence of acceptability and support for the use of remote PRO monitoring. This study expands on current research involving the value of digital health, as a social and behavioral science, augmented with technology, can begin to contribute to population health management, as it shapes psychographic segmentation by demographic, socioeconomic, health condition, or behavioral factors to group patients by their distinct personalities and motivations, which influence their choices

Use of fat mass and fat free mass standard deviation scores obtained using simple measurement methods in healthy children and patients: comparison with the reference 4-component model

Background Clinical application of body composition (BC) measurements for individual children has been limited by lack of appropriate reference data. Objectives (1) To compare fat mass (FM) and fat free mass (FFM) standard deviation scores (SDS) generated using new body composition reference data and obtained using simple measurement methods in healthy children and patients with those obtained using the reference 4-component (4-C) model; (2) To determine the extent to which scores from simple methods agree with those from the 4-C model in identification of abnormal body composition. Design FM SDS were calculated for 4-C model, dual-energy X-ray absorptiometry (DXA; GE Lunar Prodigy), BMI and skinfold thicknesses (SFT); and FFM SDS for 4CM, DXA and bioelectrical impedance analysis (BIA; height2/Z)) in 927 subjects aged 3.8–22.0 y (211 healthy, 716 patients). Results DXA was the most accurate method for both FM and FFM SDS in healthy subjects and patients (mean bias (limits of agreement) FM SDS 0.03 (±0.62); FFM SDS −0.04 (±0.72)), and provided best agreement with the 4-C model in identifying abnormal BC (SDS ≤−2 or ≥2). BMI and SFTs were reasonable predictors of abnormal FM SDS, but poor in providing an absolute value. BIA was comparable to DXA for FFM SDS and in identifying abnormal subjects

Decadal Evolution of Ocean Thermal Anomalies in the North Atlantic: The Effects of Ekman, Overturning, and Horizontal Transport

Basin-scale thermal anomalies in the North Atlantic, extending to depths of 1–2 km, are more pronounced than the background warming over the last 60 years. A dynamical analysis based on reanalyses of historical data from 1965 to 2000 suggests that these thermal anomalies are formed by ocean heat convergences, augmented by the poorly known air–sea fluxes. The heat convergence is separated into contributions from the horizontal circulation and the meridional overturning circulation (MOC), the latter further separated into Ekman and MOC transport minus Ekman transport (MOC-Ekman) cells. The subtropical thermal anomalies are mainly controlled by wind-induced changes in the Ekman heat convergence, while the subpolar thermal anomalies are controlled by the MOC-Ekman heat convergence; the horizontal heat convergence is generally weaker, only becoming significant within the subpolar gyre. These thermal anomalies often have an opposing sign between the subtropical and subpolar gyres, associated with opposing changes in the meridional volume transport driving the Ekman and MOC-Ekman heat convergences. These changes in gyre-scale convergences in heat transport are probably induced by the winds, as they correlate with the zonal wind stress at gyre boundaries

Primary succession on a seasonal tropical rocky shore: The relative roles of spatial heterogeneity and herbivory

Hong Kong is within the tropics and has a seasonal climate. In winter, shores support patches of ephemeral macroalgae and areas of seemingly bare rock close to crevices where molluscan herbivores are abundant. Using a factorial design of herbivore exclusions in areas far and close to crevices, the development of algal assemblages was monitored in mid-shore, cleared areas, in winter. To estimate the role of herbivore mucus deposition, half the treatments received a mucus application. Algal development was estimated from macroalgal and biofilm development and chlorophyll a levels. In all areas, biofilms (diatoms, unicellular cyanobacteria) developed rapidly in herbivore exclusions followed by ephemeral macroalgae (Enteromorpha spp. and Porphyra suborbiculata). In herbivore access treatments, however, the algal assemblage was influenced by treatment location; few macroalgae developed in areas close to crevices, and the rock was dominated by cyanobacteria. A negative relationship between macroalgae and biofilms suggested that ephemeral algae were competitively dominant. In areas distant from herbivore refuges, ephemeral macroalgae did develop, illustrating that the effectiveness of molluscan herbivores was limited to 50 to 100 cm from these refuges. The absence of large herbivorous fish, and the sparse numbers of herbivorous crabs at this site, means that algae can achieve a spatial escape from consumption, and where this occurs competition between producers is important in assemblage development. Mucus appeared to play a limited role, only sometimes stimulating initial stages of unicellular cyanobacteria and macroalgae. With the onset of summer, macroalgae died back, and rock space became available for colonization. Unicellular cyanobacteria developed rapidly but were replaced in all treatments by the encrusting macroalga, Hapalospongidion gelatinosum, which dominated treatments until the end of the experiment. On seasonal, tropical shores processes influencing community structure can, therefore, be temporally variable and their relative importance, even at the same shore level, can change with season.published_or_final_versio

Primary succession on a seasonal tropical rocky shore: The relative roles of spatial heterogeneity and herbivory

Hong Kong is within the tropics and has a seasonal climate. In winter, shores support patches of ephemeral macroalgae and areas of seemingly bare rock close to crevices where molluscan herbivores are abundant. Using a factorial design of herbivore exclusions in areas far and close to crevices, the development of algal assemblages was monitored in mid-shore, cleared areas, in winter. To estimate the role of herbivore mucus deposition, half the treatments received a mucus application. Algal development was estimated from macroalgal and biofilm development and chlorophyll a levels. In all areas, biofilms (diatoms, unicellular cyanobacteria) developed rapidly in herbivore exclusions followed by ephemeral macroalgae (Enteromorpha spp. and Porphyra suborbiculata). In herbivore access treatments, however, the algal assemblage was influenced by treatment location; few macroalgae developed in areas close to crevices, and the rock was dominated by cyanobacteria. A negative relationship between macroalgae and biofilms suggested that ephemeral algae were competitively dominant. In areas distant from herbivore refuges, ephemeral macroalgae did develop, illustrating that the effectiveness of molluscan herbivores was limited to 50 to 100 cm from these refuges. The absence of large herbivorous fish, and the sparse numbers of herbivorous crabs at this site, means that algae can achieve a spatial escape from consumption, and where this occurs competition between producers is important in assemblage development. Mucus appeared to play a limited role, only sometimes stimulating initial stages of unicellular cyanobacteria and macroalgae. With the onset of summer, macroalgae died back, and rock space became available for colonization. Unicellular cyanobacteria developed rapidly but were replaced in all treatments by the encrusting macroalga, Hapalospongidion gelatinosum, which dominated treatments until the end of the experiment. On seasonal, tropical shores processes influencing community structure can, therefore, be temporally variable and their relative importance, even at the same shore level, can change with season.published_or_final_versio

Interference with the germination and growth of Ulvazoospores by quorum-sensing molecules from Ulva-associated epiphytic bacteria

Ulva zoospores preferentially settle on N-acylhomoserine lactone (AHL) producing marine bacterial biofilms. To investigate whether AHL signal molecules also affect the success and rate of zoospore germination in addition to zoospore attraction, the epiphytic bacteria associated with mature Ulva linza were characterized and bacterial isolates representative of this community tested for the ability to produce AHLs. Two of these AHL-producing isolates, Sulfitobacter spp. 376 and Shewanella spp. 79, were transformed with plasmids expressing the Bacillus spp. AHL lactonase gene aiiA to generate AHL-deficient variants. The germination and growth of U. linza zoospores was studied in the presence of these AHL-deficient strains and their AHL-producing counterparts. This revealed that the AHLs produced by Sulfitobacter spp. and Shewanella spp. or the bacterial products they regulate have a negative impact on both zoospore germination and the early growth of the Ulva germling. Further experiments with Escherichia coli biofilms expressing recombinant AHL synthases and synthetic AHLs provide data to demonstrate that zoospores germinated and grown in the absence of AHLs were significantly longer than those germinated in the presence of AHLs. These results reveal an additional role for AHLs per se in the interactive relationships between marine bacteria and Ulva zoospores

The Schistosoma mansoni Cytochrome P450 (CYP3050A1) Is Essential for Worm Survival and Egg Development.

Schistosomiasis affects millions of people in developing countries and is responsible for more than 200,000 deaths annually. Because of toxicity and limited spectrum of activity of alternatives, there is effectively only one drug, praziquantel, available for its treatment. Recent data suggest that drug resistance could soon be a problem. There is therefore the need to identify new drug targets and develop drugs for the treatment of schistosomiasis. Analysis of the Schistosoma mansoni genome sequence for proteins involved in detoxification processes found that it encodes a single cytochrome P450 (CYP450) gene. Here we report that the 1452 bp open reading frame has a characteristic heme-binding region in its catalytic domain with a conserved heme ligating cysteine, a hydrophobic leader sequence present as the membrane interacting region, and overall structural conservation. The highest sequence identity to human CYP450s is 22%. Double stranded RNA (dsRNA) silencing of S. mansoni (Sm)CYP450 in schistosomula results in worm death. Treating larval or adult worms with antifungal azole CYP450 inhibitors results in worm death at low micromolar concentrations. In addition, combinations of SmCYP450-specific dsRNA and miconazole show additive schistosomicidal effects supporting the hypothesis that SmCYP450 is the target of miconazole. Treatment of developing S. mansoni eggs with miconazole results in a dose dependent arrest in embryonic development. Our results indicate that SmCYP450 is essential for worm survival and egg development and validates it as a novel drug target. Preliminary structure-activity relationship suggests that the 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol moiety of miconazole is necessary for activity and that miconazole activity and selectivity could be improved by rational drug design

Transitions in Care: Medication Reconciliation in the Community Pharmacy Setting After Discharge

Objective: To assess the feasibility of a workflow process in which pharmacists in an independent community pharmacy group conduct medication reconciliation for patients undergoing transitions in care.Methods: Three workflow changes were made to improve the medication reconciliation process in a group of three independent community pharmacies. Analysis of the process included workflow steps performed by pharmacy staff, pharmacist barriers encountered during the medication reconciliation process, number of medication discrepancies identified, and pharmacist comfort level while performing each medication reconciliation service.Key Findings: Sixty patient medication reconciliation services met the inclusion criteria for the study. Pharmacists were involved in all steps associated with the medication reconciliation workflow, and were the sole performer in four of the steps: verifying discharge medications with the pharmacy medication profile, resolving discrepancies, contacting the prescriber, and providing patient counseling. Pharmacists were least involved in entering medications into the pharmacy management system, performing that workflow step 13% of the time. The most common barriers were the absence of a discharge medication list (24%) and patient not present during consultation (11%). A total of 231 medication discrepancies were identified, with an average of 3.85 medication discrepancies per discharge. Pharmacists’ comfort level performing medication reconciliation improved through the 13 weeks of the study.Conclusions: These findings suggest that medication reconciliation for patients discharged from hospitals and long term care facilities can be successfully performed in an independent community pharmacy setting. Because many medication discrepancies were identified during this transition of care, it is highly valuable for community pharmacists to perform medication reconciliation services