A feasibility study for a triple-blind randomized controlled trial investigating the effects of oral isotretinoin on mood and quality of life in patients with acne vulgaris.

Isotretinoin is used in the treatment of severe acne vulgaris (AV), but has controversially been associated with depression and suicide. Large prospective studies have failed to translate this clinically. We undertook a feasibility study to investigate the parameters of a triple-blind, randomized controlled trial (RCT) assessing the effect of oral isotretinoin on quality of life (QoL) and mood in patients with AV. Patients meeting the inclusion criteria were randomized for 2 weeks to isotretinoin or doxycycline. Participants completed verified depression and QoL screening questionnaires at baseline and week 2. In total, 194 patients with AV were screened, with 48 meeting the inclusion criteria and 13 of these being willing to participate. The follow-up rate was 92% and questionnaire response rate was 96%. To our knowledge, this is the first study to demonstrate a successful design for a triple-blind RCT investigating the effects of isotretinoin on mood in patients with AV.

Observation of Quasichanneling Oscillations.

We report on the first experimental observations of quasichanneling oscillations, recently seen in simulations and described theoretically. Although above-barrier particles penetrating a single crystal are generally seen as behaving almost as in an amorphous substance, distinct oscillation peaks nevertheless appear for particles in that category. The quasichanneling oscillations were observed at SLAC National Accelerator Laboratory by aiming 20.35 GeV positrons and electrons at a thin silicon crystal bent to a radius of R=0.15 m, exploiting the quasimosaic effect. For electrons, two relatively faint quasichanneling peaks were observed, while for positrons, seven quasichanneling peaks were clearly identified.

Improving the mix of institutional and community care for older people with dementia: an application of the balance of care approach in eight European countries.

OBJECTIVES: To examine whether the mix of community and institutional long-term care (ILTC) for people with dementia (PwD) in Europe could be improved; assess the economic consequences of providing alternative services for particular groups of ILTC entrants and explore the transnational application of the 'Balance of Care' (BoC) approach. METHOD: A BoC study was undertaken in Estonia, Finland, France, Germany, the Netherlands, Spain, Sweden, and the UK as part of the RightTimePlaceCare project. Drawing on information about 2014 PwD on the margins of ILTC admission, this strategic planning framework identified people whose needs could be met in more than one setting, and compared the relative costs of the possible alternatives. RESULTS: The findings suggest a noteworthy minority of ILTC entrants could be more appropriately supported in the community if enhanced services were available. This would not necessarily require innovative services, but more standard care (including personal and day care), assuming quality was ensured. Potential cost savings were identified in all countries, but community care was not always cheaper than ILTC and the ability to release resources varied between nations. CONCLUSIONS: This is believed to be the first transnational application of the BoC approach, and demonstrates its potential to provide a consistent approach to planning across different health and social care systems. Better comparative information is needed on the number of ILTC entrants with dementia, unit costs and outcomes. Nevertheless, the findings offer important evidence on the appropriateness of current provision, and the opportunity to learn from different countries' experience.

Patient-reported sexual toxicity after radiation therapy in long-term prostate cancer survivors.

BACKGROUND: To present an overview of patient-reported sexual toxicity in sexually active long-term prostate cancer survivors treated with radiation therapy. METHODS: We used patient-reported outcomes from a study-specific questionnaire surveying symptoms after prostate cancer radiation therapy. Data from 518 men treated at the Sahlgrenska University Hospital in Sweden from 1993 to 2006 were analysed. The men had undergone primary or salvage external beam radiation therapy (EBRT) or EBRT combined with high-dose rate brachytherapy (BT). We also used information from 155 non-treated reference men from the general population with no history of prostate cancer, matched for age and residency. RESULTS: Median time from treatment to follow-up was 5 years (range: 1-14 years). Among the 16 investigated symptoms on erectile function, libido, orgasm, and seminal fluid, 9 symptoms in the primary EBRT group and 10 in both the salvage EBRT and the EBRT+BT groups were statistically significantly more prevalent in survivors than in reference men. Erectile dysfunction was influenced by both age and time to follow-up, whereas symptoms relating to orgasm and seminal fluid were influenced by time to follow-up only. Not being sexually active was almost one and a half times as common in survivors as in reference men. CONCLUSIONS: The presented symptom profiles can help to develop personalized therapy for prostate cancer through a better understanding of which radiation-induced toxicities to be addressed in the clinic and can also assist in identifying suitable interventions for existing symptoms.

Validation of daily increments and a marine-entry check in the otoliths of sockeye salmon Oncorhynchus nerka post-smolts.

Juvenile sockeye salmon Oncorhynchus nerka that were reared and smolted in laboratory conditions were found to produce otolith daily increments, as well as a consistently visible marine-entry check formed during their transition to salt water. Field-collected O. nerka post-smolts of an equivalent age also displayed visible checks; however, microchemistry estimates of marine-entry date using Sr:Ca ratios differed from visual estimates by c. 9 days suggesting that microstructural and microchemical processes occur on different time scales.

Status, emotional displays, and the relationally-based evaluation of criminals and their behavior.

This research uses status characteristics theory to expand our knowledge of the effects of status variables (e.g., race, education) and emotional displays on the antecedents of sentencing - evaluations of offender dangerousness and offense seriousness. We present a theoretical formulation that combines three areas of status characteristics research - reward expectations, individual evaluative settings and valued personal characteristics. The result is a quantitative measure that aggregates relative differences in demographic and emotional characteristics between offenders and their victims. The significance of this expectation advantage measure (e) in predicting evaluations of offender dangerousness and offense severity is tested using data from a vignette study. We find empirical support that expectation advantage significantly predicts these sentencing antecedents but not sentencing outcomes directly. We conclude by discussing the implications of our findings for future status and criminological research.

Recovery of severe motor deficit secondary to herniated lumbar disc prolapse: is surgical intervention important? A systematic review.

INTRODUCTION: The natural history of motor deficit due to lumbar disc herniation has been thought to be favourable. However, on closer analysis of seminal articles on this topic, this is not the case for patients with severe motor deficits (MRC grade ≤3). The aim of this study is to answer the following questions: (1) Is surgical intervention beneficial in patients with severe motor weakness (defined by MRC grade of 3 or less) due to herniated lumbar nucleus pulposus? (2) Does time to surgery from onset of motor weakness influence the outcome? (3) Are there any other prognostic factors? MATERIALS AND METHODS: A comprehensive search was conducted in MEDLINE and EMBASE from 1970 upto July 2013. Inclusion criteria for studies are: (1) minimum of three patients aged 18 and older, who had symptomatic herniated lumbar disc prolapse and underwent surgery, (2) description of pre and post-operative muscle weakness utilising the Medical Research Council (MRC) muscle power grade or equivalent, such that both reviewers could confidently identify a cohort of patients with at least grade three motor weakness or worse, (3) a minimum of 6 months follow-up. RESULTS: Seven studies were identified with a total of 354 patients. Complete recovery was seen in 38.4% of patients following surgery and 32% following non-operative treatment. Age and grade of motor deficit were identified as significant prognostic factors in some of the studies. CONCLUSION: The current available evidence is not robust enough to address the questions posed. We have proposed a framework for future studies.

Experiential dynamic therapy: a preliminary investigation into the effectiveness and process of the extended initial session.

OBJECTIVE: This study explored whether patients in specialist psychology services made early gains on theoretically relevant therapeutic processes and outcomes after a trial therapy session (one 2- to 3-hour initial Experiential Dynamic Therapy session). METHOD: This practice-based, nonrandomized trial used a pre-post design. Thirty-one patients (23 women, average age of 37) completed standardized measures of symptoms of general distress, interpersonal functioning, self-compassion, and remoralization before and after the trial therapy session. Video recordings of the sessions' therapy process were rated on the Achievement of Therapeutic Objectives Scale. RESULTS: After the trial therapy session, patients reported a significant increase in remoralization and self-compassion and a significant decrease in symptoms of general distress but not interpersonal problems. Process ratings were not significantly associated with improvement on these outcome measures. CONCLUSIONS: This initial positive effect could be due to the session or an effect of time or placebo. Future research using active control conditions is warranted.

Patient-reported genitourinary toxicity for long-term prostate cancer survivors treated with radiation therapy.

BACKGROUND: The objective of this study is to provide comprehensive overviews of patient-reported urinary symptoms for long-term prostate cancer survivors treated with radiation therapy and for untreated, healthy men. METHODS: We performed a population-based cross-sectional study using a study-specific postal questionnaire assessing symptoms among 1007 men consecutively treated at the Sahlgrenska University Hospital, Göteborg, Sweden from 1993-2006 (primary or salvage external beam radiation therapy (EBRT) or EBRT and high-dose rate brachytherapy). We also randomly recruited 350 non-pelvic-irradiated matched control men from the Swedish Total Population Register. Symptom prevalence and prevalence ratios were computed. RESULTS: Survey participation rate was 89% (874/985) for eligible survivors and 73% (243/332) for eligible controls. Median time from treatment to follow-up was 5 years (range, 1-14 years). Among the 21 investigated symptoms reflecting obstruction, frequency, urgency, pain and incontinence, we found significantly higher prevalence compared with controls for 9 symptoms in the EBRT group, 10 in the EBRT+brachytherapy group and 5 in the salvage EBRT group. The prevalence for a majority of the symptoms was stable over time. CONCLUSION: The presented toxicity profiles provide a thorough understanding of patient-reported urinary symptoms that can assist in developing personalised therapy for prostate cancer.

Prevalence of risk factors for foot ulceration in patients with end-stage renal disease on haemodialysis.

BACKGROUND: End-stage renal disease (ESRD) has been associated with foot ulceration and lower extremity amputation (LEA). However, the underlying risk factors for foot ulceration have received limited attention in this population. AIM: The aim of this study was to investigate the prevalence and type of risk factors for foot ulceration present in patients with ESRD on haemodialysis without the coexistence of diabetes mellitus (DM). METHODS: One hundred and ninety participants with ESRD and/or DM were recruited over a 6-week period. Participants were allocated into one of three groups: (i) ESRD without DM; (ii) DM without ESRD; and (iii) coexisting ESRD and DM. Participants were screened for the risk factors for foot ulceration. Statistical comparisons were made between the three groups for both the prevalence and type of risk factors using a Fisher's exact test. RESULTS: Risk factors for foot ulceration were found to be highly prevalent in the ESRD population. Participants with both ESRD and DM exhibited statistically significant differences in risk factor presentation for peripheral neuropathy (P= 0.033), vascular insufficiency (P= 0.001) and footwear (P= 0.037) in comparison with participants with DM alone. CONCLUSION: There are high prevalence rates of risk factors for foot ulceration in the ESRD population on haemodialysis and are comparable with those with DM. Individuals with coexisting ESRD and DM have an even greater risk for foot ulceration and LEA. This highlights the importance that regular foot screening, preventative education and treatment are necessary for patients with ESRD potentially to reduce the risk of foot ulcerations and LEAs.

Variations in structures, processes and outcomes of community mental health teams for older people: a systematic review of the literature.

OBJECTIVES: In the UK and elsewhere, specialist community mental health teams (CMHTs) are central to the provision of comprehensive services for older people with mental ill health. Recent guidance documents suggest a core set of attributes that such teams should encompass. This article reports on a systematic literature review undertaken to collate existing evidence regarding the structures and processes of CMHTs for older people and to evaluate evidence linking approaches to effectiveness. METHOD: Relevant publications were identified via systematic searches, both electronic and manual. Searches were limited to the UK for descriptions of organisation and practice but included international literature where comparisons between different CMHT arrangements were evaluated. Empirical, peer-reviewed studies from 1989 onward were included, extended to non peer-reviewed nationally or regionally representative reports, published after 1998, for the descriptive element. RESULTS: Forty-five studies met inclusion criteria of which seven provided comparative outcome data. All but one were UK based. The most robust evidence related to research conducted in exemplar teams. Limited evidence was found regarding the effectiveness of many of the core attributes recommended in policy directives although their presence was reported in much of the literature. CONCLUSIONS: The contrast between presentation and evaluation of attributes is stark. Whilst some gaps can be filled from related fields, further research is required that moves beyond description to evaluation of the impact of team design on service user outcomes in order to inform future policy directives and practice guidance. A framework for an evidence-based model of CMHTs for older people is provided.

Leg strength is associated with ventilatory efficiency in older women.

The aim of the present study was to determine if leg function is associated with ventilatory efficiency during exercise in healthy older adults. 24 women and 18 men aged 60-80 years performed treadmill exercise to fatigue for calculation of ventilatory efficiency using the ratio of ventilation to carbon dioxide at the anaerobic threshold (VE/VCO2@AT). On a separate day, participants performed leg strength testing and graded single-leg knee extension exercise. The VE/VCO2@AT was higher in women than men (33±3 vs. 30±3; p=0.03). After adjustment for age and VO(2max), leg strength (knee extensor isometric force) was inversely associated with VE/VCO2@AT in women (r= - 0.44, p=0.03) while no relationships were found for men. Strength-matched women and men had similar VE/VCO2@AT indicating that the correlation between leg strength and VE/VCO2@AT was strength- but not sex-specific. During knee extensor exercise, women with lower leg strength had increased VE/VCO2 slope across 0-15 W as compared to higher strength women (38±8 vs. 31±3; p<0.05), while no differences were found for men. These results find leg strength to be associated with ventilatory responses to exercise in healthy older women, a finding that might be related to lower leg strength in women than men.

Yoga lifestyle intervention reduces blood pressure in HIV-infected adults with cardiovascular disease risk factors.

OBJECTIVE: People living with HIV infection are at increased risk for developing cardiovascular disease (CVD). Safe and effective interventions for lowering CVD risk in HIV infection are high priorities. We conducted a prospective, randomized, controlled study to evaluate whether a yoga lifestyle intervention improves CVD risk factors, virological or immunological status, or quality of life (QOL) in HIV-infected adults relative to standard of care treatment in a matched control group. METHODS: Sixty HIV-infected adults with mild-moderate CVD risk were assigned to 20 weeks of supervised yoga practice or standard of care treatment. Baseline and week 20 measures were: 2-h oral glucose tolerance test with insulin monitoring, body composition, fasting serum lipid/lipoprotein profile, resting blood pressures, CD4 T-cell count and plasma HIV RNA, and the Medical Outcomes Study Short Form (SF)-36 health-related QOL inventory. RESULTS: Resting systolic and diastolic blood pressures improved more (P=0.04) in the yoga group (-5 +/- 2 and -3 +/- 1 mmHg, respectively) than in the standard of care group (+1 +/- 2 and+2 +/- 2 mmHg, respectively). However, there was no greater reduction in body weight, fat mass or proatherogenic lipids, or improvements in glucose tolerance or overall QOL after yoga. Immune and virological status was not adversely affected. CONCLUSION: Among traditional lifestyle modifications, yoga is a low-cost, simple to administer, nonpharmacological, popular behavioural intervention that can lower blood pressure in pre-hypertensive HIV-infected adults with mild-moderate CVD risk factors.

Restarting plastic surgery: Drawing on the experience of the initial COVID-19 pandemic to inform the safe resumption of services.

Coronavirus disease-2019 (COVID-19) has caused an unprecedented demand on healthcare resources globally. In the light of the arrival of a novel contagious and life-threatening virus, the NHS has responded by making difficult decisions to maintain care for patients and protect staff. The response has been frequently amended following updates in the UK Government policy as scientific understanding of the virus has improved. Our Plastic Surgery practice has adapted to mitigate risk to patients by reducing face-to-face contact, downgrading emergency procedures and deferring elective surgery where possible. This has inevitably resulted in a backlog in elective surgery and outpatient appointments. An assessment of the long-term health, social and economic impact of NHS wide service reconfiguration upon patient outcomes is yet to be seen. In this paper, we review the demonstrable early effects of service changes upon our unit and compare those to national and internationally published data. We also outline some of the considerations being made as we consider strategies to resume services in the light of the ongoing COVID-19 pandemic.

A plastic surgery service response to COVID-19 in one of the largest teaching hospitals in Europe.

COVID-19 is presenting a colossal challenge to frontline NHS staff. This paper highlights how plastic surgery teams can use their diverse skills and resources in times of crisis. Through effective strategy and leadership we present how we are adapting as a department to serve our plastic surgery patients, other hospital teams and the Trust.

A Longitudinal Analysis of First Professional Year Pharmacy Student Well-being.

Objective. To assess and characterize Doctor of Pharmacy (PharmD) students' well-being across the first professional year (P1) and determine the relationship between the number of examinations taken, student grade point average, and well-being scores. Methods. All P1 students (N=76) enrolled at one college of pharmacy self-reported their career, community, financial, physical, social, and overall well-being on a weekly basis during the fall and spring semesters. Parametric statistical tests were used to examine the extent to which students' well-being scores varied throughout the academic year, the extent to which their domain-specific well-being scores predicted overall well-being scores, and the association between their well-being scores and the number of examinations they had taken in a week and their grade point average. Results. Overall and domain-specific well-being scores significantly decreased from the beginning to the end of fall semester. Students' overall well-being across the academic year was most frequently predicted by their career well-being, physical well-being, and social well-being scores. Career, community, physical, and overall well-being scores were significantly negatively associated with the number of examinations the students completed during the week. Students' self-reported overall well-being during the fall semester was positively associated with their fall semester GPA. Conclusion. Significant variation was found in students' domain-specific and overall well-being across the P1 year. These findings can guide both the development and timing of school interventions to promote student well-being.

A glycosylphosphatidylinositol (GPI)-negative phenotype produced in Leishmania major by GPI phospholipase C from Trypanosoma brucei: topography of two GPI pathways.

The major surface macromolecules of the protozoan parasite Leishmania major, gp63 (a metalloprotease), and lipophosphoglycan (a polysaccharide), are glycosylphosphatidylinositol (GPI) anchored. We expressed a cytoplasmic glycosylphosphatidylinositol phospholipase C (GPI-PLC) in L. major in order to examine the topography of the protein-GPI and polysaccharide-GPI pathways. In L. major cells expressing GPI-PLC, cell-associated gp63 could not be detected in immunoblots. Pulse-chase analysis revealed that gp63 was secreted into the culture medium with a half-time of 5.5 h. Secreted gp63 lacked anti-cross reacting determinant epitopes, and was not metabolically labeled with [3H]ethanolamine, indicating that it never received a GPI anchor. Further, the quantity of putative protein-GPI intermediates decreased approximately 10-fold. In striking contrast, lipophosphoglycan levels were unaltered. However, GPI-PLC cleaved polysaccharide-GPI intermediates (glycoinositol phospholipids) in vitro. Thus, reactions specific to the polysaccharide-GPI pathway are compartmentalized in vivo within the endoplasmic reticulum, thereby sequestering polysaccharide-GPI intermediates from GPI-PLC cleavage. On the contrary, protein-GPI synthesis at least up to production of Man(1 alpha 6)Man(1 alpha 4)GlcN-(1 alpha 6)-myo-inositol-1-phospholipid is cytosolic. To our knowledge this represents the first use of a catabolic enzyme in vivo to elucidate the topography of biosynthetic pathways. GPI-PLC causes a protein-GPI-negative phenotype in L. major, even when genes for GPI biosynthesis are functional. This phenotype is remarkably similar to that of some GPI mutants of mammalian cells: implications for paroxysmal nocturnal hemoglobinuria and Thy-1-negative T-lymphoma are discussed.

Dedifferentiated guard cells in magnoliaceous leaves.

Evidence has been obtained that guard cells and other epidermal cells as well as mesophyll cells undergo division during wound repair of mature leaves in 26 magnoliaceous taxa in the genera Kmeria, Elmerrillia, Magnolia, Manglietia, Michelia, Paramichelia, and Talauma. Division of epidermal cells is believed to be rare in mature leaves, and division of guard cells is particularly unusual in most species previously studied.

PIP2 and PIP as determinants for ATP inhibition of KATP channels.

Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels couple electrical activity to cellular metabolism through their inhibition by intracellular ATP. ATP inhibition of KATP channels varies among tissues and is affected by the metabolic and regulatory state of individual cells, suggesting involvement of endogenous factors. It is reported here that phosphatidylinositol-4, 5-bisphosphate (PIP2) and phosphatidylinositol-4-phosphate (PIP) controlled ATP inhibition of cloned KATP channels (Kir6.2 and SUR1). These phospholipids acted on the Kir6.2 subunit and shifted ATP sensitivity by several orders of magnitude. Receptor-mediated activation of phospholipase C resulted in inhibition of KATP-mediated currents. These results represent a mechanism for control of excitability through phospholipids.

A novel KCNA1 mutation identified in an Italian family affected by episodic ataxia type 1.

Episodic ataxia type 1 (EA1) is a rare human neurological syndrome characterized by continuous myokymia and attacks of generalized ataxia that can be triggered by abrupt movements, emotional stress and fatigue. An Italian family has been identified where related members displayed continuous myokymia, episodes of ataxia, attacks characterized by myokymia only, and neuromyotonia. A novel missense mutation (F414C), in the C-terminal region of the K(+) channel Kv1.1, was identified in the affected individuals. The mutant homotetrameric channels were non-functional in Xenopus laevis oocytes. In addition, heteromeric channels resulting from the co-expression of wild-type Kv1.1 and Kv1.1(F414C), or wild-type Kv1.2 and Kv1.1(F414C) subunits displayed reduced current amplitudes and altered gating properties. This indicates that the pathogenic effect of this KCNA1 mutation is likely to be related to the defective functional properties we have identified.