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A critical step for functional recovery from peripheral nerve injury is for regenerating axons to connect with their pre-injury targets. Reestablishing pre-injury target specificity is particularly challenging for limb-innervating axons as they encounter a plexus, a network where peripheral nerves converge, axons from different nerves intermingle, and then re-sort into target-specific bundles. Here, we examine this process at a plexus located at the base of the zebrafish pectoral fin, equivalent to tetrapod forelimbs. Using live cell imaging and sparse axon labeling, we find that regenerating motor axons from 3 nerves coalesce into the plexus. There, they intermingle and sort into distinct branches, and then navigate to their original muscle domains with high fidelity that restores functionality. We demonstrate that this regeneration process includes selective retraction of mistargeted axons, suggesting active correction mechanisms. Moreover, we find that Schwann cells are enriched and associate with axons at the plexus, and that Schwann cell ablation during regeneration causes profound axonal mistargeting. Our data provide the first real-time account of regenerating vertebrate motor axons navigating a nerve plexus and reveal a previously unappreciated role for Schwann cells to promote axon sorting at a plexus during regeneration.

ObjectiveTo ascertain the burden and associated cost of adverse drug reactions (ADRs), polypharmacy and multimorbidity through a prospective analysis of all medical admissions to a large university teaching hospital over a 1-month period.DesignProspective observational study.SettingLiverpool University Hospital Foundation National Health Service (NHS) Trust, England.ParticipantsAll medical admissions with greater than 24-hour stay over a 1-month period.Main outcome measuresPrevalence of admissions due to an ADR and associated mortality, prevalence and association of multimorbidity and polypharmacy with ADRs, and estimated local financial cost of admissions where an ADR was a contributing or main reason for admission with projected costs for NHS in England.ResultsThere were 218 identified patient admissions with an ADR giving a prevalence of 18.4%. The majority of these (90.4%) were ADRs that directly resulted in or contributed to admission. ADRs thus accounted for 16.5% of total admissions. Those with an ADR were on average taking more medicines (10.5 vs 7.8, p<0.01) and had more comorbidities than those without an ADR (6.1 vs 5.2, p<0.01). Drugs most commonly implicated were diuretics, steroid inhalers, anticoagulants and antiplatelets, proton pump inhibitors, chemotherapeutic agents and antihypertensives. 40.4% of ADRs were classified avoidable or possibly avoidable. The mortality rate due to an ADR was 0.34%. The average length of stay for those with an ADR was 6 days. Direct 1-month cost to the Trust from ADR admissions was £490 716. Extrapolated nationally, the projected annual cost to the NHS in England is 2.21 billion.ConclusionThe local prevalence of admission and mortality from ADRs is higher than previously reported. Important factors that could be contributing to this include polypharmacy and multimorbidity. ADRs place a significant burden on patients and healthcare services with associated financial implications. Reducing inappropriate polypharmacy should be a major aim for preventing ADRs.

This manuscript is the first to examine the psychometric properties of the Female Sexual Distress Scale in samples of sexually functional and dysfunctional men, herein called the Sexual Distress Scale (SDS). A sample of 127 sexually dysfunctional men and 267 sexually functional men completed an online survey that included a sociodemographic questionnaire, a health questionnaire, the SDS, as well as measures of sexual bother and concerns, sexual function, sexual attitudes, and mood states. We also used a sample of 188 sexually dysfunctional and 155 sexually functional women from previous studies. Results showed that the SDS assesses one general domain of sexual distress. The factor structure was invariant across gender and sexual function status. The SDS also showed good content, construct, and criterion validity, as well as good internal consistency reliability (Cronbach’s alpha) and test–retest reliability. Finally, the SDS discriminated well between sexually functional and sexually dysfunctional men. These results show that the SDS is a reliable and valid tool for assessing sexual distress in men. This instrument can be used by researchers and clinicians to examine sexual distress and can be used to elucidate how sexual distress relates to sexual function, well-being and quality of life.

Olfactory dysfunction is a common and early symptom of many neurodegenerative diseases, particularly of Parkinson’s disease and other synucleinopathies, Alzheimer’s disease (AD), and mild cognitive impairment heralding its progression to dementia. The neuropathologic changes of olfactory dysfunction in neurodegenerative diseases may involve the olfactory epithelium, olfactory bulb/tract, primary olfactory cortices, and their secondary targets. Olfactory dysfunction is related to deposition of pathological proteins, α-synuclein, hyperphosphorylated tau protein, and neurofilament protein in these areas, featured by neurofibrillary tangles, Lewy bodies and neurites inducing a complex cascade of molecular processes including oxidative damage, neuroinflammation, and cytosolic disruption of cellular processes leading to cell death. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with severe anosmia. Recent studies of olfactory dysfunction have focused its potential as an early biomarker for the diagnosis of neurodegenerative disorders and their disease progression. Here, we summarize the current knowledge on neuropathological and pathophysiological changes of the olfactory system in the most frequent neurodegenerative diseases, in particular AD and synucleinopathies. We also present neuropathological findings in the olfactory bulb and tract in a large autopsy cohort ( n  = 536, 57.8 % female, mean age 81.3 years). The severity of olfactory bulb HPτ, Aβ, and αSyn pathology correlated and increased significantly ( P  < 0.001) with increasing neuritic Braak stages, Thal Aβ phases, and cerebral Lewy body pathology, respectively. Hence, further studies are warranted to investigate the potential role of olfactory biopsies (possibly restricted to the olfactory epithelium) in the diagnostic process of neurodegenerative diseases in particular in clinical drug trials to identify subjects showing early, preclinical stages of neurodegeneration and to stratify clinically impaired cohorts according to the underlying cerebral neuropathology.

Abstract Decreased olfactory function is very common in the older population, being present in >50% of individuals aged between 65 and 80 years and in 62-80% of those >80 years of age. Smell dysfunction significantly influences physical well-being, quality of life, nutritional status as well as everyday safety and is associated with increased mortality. Multiple factors contribute to age-related olfactory sensory loss, including nasal engorgement, cumulative damage of the olfactory epithelium from environmental insults, a reduction in mucosal metabolizing enzymes, sensory loss of receptor cells to odorants, and changes in neurotransmitter and neuromodulator systems. In addition, structural and functional abnormalities of the olfactory epithelium, olfactory bulb, central olfactory cortex, and basic olfactory circuitry, which are related to the neuronal expression of aberrant proteins in these areas, may result in olfactory sensory impairment in aging and neurodegenerative diseases. Impaired odour identification is associated with a decrease in cognitive abilities and memory decline. A reduction in the sense of smell is considered to potentially represent an early and important warning of neurodegenerative disorders, particularly of Parkinson's disease and Alzheimer's disease, and, in mild cognitive impairment, olfactory impairment may herald progression to dementia. Further investigations of the potential role of olfactory dysfunction in the early diagnosis and treatment of neurodegenerative diseases are warranted.

Sexual recovery after prostate cancer (PCa) treatment is challenging. When expectations are that erectile response will quickly return to baseline, patients can often struggle when this does not happen. Further difficulty is experienced when patients encounter physical, psychological, and relational barriers to sexual adjustment. Drawing on the psychosocial research literature and on 15 years of clinical experience counseling PCa patients about sexual recovery, this paper outlines considerations for clinical practice. Suggestions include broadening the target for successful outcomes after Pca treatment beyond erectile function to include sexual distress and other sources of sexual concern. Clinicians are urged to consider individual differences such as the larger context of the patient, including their values and preferences, their treatment goals, and their relationship situation and status, in order to promote successful sexual adaptation. When introducing treatment approaches, the role of grief and loss should be assessed, and patients should be supported to foster realistic expectations about the recovery process. Suggestions for how to introduce various sexual strategies to patients are also offered, including ways to support patients in making and sustaining behavioral changes associated with sexual intervention. Clinicians are offered suggestions to promote patients’ sexual flexibility, prevent long periods of sexual inactivity, and help patients to identify various sexual motivators. Consideration of these psychological, relational, and social factors are all likely to help facilitate better sexual outcomes for PCa patients.

Background There is increasing recognition of the therapeutic function pets can play in relation to mental health. However, there has been no systematic review of the evidence related to the comprehensive role of companion animals and how pets might contribute to the work associated with managing a long-term mental health condition. The aim of this study was to explore the extent, nature and quality of the evidence implicating the role and utility of pet ownership for people living with a mental health condition. Methods A systematic search for studies exploring the role of companion animals in the management of mental health conditions was undertaken by searching 9 databases and undertaking a scoping review of grey literature from the earliest record until March 2017. To be eligible for inclusion, studies had to be published in English and report on primary data related to the relationship between domestic animal ownership and the management of diagnosable mental health conditions. Synthesis of qualitative and quantitative data was undertaken in parallel using a narrative synthesis informed by an illness work theoretical framework. Results A total of 17 studies were included in the review. Quantitative evidence relating to the benefits of pet ownership was mixed with included studies demonstrating positive, negative and neutral impacts of pet ownership. Qualitative studies illuminated the intensiveness of connectivity people with companion animals reported, and the multi-faceted ways in which pets contributed to the work associated with managing a mental health condition, particularly in times of crisis. The negative aspects of pet ownership were also highlighted, including the practical and emotional burden of pet ownership and the psychological impact that losing a pet has. Conclusion This review suggests that pets provide benefits to those with mental health conditions. Further research is required to test the nature and extent of this relationship, incorporating outcomes that cover the range of roles and types of support pets confer in relation to mental health and the means by which these can be incorporated into the mainstay of support for people experiencing a mental health problem.

Erectile difficulties are common after prostate cancer (PCa) treatment and are associated with sexual distress. However, the relationship between erectile function and sexual distress has yet to be carefully examined. This study had three goals: (1) examine the relationship between erectile function and sexual distress; (2) determine groups of men based on erectile function and sexual distress; and (3) examine the psychosexual characteristics of these groups. A cross section of 233 sexually active men after PCa treatment (age M  = 64.90 years, SD = 7.50) completed an online survey containing demographic, health, and sexuality and relationship questionnaires. The relationship between erectile function and sexual distress was curvilinear. Four groups of men were found: good erectile function and low sexual distress, poor erectile function and high sexual distress, but also good erectile function yet high sexual distress, and poor erectile function and low sexual distress. Regardless of erectile function, men with greater sexual distress were more depressed, reported additional sexual concerns, placed less value on sex, were less sexually satisfied, and used protective buffering communication more frequently. They were also less likely to be satisfied with their adaptation to sexual changes and less likely to have found a solution to those changes. The relationship between erectile function and sexual distress is complex, characterized by a wide array of responses to erectile function (high and low distress) and multiple correlates of sexual distress. These results broaden the concept of sexual recovery after PCa treatment, which may assist clinicians and researchers to better address sexual problems after PCa treatment.

Sexual adverse effects from prostate cancer treatment are a substantial burden for patients. An online biopsychosocial sexual rehabilitation intervention for patients with prostate cancer (TrueNTH) was implemented in several cancer centres in the USA. Outcomes from this intervention show no improvements in sexual satisfaction after 6 months; however, earlier resumption of sexual activities was observed 3 months after the intervention.

PurposeErectile function changes after prostate cancer (PCa) treatment are well documented, but less understood is the relative impact of prostate biopsy and active surveillance on sexual well-being. It is unknown whether potential negative impacts are exclusive to patients who have been treated for PCa, or whether the diagnosis itself or the experience of biopsy may also impact sexual well-being. Sexual satisfaction is an important yet understudied indicator of sexual well-being in this population. This study examines sexual satisfaction and its predictors across several comparison groups to explore relative impact.MethodsAt baseline and 12 months, questionnaire data was collected in four samples: (1) following PCa treatment, (2) active surveillance, (3) negative prostate biopsy result, and (4) controls receiving no biopsy or treatment. Predictors assessed included group, erectile function, communication style, and partner involvement.ResultsSexual satisfaction declined in the active treatment group, no changes were observed in active surveillance or non-PCa control, and improvements were observed in the biopsy group. Predictors of sexual satisfaction over and above erectile function included restrictive communication (i.e. protective buffering) and perceived partner involvement. For higher levels of erectile function, a higher perceived degree of partner involvement was protective of sexual satisfaction.ConclusionSexual satisfaction is an important indicator of sexual well-being and is negatively impacted following PCa treatment, but not active surveillance or prostate biopsy.Implications for Cancer SurvivorsCommunication and partner involvement are potentially modifiable factors to be considered for intervention and may promote sexual satisfaction following PCa treatment. Patients experiencing negative biopsy, who note lower sexual satisfaction may experience improved satisfaction with time, and those under active surveillance who worry about sexual satisfaction may find reassurance from these results.