Deficiência Androgênica do envelhecimento masculino: Revisão de literatura

Segundo dados do Instituto Brasileiro de Geografia e Estatística (IBGE) e da Organização Mundial da Saúde (OMS), estima-se que até 2020 a população brasileira contará com mais de 30 milhões de homens acima dos 60 anos e 1/4 desses homens apresentará Deficiência Androgênica do Envelhecimento Masculino - DAEM -, que consiste em um quadro de hipogonadismo tardio, devido um declínio nos níveis de testosterona biodisponível, que ocorre de maneira progressiva e insidiosa. Os pacientes apresentam comumente sintomas como: redução do libido, redução de ereções espontâneas, ginecomastia, aumento da gordura corporal, perda de massa muscular, baixa densidade óssea, rarefação de pelos, anemia, a prevalência pode chegar a 7% nos pacientes entre 40-50 anos, alcançando 35% dos pacientes com mais de 80 anos. Com aumento da sobrevida e da população idosa essa patologia vem ganhando grande importância, devido seu caráter insidioso, aos seus sintomas poucos específicos e o não diagnóstico da maioria dos pacientes, para isso foram analisadas diferentes literaturas que indicam efeitos benéficos, contra indicações e tipos de tratamento de reposição de testosterona de forma segura naqueles pacientes diagnosticados com DAEM

Relato de caso: Diabetes tipo LADA ou “Double Diabetes” ? Nem todo diabético é Tipo 1 ou Tipo 2

O diabetes é uma doença endócrina com múltiplas vias patogênicas altamente prevalente em todo o mundo. A mais recente expressão “Double Diabetes” (DD) veio caracterizar uma nova forma de diabetes que é essencialmente composta por uma intersecção de características clínicas do diabetes tipo 1 (DM1) e tipo 2 (DM2). Entretanto, na prática clínica, existem outros fenótipos da doença que dificultam o diagnóstico, como o Diabetes latente autoimune do adulto (LADA). O vigente esquema de classificação não contempla as novas evidências científicas sobre esta patologia endócrina, contribuindo assim, para condutas equivocadas que levam à um mau controle glicêmico predispondo à complicações micro e macrovasculares. Este relato de caso tem como objetivo chamar atenção para a importância da investigação diagnóstica de um quadro clínico de diabetes imuno mediado. Outro aspecto importante, é a necessidade de revisar os critérios diagnósticos que por vezes são inconclusivos. Relata-se o caso de uma paciente de 44 anos que foi diagnosticada com diabetes aos 24 anos durante o pré-natal, porém somente iniciou o tratamento com insulina após 2 anos, mediante um quadro de perda de peso, diplopia e polidpsia, tendo na ocasião sido diagnosticada como DM1. A paciente apresenta síndrome metabólica, dislipidemia, sobrepeso (IMC:26,7), anti-GAD positivo (159,6) e história familiar paterna de DM2. O caso clínico contempla ainda, outra doença autoimune: o hipotireoidismo (Tireoidite de Hashimoto), possibilitando o diagnóstico de síndrome poliglandular do tipo 3. Esta paciente preenche critérios tanto para LADA quanto para DD, como positividade de anticorpo contra células β e aumento do IMC. Porém, o que mais os distingue, com base em características clínicas, é a faixa etária >30 anos para LADA e o período de infância e juventude para o DD. Mais pesquisas devem ser realizadas com o intuito de melhorar o diagnóstico e consequentemente o tratamento dessa enfermidade crônica extremamente prevalente. Os moldes terapêuticos atuais que priorizam esquemas baseados na doença e não no paciente, são questionáveis e as novas tendências apontam para uma abordagem mais ampla vendo as drogas como opções terapêuticas adjuvantes. Embora seja uma das doenças mais estudadas no mundo, a cada nova evidência científica um antigo conceito “cai por terra” e percebe-se o quão leigos ainda somos quando se trata de diabetes

Associação entre qualidade do sono e excesso de peso entre estudantes de medicina da Universidade Severino Sombra, Vassouras – RJ

A privação das horas de sono tornou-se um fato comum na atualidade devido à rotina estressante do dia à dia. A importância do sono é observada quando constata-se os efeitos negativos causados pela sua privação, como déficit cognitivo, alteração de humor, fadiga e lentificação na execução de tarefas do dia. Além disso, a privação do sono gera alterações endócrinas responsáveis pelo controle alimentar como a diminuição do hormônio anorexígeno leptina e aumento do hormônio orexígeno grelina, ocasionando um aumento do apetite. A perda de sono é considerada um problema de saúde pública, uma vez que aumenta os casos de sobrepeso e obesidade, morbidade e mortalidade. Quando comparamos grupos universitários de diferentes cursos, observa-se que alterações no estilo de vida são mais comumente encontradas nos acadêmicos de Medicina que estão sujeitos ao excesso de peso pela redução das horas de sono que a vida universitária impõe e pela redução do tempo para realizar refeições completas ou prática de atividades físicas regulares. Avaliar a associação entre a qualidade do sono e o estado nutricional de acadêmicos de Medicina da Universidade Severino Sombra, instituição privada situada na cidade de Vassouras (Rio de Janeiro). Auto-aplicação do questionário do Índice de Qualidade do Sono de Pittsburgh (PSQI) e avaliação do Índice de Massa Corporal (IMC). Houve uma associação entre qualidade do sono ruim e excesso de peso dentre os avaliados, mostrando que a alteração na qualidade do sono aumentou em 2,3 vezes a chance de se ter excesso de peso. Os acadêmicos avaliados apresentaram uma média de duração do sono de 6,5 horas/noite. Esses valores estão abaixo do recomendado a um adulto que para ser considerado como um estado ótimo de vigília é necessário de 7-8 horas de sono em 24 horas. A restrição do sono se relaciona com aumento do apetite, consumo de alimentos mais calóricos e como conseqüência há o ganho de peso. Com base nos dados analisados, conclui-se que acadêmicos de medicina estão sobre grande risco de desenvolverem sobrepeso e obesidade tanto pelo sedentarismo quanto pelos maus hábitos alimentares que podem ser conseqüência da privação das horas de sono que a rotina estressante impõe a essa população. Ainda são necessários estudos mais aprofundados que busquem essa relação entre sono e hábitos alimentares, visto que outros fatores podem estar envolvidos nessa associação

SIRNA-Directed In Vivo Silencing of Androgen Receptor Inhibits the Growth of Castration-Resistant Prostate Carcinomas

BACKGROUND: Prostate carcinomas are initially dependent on androgens, and castration or androgen antagonists inhibit their growth. After some time though, tumors become resistant and recur with a poor prognosis. The majority of resistant tumors still expresses a functional androgen receptor (AR), frequently amplified or mutated. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis that AR is not only expressed, but is still a key therapeutic target in advanced carcinomas, we injected siRNA targeting AR into mice bearing exponentially growing castration-resistant tumors. Quantification of siRNA into tumors and mouse tissues demonstrated their efficient uptake. This uptake silenced AR in the prostate, testes and tumors. AR silencing in tumors strongly inhibited their growth, and importantly, also markedly repressed the VEGF production and angiogenesis. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that carcinomas resistant to hormonal manipulations still depend on the expression of the androgen receptor for their development in vivo. The siRNA-directed silencing of AR, which allows targeting overexpressed as well as mutated isoforms, triggers a strong antitumoral and antiangiogenic effect. siRNA-directed silencing of this key gene in advanced and resistant prostate tumors opens promising new therapeutic perspectives and tools

Environmental footprint family to address local to planetary sustainability and deliver on the SDGs

peer-reviewedThe number of publications on environmental footprint indicators has been growing rapidly, but with limited efforts to integrate different footprints into a coherent framework. Such integration is important for comprehensive understanding of environmental issues, policy formulation and assessment of trade-offs between different environmental concerns. Here, we systematize published footprint studies and define a family of footprints that can be used for the assessment of environmental sustainability. We identify overlaps between different footprints and analyse how they relate to the nine planetary boundaries and visualize the crucial information they provide for local and planetary sustainability. In addition, we assess how the footprint family delivers on measuring progress towards Sustainable Development Goals (SDGs), considering its ability to quantify environmental pressures along the supply chain and relating them to the water-energy-food-ecosystem (WEFE) nexus and ecosystem services. We argue that the footprint family is a flexible framework where particular members can be included or excluded according to the context or area of concern. Our paper is based upon a recent workshop bringing together global leading experts on existing environmental footprint indicators

Acetaminophen Modulates the Transcriptional Response to Recombinant Interferon-β

BACKGROUND: Recombinant interferon treatment can result in several common side effects including fever and injection-site pain. Patients are often advised to use acetaminophen or other over-the-counter pain medications as needed. Little is known regarding the transcriptional changes induced by such co-administration. METHODOLOGY/PRINCIPAL FINDINGS: We tested whether the administration of acetaminophen causes a change in the response normally induced by interferon-beta treatment. CD-1 mice were administered acetaminophen (APAP), interferon-beta (IFN-beta) or a combination of IFN-beta+APAP and liver and serum samples were collected for analysis. Differential gene expression was determined using an Agilent 22 k whole mouse genome microarray. Data were analyzed by several methods including Gene Ontology term clustering and Gene Set Enrichment Analysis. We observed a significant change in the transcription profile of hepatic cells when APAP was co-administered with IFN-beta. These transcriptional changes included a marked up-regulation of genes involved in signal transduction and cell differentiation and down-regulation of genes involved in cellular metabolism, trafficking and the IkappaBK/NF-kappaB cascade. Additionally, we observed a large decrease in the expression of several IFN-induced genes including Ifit-3, Isg-15, Oasl1, Zbp1 and predicted gene EG634650 at both early and late time points. CONCLUSIONS/SIGNIFICANCE: A significant change in the transcriptional response was observed following co-administration of IFN-beta+APAP relative to IFN-beta treatment alone. These results suggest that administration of acetaminophen has the potential to modify the efficacy of IFN-beta treatment

The Atacama Cosmology Telescope: A Measurement of the DR6 CMB Lensing Power Spectrum and its Implications for Structure Growth

We present new measurements of cosmic microwave background (CMB) lensing over $9400$ sq. deg. of the sky. These lensing measurements are derived from the Atacama Cosmology Telescope (ACT) Data Release 6 (DR6) CMB dataset, which consists of five seasons of ACT CMB temperature and polarization observations. We determine the amplitude of the CMB lensing power spectrum at $2.3\%$ precision ($43\sigma$ significance) using a novel pipeline that minimizes sensitivity to foregrounds and to noise properties. To ensure our results are robust, we analyze an extensive set of null tests, consistency tests, and systematic error estimates and employ a blinded analysis framework. The baseline spectrum is well fit by a lensing amplitude of $A_{\mathrm{lens}}=1.013\pm0.023$ relative to the Planck 2018 CMB power spectra best-fit $\Lambda$CDM model and $A_{\mathrm{lens}}=1.005\pm0.023$ relative to the $\text{ACT DR4} + \text{WMAP}$ best-fit model. From our lensing power spectrum measurement, we derive constraints on the parameter combination $S^{\mathrm{CMBL}}_8 \equiv \sigma_8 \left({\Omega_m}/{0.3}\right)^{0.25}$ of $S^{\mathrm{CMBL}}_8= 0.818\pm0.022$ from ACT DR6 CMB lensing alone and $S^{\mathrm{CMBL}}_8= 0.813\pm0.018$ when combining ACT DR6 and Planck NPIPE CMB lensing power spectra. These results are in excellent agreement with $\Lambda$CDM model constraints from Planck or $\text{ACT DR4} + \text{WMAP}$ CMB power spectrum measurements. Our lensing measurements from redshifts $z\sim0.5$--$5$ are thus fully consistent with $\Lambda$CDM structure growth predictions based on CMB anisotropies probing primarily $z\sim1100$. We find no evidence for a suppression of the amplitude of cosmic structure at low redshiftsComment: 45+21 pages, 50 figures. Prepared for submission to ApJ. Also see companion papers Madhavacheril et al and MacCrann et a

The Atacama Cosmology Telescope: High-resolution component-separated maps across one-third of the sky

Observations of the millimeter sky contain valuable information on a number of signals, including the blackbody cosmic microwave background (CMB), Galactic emissions, and the Compton-$y$ distortion due to the thermal Sunyaev-Zel'dovich (tSZ) effect. Extracting new insight into cosmological and astrophysical questions often requires combining multi-wavelength observations to spectrally isolate one component. In this work, we present a new arcminute-resolution Compton-$y$ map, which traces out the line-of-sight-integrated electron pressure, as well as maps of the CMB in intensity and E-mode polarization, across a third of the sky (around 13,000 sq.~deg.). We produce these through a joint analysis of data from the Atacama Cosmology Telescope (ACT) Data Release 4 and 6 at frequencies of roughly 93, 148, and 225 GHz, together with data from the \textit{Planck} satellite at frequencies between 30 GHz and 545 GHz. We present detailed verification of an internal linear combination pipeline implemented in a needlet frame that allows us to efficiently suppress Galactic contamination and account for spatial variations in the ACT instrument noise. These maps provide a significant advance, in noise levels and resolution, over the existing \textit{Planck} component-separated maps and will enable a host of science goals including studies of cluster and galaxy astrophysics, inferences of the cosmic velocity field, primordial non-Gaussianity searches, and gravitational lensing reconstruction of the CMB.Comment: The Compton-y map and associated products will be made publicly available upon publication of the paper. The CMB T and E mode maps will be made available when the DR6 maps are made publi

Both “illness and temptation of the enemy”: melancholy, the medieval patient and the writings of King Duarte of Portugal (r. 1433–38)

Recent historians have rehabilitated King Duarte of Portugal, previously maligned and neglected, as an astute ruler and philosopher. There is still a tendency, however, to view Duarte as a depressive or a hypochondriac, due to his own description of his melancholy in his advice book, the Loyal Counselor. This paper reassesses Duarte's writings, drawing on key approaches in the history of medicine, such as narrative medicine and the history of the patient. It is important to take Duarte's views on his condition seriously, placing them in the medical and theological contexts of his time and avoiding modern retrospective diagnosis. Duarte's writings can be used to explore the impact of plague, doubt and death on the life of a well-educated and conscientious late-medieval ruler

The Atacama Cosmology Telescope: DR6 Gravitational Lensing Map and Cosmological Parameters

We present cosmological constraints from a gravitational lensing mass map covering 9400 sq. deg. reconstructed from CMB measurements made by the Atacama Cosmology Telescope (ACT) from 2017 to 2021. In combination with BAO measurements (from SDSS and 6dF), we obtain the amplitude of matter fluctuations $\sigma_8 = 0.819 \pm 0.015$ at 1.8% precision, $S_8\equiv\sigma_8({\Omega_{\rm m}}/0.3)^{0.5}=0.840\pm0.028$ and the Hubble constant $H_0= (68.3 \pm 1.1)\, \text{km}\,\text{s}^{-1}\,\text{Mpc}^{-1}$ at 1.6% precision. A joint constraint with CMB lensing measured by the Planck satellite yields even more precise values: $\sigma_8 = 0.812 \pm 0.013$, $S_8\equiv\sigma_8({\Omega_{\rm m}}/0.3)^{0.5}=0.831\pm0.023$ and $H_0= (68.1 \pm 1.0)\, \text{km}\,\text{s}^{-1}\,\text{Mpc}^{-1}$. These measurements agree well with $\Lambda$CDM-model extrapolations from the CMB anisotropies measured by Planck. To compare these constraints to those from the KiDS, DES, and HSC galaxy surveys, we revisit those data sets with a uniform set of assumptions, and find $S_8$ from all three surveys are lower than that from ACT+Planck lensing by varying levels ranging from 1.7-2.1$\sigma$. These results motivate further measurements and comparison, not just between the CMB anisotropies and galaxy lensing, but also between CMB lensing probing $z\sim 0.5-5$ on mostly-linear scales and galaxy lensing at $z\sim 0.5$ on smaller scales. We combine our CMB lensing measurements with CMB anisotropies to constrain extensions of $\Lambda$CDM, limiting the sum of the neutrino masses to $\sum m_{\nu} < 0.12$ eV (95% c.l.), for example. Our results provide independent confirmation that the universe is spatially flat, conforms with general relativity, and is described remarkably well by the $\Lambda$CDM model, while paving a promising path for neutrino physics with gravitational lensing from upcoming ground-based CMB surveys.Comment: 30 pages, 16 figures, prepared for submission to ApJ. Cosmological likelihood data is here: https://lambda.gsfc.nasa.gov/product/act/actadv_prod_table.html ; likelihood software is here: https://github.com/ACTCollaboration/act_dr6_lenslike . Also see companion papers Qu et al and MacCrann et al. Mass maps will be released when papers are publishe