Anabolic steroids, acute myocardial infarction and polycythemia: A case report and review of the literature

The association between testosterone-replacement therapy and cardiovascular risk remains unclear with most reports suggesting a neutral or possibly beneficial effect of the hormone in men and women. However, several cardiovascular complications including hypertension, cardiomyopathy, stroke, pulmonary embolism, fatal and nonfatal arrhythmias, and myocardial infarction have been reported with supraphysiologic doses of anabolic steroids. We report a case of an acute ST-segment elevation myocardial infarction in a patient with traditional cardiac risk factors using supraphysiologic doses of supplemental, intramuscular testosterone. In addition, this patient also had polycythemia, likely secondary to high-dose testosterone. The patient underwent successful percutaneous intervention of the right coronary artery. Phlebotomy was used to treat the polycythemia acutely. We suggest that the chronic and recent “stacked” use of intramuscular testosterone as well as the resultant polycythemia and likely increased plasma viscosity may have been contributing factors to this cardiovascular event, in addition to traditional coronary risk factors. Physicians and patients should be aware of the clinical consequences of anabolic steroid abuse

Dye molecules in electrolytes: new approach for suppression of dye-desorption in dye-sensitized solar cells

The widespread commercialization of dye-sensitized solar cells remains limited because of the poor long-term stability. We report on the influence of dye-molecules added in liquid electrolyte on long-term stability of dye-sensitized solar cells. Dye-desorption from the TiO2 surface during long-term cycling is one of the decisive factors that degrade photocurrent densities of devices which in turn determine the efficiencies of the devices. For the first time, desorption of dye from the TiO2 surface could be suppressed by controlling thermodynamic equilibrium; by addition of dye molecules in the electrolyte. The dye molecules in the electrolyte can suppress the driving forces for the adsorbed dye molecules to be desorbed from TiO2 nanoparticles. As a result, highly enhanced device stabilities were achieved due to the reduction of dye-desorption although there was a little decrease in the initial efficiencies.open4

Depression and anxiety in adults with hidradenitis suppurativa

Importance Previous studies suggest that depression and anxiety are common in patients with hidradenitis suppurativa (HS), more so than other dermatological conditions. Yet, to the authors’ knowledge, no previous systematic review or meta-analysis has estimated the prevalence or odds ratio (OR) for those psychiatric comorbidities in this population. Objective To assess the prevalence and odds for depression and anxiety in patients with HS. Data Sources From July 25 to September 30, 2018, observational studies investigating the prevalence and odds for depression and anxiety in adults with HS were systematically searched without language restriction from the inception of each database to July 25, 2018, in PubMed/MEDLINE, Embase, and PsycINFO databases. Searches used various configurations of the terms hidradenitis suppurativa; acne inversa; depressive disorder; depression; anxiety; anxiety disorders; phobia, social; suicide; and suicide, attempted. In addition, the reference lists of included references were screened manually. Study Selection Two investigators independently screened references that measured prevalence rates and odds for depressive and anxiety symptoms in patients with HS. Of 136 unique references, 10 ultimately met inclusion criteria. Data Extraction and Synthesis Relevant data were extracted from eligible references. Authors were contacted to provide further information when necessary. Methodological quality of included studies was assessed through a modified version of the Newcastle-Ottawa Scale. Random-effects models were used to synthesize available evidence. Main Outcomes and Measures Prevalence rates and ORs for depression and anxiety in adults with HS were the primary outcome measures. Heterogeneity across studies was assessed with the I2 statistic. Sources of heterogeneity were explored through subgroup and meta-regression analyses. Results Ten studies comprising 40 307 participants with HS met inclusion criteria. The overall prevalence of depression was 16.9% (95% CI, 9.9%-27.2%). Heterogeneity was large. In the subgroup of studies that considered a clinical criteria–based diagnosis of depression, the prevalence of depression was 11.9% (95% CI, 4.9%-26.2%), compared with 26.8% (95% CI, 20.4%-34.5%) in studies that used a screening instrument. The methodological quality of included studies moderated those findings. The OR for depression in individuals with HS compared with individuals without HS was 1.84 (95% CI, 1.57-2.15). The prevalence of anxiety was 4.9% (95% CI, 1.7%-13.2%); there were insufficient data to determine an odds ratio for anxiety in persons with HS because 2 studies included a comparison group. Conclusions and Relevance This systematic review and meta-analysis indicates that depression and anxiety are common comorbid conditions in patients with HS. Results suggest that the development of strategies to recognize and treat those psychiatric comorbidities in patients with HS is warranted

Effector diversification within compartments of the Leptosphaeria maculans genome affected by Repeat-Induced Point mutations

Fungi are of primary ecological, biotechnological and economic importance. Many fundamental biological processes that are shared by animals and fungi are studied in fungi due to their experimental tractability. Many fungi are pathogens or mutualists and are model systems to analyse effector genes and their mechanisms of diversification. In this study, we report the genome sequence of the phytopathogenic ascomycete Leptosphaeria maculans and characterize its repertoire of protein effectors. The L. maculans genome has an unusual bipartite structure with alternating distinct guanine and cytosine-equilibrated and adenine and thymine (AT)-rich blocks of homogenous nucleotide composition. The AT-rich blocks comprise one-third of the genome and contain effector genes and families of transposable elements, both of which are affected by repeat-induced point mutation, a fungal-specific genome defence mechanism. This genomic environment for effectors promotes rapid sequence diversification and underpins the evolutionary potential of the fungus to adapt rapidly to novel host-derived constraints

Interventions to improve work outcomes in work-related PTSD: a systematic review

<p>Abstract</p> <p>Background</p> <p>Posttraumatic stress disorder acquired at work can be debilitating both for workers and their employers. The disorder can result in increased sick leave, reduced productivity, and even unemployment. Furthermore, workers are especially unlikely to return to their previous place of employment after a traumatic incident at work because of the traumatic memories and symptoms of avoidance that typically accompany the disorder. Therefore, intervening in work-related PTSD becomes especially important in order to get workers back to the workplace.</p> <p>Methods</p> <p>A systematic literature search was conducted using Medline, PsycINFO, Embase, and Web of Science. The articles were independently screened based on inclusion and exclusion criteria, followed by a quality assessment of all included articles.</p> <p>Results</p> <p>The systematic search identified seven articles for inclusion in the review. These consisted of six research articles and one systematic review. The review focused specifically on interventions using real exposure techniques for anxiety disorders in the workplace. In the research articles addressed in the current review, study populations included police officers, public transportation workers, and employees injured at work. The studies examined the effectiveness of EMDR, cognitive-behavioural techniques, and an integrative therapy approach called brief eclectic psychotherapy. Interestingly, 2 of the 6 research articles addressed add-on treatments for workplace PTSD, which were designed to treat workers with PTSD who failed to respond to traditional evidence-based psychotherapy.</p> <p>Conclusions</p> <p>Results of the current review suggest that work-related interventions show promise as effective strategies for promoting return to work in employees who acquired PTSD in the workplace. Further research is needed in this area to determine how different occupational groups with specific types of traumatic exposure might respond differently to work-tailored treatments.</p

Clinical and echocardiographic predictors of mortality in acute pulmonary embolism

Purpose: The aim of this study was to evaluate the utility of adding quantitative assessments of cardiac function from echocardiography to clinical factors in predicting the outcome of patients with acute pulmonary embolism (PE). Methods: Patients with a diagnosis of acute PE, based on a positive ventilation perfusion scan or computed tomography (CT) chest angiogram, were identified using the Duke University Hospital Database. Of these, 69 had echocardiograms within 24–48 h of the diagnosis that were suitable for offline analysis. Clinical features that were analyzed included age, gender, body mass index, vital signs and comorbidities. Echocardiographic parameters that were analyzed included left ventricular (LV) ejection fraction (EF), regional, free wall and global RV speckle-tracking strain, RV fraction area change (RVFAC), Tricuspid Annular Plane Systolic Excursion (TAPSE), pulmonary artery acceleration time (PAAT) and RV myocardial performance (Tei) index. Univariable and multivariable regression statistical analysis models were used. Results: Out of 69 patients with acute PE, the median age was 55 and 48 % were female. The median body mass 2 index (BMI) was 27 kg/m . Twenty-nine percent of the cohort had a history of cancer, with a significant increase in cancer prevalence in non-survivors (57 % vs 29 %, p = 0.02). Clinical parameters including heart rate, respiratory rate, troponin T level, active malignancy, hypertension and COPD were higher among non-survivors when compared to survivors (p ≤ 0.05). Using univariable analysis, NYHA class III symptoms, hypoxemia on presentation, tachycardia, tachypnea, elevation in Troponin T, absence of hypertension, active malignancy and chronic obstructive pulmonary disease (COPD) were increased in non-survivors compared to survivors (p ≤ 0.05). In multivariable models, RV Tei Index, global and free (lateral) wall RVLS were found to be negatively associated with survival probability after adjusting for age, gender and systolic blood pressure (p ≤ 0.05). Conclusion: The addition of echocardiographic assessment of RV function to clinical parameters improved the prediction of outcomes for patients with acute PE. Larger studies are needed to validate these findings

The Cysteine Rich Necrotrophic Effector SnTox1 Produced by Stagonospora nodorum Triggers Susceptibility of Wheat Lines Harboring Snn1

The wheat pathogen Stagonospora nodorum produces multiple necrotrophic effectors (also called host-selective toxins) that promote disease by interacting with corresponding host sensitivity gene products. SnTox1 was the first necrotrophic effector identified in S. nodorum, and was shown to induce necrosis on wheat lines carrying Snn1. Here, we report the molecular cloning and validation of SnTox1 as well as the preliminary characterization of the mechanism underlying the SnTox1-Snn1 interaction which leads to susceptibility. SnTox1 was identified using bioinformatics tools and verified by heterologous expression in Pichia pastoris. SnTox1 encodes a 117 amino acid protein with the first 17 amino acids predicted as a signal peptide, and strikingly, the mature protein contains 16 cysteine residues, a common feature for some avirulence effectors. The transformation of SnTox1 into an avirulent S. nodorum isolate was sufficient to make the strain pathogenic. Additionally, the deletion of SnTox1 in virulent isolates rendered the SnTox1 mutated strains avirulent on the Snn1 differential wheat line. SnTox1 was present in 85% of a global collection of S. nodorum isolates. We identified a total of 11 protein isoforms and found evidence for strong diversifying selection operating on SnTox1. The SnTox1-Snn1 interaction results in an oxidative burst, DNA laddering, and pathogenesis related (PR) gene expression, all hallmarks of a defense response. In the absence of light, the development of SnTox1-induced necrosis and disease symptoms were completely blocked. By comparing the infection processes of a GFP-tagged avirulent isolate and the same isolate transformed with SnTox1, we conclude that SnTox1 may play a critical role during fungal penetration. This research further demonstrates that necrotrophic fungal pathogens utilize small effector proteins to exploit plant resistance pathways for their colonization, which provides important insights into the molecular basis of the wheat-S. nodorum interaction, an emerging model for necrotrophic pathosystems

Identification of Hyaloperonospora arabidopsidis Transcript Sequences Expressed during Infection Reveals Isolate-Specific Effectors

Biotrophic plant pathogens secrete effector proteins that are important for infection of the host. The aim of this study was to identify effectors of the downy mildew pathogen Hyaloperonospora arabidopsidis (Hpa) that are expressed during infection of its natural host Arabidopsis thaliana. Infection-related transcripts were identified from Expressed Sequence Tags (ESTs) derived from leaves of the susceptible Arabidopsis Ws eds1-1 mutant inoculated with the highly virulent Hpa isolate Waco9. Assembly of 6364 ESTs yielded 3729 unigenes, of which 2164 were Hpa-derived. From the translated Hpa unigenes, 198 predicted secreted proteins were identified. Of these, 75 were found to be Hpa-specific and six isolate Waco9-specific. Among 42 putative effectors identified there were three Elicitin-like proteins, 16 Cysteine-rich proteins and 18 host-translocated RXLR effectors. Sequencing of alleles in different Hpa isolates revealed that five RXLR genes show signatures of diversifying selection. Thus, EST analysis of Hpa-infected Arabidopsis is proving to be a powerful method for identifying pathogen effector candidates expressed during infection. Delivery of the Waco9-specific protein RXLR29 in planta revealed that this effector can suppress PAMP-triggered immunity and enhance disease susceptibility. We propose that differences in host colonization can be conditioned by isolate-specific effectors

Finished genome of the fungal wheat pathogen Mycosphaerella graminicola Reveals dispensome structure, chromosome plasticity, and stealth pathogenesis.

201

Fungicide-Driven Evolution and Molecular Basis of Multidrug Resistance in Field Populations of the Grey Mould Fungus Botrytis cinerea

The grey mould fungus Botrytis cinerea causes losses of commercially important fruits, vegetables and ornamentals worldwide. Fungicide treatments are effective for disease control, but bear the risk of resistance development. The major resistance mechanism in fungi is target protein modification resulting in reduced drug binding. Multiple drug resistance (MDR) caused by increased efflux activity is common in human pathogenic microbes, but rarely described for plant pathogens. Annual monitoring for fungicide resistance in field isolates from fungicide-treated vineyards in France and Germany revealed a rapidly increasing appearance of B. cinerea field populations with three distinct MDR phenotypes. All MDR strains showed increased fungicide efflux activity and overexpression of efflux transporter genes. Similar to clinical MDR isolates of Candida yeasts that are due to transcription factor mutations, all MDR1 strains were shown to harbor activating mutations in a transcription factor (Mrr1) that controls the gene encoding ABC transporter AtrB. MDR2 strains had undergone a unique rearrangement in the promoter region of the major facilitator superfamily transporter gene mfsM2, induced by insertion of a retrotransposon-derived sequence. MDR2 strains carrying the same rearranged mfsM2 allele have probably migrated from French to German wine-growing regions. The roles of atrB, mrr1 and mfsM2 were proven by the phenotypes of knock-out and overexpression mutants. As confirmed by sexual crosses, combinations of mrr1 and mfsM2 mutations lead to MDR3 strains with higher broad-spectrum resistance. An MDR3 strain was shown in field experiments to be selected against sensitive strains by fungicide treatments. Our data document for the first time the rising prevalence, spread and molecular basis of MDR populations in a major plant pathogen in agricultural environments. These populations will increase the risk of grey mould rot and hamper the effectiveness of current strategies for fungicide resistance management