Summary Background In patients with chronic spinal cord injury, imaging of the spinal cord and brain above the level of the lesion provides evidence of neural degeneration; however, the spatial and ...temporal patterns of progression and their relation to clinical outcomes are uncertain. New interventions targeting acute spinal cord injury have entered clinical trials but neuroimaging outcomes as responsive markers of treatment have yet to be established. We aimed to use MRI to assess neuronal degeneration above the level of the lesion after acute spinal cord injury. Methods In our prospective longitudinal study, we enrolled patients with acute traumatic spinal cord injury and healthy controls. We assessed patients clinically and by MRI at baseline, 2 months, 6 months, and 12 months, and controls by MRI at the same timepoints. We assessed atrophy in white matter in the cranial corticospinal tracts and grey matter in sensorimotor cortices by tensor-based analyses of T1-weighted MRI data. We used cross-sectional spinal cord area measurements to assess atrophy at cervical level C2/C3. We used myelin-sensitive magnetisation transfer (MT) and longitudinal relaxation rate (R1) maps to assess microstructural changes associated with myelin. We also assessed associations between MRI parameters and clinical improvement. All analyses of brain scans done with statistical parametric mapping were corrected for family-wise error. Findings Between Sept 17, 2010, and Dec 31, 2012, we recruited 13 patients and 18 controls. In the 12 months from baseline, patients recovered by a mean of 5·27 points per log month (95% CI 1·91–8·63) on the international standards for the neurological classification of spinal cord injury (ISNCSCI) motor score (p=0·002) and by 10·93 points per log month (6·20–15·66) on the spinal cord independence measure (SCIM) score (p<0·0001). Compared with controls, patients showed a rapid decline in cross-sectional spinal cord area (patients declined by 0·46 mm per month compared with a stable cord area in controls; p<0·0001). Patients had faster rates than controls of volume decline of white matter in the cranial corticospinal tracts at the level of the internal capsule (right Z score 5·21, p=0·0081; left Z score 4·12, p=0·0004) and right cerebral peduncle ( Z score 3·89, p=0·0302) and of grey matter in the left primary motor cortex ( Z score 4·23, p=0·041). Volume changes were paralleled by significant reductions of MT and R1 in the same areas and beyond. Improvements in SCIM scores at 12 months were associated with a reduced loss in cross-sectional spinal cord area over 12 months (Pearson's correlation 0·77, p=0·004) and reduced white matter volume of the corticospinal tracts at the level of the right internal capsule ( Z score 4·30, p=0·0021), the left internal capsule ( Z score 4·27, p=0·0278), and left cerebral peduncle ( Z score 4·05, p=0·0316). Improvements in ISNCSCI motor scores were associated with less white matter volume change encompassing the corticospinal tract at the level of the right internal capsule ( Z score 4·01, p<0·0001). Interpretation Extensive upstream atrophic and microstructural changes of corticospinal axons and sensorimotor cortical areas occur in the first months after spinal cord injury, with faster degenerative changes relating to poorer recovery. Structural volumetric and microstructural MRI protocols remote from the site of spinal cord injury could serve as neuroimaging biomarkers in acute spinal cord injury. Funding SRH Holding, Swiss National Science Foundation, Clinical Research Priority Program “NeuroRehab” University of Zurich, Wellcome Trust.
Industry placements are popular means to provide students with an opportunity to apply their skills, knowledge and experience in a 'real world' setting. Within this context, supervisor feedback ...allows educators to measure students' performance beyond academic objectives, by benchmarking it against industry expectations. However, industry assessments appear to be frequently clouded and overwhelmingly positive by nature, which questions the reliability and validity of supervisors' judgement of competencies. Supervisor bias has been paid much attention within the context of clinical placements, as well as within the domain of social work. However, the concept has been largely ignored within business education, despite the increasing emphasis on - and deep integration of - work-integrated learning in the business curriculum. This paper sets out to address this gap by examining variances in mark distribution and apparent leniency in the context of a final-year, compulsory placement unit, based on observations and data collected over nine semesters (n = 546). The focus of this study is on gaining an understanding of the reasons behind assessment bias and the pressures placed on industry assessors. The data indicate that different types of placement locations apply dissimilar standards when assessing student performance. The author identifies three statistically different placement types (small business, not-for-profit and professional), which influence the strength and risk of grader bias, hence ultimately the assessment outcome.
The Mas-related G protein–coupled receptor X2 (MRGPRX2) is a multiligand receptor responding to various exogenous and endogenous stimuli. Being highly expressed on skin mast cells, MRGPRX2 triggers ...their degranulation and release of proinflammatory mediators, and it promotes multicellular signaling cascades, such as itch induction and transmission in sensory neurons. The expression of MRGPRX2 by skin mast cells and the levels of the MRGPRX2 agonists (eg, substance P, major basic protein, eosinophil peroxidase) are upregulated in the serum and/or skin of patients with inflammatory and pruritic skin diseases, such as chronic spontaneous urticaria or atopic dermatitis. Therefore, MRGPRX2 and its agonists might be potential biomarkers for the progression of cutaneous inflammatory diseases and the response to treatment. In addition, they may represent promising targets for prevention and treatment of signs and symptoms in patients with skin diseases or drug reactions. To assess this possibility, this review explores the role and relevance of MRGPRX2 and its activators in cutaneous inflammatory disorders and chronic pruritus.
To investigate the association of psychotropic drug use with falls among older adults in Germany based on data from the National Health Interview and Examination Survey for Adults 2008-2011 (DEGS1).
...DEGS1 collected data on drug use in the past 7 days and on falls occurred in the last 12 months. Study participants were older adults aged 65-79 years with complete data on drug use and falls (N = 1,833). Odds ratio (OR) and 95% confidence intervals (95% CI) were derived from logistic regression models adjusting for potential confounders including socio-demographic characteristics, health-related behaviors (alcohol drinking), body mass index and health conditions (frailty, vision impairment, disability, polypharmacy, blood pressure) as well as use of potential falls-risk-increasing drugs. SPSS complex sample methods were used for statistical analysis.
Compared to people without falls, people with falls (n = 370) had a higher psychotropic drug use (33.1% vs. 20.7%, p < .001). After adjusting for potential confounders, use of psychotropic drugs overall was associated with a higher risk of falls (OR 1.64, 95% CI 1.14-2.37). This was particularly true for the use of synthetic psychotropic drugs (1.57, 1.08-2.28), antidepressants overall (2.88, 1.63-5.09) or synthetic antidepressants (2.66, 1.50-4.73), specifically, selective serotonin reuptake inhibitors (SSRIs) (6.22, 2.28-17.0). Similar results were found for recurrent falls.
Use of psychotropic drugs overall, especially synthetic antidepressants like SSRIs, is associated with higher risks of falls and recurrent falls among community dwelling older adults aged 65-79 years in Germany.
The social media landscape is now ubiquitous in people's everyday lives. It is a space where culture, politics, economics and sociological and public health discourses occur. There is mounting ...evidence that e-cigarette products are being promoted and advertised on social media, a media platform particularly popular with young people. Our research aimed to understand industry professionals' perceptions of social media harms and potential management strategies using vaping as a case study.
A critical realist perspective guided reflexive thematic analysis of the qualitative in depth, semi structured interviews. Data collection occurred in January and February 2023 with 13 participants working in the areas of public health, digital media, law, governance, tobacco control and advocacy.
Two superordinate themes emerged from the data: (1) Fathoming a complex system (social media) that contained the subordinate themes of Traversing Boundaries (crossing borders, crossing sectors) and Ungovernable (global and local landscapes, vested interests, self-regulation and opacity). (2) Addressing complexity (social media)- that contained the subordinate themes of Strengthening Institutions (global to local, policy and legislation, individuals and organisations); Defanging Industry (responsibility and transparency, moderation and algorithms, complaints); and Engaging Citizens (raising awareness, framing messaging).
There was consensus among participants that e-cigarette related social media content can be harmful and government action is urgently needed. There was an identified need for the development of government led national-level regulatory frameworks, with government led appropriate legislation; identification of an organisation or organisations with suitable levels of regulatory power and resources to monitor, enforce and penalise noncompliant social media companies; accompanied by increased community awareness raising of harmful social media content and improved digital literacy.
Use of psychotropic drugs is common among older adults. Population-based studies on the associations of psychotropic drug use with mortality are sparse.
To investigate the associations between the ...use of specific psychotropic drug groups (opioids, antipsychotics, antidepressants and benzodiazepines) and all-cause mortality among community-dwelling older adults in Germany.
Participants of the German National Health Interview and Examination Survey 1998 were followed up for mortality from 1997 to 2011. Persons aged 60-79 years with complete data on psychotropic drug use at baseline and on mortality follow-up were considered as study population (N = 1,563). Associations between the use of opioids, antipsychotics, antidepressants and benzodiazepines and all-cause mortality were examined by Cox proportional hazards models adjusted for sociodemographics (sex, age, community size, region, socioeconomic status), life style (smoking, sports, risky alcohol drinking) and health conditions (obesity, disability, history of cardiovascular diseases, diabetes, hyperlipidemia, hypertension, any cancers, any mental disorders) at baseline.
After a median follow-up of 11.4 years, 21, 18, 23 and 26 deaths were documented among those who used at baseline opioids (n = 39), antipsychotics (n = 30), antidepressants (n = 53) and benzodiazepines (n = 54) with an unadjusted mortality rate (MR) of 57.7, 59.1, 44.6 and 53.7 per 1000 person-years, respectively. Meanwhile, 400 deaths were documented among 1,406 nonusers of any of the above mentioned psychotropic drugs with a MR of 26.7 per 1000 person-years. The age and sex adjusted mortality rate ratios in comparison with nonusers were 2.20 (95% confidence intervals 1.42-3.41), 1.66(1.03-2.70), 1.56(1.06-2.28), and 1.57(1.07-2.31) for the use of opioids, antipsychotics, antidepressants and benzodiazepines, respectively. In the fully adjusted Cox models, use of opioids (hazardous ratio 2.04, 95% confidence intervals 1.07-3.89), antipsychotics (2.15, 1.11-4.15) and benzodiazepines (1.76, 1.09-2.82), but not antidepressants, were significantly associated with an increased risk of mortality.
Use of opioids, antipsychotics, benzodiazepines is significantly associated with an increased risk of all-cause mortality among community-dwelling older adults in Germany. Clinicians should be careful in prescribing these psychotropic drugs to older adults while patients already under psychotropic therapy should well balance the risks and benefits of drug use. Further studies with a larger sample size and information on specific indications for psychotropic drug use and mental comorbidities are required to confirm the findings of the present study.
Female sexual problems and dysfunctions have a high prevalence, ranging from 12% to 80%, depending on the definition being used, underlying comorbidities, and age. Despite the high prevalence, there ...are only scarce data about the approach gynecologists use to address female sexual dysfunction.
The aim of this study is to evaluate the approach of Swiss gynecologists to addressing sexual problems among their outpatients.
After a pilot study including 56 physicians, a modified 19‐item self‐administered questionnaire was sent to 856 Swiss gynecologists to evaluate their methods of management of patients with sexual issues and their attitudes regarding the integration of sexual health issues into the gynecological consultation.
Besides demographic information, the self‐administered questionnaire included questions about addressing sexual health as part of consultation routine, estimated frequency of symptoms, reasons for not addressing sexuality, clinical conditions in which sexuality was addressed, and methods of management of sexual problems.
Of the 341 responding gynecologists (39.8% response rate), 40.4% reported having at least brief (at least 1–2 days) of training in sexual medicine, 7.9% of the respondents routinely explored sexual issues with more than 80% of their patients, 28.2% of the respondents offered appointments specifically for sexual issues, and 85% proposed referrals to specialized colleagues. Lack of motivation for therapy on the part of the patient was mentioned as the most common cause for persisting symptoms (63.3%). Dyspareunia was quoted as the most/second most prevalent type of female sexual dysfunction by 77.1% of the respondents.
We conclude that among Swiss gynecologists, sexual problems are regarded as an important issue in gynecological outpatient care, but addressing patients' sexuality is not yet part of routine practice. Swiss gynecologists seem to be most likely to consider hormonal changes (although not so much those due to oral contraceptives) to necessitate discussion of sexual health issues, while psychosocial transitions or stress seem to be considered less important. Kottmel A, Ruether‐Wolf KV, and Bitzer J. Do gynecologists talk about sexual dysfunction with their patients? J Sex Med 2014;11;2048–2054.
Die Konstellationen rund um Reproduktion sind hoch dynamisch und stets erklärungsbedürftig. Das zeigen die Debatten und Konflikte um Entscheidungsprozesse im Kontext von Schwangerschaft und Geburt, ...die Kritik am Status quo von Versorgungsinfrastrukturen sowie die Aushandlungen von Sorgearbeit. Die Beiträger*innen des Bandes loten ein weites Spektrum an Politiken der Reproduktion aus und fragen aus intersektional-feministischer Perspektive nach Verbindendem und Spezifischem in Feldern der Regulierung und des Erlebens von Körpern, Wissen und Lebenschancen. Die interdisziplinären Perspektiven ermöglichen dabei einen Dialog zwischen Wissenschaft, Praxis und Aktivismus.
Psychotropic drug use and alcohol consumption among older adults need to be monitored over time as their use or combined use bears risks of harms. Representative data on changes in prevalence, ...patterns and co-relates of substance use are lacking in Germany.
Participants were older adults (60-79 years) from two German National Health Surveys: 1997-99 (GNHIES98, N = 1,606) and 2008-11 (DEGS1, N = 2,501). Included were drugs acting on the nervous system used during the last 7 days. Alcohol consumption was measured by frequency (daily drinking) and quantity (risky drinking: ≥20/10 g/day alcohol for men/women). Changes in prevalence adjusted for potential socio-economic and health-related confounders were calculated by logistic regression models approximated by the SAS LSMEANS statement.
The prevalence of overall psychotropic drug use (20.5% vs. 21.4%) remained constant between the two surveys. Significant changes were observed in the use of some psychotropics (all GNHIES98 vs. DEGS1): Synthetic antidepressants (3.9% vs. 6.9%), St. John's wort (2.9% vs. 1.1%), benzodiazepines (3.7% vs. 2.5%), benzodiazepine related drugs (0.2% vs. 0.8%), narcotic analgesics (3.0% vs. 4.1%), anti-dementia drugs (2.2% vs. 4.2%) and anti-epileptics (1.0% vs. 2.3%). Significant changes were also observed in long-term use of synthetic anti-depressants (3.2% vs. 5.9%), St. John's wort (2.0% vs. 0.6%) and opioid analgesics (1.0% vs. 2.2%). Further, we found significant changes in benzodiazepines use (3.3% vs. 1.4%) among men, opioids use (2.9% vs. 7.3%) among people with a lower social status, and overall psychotropics (26.8% vs. 32.5%) as well as opioids use (4.4% vs. 8.1%) among those with a worse health status. Moderate alcohol consumption increased significantly (58.0% vs. 66.9%). Risky drinking remained unchanged (16.6% vs. 17.0%). In spite of significant increases in daily alcohol drinking (13.2% vs. 18.4%) psychotropic drug use combined with daily drinking remained unchanged (1.8% vs. 2.7%).
Although prevalence of overall psychotropic drug use remained stable, changes in the use of some psychotropic drug groups and alcohol consumption patterns have been observed. Further studies are required to investigate resulting health consequences and public health relevance of those outcomes.
Herpes simplex virus 1 (HSV-1) infection and stress responses disrupt transcription termination by RNA Polymerase II (Pol II). In HSV-1 infection, but not upon salt or heat stress, this is ...accompanied by a dramatic increase in chromatin accessibility downstream of genes. Here, we show that the HSV-1 immediate-early protein ICP22 is both necessary and sufficient to induce downstream open chromatin regions (dOCRs) when transcription termination is disrupted by the viral ICP27 protein. This is accompanied by a marked ICP22-dependent loss of histones downstream of affected genes consistent with impaired histone repositioning in the wake of Pol II. Efficient knock-down of the ICP22-interacting histone chaperone FACT is not sufficient to induce dOCRs in ΔICP22 infection but increases dOCR induction in wild-type HSV-1 infection. Interestingly, this is accompanied by a marked increase in chromatin accessibility within gene bodies. We propose a model in which allosteric changes in Pol II composition downstream of genes and ICP22-mediated interference with FACT activity explain the differential impairment of histone repositioning downstream of genes in the wake of Pol II in HSV-1 infection.
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