EuroGuiderm guideline on lichen sclerosus-introduction into lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness. It may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are redness and oedema, typically followed by whitening of the genital skin; sometimes fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS, highlight important aspects in the care of LS patients (part 1), generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

EuroGuiderm guideline on lichen sclerosus-Treatment of lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness; it may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are usually a whitening of the genital skin, sometimes preceded by redness and oedema; fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS (part 1), highlight important aspects in the care of LS patients, generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

Diverging trends for onset of acute myocardial infarction, heart failure, stroke and mortality in young males: role of changes in obesity and fitness.

BACKGROUND: As opposed to the decreasing overall rates of coronary heart disease (CHD) incidence and overall cardiovascular disease (CVD) mortality, heart failure (HF) and stroke incidence are increasing in young people, potentially due to rising rates of obesity and reduced cardiorespiratory fitness (CRF). OBJECTIVES: We investigated trends in early major CVD outcomes in a large cohort of young men. METHODS: Successive cohorts of Swedish military conscripts from 1971 to 1995 (N = 1,258,432; mean age, 18.3 years) were followed, using data from the National Inpatient and Cause of Death registries. Cox proportional hazard models were used to analyse changes in 21-year CVD event rates. RESULTS: 21-year CVD and all-cause mortality and incidence of acute myocardial infarction (AMI) decreased progressively. Compared with the cohort conscripted in 1971-1975 (reference), the hazard ratios (HRs) for the last 1991-1995 cohort were 0.50 [95% confidence interval (CI) 0.42-0.59] for CVD mortality; 0.57 (95% CI 0.54-0.60) for all-cause mortality; and 0.63 (95% CI 0.53-0.75) for AMI. In contrast, the incidence of ischaemic stroke, intracerebral haemorrhage and HF increased with HRs of 1.43 (95% CI 1.17-1.75), 1.30 (95% CI 1.01-1.68) and 1.84 (95% CI 1.47-2.30), respectively. During the period, rates of obesity increased from 1.04% to 2.61%, whilst CRF scores decreased slightly. Adjustment for these factors influenced these secular trends only moderately. CONCLUSION: Secular trends of young-onset CVD events demonstrated a marked shift from AMI and CVD mortality to HF and stroke incidence. Trends were significantly, though moderately, influenced by changing baseline BMI and CRF.

Exhaustion disorder and altered brain activity in frontal cortex detected with fNIRS.

Patients with stress-related Exhaustion Disorder (ED) have problems with memory and executive function. These problems have been associated with deviant activity in prefrontal cortex (PFC). We investigated cognitive performance and functional activity in the PFC during prolonged mental activity in patients with ED (n = 20, 16 women) with a mean duration since diagnosis of 46 ± 23 months in comparison to healthy individuals (n = 20, 12 women). A block of six neuropsychological tests was performed in a sequence that was repeated once. The brain imaging technique, functional near infrared spectroscopy (fNIRS) was used for all tests. There were no differences between the groups in terms of changes over time, i.e. difference between first and second test block. In the Stroop-Simon test, the controls showedhigher functional activity in the frontal cortex. In the left ventrolateral PFC, we observed an increased activity in controls in the incongruent compared to the congruent trials, whereas no changes were detected in the ED patient group. During processing speed tasks, only ED patients showed higher functional activity in right dorsolateral PFC. The ED patients reported lower subjective energy level and they also performed less well on a mental control task compared to healthy individuals. In conclusion, ED patients showed altered functional activity compared to controls, indicating that ED patients process information differently in the prefrontal cortex, but the functional activity did not change during the 2½ hr procedure, as revealed by the test-retest design. Lay summary In this paper we show that patient with exhaustion disorder have a reduced functional activity in the prefrontal cortex. This functional activity was not affected by 2.5 hours mental activity.

Anxiety severity and cognitive function in primary care patients with anxiety disorder: a cross-sectional study.

BACKGROUND: Deficits in cognitive performance are reported in patients with anxiety disorders, but research is limited and inconsistent. We aimed to investigate cross-sectional associations between cognitive function, with focus on executive function, and anxiety severity in primary care patients diagnosed with anxiety disorders. METHODS: 189 Swedish patients aged 18-65 years (31% men) with anxiety disorders diagnosed according to Mini International Neuropsychiatric Interview were included. Severity of anxiety was assessed using Beck Anxiety Inventory self-assessment scale. Digit span, block design and matrix reasoning tests from the Wechsler Adult Intelligence Scale IV, and the design fluency test from the Delis-Kaplan Executive Function System were used. Multivariable linear regression models were applied to investigate the relationship of anxiety severity and cognitive functioning. Comparisons were also performed to a normed non-clinical population, using the Wilcoxon signed rank test. RESULTS: More severe anxiety was associated with lower digit span test scores (R2 = 0.109, B = -0.040, p = 0.018), but not with block design, matrix reasoning or design fluency tests scores, after adjustment for comorbid major depression in a multivariable model. When compared to a normed population, patients with anxiety performed significantly lower on the block design, digit span forward, digit span sequencing and matrix reasoning tests. CONCLUSIONS: Severity of anxiety among patients with anxiety disorder was associated with executive functions related to working memory, independently of comorbid major depression, but not with lower fluid intelligence. A further understanding of the executive behavioral control in patients with anxiety could allow for more tailored treatment strategies including medication, therapy and interventions targeted to improve specific cognitive domains.

Late-adolescent risk factors for suicide and self-harm in middle-aged men: explorative prospective population-based study.

BACKGROUND: Recent reports show alarmingly high rates of suicide in middle-aged men, yet there are few long-term prospective studies that focus on suicidal behaviour in men in this age group. AIMS: To prospectively explore associations of potential risk factors at age 18 with suicide and self-harm in middle-aged men. METHOD: A population-based Swedish longitudinal cohort study of male conscripts with no history of self-harm at enlistment in 1968-1989 (n = 987 583). Conscription examinations included measures of cognitive performance, stress resilience, psychiatric diagnoses, body mass index (BMI), cardiovascular fitness and muscle strength. Suicides and self-harm at age 45-65 years were identified in the National Hospital Register and Swedish Cause of Death Register. Risks were calculated using Cox proportional hazards models. RESULTS: Low stress resilience (cause-specific hazard ratio CHR = 2.31, 95% CI 1.95-2.74), low cognitive ability (CHR = 2.01, 95% CI 1.71-2.37) as well as psychiatric disorders and low cardiovascular fitness in late adolescence were associated with increased risk for suicide in middle-aged men. Similar risk estimates were obtained for self-harm. In addition, high and low BMI as well as low muscle strength were associated with increased risk of self-harm. Associations also remained significant after exclusion of men with self-harm before age 45. CONCLUSIONS: This prospective study provides life-course perspective support that psychological and physical characteristics in late adolescence may have long-lasting consequences for suicidal behaviour in middle-aged men, a very large population at heightened risk of suicide.

Enriched, Task-Specific Therapy in the Chronic Phase After Stroke: An Exploratory Study.

BACKGROUND AND PURPOSE: There is a need to translate promising basic research about environmental enrichment to clinical stroke settings. The aim of this study was to assess the effectiveness of enriched, task-specific therapy in individuals with chronic stroke. METHODS: This is an exploratory study with a within-subject, repeated-measures design. The intervention was preceded by a baseline period to determine the stability of the outcome measures. Forty-one participants were enrolled at a mean of 36 months poststroke. The 3-week intervention combined physical therapy with social and cognitive stimulation inherent to environmental enrichment. The primary outcome was motor recovery measured by Modified Motor Assessment Scale (M-MAS). Secondary outcomes included balance, walking, distance walked in 6 minutes, grip strength, dexterity, and multiple dimensions of health. Assessments were made at baseline, immediately before and after the intervention, and at 3 and 6 months. RESULTS: The baseline measures were stable. The 39 participants (95%) who completed the intervention had increases of 2.3 points in the M-MAS UAS and 5 points on the Berg Balance Scale (both P < 0.001; SRM >0.90), an improvement of comfortable and fast gait speed of 0.13 and 0.23 m/s, respectively. (P < 0.001; SRM = 0.88), an increased distance walked over 6 minutes (24.2 m; P < 0.001; SRM = 0.64), and significant improvements in multiple dimensions of health. The improvements were sustained at 6 months. DISCUSSION AND CONCLUSIONS: Enriched, task-specific therapy may provide durable benefits across a wide spectrum of motor deficits and impairments after stroke. Although the results must be interpreted cautiously, the findings have implications for enriching strategies in stroke rehabilitation.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A304).

Thr92Ala polymorphism in the type 2 deiodinase gene: an evolutionary perspective.

PURPOSE: In the past, a role of thyroid hormones in human evolution has been hypothesized. T3, the metabolically active form, derives from extrathyroidal conversion of T4 by deionidase 2 (D2) enzyme encoded by DIO2 gene. In thyroid-deficient patients, decreased levels of free T3 have been associated with the polymorphism rs225014 A/G in DIO2, which causes the substitution of Threonine with Alanine (p.Thr92Ala) at protein level. METHODS: We compared DNA and protein sequences of D2 from archaic human subspecies with those of contemporary humans. RESULTS: Neanderthals and Denisovans displayed only the G allele at the rs225014 polymorphism, which encodes for an Alanine on the amino acid level. These data suggest that these hominines were homozygous for the Ala amino acid. These arcaic humans often lived in condition of iodine deficiency and thus, defective mechanisms of T3 biosynthesis could be life threatining. A reduced D2 activity is likely to cause decreased T3 levels, which could be critical for those individuals. Neanderthals and Denisovans were hunters/gatherers, and their diet was mainly based on the consumption of meat, with a low intake of carbohydrates. The need for circulating T3 is reduced at such alimentary conditions. On the basis of our genome comparisons the A allele, corresponding to Threonine and associated with higher levels of circulating T3 in thyroid-deficient patients, appeared for the first time during evolution in Anatomically Modern Humans during the Upper Pleistocene and has been conserved during the Neolithic age. With the advent of agriculture and herding, individuals carrying A allele might have a higher probability for surviving and reproducing. Thus, the variant was positively selected during the evolution. CONCLUSION: Here we present an evolutionary perspective for p.Thr92Ala variant of D2 from Neanderthals to Anatomically Modern Humans.

Adult Hippocampal Neurogenesis: A Coming-of-Age Story.

What has become standard textbook knowledge over the last decade was a hotly debated matter a decade earlier: the proposition that new neurons are generated in the adult mammalian CNS. The early discovery by Altman and colleagues in the 1960s was vulnerable to criticism due to the lack of technical strategies for unequivocal demonstration, quantification, and physiological analysis of newly generated neurons in adult brain tissue. After several technological advancements had been made in the field, we published a paper in 1996 describing the generation of new neurons in the adult rat brain and the decline of hippocampal neurogenesis during aging. The paper coincided with the publication of several other studies that together established neurogenesis as a cellular mechanism in the adult mammalian brain. In this Progressions article, which is by no means a comprehensive review, we recount our personal view of the initial setting that led to our study and we discuss some of its implications and developments that followed. We also address questions that remain regarding the regulation and function of neurogenesis in the adult mammalian brain, in particular the existence of neurogenesis in the adult human brain.

Effects of exercise on symptoms of anxiety, cognitive ability and sick leave in patients with anxiety disorders in primary care: study protocol for PHYSBI, a randomized controlled trial.

BACKGROUND: Anxiety disorders are common and associated with reduced quality of life, impaired physical and mental health and an increased economic burden for society. While evidence exists for the effectiveness of exercise treatment for depression, there is a need for high-quality randomized clinical trials (RCT) with a focus on anxiety disorders. Further research is also warranted regarding outcomes of cognitive function, other health-related variables, dose-response effects, work ability and potential mechanisms. METHOD/DESIGN: Using a parallel, RCT design with three assessment points (baseline, post-intervention and one-year follow-up), we aim to assess the effect of a 12-week exercise intervention in primary care patients with anxiety disorders (n = 180), diagnosed using the Mini International Neuropsychiatric Interview (M.I.N.I; Swedish version 6.0.0d DSM-IV). Participants are randomly assigned to three physical exercise groups: one low-intensity training group, one moderate- to high intensity training group and one control non-exercise group. Assessments include measures of anxiety symptoms, cognitive function, physical health variables such as cardiovascular fitness, sick-leave and levels of hormones/cytokines in blood samples. DISCUSSION: Findings from this study will provide novel insights regarding the effects of exercise treatment on not only anxiety symptoms but also other outcomes including mental and physical health, cognitive function, dose-response effects, work ability/sick leave and on biomarkers that may help explain underlying mechanisms. TRIAL REGISTRATION: The trial was registered at ClinicalTrial.gov NCT03247270 August 8, 2017.