Background There is strong evidence that suicides increase after media stories about suicides by celebrities, particularly those that highlight the suicide method (the Werther effect). Much less is known about the Papageno effect-the protective effects of media stories of hope and recovery from suicidal crises. A synthesis of the retrievable evidence is lacking. We aim to summarise findings from randomised controlled trials about the effects of stories of hope and recovery on individuals with some degree of vulnerability to suicide.Methods For this systematic review and individual participant data meta-analysis, we searched PubMed (including MEDLINE), Scopus, Embase, PsycInfo, Web of Science, and Google Scholar published from inception to Sept 6, 2021, without language restrictions. We included trials that reported suicidal ideation (the primary outcome) or helpseeking attitudes or intentions (the secondary outcome) and tested a media narrative of hope and recovery. Studies were excluded if they did not feature a clearly positive story of hope and recovery, or had a control group exposed to suicide-related stimulus material. We contacted the lead or senior authors of all original studies to obtain participantlevel data for this study. The primary analysis was restricted to individuals with some vulnerability to suicide. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomised trials. The study is registered with PROSPERO, number CRD42020221341.Findings Our search yielded 7347 records. 3920 records were screened by title and abstract, and 25 full-text records assessed for eligibility. There were eight eligible studies with 2350 participants for which individual participant data were sought. For suicidal ideation, six studies met the inclusion criteria for the primary analysis. Follow-up responses were available for 569 (90%) of 633 participants who were randomised with high vulnerability (345 [55%] allocated to the intervention group and 288 [45%] to the control group). The pooled standardised mean difference (SMD) indicated a small reduction in suicidal ideation of -0•22 (95% CI -0•39 to -0•04, p=0•017; six studies) in the intervention group. For help-seeking attitudes and intentions, four studies met the inclusion criteria and follow-up data were available for 362 (86%) of 420 participants (247 [59%] allocated to the intervention group and 173 [41%] to the control group). The pooled SMD showed no evidence of a difference between the groups (SMD=0•14, 95% CI -0•15 to 0•43, p=0•35; four studies). Low levels of cross-study heterogeneity effects were observed for both analyses (I²=5% [suicidal ideation] and I²=36% [help-seeking attitudes and intentions]). We found no evidence of publication bias.Interpretation Media narratives of hope and recovery from suicidal crises appear to have a beneficial effect on suicidal ideation in individuals with some vulnerability, but there is insufficient evidence regarding help-seeking attitudes and intentions. These findings provide new evidence about narrative...

Background Hidradenitis suppurativa (HS), a chronic, recurrent, debilitating skin disease, is characterized by painful, inflammatory, subcutaneous lesions of the axilla, inguinal and anogenital regions. Overall prevalence of HS is ˜1%, and the impact of disease on patient quality of life (QoL) and healthcare resource utilization (HRU) is high.Objectives To estimate the real-world effectiveness of adalimumab (Humiraâ) treatment in patients with moderate-tosevere HS on disease severity, pain, QoL, work productivity and HRU.Methods HARMONY (Effectiveness of Adalimumab in Moderate to Severe HidrAdenitis SuppuRativa Patientsa Multi-cOuNtry studY in Real Life Setting) is a multicentre, postmarketing observational study in adult patients with moderate-to-severe HS. Disease severity and QoL parameters were evaluated using validated measures at 12-week intervals over 52 weeks of treatment. The primary endpoint was the proportion of patients achieving a Hidradenitis Suppurativa Clinical Response (HiSCR: ≥50% reduction in abscess and inflammatory nodule count, with no increase in abscess and draining fistula counts relative to baseline) at 12 weeks. Secondary endpoints were HiSCR at 24, 36 and 52 weeks and changes in QoL parameters and work productivity assessments. Analyses were conducted using asobserved data. ResultsThe proportion of patients reaching the primary HiSCR endpoint was 70.2% (n = 132/188 enrolled) and remained ≥70% until study completion. There were statistically significant (P < 0.0001) reductions in worst and average skin pain. All of the QoL measures evaluated improved significantly (P < 0.0001) by 12 weeks of adalimumab treatment, as did work productivity assessments (P < 0.05), and there was a ˜50% decrease in HRU between baseline and week 52. Adalimumab was well tolerated.Conclusions In this real-world setting, adalimumab treatment of moderate-to-severe HS resulted in decreased disease severity and improvements in QoL and productivity. Response to adalimumab was rapid (within 12 weeks) and sustained (52 weeks). No unexpected safety signals were reported.

The aim of this study was to investigate the efficacy of the sequential combined 585 nm PDL and the 1064 nm neodymium:yttrium-aluminium-garnet laser (PDL/Nd:YAG) in the treatment of surgical scars and to evaluate the short-term effects by in vivo confocal microscopy (RCM) and the long-term effects by clinical assessment of the scars. Twenty-five patients were enrolled with 39 postoperative linear scars; each scar was divided into two fields. One half was treated with the combined PDL/Nd:YAG laser, whereas the other half remained untreated. Each scar was treated three times at monthly intervals. Scars were evaluated by an independent examiner, using the Vancouver Scar Scale. The combined PDL/Nd:YAG laser significantly improved the appearance of the scars. In order to study the short-term effects of combined laser treatment, six additional patients were enrolled with 7 postoperative linear scars. One half of scars was treated once with the combined PDL/Nd:YAG laser. One week after this laser treatment, both the treated and the nontreated parts of the scars were examined by dermoscopy and RCM. The dermoscopic pictures revealed improvements even in treated areas. In conclusion, the combined PDL/Nd:YAG laser was found to be effective in improving the quality and appearance of the surgical scars.

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Solobacterium moorei is a strict anaerobic gram-positive rod. It is found in the human microbiota in different parts of the body, but it also appears to be an opportunistic pathogen in some infectious processes. We describe six cases of severe infections identified in 2016 in which S. moorei was isolated alone or in mixed culture involving other anaerobes or both aerobic and anaerobic bacteria. Three cases were associated with the oral cavity, including a middle ear infection, a wound infection after total laryngectomy, and a mandibular abscess as a result of bisphosphonate therapy. In the other three patients, the sites of infection had no connections with the oral cavity and included chronic osteomyelitis of the tibia, a superinfection of cutaneous tuberculosis associated with hidradenitis suppurativa, and the isolation of S. moorei from the blood culture of a cachectic man with several comorbidities. Based on our findings, S. moorei does not appear to be that virulent of a bacterium; except for the case with bacteraemia, S. moorei was recovered as a co-pathogen in patients with several immunosuppressive predisposing factors. We highlight the finding that the routine use of MALDI-TOF MS in microbiology laboratories can in a timely and detailed manner identify members of mixed infections involving different anaerobic bacteria that may be rare and difficult-to-culture and identify species, such as S. moorei.

Demyelination in multiple sclerosis (MS) may cause damage to the vegetative nervous system. Our objective was to examine cerebral autoregulation assessed via blood pressure and cerebral blood flow velocity fluctuations during head-up tilt table testing. We also investigated the effects of high-dose intravenous corticosteroid treatment. Transcranial Doppler registration of middle cerebral artery blood flow velocity and continuous blood pressure and heart rate monitoring were performed at rest and during tilt table testing in 30 MS patients. Ten age-matched healthy subjects were also examined as controls. Correlations between mean arterial blood pressure (MBP) and cerebral blood flow velocity (CBF) fluctuations were averaged, yielding the correlation coefficient index Mx. For a subgroup of 11 patients with acute exacerbations, results were also evaluated before and after methylprednisolone treatment (1 g/day intravenously for 5 days). No significant differences in the autoregulatory indices were seen between patients and controls, or between pre- and post-steroid results. Modeling CBF velocity changes associated with a 1-mmHg increase in MBP, significant differences (p < 0.05) were detected in patients vs. controls, and also after vs. before steroid administration. We conclude that cerebrovascular autoregulation impairments are detectable in early phase MS. Corticosteroid treatment has a significant effect on hemodynamic changes in acute exacerbations.

It is infrequent to have only necrolytic migratory erythema, hyperglucagonaemia and islet-cell tumor but no other extracutaneous symptoms in glucagonoma syndrome. To our knowledge, ours is the second such case reported in the literature. Skin symptoms are important, often they are the clue to the diagnosis of glucagonoma syndrome.

Glutathione (GSH) is an abundant tripeptide that plays a crucial role in shielding cellular macromolecules from various reactive oxygen and nitrogen species in fungi. Understanding GSH metabolism is of vital importance to deciphering redox regulation in these microorganisms. In the present study, to better understand the GSH metabolism in filamentous fungi, we investigate functions of the dugB and dugC genes in the model fungus Aspergillus nidulans. These genes are orthologues of dug2-3 involved in cytosolic GSH degradation in the yeast. The deletion (Δ) of dugB, dugC, or both resulted in a moderate increase in the GSH content in the mycelia grown on glucose, reduced conidia production, and disturbed sexual development. In agreement with these observations, transcriptome data showed that genes encoding MAP kinase pathway elements (e.g. steC, sskB, hogA, mkkA) or regulatory proteins of conidiogenesis and sexual differentiation (e.g. flbA,C,E, nosA, rosA, nsdC,D) were down-regulated in the ΔdugBΔdugC mutant. Deletion of dugB and/or dugC slowed down the depletion of GSH pools under carbon starvation. It also reduced accumulation of reactive oxygen species, decreased autolytic cell wall degradation and enzyme secretion but increased sterigmatocystin formation. Transcriptome data demonstrated that enzyme secretions - in contrast to mycotoxin production - were controlled at post-transcriptional level. We suggest that GSH connects starvation and redox regulation to each other: Cells utilize GSH as stored carbon source during starvation. The reduction of GSH content alters the redox state activating regulatory pathways responsible for carbon starvation stress responses. Importance Glutathione (GSH) is a widely distributed tripeptide in both eukaryotes and prokaryotes. Owing to its very low redox potential, antioxidative character and high intracellular concentration, GSH profoundly shapes the redox status of cells. Our observations suggest that GSH metabolism and/or the redox status of cells plays a determinative role in several important aspects of fungal life, including oxidative stress defense, protein secretion, secondary metabolite production (including mycotoxin formation) as well as sexual and asexual differentiations. We demonstrated that even a slightly elevated GSH level can substantially disturb the homeostasis of fungi. This information could be important for development of new GSH producing strains or for any biotechnologically relevant processes where the GSH content, antioxidant capacity or oxidative stress tolerance of a fungal strain is manipulated.