Infectious Diseases and Secondary Antibody Deficiency in Patients from a Mesoregion of São Paulo State, Brazil.

Our aim was to determine the secondary antibody deficiency (SAD) profiles of patients in a mesoregion of São Paulo state, Brazil, focusing on infectious diseases. Demographic characteristics, and clinical and laboratory data were obtained from electronic files; infections were classified as organ-specific and graded as mild, moderate, life-threatening, and fatal. Non-Hodgkin's lymphoma (NHL) accounted for 30% of patients, nephrotic syndrome (NS) 25%, chronic lymphocyte leukemia 20%, and multiple myeloma 15%. Patients with NS were younger than those in other groups, and hypo-γ-globulinemia was detected in 94.1%, IgG < 400 mg/dL in 60.0%, IgA < 40 mg/dL in 55.0%, and CD19 < 20 cells/mm3 in 30.0%. One hundred and one infections were found; 82.1% were classified as mild or moderate, 7.9% as life-threatening, and 3.0% as fatal. Respiratory tract infections were more prevalent (41.5%), and pneumonia accounted for 19.8%. Lower levels of infections were found in patients with NS compared with NHL (p = 0.0001). Most patients progressed to hypo-γ-globulinemia and SAD after treatment with immunosuppressants, and mild and moderate infections were predominant. These therapies are increasing in patients with different diseases; therefore, monitoring hypo-γ-globulinemia and infections may help to identify patients at high risk for severe complications, antibiotic prophylaxis or treatment, and immunoglobulin replacement.

Incomplete recovery of the CD4+/CD8+ ratio is associated with the late introduction of antiretroviral therapy among people living with HIV infection.

Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.

Individualized spectral filters alleviate persistent photophobia, headaches and migraines in active duty military and Veterans following brain trauma.

PURPOSE: Consistent with association between photophobia and headache, growing evidence suggests an underlying causal relationship between light sensitivity and central pain. We investigated whether an intervention to regulate light sensitivity by filtering only wavelengths causing difficulties for the specific individual could alleviate headaches/migraines resulting from traumatic brain injury (TBI). METHODS: Secondary data analysis of a clinical database including N = 392 military personnel (97% men, 3% women), ranging in age from 20 to 51 years, diagnosed with TBI, persistent headaches/migraines, and light sensitivity. The average elapsed time from TBI diagnosis to intervention was 3 years. Headache/migraine severity, frequency, medication use, and difficulties related to daily functioning were assessed pre and 4-12 weeks post-intervention with individualized spectral filters. RESULTS: Monthly migraine frequency decreased significantly from an average of 14.8 to 1.9, with 74% reporting no migraines post-intervention. Prescription and over-the-counter medication use decreased by more than 70%. Individuals also reported significant improvement in light sensitivity, headaches/migraine severity, and physical and perceptual symptoms. CONCLUSIONS: Wearing individualized spectral filters was associated with symptom relief, increased subjective quality of reported health and well-being, and decreased objective medication use for TBI-related persistent headaches/migraines. These results support a suggested relationship between dysregulated light sensitivity and central regulation of pain.

Protein constraints in genome-scale metabolic models: Data integration, parameter estimation, and prediction of metabolic phenotypes.

Genome-scale metabolic models provide a valuable resource to study metabolism and cell physiology. These models are employed with approaches from the constraint-based modeling framework to predict metabolic and physiological phenotypes. The prediction performance of genome-scale metabolic models can be improved by including protein constraints. The resulting protein-constrained models consider data on turnover numbers (kcat ) and facilitate the integration of protein abundances. In this systematic review, we present and discuss the current state-of-the-art regarding the estimation of kinetic parameters used in protein-constrained models. We also highlight how data-driven and constraint-based approaches can aid the estimation of turnover numbers and their usage in improving predictions of cellular phenotypes. Finally, we identify standing challenges in protein-constrained metabolic models and provide a perspective regarding future approaches to improve the predictive performance.

Incomplete recovery of the CD4+/CD8+ ratio is associated with the late introduction of antiretroviral therapy among people living with HIV infection

ABSTRACT Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.

Relationship between Femoroacetabular Impingement and Pubalgia in Professional Soccer Players.

Objective To analyze the relationship between pubalgia and femoroacetabular impingement (FAI) in professional athletes of a soccer club, defining the prevalence of these conditions in the sample studied. Methods It is an epidemiological, cross-sectional, and analytical study including 90 professional soccer players active from 2019 to 2021. We accessed the medical records of the subjects to retrieve information from the modified Pre-Competition Medical Assessment (PCMA) protocol, orthopedic physical examination, and anteroposterior pelvic radiographs to assess pubalgia and FAI, respectively. Inclusion criteria were athletes playing in the professional soccer club in the 2019 to 2021 season, who underwent a modified PCMA upon admission, and who signed an informed consent form. Results FAI was highly prevalent (85.6%) in the sample. This prevalence may occur because, in Brazil, people start playing sports early, not always in suitable fields, or with no proper equipment and supervision. In addition, the CAM-type impingement was the most frequent (62.2%). These injuries are related to high-intensity movements, including those associated with soccer. Furthermore, there is no dependency correlation between pubalgia and FAI. FAI was present in only 20% of athletes with pubalgia complaints. Conclusion There was a high prevalence of FAI in professional soccer players in the studied population (85.6%) but with no relationship between FAI and pubalgia.

Accurate prediction of in vivo protein abundances by coupling constraint-based modelling and machine learning.

Quantification of how different environmental cues affect protein allocation can provide important insights for understanding cell physiology. While absolute quantification of proteins can be obtained by resource-intensive mass-spectrometry-based technologies, prediction of protein abundances offers another way to obtain insights into protein allocation. Here we present CAMEL, a framework that couples constraint-based modelling with machine learning to predict protein abundance for any environmental condition. This is achieved by building machine learning models that leverage static features, derived from protein sequences, and condition-dependent features predicted from protein-constrained metabolic models. Our findings demonstrate that CAMEL results in excellent prediction of protein allocation in E. coli (average Pearson correlation of at least 0.9), and moderate performance in S. cerevisiae (average Pearson correlation of at least 0.5). Therefore, CAMEL outperformed contending approaches without using molecular read-outs from unseen conditions and provides a valuable tool for using protein allocation in biotechnological applications.

PARROT: Prediction of enzyme abundances using protein-constrained metabolic models.

Protein allocation determines the activity of cellular pathways and affects growth across all organisms. Therefore, different experimental and machine learning approaches have been developed to quantify and predict protein abundance and how they are allocated to different cellular functions, respectively. Yet, despite advances in protein quantification, it remains challenging to predict condition-specific allocation of enzymes in metabolic networks. Here, using protein-constrained metabolic models, we propose a family of constrained-based approaches, termed PARROT, to predict how much of each enzyme is used based on the principle of minimizing the difference between a reference and an alternative growth condition. To this end, PARROT variants model the minimization of enzyme reallocation using four different (combinations of) distance functions. We demonstrate that the PARROT variant that minimizes the Manhattan distance between the enzyme allocation of a reference and an alternative condition outperforms existing approaches based on the parsimonious distribution of fluxes or enzymes for both Escherichia coli and Saccharomyces cerevisiae. Further, we show that the combined minimization of flux and enzyme allocation adjustment leads to inconsistent predictions. Together, our findings indicate that minimization of protein allocation rather than flux redistribution is a governing principle determining steady-state pathway activity for microorganism grown in alternative growth conditions.

Environmental Planning and Non-Communicable Diseases: A Systematic Review on the Role of the Metabolomic Profile.

Non-communicable diseases (NCDs) are the major cause of death worldwide and have economic, psychological, and social impacts. Air pollution is the second, contributing to NCDs-related deaths. Metabolomics are a useful diagnostic and prognostic tool for NCDs, as they allow the identification of biomarkers linked to emerging pathologic processes. The aim of the present study was to review the scientific literature on the application of metabolomics profiling in NCDs and to discuss environmental planning actions to assist healthcare systems and public managers based on early metabolic diagnosis. The search was conducted following PRISMA guidelines using Web of Science, Scopus, and PubMed databases with the following MeSH terms: "metabolomics" AND "noncommunicable diseases" AND "air pollution". Twenty-nine studies were eligible. Eleven involved NCDs prevention, eight addressed diabetes mellitus, insulin resistance, systemic arterial hypertension, or metabolic syndrome. Six studies focused on obesity, two evaluated nonalcoholic fatty liver disease, two studied cancer, and none addressed chronic respiratory diseases. The studies provided insights into the biological pathways associated with NCDs. Understanding the cost of delivering care where there will be a critical increase in NCDs prevalence is crucial to achieving universal health coverage and improving population health by allocating environmental planning and treatment resources.

A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2).

INTRODUCTION: The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. PATIENTS AND METHODS: This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. RESULTS: Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. CONCLUSION: The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).

Challenges to Promote Sustainability in Urban Agriculture Models: A Review.

Urban agriculture (UA) can be used as an action to promote sustainability in cities and inform public health policies for urban populations. Despite this growing recognition, its implementation still presents challenges in countries in the Global North and Global South. BACKGROUND: In this context, this systematic review aims to identify the development of frameworks for the implementation of UA as a sustainable action and its main opportunities and shortcomings in meeting urban socio-environmental demands. METHODS: In this review, using the PRISMA protocol, we evaluated 26 studies on the interplay between UA and sustainability surveyed on the Web of Science to provide an overview of the state of the art. CONCLUSIONS: In summary, it was possible to identify many key challenges in UA adoption, which regard air and soil contamination, availability of green areas, layout of urban infrastructure, food distribution, among others. Due to numerous socio-economic and environmental contextual factors in cities, especially when comparing realities of the Global North and Global South, there is a need to develop a model that can be adaptable to these different contexts. Thus, it is recognized that the concept of sustainability does not present a universal understanding and that in its search it could be argued that one of the most important gaps is still to address social issues in relation to environmental ones.

Importância e aspectos clínicos da dermatite de contato por própolis / Importance and clinical aspects of propolis contact dermatitis

Objetivos: própolis é a substância resinosa que as abelhas coletam de plantas para a construção de suas colmeias. O objetivo dessa revisão foi ressaltar a importância do diagnóstico de dermatite de contato relacionada com própolis e aspectos clínicos relevantes dessa doença. Métodos: revisão narrativa da literatura realizada através da pesquisa nas bases de dados National Library of Medicine (PubMed) e Scientific Eletronic Library Online (SciELO). Resultados: foram encontrados 246 artigos e, após o processo de seleção e leitura, foram incluídas 32 publicações. Conclusões: a hipersensibilidade tardia ao própolis é de extrema importância pois a prevalência dessa alergia é crescente em diversas partes do mundo. Precisamos de estudos nacionais para avaliar nossa realidade. A comprovação de alta prevalência em nosso meio permitirá a inclusão desta substância em outras baterias de testes de contato em nosso país

Aims: propolis is the resinous substance that bees collect from plants to build their hives. The aim of this review was to highlight the importance of diagnosing propolis-related contact dermatitis and relevant clinical aspects of this disease. Methods: narrative literature review carried out by searching the National Library of Medicine (PubMed) and Scientific Electronic Library Online (SciELO) databases. Results: a total of 246 articles were found and, after the selection and reading process, 32 publications were included. Conclusions: delayed-type hypersensitivity to propolis is extremely important because the prevalence of this allergy is increasing in various parts of the world. We need national studies to assess our reality. Proof of the high prevalence in our country will allow this substance to be included in other patch tests series in our country

Relationship between Femoroacetabular Impingement and Pubalgia in Professional Soccer Players / Relação do impacto femoroacetabular e pubalgia em jogadores profissionais de futebol de campo

Abstract Objective To analyze the relationship between pubalgia and femoroacetabular impingement (FAI) in professional athletes of a soccer club, defining the prevalence of these conditions in the sample studied. Methods It is an epidemiological, cross-sectional, and analytical study including 90 professional soccer players active from 2019 to 2021. We accessed the medical records of the subjects to retrieve information from the modified Pre-Competition Medical Assessment (PCMA) protocol, orthopedic physical examination, and anteroposterior pelvic radiographs to assess pubalgia and FAI, respectively. Inclusion criteria were athletes playing in the professional soccer club in the 2019 to 2021 season, who underwent a modified PCMA upon admission, and who signed an informed consent form. Results FAI was highly prevalent (85.6%) in the sample. This prevalence may occur because, in Brazil, people start playing sports early, not always in suitable fields, or with no proper equipment and supervision. In addition, the CAM-type impingement was the most frequent (62.2%). These injuries are related to high-intensity movements, including those associated with soccer. Furthermore, there is no dependency correlation between pubalgia and FAI. FAI was present in only 20% of athletes with pubalgia complaints. Conclusion There was a high prevalence of FAI in professional soccer players in the studied population (85.6%) but with no relationship between FAI and pubalgia.

Resumo Objetivo Analisar a relação entre a pubalgia e o impacto femoroacetabular (IFA) em atletas profissionais de um clube de futebol, definindo a prevalência de pubalgia e de impacto femoroacetabular na casuística estudada. Métodos É um estudo epidemiológico, transversal e analítico. Foram selecionados 90 atletas profissionais de futebol atuantes no período de 2019-2021. Foram acessados os prontuários para obtenção do protocolo PCMA modificado, além de exame físico ortopédico e de radiografias da bacia com incidência anteroposterior para avaliação de pubalgia e IFA, respectivamente. Critérios de Inclusão: Atletas que atuaram no clube de futebol de campo profissional na temporada de 2019 a 2021, que foram submetidos a aplicação do PCMA modificado na admissão e que assinaram o TCLE. Resultados O IFA apresentou elevada prevalência na amostra (85.6%), o que pode ocorrer pois, no Brasil, os jovens iniciam a prática esportiva em idade muito precoce, além do fato de os jogadores nem sempre praticarem o esporte em campos adequados ou com equipamentos e supervisão adequada. Ademais, o impacto tipo CAM foi o mais frequente (62.2%). O surgimento dessas lesões é relacionado a movimentos de alta intensidade, como os vistos no futebol. Outrossim, observou-se que não há correlação de dependência entre a pubalgia e o IFA. Foi visto que o IFA estava presente em apenas 20% dos atletas queixosos de pubalgia. Conclusão Há elevada prevalência de IFA em atletas de futebol profissional na população estudada (85.6%) e não houve relação entre o IFA e a presença de pubalgia.

A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2)

Abstract Introduction The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. Patients and methods This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. Results Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. Conclusion The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).

Papiliotrema laurentii: general features and biotechnological applications.

Papiliotrema laurentii, previously classified as Cryptococcus laurentii, is an oleaginous yeast that has been isolated from soil, plants, and agricultural and industrial residues. This variety of habitats reflects the diversity of carbon sources that it can metabolize, including monosaccharides, oligosaccharides, glycerol, organic acids, and oils. Compared to other oleaginous yeasts, such as Yarrowia lipolytica and Rhodotorula toruloides, there is little information regarding its genetic and physiological characteristics. From a biotechnological point of view, P. laurentii can produce surfactants, enzymes, and high concentrations of lipids, which can be used as feedstock for fatty acid-derived products. Moreover, it can be applied for the biocontrol of phytopathogenic fungi, contributing to quality maintenance in post- and pre-harvest fruits. It can also improve mycorrhizal colonization, nitrogen nutrition, and plant growth. P. laurentii is also capable of degrading polyester and diesel derivatives and acting in the bioremediation of heavy metals. In this review, we present the current knowledge about the basic and applied aspects of P. laurentii, underscoring its biotechnological potential and future perspectives. KEY POINTS: • The physiological characteristics of P. laurentii confer a wide range of biotechnological applications. • The regulation of the acetyl-CoA carboxylase in P. laurentii is different from most other oleaginous yeasts. • The GEM is a valuable tool to guide the construction of engineered P. laurentii strains with improved features for bio-based products.

Isotopic composition (δ13C and δ15N) in the soil-plant system of subtropical urban forests.

This study brings information on the dynamics of C and N in urban forests in a subtropical region. We tested the hypothesis that C and N isotopic sign of leaves and soil and physiological traits of trees would vary from center to periphery in a megacity, considering land uses, intensity of automotive fleet and microclimatic conditions. 800 trees from four fragments were randomly chosen. Soil samples were collected at every 10 cm in trenches up to 1 m depth to analyze C and N contents. Both, plants and soil were assessed for δ13C, δ15N, %C and %N. Physiological traits [carbon assimilation (A)], CO2 internal and external pressure ratio (Pi/Pa) and intrinsic water use efficiency iWUE were estimated from δ13C and Δ Î´13C in leaves and soil ranged from -27.42 ‰ to -35.39 ‰ and from -21.22 ‰ to -28.18 ‰, respectively, and did not vary along the areas. Center-periphery gradient was not evidenced by C. Emissions derived from fossil fuel and distinct land uses interfered at different levels in δ13C signature. δ15N in the canopy and soil varied clearly among urban forests, following center-periphery gradient. Leaf δ15N decreased from the nearest forest to the city center to the farthest, ranging from <3 ‰ to <-3 ‰. δ15N was a good indicator of atmospheric contamination by NOx emitted by vehicular fleet and a reliable predictor of land use change. %N followed the same trend of δ15N either for soils or leaves. Forest fragments located at the edges of the center-periphery gradient presented significantly lower A and Pi/Pa ratio and higher iWUE. These distinct physiological traits were attributed to successional stage and microclimatic conditions. Results suggest that ecosystem processes related to C and N and ecophysiological responses of urban forests vary according to land use and vehicular fleet.

SARS-CoV-2/COVID-19: Clinical Course Among Subjects HIV-1-Infected in Sao Paulo.

INTRODUCTION: People living with Human Immunodeficiency Virus (HIV) are under risk for co-infection with SARS-CoV-2. This population may be more prone to complications from COVID-19 due to persistent inflammation caused by HIV and higher incidence of metabolic syndromes, cardiovascular diseases, and malignancies, as well as being considered elderly at 50 years of age. The objective of this study was to report SARS-CoV-2 infection frequency, clinical evolution, and mortality in HIV-positive patients on antiretroviral therapy. METHODS: The period of inquiry ranged from January to September 2020. Due to the social distance and the suspension of in-person medical care during the time of the investigation, we sent electronic questions about demographic, epidemiological, and clinical data to 403 HIV-infected patients. RESULTS: Among 260 patients who answered the questionnaire, thirty-nine patients (15%) had suggestive symptoms and were tested for SARS-CoV-2 infection. Of this, 11 had positive results (32.4%) and no patient died of COVID-19 complications. Nine were male (3.4%), and the mean age of the patients with positive results was 43.2 years (± 9.6). 107 patients (41.1%) were over 50 years of age and their mean T-CD4+ cell count was 768. Eleven patients (4.2%) had a detectable HIV RNA viral load and 127 (48.8%) had comorbidities. These variables were not associated with an increased risk for infection. CONCLUSION: The frequency of SARS-COV2 infection among HIV-infected is similar to the general population, and the clinical course is associated with the presence of comorbidities and not due to the HIV infection. However, new studies should be done to assess if this vulnerable population could answer the vaccine anti-SARS-Cov2.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and esophageal rupture by candida infection: A case report and review.

We probably describe the first report of esophageal rupture in a patient with autoimmune polyendocrinopathy - candidiasis - ectodermal dystrophy (APECED, OMIM # 240300), who had candida esophagitis as the main feature for decades. Strong evidence shows that this rupture may have been caused directly and indirectly by chronic candidiasis. In this way, we demonstrate how severe and harmful the persistent esophageal candidiasis can cause in the esophagus, especially in immunodeficient patients.

Long-term testosterone replacement therapy reduces fatigue in men with hypogonadism.

BACKGROUND: Testosterone replacement therapy (TRT) is one of the main lines of treatment for men with hypogonadism. This study sought to evaluate the influence of TRT in men with late-onset hypogonadism (LOH), regarding fatigue, coronary artery disease (CAD), carotid intima-media thickness (CIMT) and cardiovascular risk. METHODS: This study compared men with LOH already on TRT for >1 year to newly diagnosed men with LOH who recently started TRT (controls). We included men aged >18 years with clinical manifestations of testosterone deficiency and testosterone levels of <300 ng/dL documented in two separate occasions. RESULTS: A total of 33 patients were included in the study group and 30 in the control group. Mean age was 49.1 years (±11.5) in those already under TRT for >1 year and 45 (±12.2) years in the control group (p=0.18). CAD was present in 14 (46.7%) patients in the control group and in 3 (9.1%) in the study group (p<0.001). TRT >1 year was not associated with lower rates of CAD in multivariable analysis. Fatigue Severity Score was significantly higher in the control group (39.2±15.0), compared to TRT >1 year (23.5±8.1; p<0.001). In a multivariable analysis adjusted for age and hypertension, TRT >1 year was associated with a 14.8-point decrease in Fatigue Severity Score (p<0.001). Overall, there were no differences between the study group and the control group regarding cardiovascular risk (p=0.31). CONCLUSION: TRT for >1 year was associated with significantly lower fatigue scores. No differences were observed regarding CIMT, CAD and cardiovascular risk according to the WHO-ISH scale.

Ethanol stress responses in Kluyveromyces marxianus: current knowledge and perspectives.

The rising concern with the emission of greenhouse gases has boosted new incentives for biofuels production, which are less polluting than fossil fuels. Special attention has been given to the second-generation ethanol, as it is produced from abundant feedstocks which do not compete with food production, such as lignocellulosic biomass and whey. Kluyveromyces marxianus stands out in second-generation ethanol production due to its capacity of assimilating lactose, the sugar found in whey, and tolerating high temperatures used in simultaneous saccharification processes. Nonetheless, contrary to Saccharomyces cerevisiae, K. marxianus does not tolerate high ethanol concentrations. Ethanol causes a broad range of toxic effects on yeasts, acting on cell membrane and proteins, as well as inducing the generation of reactive oxygen species (ROS). The ethanol stress responses are not fully understood, mainly in non-conventional yeasts such as K. marxianus. Indeed, many molecular responses to ethanol stress are still inferred from S. cerevisiae. As such, a better understanding of the ethanol stress responses in K. marxianus may provide the basis for improving its use in the biofuel industry. Additionally, the selection of ethanol-tolerant strains by metabolic engineering is useful to provide strains with improved capacity to withstand stressful conditions, as well as to obtain new insights about the ethanol stress responses. Key points • It is still not totally clear why K. marxianus is less tolerant to ethanol than S. cerevisiae. • Understanding the ethanol stress response in K. marxianus is pivotal for improving its application in the biofuel industry. • The Metabolic engineering is expected to improve the ethanol tolerance in K. marxianus.