High Prevalence of Skin Disorders among HTLV-1\ud Infected Individuals Independent of Clinical Status

Background\ud Human T-cell lymphotropic virus type 1 (HTLV-1) infection can increase the risk of developing skin disorders. This study evaluated the correlation between HTLV-1 proviral load and CD4+ and CD8+ T cells count among HTLV-1 infected individuals, with or without skin disorders (SD) associated with HTLV-1 infection [SD-HTLV-1: xerosis/ichthyosis, seborrheic dermatitis or infective dermatitis associated to HTLV-1 (IDH)].\ud \ud Methods\ud A total of 193 HTLV-1-infected subjects underwent an interview, dermatological examination, initial HTLV-1 proviral load assay, CD4+ and CD8+ T cells count, and lymphproliferation assay (LPA).\ud \ud Results\ud A total of 147 patients had an abnormal skin condition; 116 (79%) of them also had SD-HTLV-1 and 21% had other dermatological diagnoses. The most prevalent SD-HTLV-1 was xerosis/acquired ichthyosis (48%), followed by seborrheic dermatitis (28%). Patients with SD-HTLV-1 were older (51 vs. 47 years), had a higher prevalence of myelopathy/tropical spastic paraparesis (HAM/TSP) (75%), and had an increased first HTLV-1 proviral load and basal LPA compared with patients without SD-HTLV-1. When excluding HAM/TSP patients, the first HTLV-1 proviral load of SD-HTLV-1 individuals remains higher than no SD-HTLV-1 patients.\ud \ud Conclusions\ud There was a high prevalence of skin disorders (76%) among HTLV-1-infected individuals, regardless of clinical status, and 60% of these diseases are considered skin disease associated with HTLV-1 infection.This work was partly supported by Fundac¸a˜o de Amparo a` Pesquisa o Estado de Sa˜o Paulo (FAPESP), Grant 2008/56427-4. JC is senior researcher from the National Research Council of Brazil. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Melanoma cutâneo em capital da Amazônia: perfil de casos atendidos em ambulatório universitário de dermatologia

Introduction: Melanoma is a type of cancer derived from melanocytic cells, the most aggressive and lethal among skin cancers. The research’s purpose was to characterize the epidemiological profile of patients diagnosed with melanoma at the Dermatology Service of the Federal University of Pará. Methods: An observational, cross-sectional and retrospective analytical study was carried out, based on information from medical records and histopathological reports of patients with confirmed diagnoses by biopsy between January 2010 and December 2019. Results: 33 lesions of 32 patients were studied. North’s region peculiarity was observed on the greater impairment of phototypes III, IV and V. Extensive superficial was the most frequent clinical type, as well as the region of the lower limbs, lesion diameter greater than 1 cm, Breslow stage V and vertical growth phase were the most prevalent. Discussion: A higher Breslow score was positively correlated with older age, nodular melanoma subtype, and vertical growth phase. A greater skin phototype was related to a greater diameter and location of the lesion on the lower limb. The clinical type of lesion had positive correlations with age group, site of lesion and phase of growth. Conclusion: Notably, the number of studies published on the disease in the region is not very expressive, probably due to the lower frequency of melanoma cases in the North region, which demonstrates the need for more studies on the subject in this region.Introdução: o melanoma é um tipo de câncer derivado de células melanocíticas, o mais agressivo e letal entre os cânceres de pele. Objetivo: caracterizar o perfil epidemiológico dos pacientes diagnosticados com melanoma no Serviço de Dermatologia da Universidade Federal do Pará. Métodos: foi realizado um estudo observacional, transversal e analítico retrospectivo, baseado em informações de prontuários e laudos histopatológicos de pacientes com diagnóstico confirmado por biópsia entre janeiro de 2010 e dezembro de 2019. Resultados: foram estudadas 33 lesões de 32 pacientes. A peculiaridade da Região Norte foi observada no maior comprometimento dos fototipos III, IV e V. Extensivo superficial foi o tipo clínico mais frequente, assim como a região dos membros inferiores, diâmetro da lesão maior que 1 cm, estágio V de Breslow e fase de crescimento vertical foram os achados mais prevalentes. Discussão: um escore de Breslow mais alto foi positivamente correlacionado com idade avançada, subtipo de melanoma nodular e fase de crescimento vertical. O maior fototipo de pele esteve relacionado ao maior diâmetro e localização da lesão no membro inferior. O tipo clínico da lesão teve correlações positivas com faixa etária, local da lesão e fase de crescimento. Conclusão: notavelmente, o número de estudos publicados sobre a doença na região é pouco expressivo, provavelmente devido à menor frequência de casos de melanoma na Região Norte, o que demonstra a necessidade de mais estudos sobre o tema nessa região

Imprint of Climate Change on Pan-Arctic Marine Vegetation

The Arctic climate is changing rapidly. The warming and resultant longer open water periods suggest a potential for expansion of marine vegetation along the vast Arctic coastline. We compiled and reviewed the scattered time series on Arctic marine vegetation and explored trends for macroalgae and eelgrass (Zostera marina). We identified a total of 38 sites, distributed between Arctic coastal regions in Alaska, Canada, Greenland, Iceland, Norway/Svalbard, and Russia, having time series extending into the 21st Century. The majority of these exhibited increase in abundance, productivity or species richness, and/or expansion of geographical distribution limits, several time series showed no significant trend. Only four time series displayed a negative trend, largely due to urchin grazing or increased turbidity. Overall, the observations support with medium confidence (i.e., 5–8 in 10 chance of being correct, adopting the IPCC confidence scale) the prediction that macrophytes are expanding in the Arctic. Species distribution modeling was challenged by limited observations and lack of information on substrate, but suggested a current (2000–2017) potential pan-Arctic macroalgal distribution area of 820.000 km2 (145.000 km2 intertidal, 675.000 km2 subtidal), representing an increase of about 30% for subtidal- and 6% for intertidal macroalgae since 1940–1950, and associated polar migration rates averaging 18–23 km decade–1. Adjusting the potential macroalgal distribution area by the fraction of shores represented by cliffs halves the estimate (412,634 km2). Warming and reduced sea ice cover along the Arctic coastlines are expected to stimulate further expansion of marine vegetation from boreal latitudes. The changes likely affect the functioning of coastal Arctic ecosystems because of the vegetation’s roles as habitat, and for carbon and nutrient cycling and storage. We encourage a pan-Arctic science- and management agenda to incorporate marine vegetation into a coherent understanding of Arctic changes by quantifying distribution and status beyond the scattered studies now available to develop sustainable management strategies for these important ecosystems.publishedVersio

Corrigendum:Multidisciplinary Tinnitus Research: Challenges and Future Directions From the Perspective of Early Stage Researchers (Front. Aging Neurosci., (2021), 13, (647285), 10.3389/fnagi.2021.647285)

In the original article, there was an error. For the sentence “NMDA receptor antagonists (AM-101) have been discontinued in phase III for not meeting endpoints (van de Heyning et al., 2014)” there was a typographical error (phase III should have been phase II). In addition, it was brought to our attention that clinical trials for AM-101 are ongoing. A correction has been made to section 6. Treatment Development, Subsection 6.4. Pharmacology-Based Interventions, paragraph 1. The corrected paragraph is below. A wide variety of therapeutic drugs have been used to relieve tinnitus (Elgoyhen and Langguth, 2010). For acute tinnitus, a dose-dependent reduction in tinnitus intensity was observed with intravenous lidocaine (Trellakis et al., 2006). However, its use is controversial due to its short-lasting response, its potentially life threatening arrhythmogenic side effects, and the low bioavailability of its oral form (Israel et al., 1982; Trellakis et al., 2007; Gil-Gouveia and Goadsby, 2009). A potential goal of pharmacologic tinnitus research could be to identify the mechanism by which lidocaine interferes with tinnitus and mimic this effect using a drug with better tolerance that can be orally administered. For chronic tinnitus, the off-label use of medicines like betahistine (Hall et al., 2018d), anticonvulsants (Hoekstra et al., 2011), and glutamate receptor antagonists have shown little or no effect in clinical trials. Prescription of antidepressants and benzodiazepines is limited to tinnitusassociated comorbidities such as depression, insomnia and anxiety (Langguth et al., 2019). Moreover, three clinical research programs, in the last few years, were discontinued in phase II and III. AMPA antagonist selurampanel (BGG492) has not resulted in a new compound (Cederroth et al., 2018). NMDA receptor antagonists (AM-101) did not meet the primary endpoint of improving minimum masking level in acute tinnitus in a phase II clinical trial but showed improvement for tinnitus loudness, annoyance, sleep difficulties, and tinnitus impact in patients with tinnitus after noise trauma or otitis media (van de Heyning et al., 2014). Many other treatments decreasing tinnitus percept or targeting central auditory processing pathways are at a preclinical phase (Schilder et al., 2019). The modulator of voltage-gated potassium channels (Kv3.1) (AUT00063) was not effective in alleviating tinnitus symptoms (Hall et al., 2019b). The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated

Genome-wide associations spanning 194 in-hospital drug dosage change phenotypes highlight diverse genetic backgrounds in concurrent drug therapy

As populations get older and medicine consumption rises, the rate of concurrent drug use and polypharmacy among patients is increasing. Polypharmacy is known to complicate therapy and increase the risk of drug-drug interactions, the individuality of which remain largely unexplored. Here, we perform a series of genome-wide association studies to identify variants associated with dosage changes during episodes of concurrent drug therapy. We extracted in-hospital drug prescription records from 847,537 patients in a population-wide Danish hospital cohort. Using imputed genotype data from the Copenhagen Hospital Biobank and the Danish Blood Donor Study we then performed a series of genome-wide association analyses across 194 drug pair phenotypes fulfilling selection criteria. We identified 51 genome-wide significant (p < 5E-08) loci, 49 so far unreported in any genome-wide association studies, associated with dosage changes across 42 different drug pair phenotypes. 49 of the identified loci were unique to the respective drug pairs. Through annotation of the identified loci, expression quantitative trait loci analyses, and gene-based tests we found links to 57 distinct genes, several of which have previously been associated with disease. This study identifies genes that may modulate response to drug therapy in the context of polypharmacy. Our findings reveal distinct patterns of genetic variation across different drug pairs, suggesting a diverse set of genes involved in drug efficacy and drug response. This study may give a better understanding of the individuality of such mechanisms and may aid the development personalized treatment approaches

Sirtuin-2, NAD-Dependent Deacetylase, is a new potential therapeutic target for HIV-1 infection and HIV-related neurological dysfunction

The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate (n = 9) or delayed initiation (n = 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in in vitro systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure. IMPORTANCE Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD+ deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection. In vitro infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction

Multidisciplinary Tinnitus Research: Challenges and Future Directions from the Perspective of Early Stage Researchers

Tinnitus can be a burdensome condition on both individual and societal levels. Many aspects of this condition remain elusive, including its underlying mechanisms, ultimately hindering the development of a cure. Interdisciplinary approaches are required to overcome long-established research challenges. This review summarizes current knowledge in various tinnitus-relevant research fields including tinnitus generating mechanisms, heterogeneity, epidemiology, assessment, and treatment development, in an effort to highlight the main challenges and provide suggestions for future research to overcome them. Four common themes across different areas were identified as future research direction: (1) Further establishment of multicenter and multidisciplinary collaborations; (2) Systematic reviews and syntheses of existing knowledge; (3) Standardization of research methods including tinnitus assessment, data acquisition, and data analysis protocols; (4) The design of studies with large sample sizes and the creation of large tinnitus-specific databases that would allow in-depth exploration of tinnitus heterogeneity

Multidisciplinary Tinnitus Research: Challenges and Future Directions from the Perspective of Early Stage Researchers

Tinnitus can be a burdensome condition on both individual and societal levels. Many aspects of this condition remain elusive, including its underlying mechanisms, ultimately hindering the development of a cure. Interdisciplinary approaches are required to overcome long-established research challenges. This review summarizes current knowledge in various tinnitus-relevant research fields including tinnitus generating mechanisms, heterogeneity, epidemiology, assessment, and treatment development, in an effort to highlight the main challenges and provide suggestions for future research to overcome them. Four common themes across different areas were identified as future research direction: (1) Further establishment of multicenter and multidisciplinary collaborations; (2) Systematic reviews and syntheses of existing knowledge; (3) Standardization of research methods including tinnitus assessment, data acquisition, and data analysis protocols; (4) The design of studies with large sample sizes and the creation of large tinnitus-specific databases that would allow in-depth exploration of tinnitus heterogeneity

Severe plastic deformation for producing superfunctional ultrafine-grained and heterostructured materials: An interdisciplinary review

Ultrafine-grained and heterostructured materials are currently of high interest due to their superior mechanical and functional properties. Severe plastic deformation (SPD) is one of the most effective methods to produce such materials with unique microstructure-property relationships. In this review paper, after summarizing the recent progress in developing various SPD methods for processing bulk, surface and powder of materials, the main structural and microstructural features of SPD-processed materials are explained including lattice defects, grain boundaries and phase transformations. The properties and potential applications of SPD-processed materials are then reviewed in detail including tensile properties, creep, superplasticity, hydrogen embrittlement resistance, electrical conductivity, magnetic properties, optical properties, solar energy harvesting, photocatalysis, elec- trocatalysis, hydrolysis, hydrogen storage, hydrogen production, CO$_ 2$ conversion, corrosion resistance and biocompatibility. It is shown that achieving such properties is not limited to pure metals and conventional metallic alloys, and a wide range of materials are currently processed by SPD, including high-entropy alloys, glasses, semiconductors, ceramics and polymers. It is particularly emphasized that SPD has moved from a simple metal processing tool to a powerful means for the discovery and synthesis of new superfunctional metallic and nonmetallic materials. The article ends by declaring that the borders of SPD have been extended from materials science and it has become an interdisciplinary tool to address scientific questions such as the mechanisms of geological and astronomical phenomena and the origin of life