Basal bodies exhibit polarized positioning in zebrafish cone photoreceptors

The asymmetric positioning of basal bodies, and therefore cilia, is often critical for proper cilia function. This planar polarity is critical for motile cilia function but has not been extensively investigated for nonmotile cilia or for sensory cilia such as vertebrate photoreceptors. Zebrafish photoreceptors form an organized mosaic ideal for investigating cilia positioning. We report that, in the adult retina, the basal bodies of red‐, green‐, and blue‐sensitive cone photoreceptors localized asymmetrically on the cell edge nearest the optic nerve. In contrast, no patterning was seen in the basal bodies of ultraviolet‐sensitive cones or in rod photoreceptors. The asymmetric localization of basal bodies was consistent in all regions of the adult retina. Basal body patterning was unaffected in the cones of the XOPS‐mCFP transgenic line, which lacks rod photoreceptors. Finally, the adult pattern was not seen in 7‐days‐postfertilization (dpf) larvae; basal bodies were randomly distributed in all the photoreceptor subtypes. These results establish the asymmetrical localization of basal bodies in red‐, green‐, and blue‐sensitive cones in adult zebrafish retinas but not in larvae. This pattern suggests an active cellular mechanism regulated the positioning of basal bodies after the transition to the adult mosaic and that rods do not seem to be necessary for the patterning of cone basal bodies. J. Comp. Neurol. 521:1803–1816, 2013. © 2012 Wiley Periodicals, Inc.     

Perceived Value of Teaching and Learning Curriculum Programs Among Pharmacy Practice Department Chairs

Objective. To determine the perceived value that pharmacy practice department chairs ascribe to pharmacy faculty candidates having completed a teaching and learning curriculum (TLC) program and related activities.Methods. An 18-item survey instrument was created that was intended to capture the overall impressions of pharmacy practice chairs regarding the value of TLC programs, relative importance compared to other accomplishments (eg, residency completion, board certification), and importance of specific activities. Following pilot testing and establishment of intra-rater reliability, invitations to complete the electronic survey instrument were sent to pharmacy practice chairs (or their equivalent) at accredited Doctor of Pharmacy (PharmD) programs in the United States.Results. Of the 127 pharmacy practice chairs invited, 53 completed the survey (response rate of 41.7%). The majority of respondents held a PharmD degree (90.6%), had been in their role of chair for zero to five years (60.4%), and represented a private institution (54.7%). The majority of respondents who answered the question (32 of 49) felt it was very important or important (16.3% and 49.0%, respectively) that teaching experiences be completed within a formal teaching and learning curriculum program. These programs were believed to be most important for candidates with less than five years of professional experience. Teaching and learning curriculum programs were not deemed to be more important than other accomplishments by most responders. The perceived most important TLC program activities were instruction on didactic and experiential teaching strategies, and experience developing learning objectives, developing examination items, evaluating examination results, and facilitating case conferences or practice laboratory activities.Conclusion. Teaching and learning curriculum programs may provide the foundational experiences needed for pharmacy graduates to stand out among other candidates, although department chairs’ perceptions of the value of teaching and learning curriculum experiences varied.     

Physicians' interactions with health care teams and systems in the care of dying patients: perspectives of dying patients,family members,and health care professionals

This study investigated the specific physician skills required to interact with health care systems in order to provide high quality care at the end of life. We used focus groups of patients with terminal diseases, family members, nurses and social workers from hospice or acute care settings, and physicians. We performed content analysis based on grounded theory. Groups were interviewed. Two domains were found related to physician interactions with health care systems: 1) access and continuity, and 2) team communication and coordination. Components of these domains most frequently mentioned included taking as much time as needed with the patient, accessibility, and respect shown in working with health team members. This study highlights the need for both physicians and health care systems to improve accessibility for patients and families and increase coordination of efforts between health care team members when working with dying patients and their families.     

Magnetic silica extraction for low-viremia human immunodeficiency virus type 1 genotyping

Nucleic acid extraction and human immunodeficiency virus type 1 (HIV-1) genotyping using the NucliSens miniMAG platform and the TruGene HIV-1 genotyping kit gave HIV-1 sequence data from HIV-1-negative plasma spiked with 100 copies/ml reference HIV-1 RNA and from low-viremia clinical samples (<500 copies/ml) without the need for ultracentrifugation or nested second-round PCR.     

Lower limb immobilization is associated with increased corticospinal excitability

Temporary immobilization of the leg serves as a useful model for the brain’s adaptive responses to casting, long-term confinement to bed rest and possibly to trauma. As part of a larger program using TMS to investigate changes associated with bed rest, we sought to determine whether casting of the leg causes brain excitability changes measurable with TMS, and the time course of resolution of these changes. In this study, eight adults wore a full leg cast for 10 days. TMS measures of motor cortex excitability were gathered before the cast was placed, and then immediately after cast removal, and 24 and 48 h later. A control group did not wear a cast and underwent the same TMS sessions. Significant excitability changes occurred and peaked at 24 h post cast removal in the TMS experimental group but not the non-casted group.     

Transition from methylphenidate or amphetamine to atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder--a preliminary tolerability and efficacy study

BACKGROUND: The primary treatment for attention-deficit/hyperactivity disorder (ADHD) has been psychostimulants. Recently developed nonpsychostimulant treatments have allowed certain patients to switch from a psychostimulant to a nonpsychostimulant. However, the outcomes of such switches have not been systematically studied. OBJECTIVE: The purpose of this pilot study was to assess treatment tolerance and efficacy during a cross-taper transition from methylphenidate or amphetamine to atomoxetine among children and adolescents with ADHD. METHODS: This pilot study was conducted in patients (aged 6-17 years) with incomplete responses (failure to obtain full reduction/elimination of symptoms) or intolerance of adverse events (AEs) during psychostimulant treatment. Patients continued ongoing psychostimulant treatment during the first week of the study. Transition to atomoxetine began by administering atomoxetine 0.5 mg/kg . d plus full-dose psychostimulant for 1 week, followed in the second week by 1.2 mg/kg . d atomoxetine plus half-dose psychostimulant. Patients remained on 1.2 mg/kg . d atomoxetine monotherapy for the remaining 5 weeks. This stepwise transition was enacted due to the difference in pharmacodynamics between the psychostimulants and atomoxetine. Applying a stepwise cross-titration allowed for better control of ADHD symptoms during the intervening period. Change in ADHD symptoms, as measured by the mean change in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-administered and -scored (ADHDRS-IV-Parent:Inv), was assessed from baseline to end point. RESULTS: Of the 62 subjects enrolled in the study, 39 (62.9%) were diagnosed as ADHD-combined type. Similar proportions were receiving methylphenidate (51.6%) and amphetamine (48.4%). Slightly more wished to switch due to inadequate response (53.2%) than intolerability (46.8%). Nine subjects discontinued at various times during the course of the study (patient or parent/caregiver decision [4], AE [2], protocol violation [2], and lack of efficacy [1]). Mean (SD) ADHDRS-IV-Parent:Inv total scores (n = 59, last-observation-carried-forward) improved significantly from baseline (visit 2) to an end point (32.1 [10.5] vs 22.6 [14.0]; P < 0.001). Of the 58 subjects answering in the atomoxetine monotherapy phase, 38 (65.5%) reported a preference for atomoxetine treatment over their previous psychostimulant. Tolerability results were as follows: 26 (44.1%) of 59 patients reported >or=1 AE, the most common being somnolence (4 [6.8%]), fatigue (3 [5.1%]), decreased appetite (3 [5.1%]), cough (3 [5.1%]), headache (3 [5.1%]), and contact dermatitis (2 [3.4%]). No clinically severe AEs were reported. Both mean (SD) diastolic (2.4 [7.8] mm Hg; P = 0.031) and systolic (2.4 [7.9] mm Hg; P = 0.029) blood pressures increased significantly from baseline to end point. Electrocardiography revealed a significant increase in mean (SD) heart rate (9.2 [11.6] bpm; P < 0.001) and a corresponding decrease in mean (SD) RR interval (-77.8 [98.2] ms; P < 0.001). Statistically significant, but mild, increases in diastolic pressure and heart rate were observed. CONCLUSION: These children and adolescent patients were successfully switched from methylphenidate or amphetamine to atomoxetine treatment, with resulting improvement in ADHD symptom severity from baseline in this pilot study.     

Methods for siting emergency stomas in the absence of a stoma therapist

Introduction

Stomas often have to be sited in emergencies by trainees who may have had little training in this. Emergency stomas and stomas where the site has not been marked preoperatively by a stoma therapist are more prone to complications. These complications may severely affect a patient’s quality of life. Advice in the literature on how to best site stomas is conflicting. We compared two easy anatomical methods of siting stomas to sites chosen by a stoma therapist and looked at how this site was affected by the patients’ body mass index (BMI).

Methods

Patients undergoing elective colorectal surgery were seen either pre or postoperatively. Each patient’s BMI was recorded and the positions of three different potential stoma positions (site G: the gold standard, marked by a stoma therapist; site S: marked using a pair of scissors against the umbilicus; site H: halfway between the umbilicus and anterior superior iliac spine) were compared.

Results

The two fixed anatomical methods described (method S and method H) both gave poor results. The most common reason for poor siting was the proximity of a skin crease. There was a statistically significant correlation between the patient’s BMI and the laterality of the gold standard site.

Conclusions

The two simple anatomical methods described here do not provide a shortcut to effective siting. A more effective method may be calculating the laterality of the site using the patient’s BMI, and then moving up/down to avoid a skin crease and improve the patient’s view for changing the bag. This deserves further study.     

Identification of Subgroups of Schizophrenia Patients With Changes in Either Immune or Growth Factor and Hormonal Pathways

Schizophrenia is a heterogeneous disorder normally diagnosed using the Diagnostic and Statistical Manual of Mental Disorders criteria. However, these criteria do not necessarily reflect differences in underlying molecular abnormalities of the disorder. Here, we have used multiplexed immunoassay analyses to measure immune molecules, growth factors, and hormones important to schizophrenia in acutely ill antipsychotic-naive patients (n = 180) and matched controls (n = 398). We found that using the resulting molecular profiles, we were capable of separating schizophrenia patients into 2 significantly distinct subgroups with predominant molecular abnormalities in either immune molecules or growth factors and hormones. These molecular profiles were tested using an independent cohort, and this showed the same separation into 2 subgroups. This suggests that distinct abnormalities occur in specific molecular pathways in schizophrenia patients. This may be of relevance for intervention studies that specifically target particular molecular mechanisms and could be a first step to further define the complex schizophrenia syndrome based on molecular profiles.Key words: schizophrenia, subtypes, diagnosis, molecular profiling, immune factors, growth factors