Genomic surveillance and sequencing of SARS-CoV-2 across South America.

After 2 years of the COVID-19 pandemic, the protocols used to control infection lack attention and analysis. We present data about deposits of complete genomic sequences of SARS-CoV-2 in the Global Initiative on Sharing All Influenza Data (GISAID) database made between January 2021 and May 31, 2022. We build the distribution profile of SARS-CoV-2 variants across South America, highlighting the contribution and influence of each variant over time. Monitoring the genomic sequences in GISAID illustrates negligence in the follow up of infected patients in South America and also the discrepancies between the number of complete genomes deposited throughout the pandemic by developed and developing countries. While Europe and North America account for more than 9 million of the genomes deposited in GISAID, Africa and South America deposited less than 400 000 genome sequences. Genomic surveillance is important for detecting early warning signs of new circulating viruses, assisting in the discovery of new variants and controlling pandemics.

Tras dos años de pandemia del COVID-19, los protocolos empleados para controlar la infección carecen de atención y análisis. En este artículo se presentan datos sobre depósitos de secuencias genómicas completas del SARS-CoV-2 en la base de datos de secuenciación GISAID, la Iniciativa mundial para intercambiar todos los datos sobre la gripe aviar, realizadas entre enero del 2021 y el 31 de mayo del 2022. Se creó el perfil de distribución de las variantes del SARS-CoV-2 en América del Sur, en el que se destacaron la contribución y la influencia de cada variante a lo largo del tiempo. El monitoreo de las secuencias genómicas en GISAID ilustra la negligencia en el seguimiento de los pacientes infectados en América del Sur, así como las discrepancias entre el número de genomas completos depositados a lo largo de la pandemia por parte de los países desarrollados y los países en desarrollo. Mientras que Europa y América del Norte han depositado más de 9 millones de genomas en GISAID, África y América del Sur han aportado menos de 400 000 secuencias genómicas. La vigilancia genómica es importante para detectar los primeros signos de alerta de virus nuevos en circulación, ayudar en el descubrimiento de nuevas variantes y controlar las pandemias.

Após 2 anos da pandemia de covid-19, os protocolos usados para controlar a infecção necessitam maior atenção e análise. Apresentamos dados sobre as sequências genômicas completas do SARS-CoV-2 depositadas no banco de dados do a iniciativa internacional para o intercâmbio de dados sobre os vírus da influenza (GISAID) entre janeiro de 2021 e 31 de maio de 2022. Construímos o perfil de distribuição das variantes do SARS-CoV-2 na América do Sul, destacando a contribuição e a influência de cada variante ao longo do tempo. O monitoramento das sequências genômicas do GISAID ilustra a negligência no acompanhamento de pacientes infectados na América do Sul e as discrepâncias entre os países desenvolvidos e em desenvolvimento com relação ao número de genomas completos depositados ao longo da pandemia. Enquanto a Europa e a América do Norte respondem por mais de 9 milhões dos genomas depositados no GISAID, a África e a América do Sul depositaram menos de 400 000 sequências genômicas. A vigilância genômica é importante para detectar sinais de alerta precoces de novos vírus circulantes, auxiliar na descoberta de novas variantes e controlar pandemias.

Genomic surveillance and sequencing of SARS-CoV-2 across South America

[ABSTRACT]. After 2 years of the COVID-19 pandemic, the protocols used to control infection lack attention and analysis. We present data about deposits of complete genomic sequences of SARS-CoV-2 in the Global Initiative on Sharing All Influenza Data (GISAID) database made between January 2021 and May 31, 2022. We build the distribution profile of SARS-CoV-2 variants across South America, highlighting the contribution and influence of each variant over time. Monitoring the genomic sequences in GISAID illustrates negligence in the follow up of infected patients in South America and also the discrepancies between the number of complete genomes deposited throughout the pandemic by developed and developing countries. While Europe and North America account for more than 9 million of the genomes deposited in GISAID, Africa and South America deposited less than 400 000 genome sequences. Genomic surveillance is important for detecting early warning signs of new circulating viruses, assisting in the discovery of new variants and controlling pandemics.

[RESUMEN]. Tras dos años de pandemia del COVID-19, los protocolos empleados para controlar la infección carecen de atención y análisis. En este artículo se presentan datos sobre depósitos de secuencias genómicas completas del SARS-CoV-2 en la base de datos de secuenciación GISAID, la Iniciativa mundial para intercambiar todos los datos sobre la gripe aviar, realizadas entre enero del 2021 y el 31 de mayo del 2022. Se creó el perfil de distribución de las variantes del SARS-CoV-2 en América del Sur, en el que se destacaron la contribución y la influencia de cada variante a lo largo del tiempo. El monitoreo de las secuencias genómicas en GISAID ilustra la negligencia en el seguimiento de los pacientes infectados en América del Sur, así como las discrepancias entre el número de genomas completos depositados a lo largo de la pandemia por parte de los países desarrollados y los países en desarrollo. Mientras que Europa y América del Norte han depositado más de 9 millones de genomas en GISAID, África y América del Sur han aportado menos de 400 000 secuencias genómicas. La vigilancia genómica es importante para detectar los primeros signos de alerta de virus nuevos en circulación, ayudar en el descubrimiento de nuevas variantes y controlar las pandemias.

[RESUMO]. Após 2 anos da pandemia de covid-19, os protocolos usados para controlar a infecção necessitam maior atenção e análise. Apresentamos dados sobre as sequências genômicas completas do SARS-CoV-2 depositadas no banco de dados do a iniciativa internacional para o intercâmbio de dados sobre os vírus da influenza (GISAID) entre janeiro de 2021 e 31 de maio de 2022. Construímos o perfil de distribuição das variantes do SARS-CoV-2 na América do Sul, destacando a contribuição e a influência de cada variante ao longo do tempo. O monitoramento das sequências genômicas do GISAID ilustra a negligência no acompanhamento de pacientes infectados na América do Sul e as discrepâncias entre os países desenvolvidos e em desenvolvimento com relação ao número de genomas completos depositados ao longo da pandemia. Enquanto a Europa e a América do Norte respondem por mais de 9 milhões dos genomas depositados no GISAID, a África e a América do Sul depositaram menos de 400 000 sequências genômicas. A vigilância genômica é importante para detectar sinais de alerta precoces de novos vírus circulantes, auxiliar na descoberta de novas variantes e controlar pandemias.

Genomic surveillance and sequencing of SARS-CoV-2 across South America / Vigilancia genómica y secuenciación del SARS-CoV-2 en América del Sur / Vigilância genômica e sequenciamento do SARS-CoV-2 na América do Sul

ABSTRACT After 2 years of the COVID-19 pandemic, the protocols used to control infection lack attention and analysis. We present data about deposits of complete genomic sequences of SARS-CoV-2 in the Global Initiative on Sharing All Influenza Data (GISAID) database made between January 2021 and May 31, 2022. We build the distribution profile of SARS-CoV-2 variants across South America, highlighting the contribution and influence of each variant over time. Monitoring the genomic sequences in GISAID illustrates negligence in the follow up of infected patients in South America and also the discrepancies between the number of complete genomes deposited throughout the pandemic by developed and developing countries. While Europe and North America account for more than 9 million of the genomes deposited in GISAID, Africa and South America deposited less than 400 000 genome sequences. Genomic surveillance is important for detecting early warning signs of new circulating viruses, assisting in the discovery of new variants and controlling pandemics.

RESUMEN Tras dos años de pandemia del COVID-19, los protocolos empleados para controlar la infección carecen de atención y análisis. En este artículo se presentan datos sobre depósitos de secuencias genómicas completas del SARS-CoV-2 en la base de datos de secuenciación GISAID, la Iniciativa mundial para intercambiar todos los datos sobre la gripe aviar, realizadas entre enero del 2021 y el 31 de mayo del 2022. Se creó el perfil de distribución de las variantes del SARS-CoV-2 en América del Sur, en el que se destacaron la contribución y la influencia de cada variante a lo largo del tiempo. El monitoreo de las secuencias genómicas en GISAID ilustra la negligencia en el seguimiento de los pacientes infectados en América del Sur, así como las discrepancias entre el número de genomas completos depositados a lo largo de la pandemia por parte de los países desarrollados y los países en desarrollo. Mientras que Europa y América del Norte han depositado más de 9 millones de genomas en GISAID, África y América del Sur han aportado menos de 400 000 secuencias genómicas. La vigilancia genómica es importante para detectar los primeros signos de alerta de virus nuevos en circulación, ayudar en el descubrimiento de nuevas variantes y controlar las pandemias.

RESUMO Após 2 anos da pandemia de covid-19, os protocolos usados para controlar a infecção necessitam maior atenção e análise. Apresentamos dados sobre as sequências genômicas completas do SARS-CoV-2 depositadas no banco de dados do a iniciativa internacional para o intercâmbio de dados sobre os vírus da influenza (GISAID) entre janeiro de 2021 e 31 de maio de 2022. Construímos o perfil de distribuição das variantes do SARS-CoV-2 na América do Sul, destacando a contribuição e a influência de cada variante ao longo do tempo. O monitoramento das sequências genômicas do GISAID ilustra a negligência no acompanhamento de pacientes infectados na América do Sul e as discrepâncias entre os países desenvolvidos e em desenvolvimento com relação ao número de genomas completos depositados ao longo da pandemia. Enquanto a Europa e a América do Norte respondem por mais de 9 milhões dos genomas depositados no GISAID, a África e a América do Sul depositaram menos de 400 000 sequências genômicas. A vigilância genômica é importante para detectar sinais de alerta precoces de novos vírus circulantes, auxiliar na descoberta de novas variantes e controlar pandemias.

Impact of Pectoralis Nerve Block (PECS) on postoperative pain in patients submitted to mastectomy with lymphadenectomy.

OBJECTIVE: Breast cancer is the most common malignant neoplasm in women worldwide. Surgery has been traditional treatment and, generally, it´s mastectomy with lymphadenectomy, that can causes postoperative pain. Therefore, we seek to study regional anesthesic techniques that can minimize this effect, such as the interpectoral block (PECS). METHODS: randomized controlled study with 82 patients with breast cancer who underwent mastectomy with lymphadenectomy from January 2020 to October 2021 in oncology hospital. INTERVENTIONS: two randomized groups (control - exclusive general anesthesia and PECS group - received PECS block with levobupivacaine/ropivacaine and general anesthesia). We applied a questionnaire with Numeric Rating Scale for pain 24h after surgery. We used Shapiro-Wilk, Mann-Whitney and Chi-square tests, and analyzed the data in R version 4.0.0 (ReBEC). RESULTS: in the PECS group, 50% were pain-free 24h after surgery and in the control group it was 42.86%. The majority who presented pain classified it as mild pain (VAS from 1 to 3) - (42.50%) PECS group and (40.48%) control group (p=0.28). Only 17.50% consumed opioids in the PECS group, similar to the control group with 21.43%. (p=0.65). There was a low rate of complications such as PONV in both groups. In the subgroup analysis, there was no statistical difference between the groups that used levobupivacaine or ropivacaine regarding postoperative pain and opioid consumption. DISCUSSION: the studied group had a low rate of pain in the postoperative period and it influenced the statistical analysis. There wasn´t difference in postoperative pain in groups. CONCLUSION: was not possible to demonstrate better results with the association of the PECS block with total intravenous analgesia. Need further studies to assess the efficacy of the nerve block.

Schools reopening and the COVID-19 pandemic: a case study from Macaé, Rio de Janeiro, Brazil.

Since the first reported case of COVID-19 in Brazil, the public and private educational system started to close. Up to November 2020, scientific discussions about the return of schooling activities have been rarely performed by the national scientific community and police-makers. The great delay of school returning in Brazil contrasts with successful international strategies of school reopening worldwide and seems counterintuitive with the reopening of non-essential activities. Here, important issues to be considered before and during school reopening are reviewed and discussed. COVID-19 testing is essential to avoid disease spreading, but high cost of individual RT-qPCRs impairs an extensive testing strategy for school returning. To reduce costs and increase the speed of diagnosis, we tested the efficiency of a pooled-sample PCR strategy in a cohort of the educational staff in the city of Macaé/RJ, finding five asymptomatic individuals (0,66%) among the 754 people tested. Thus, a polled-sample PCR testing strategy of the educational staff might prevent infection spreading in schools at a reasonable cost. We discuss how our test strategy could be coupled with internationally recognized safety rules to allow for a safe school return and how countries from different world regions are dealing with educational activities during COVID-19 pandemic.

Physical exercise improves mitochondrial function in ovariectomized rats.

Estrogen deficiency causes metabolic disorders in humans and rodents, including in part due to changes in energy expenditure. We have shown previously that skeletal muscle mitochondrial function is compromised in ovariectomized (Ovx) rats. Since physical exercise is a powerful strategy to improve skeletal muscle mitochondrial content and function, we hypothesize that exercise training would counteract the deficiency-induced skeletal muscle mitochondrial dysfunction in Ovx rats. We report that exercised Ovx rats, at 60-65% of maximal exercise capacity for 8 weeks, exhibited less fat accumulation and body weight gain compared with sedentary controls. Treadmill exercise training decreased muscle lactate production, indicating a shift to mitochondrial oxidative metabolism. Furthermore, reduced soleus muscle mitochondrial oxygen consumption confirmed that estrogen deficiency is detrimental to mitochondrial function. However, exercise restored mitochondrial oxygen consumption in Ovx rats, achieving similar levels as in exercised control rats. Exercise-induced skeletal muscle peroxisome proliferator-activated receptor-γ coactivator-1α expression was similar in both groups. Therefore, the mechanisms by which exercise improves mitochondrial oxygen consumption appears to be different in Ovx-exercised and sham-exercised rats. While there was an increase in mitochondrial content in sham-exercised rats, demonstrated by a greater citrate synthase activity, no induction was observed in Ovx-exercised rats. Normalizing mitochondrial respiratory capacity by citrate synthase activity indicates a better oxidative phosphorylation efficiency in the Ovx-exercised group. In conclusion, physical exercise sustains mitochondrial function in ovarian hormone-deficient rats through a non-conventional mitochondrial content-independent manner.

Impact of Pectoralis Nerve Block (PECS) on postoperative pain in patients submitted to mastectomy with lymphadenectomy / Impacto do Bloqueio Peitoral (PEC) na dor pós-operatória em pacientes submetidos a mastectomia com linfadenectomia

ABSTRACT Objective: Breast cancer is the most common malignant neoplasm in women worldwide. Surgery has been traditional treatment and, generally, it´s mastectomy with lymphadenectomy, that can causes postoperative pain. Therefore, we seek to study regional anesthesic techniques that can minimize this effect, such as the interpectoral block (PECS). Methods: randomized controlled study with 82 patients with breast cancer who underwent mastectomy with lymphadenectomy from January 2020 to October 2021 in oncology hospital. Interventions: two randomized groups (control - exclusive general anesthesia and PECS group - received PECS block with levobupivacaine/ropivacaine and general anesthesia). We applied a questionnaire with Numeric Rating Scale for pain 24h after surgery. We used Shapiro-Wilk, Mann-Whitney and Chi-square tests, and analyzed the data in R version 4.0.0 (ReBEC). Results: in the PECS group, 50% were pain-free 24h after surgery and in the control group it was 42.86%. The majority who presented pain classified it as mild pain (VAS from 1 to 3) - (42.50%) PECS group and (40.48%) control group (p=0.28). Only 17.50% consumed opioids in the PECS group, similar to the control group with 21.43%. (p=0.65). There was a low rate of complications such as PONV in both groups. In the subgroup analysis, there was no statistical difference between the groups that used levobupivacaine or ropivacaine regarding postoperative pain and opioid consumption. Discussion: the studied group had a low rate of pain in the postoperative period and it influenced the statistical analysis. There wasn´t difference in postoperative pain in groups. Conclusion: was not possible to demonstrate better results with the association of the PECS block with total intravenous analgesia. Need further studies to assess the efficacy of the nerve block.

RESUMO Introdução: o câncer de mama é a neoplasia maligna mais comum em mulheres no mundo. A cirurgia tem sido o tratamento tradicional e, geralmente consiste em mastectomia com linfadenectomia, podendo causar dor pós-operatória. Por isso, buscamos estudar técnicas anestésicas regionais que possam minimizar esse efeito, como o bloqueio interpeitoral (PEC). Métodos: estudo controlado randomizado com 82 pacientes com câncer de mama submetidos à mastectomia com linfadenectomia de Janeiro de 2020 a Outubro de 2021, em hospital oncológico. Intervenções: dois grupos randomizados (controle - anestesia geral exclusiva e grupo PECS - anestesia geral e bloqueio PEC com levobupivacaína/ropivacaína). Aplicou-se um questionário com Escala Visual Analógica da dor 24h pós-cirurgia. Utilizamos os testes de Shapiro-Wilk, Mann-Whitney e Quiquadrado e analisamos os dados em R versão 4.0.0. Estudo registrado em Ensaios Clínicos Brasileiros (REBec). Resultados: no grupo PEC, 50% não apresentava dor 24 horas após a cirurgia enquanto no grupo controle, 42,86% negava quadro álgico. A maioria que apresentou dor classificou-a como dor leve (EVA de 1 a 3) - (42,50%) grupo PEC e (40,48%) controle (p=0,28). Apenas 17,50% consumiram opioides no grupo PEC, semelhante ao grupo controle com 21,43%. (p=0,65), (17,50%) grupo PEC e (21,43%) grupo controle (p=0,65). Houve baixo índice de complicações como PONV (náuseas, vômitos, cefaleia) em ambos os grupos. Na análise de subgrupo, não houve diferença estatística entre os grupos que usaram Levobupivacaína ou Ropivacaína quanto a dor pós-operatória e o consumo de opioides. Discussão: o grupo estudado apresentou baixa taxa de dor no pós-operatório e isso influenciou na análise estatística. Não houve diferença estatística quanto a dor pós-operatória entre grupos. Conclusão: não foi possível demonstrar melhores resultados com a associação do bloqueio PEC com analgesia intravenosa total. São necessários novos estudos para avaliar a eficácia do bloqueio anestésico no intraoperatório e pós-operatório.

Molecular testing and analysis of disease spreading during the emergence of COVID-19 in Macaé, the Brazilian National Capital of Oil.

The Brazilian strategy to overcome the spread of COVID-19 has been particularly criticized due to the lack of a national coordinating effort and an appropriate testing program. Here, a successful approach to control the spread of COVID-19 transmission is described by the engagement of public (university and governance) and private sectors (hospitals and oil companies) in Macaé, state of Rio de Janeiro, Brazil, a city known as the National Oil Capital. In 2020 between the 17th and 38th epidemiological week, over two percent of the 206,728 citizens were subjected to symptom analysis and RT-qPCR testing by the Federal University of Rio de Janeiro, with positive individuals being notified up to 48 h after swab collection. Geocodification and spatial cluster analysis were used to limit COVID-19 spreading in Macaé. Within the first semester after the outbreak of COVID-19 in Brazil, Macaé recorded 1.8% of fatalities associated with COVID-19 up to the 38th epidemiological week, which was at least five times lower than the state capital (10.6%). Overall, considering the successful experience of this joint effort of private and public engagement in Macaé, our data suggest that the development of a similar strategy countrywise could have contributed to a better control of the COVID-19 spread in Brazil. Quarantine decree by the local administration, comprehensive molecular testing coupled to scientific analysis of COVID-19 spreading, prevented the catastrophic consequences of the pandemic as seen in other populous cities within the state of Rio de Janeiro and elsewhere in Brazil.

The RNA-binding protein LARP1 is dispensable for pancreatic ß-cell function and mass.

Mechanistic target of rapamycin complex 1 (mTORC1) deficiency or chronic hyperactivation in pancreatic ß-cells leads to diabetes. mTORC1 complexes with La-related protein 1 (LARP1) to specifically regulate the expression of 5' terminal oligopyrimidine tract (5'TOP) mRNAs which encode proteins of the translation machinery and ribosome biogenesis. Here we show that LARP1 is the most expressed LARP in mouse islets and human ß-cells, being 2-4-fold more abundant than LARP1B, a member of the family that also interacts with mTORC1. Interestingly, ß-cells from diabetic patients have higher LARP1 and LARP1B expression. However, specific deletion of Larp1 gene in ß-cells (ß-Larp1KO mice) did not impair insulin secretion and glucose metabolism in male and female mice. High fat or high branched-chain amino acid (BCAA) diets did not disturb glucose homeostasis compared to control littermates up to 8 weeks; BCAA diet slightly impaired glucose tolerance in the ß-Larp1KO mice at 16 weeks. However, no differences in plasma insulin levels, non-fasting glycemia and ß-cell mass were observed in the ß-Larp1KO mice. In conclusion, LARP1 is the most abundant LARP in mouse islets and human ß-cells, and it is upregulated in diabetic subjects. However, genetically disruption of Larp1 gene did not impact glucose homeostasis in basal and diabetogenic conditions, suggesting no major role for LARP1 in ß-cells.

A Controlled Clinical Trial on the Effects of Exercise on Cognition and Mobility in Adults With Multiple Sclerosis.

OBJECTIVE: The aim of the study was to investigate the effects of a 6-mo exercise program on cognition and mobility in participants with multiple sclerosis. DESIGN: This is a prospective, single-blind, controlled clinical trial. SETTING: A community rehabilitation program within a large metropolitan health service. PARTICIPANTS: Twenty-eight patients with multiple sclerosis were referred for outpatient rehabilitation. INTERVENTIONS: Participants were allocated to one of two groups and undertook a cognitive-motor exercise program or monitoring (control group). MAIN OUTCOME MEASURES: Cognition and mobility were the main outcome measures. Cognition was evaluated using the Mini-Mental State Examination and the Frontal Assessment Battery. Mobility was assessed with the Timed Get Up and Go test, applied with and without dual task distractors. RESULTS: The findings showed benefits provided by exercise on cognition and mobility. Differently, participants of the control group did not have significant changes in cognition scores after 6 mos of follow-up and had a worse performance in mobility tests. CONCLUSION: Six months of exercise provided benefits to cognition and mobility in adults with multiple sclerosis. This trial was registered prospectively with the Brazilian Clinical Trials Register, ID: RBR-9gh4km (http://www.ensaiosclinicos.gov.br/rg/?q=RBR-9gh4km). TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Recognize the physical and cognitive decline in multiple sclerosis; (2) Identify the importance of exercise on cognition and mobility in patients with multiple sclerosis; and (3) Appreciate the potential benefit of dual tasking in the rehabilitation of individuals with multiple sclerosis.Level: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Heart rate response to graded exercise test of elderly subjects in different ranges of TSH levels

ABSTRACT Objective: Life expectancy is increasing worldwide and studies have been demonstrating that elevated serum thyroid stimulating hormone (TSH) concentration in elderly is associated with some better health outcomes. This elevation is somewhat physiological as aging. The aim of this study was to investigate the heart rate (HR) response during a graded exercise test and its recovery in healthy elderly, comparing subjects within serum TSH in the lower limit of reference range to those within the TSH in the upper limit. Subjects and methods: A cross-sectional study was conducted with 86 healthy elderly aged 71.5 ± 5.1 years, with serum TSH between 0.4 - 4.0 mUl/mL. The participants were divided into two groups according to TSH level: < 1.0 mUl/mL (n = 13) and ≥ 1.0 µUI/mL (n = 73). All participants performed an ergometric test on a treadmill. The HR was recorded and analyzed at rest, during exercise and during the three minutes immediately after exercise. Results: No differences were observed in relation to HR at peak of exercise (TSH < 1.0 µUI/mL: 133.9 ± 22.5 bpm vs. TSH ≥ 1.0 µUI/mL: 132.4 ± 21.3 bpm; p = 0.70) and during the first minute of recovery phase (TSH < 1.0 µUI/mL: 122.3 ± 23.1 bpm vs. TSH ≥ 1.0 µUI/mL: 115.7 ± 18.4 bpm p = 0.33). The groups also presented similar chronotropic index (TSH < 1.0 µUI/mL: 78.1 ± 30.6 vs. TSH ≥ 1.0 µUI/mL: 79.5 ± 26.4; p = 0.74). Conclusion: In this sample studied, there were no difference between lower and upper TSH level concerning HR response during rest, peak of exercise and exercise recovery.

Heart rate response to graded exercise test of elderly subjects in different ranges of TSH levels.

OBJECTIVE: Life expectancy is increasing worldwide and studies have been demonstrating that elevated serum thyroid stimulating hormone (TSH) concentration in elderly is associated with some better health outcomes. This elevation is somewhat physiological as aging. The aim of this study was to investigate the heart rate (HR) response during a graded exercise test and its recovery in healthy elderly, comparing subjects within serum TSH in the lower limit of reference range to those within the TSH in the upper limit. SUBJECTS AND METHODS: A cross-sectional study was conducted with 86 healthy elderly aged 71.5 ± 5.1 years, with serum TSH between 0.4 - 4.0 mUl/mL. The participants were divided into two groups according to TSH level: < 1.0 mUl/mL (n = 13) and ≥ 1.0 µUI/mL (n = 73). All participants performed an ergometric test on a treadmill. The HR was recorded and analyzed at rest, during exercise and during the three minutes immediately after exercise. RESULTS: No differences were observed in relation to HR at peak of exercise (TSH < 1.0 µUI/mL: 133.9 ± 22.5 bpm vs. TSH ≥ 1.0 µUI/mL: 132.4 ± 21.3 bpm; p = 0.70) and during the first minute of recovery phase (TSH < 1.0 µUI/mL: 122.3 ± 23.1 bpm vs. TSH ≥ 1.0 µUI/mL: 115.7 ± 18.4 bpm p = 0.33). The groups also presented similar chronotropic index (TSH < 1.0 µUI/mL: 78.1 ± 30.6 vs. TSH ≥ 1.0 µUI/mL: 79.5 ± 26.4; p = 0.74). CONCLUSION: In this sample studied, there were no difference between lower and upper TSH level concerning HR response during rest, peak of exercise and exercise recovery.

A Single Dose of Beetroot Gel Rich in Nitrate Does Not Improve Performance but Lowers Blood Glucose in Physically Active Individuals.

Background. Beetroot consumption has been proposed to improve exercise performance, since the nitrate content of this food is able to stimulate the synthesis of nitric oxide. Objective. The acute effect of 100 g of a beetroot gel containing ~10 mmol of nitrate was tested on the nitric oxide synthesis, on metabolic and biochemical parameters, and on performance in physically active individuals. Methods. Through a double blind, crossover, placebo-controlled study, 25 healthy runners ingested a single dose of beetroot and placebo gels. Participants performed an aerobic exercise protocol on a treadmill (3 min warm-up of 40% peak oxygen consumption, 4 min at 90% of gas exchange threshold I and 70% (Δ) maximal end speed until volitional fatigue). Results. Urinary levels of nitrite and nitrate increased after 90 min of beetroot gel ingestion. Plasma glucose concentrations lowered after the exercise and the decrease was maintained for 20 min. Systolic and diastolic blood pressures, serum cortisol, and blood lactate were not altered after the beetroot gel ingestion compared to a placebo gel. Conclusion. The single dose of beetroot gel provoked an increase of nitric oxide synthesis although no improvement on the physical performance of athletes during aerobic submaximal exercise was observed.

Growth hormone and cortisol secretion in the elderly evaluated using the glucagon stimulation test.

OBJECTIVES: The glucagon stimulation test is a reliable alternative test to assess growth hormone and cortisol secretion, but has not been widely used in the elderly population. The aim of this study was to evaluate growth hormone and cortisol secretion using the glucagon stimulation test in an elderly population without known hypothalamic-pituitary disease and to correlate growth hormone and cortisol peaks with age (less than or greater than 80 years) and body mass index. METHODS: Forty-two subjects (67-88 years) from the geriatric ambulatory unit were submitted and 41 subjects completed the glucagon stimulation test. RESULTS: Median growth hormone peak was 5.99 µg/L and median cortisol peak was 21.6 µg/dL. Growth hormone peak was >3 µg/L in 73.2%, and cortisol peak was >18 µg/dL in 65.8% of patients. There was a statistically significant positive correlation between the growth hormone peak and the cortisol peak. The cortisol peak was significantly different between subjects stratified by growth hormone peak of < or >3 µg/L (15.7 and 21.8 µg/dL, respectively). There was a statistically significant difference in cortisol peak according to age < or > 80 years (22.4 and 18.5 µg/dL, respectively). Considering lower cut-offs recently proposed for growth hormone peak (1.0 µg/L for overweight subjects) and cortisol peak (9.1 µg/dL), only two patients had a growth hormone peak below this value, and all patients had preserved cortisol secretion. CONCLUSIONS: We did find a positive correlation between growth hormone and cortisol peaks in the glucagon stimulation test in the elderly, confirming the capacity of the glucagon stimulation test to stimulate both axes. According to the new proposed cut-points for growth hormone and cortisol, we had 95% of normal growth hormone and 100% of normal cortisol responses.

Early Developmental Disruption of Type 2 Deiodinase Pathway in Mouse Skeletal Muscle Does Not Impair Muscle Function.

BACKGROUND: Myogenesis is positively regulated by thyroid hormone (triiodothyronine [T3]), which is amplified by the type 2 deiodinase (D2) activation of thyroxine to T3. Global inactivation of the Dio2 gene impairs skeletal muscle (SKM) differentiation and regeneration in response to muscle injury. Given that newborn and adult mice with late developmental SKM Dio2 disruption do not develop a significant phenotype, it was hypothesized that D2 plays an early role in this process. METHODS: This was tested in mice with SKM disruption of Dio2 driven by two early developmental promoters: MYF5 and MYOD. RESULTS: MYF5 myoblasts in culture differentiate normally into myotubes, despite loss of almost all D2 activity. Dio2 mRNA levels in developing SKM obtained from MYF5-D2KO embryos (E18.5) were about 54% of control littermates, but the expression of the T3-responsive genes Myh1 and 7 and Atp2a1 and 2 were not affected. In MYF5-D2KO and MYOD-D2KO neonatal hind-limb muscle, the expression of Myh1 and 7 and Atp2a2 remained unaffected, despite 60-70% loss in D2 activity and/or mRNA. Only in MYOD-D2KO neonatal muscle was there a 40% reduction in Atp2a1 mRNA. Postnatal growth of both mouse models and SKM function as assessed by exercise capacity and measurement of muscle strength were normal. Furthermore, an analysis of the adult soleus revealed no changes in the expression of T3-responsive genes, except for an about 18% increase in MYOD-D2KO SOL Myh7 mRNA. CONCLUSION: Two mouse models of early developmental disruption of Dio2 in myocyte precursor exhibit no significant SKM phenotype.

Thyroid hormone activation by type 2 deiodinase mediates exercise-induced peroxisome proliferator-activated receptor-γ coactivator-1α expression in skeletal muscle.

KEY POINTS: In skeletal muscle, physical exercise and thyroid hormone mediate the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1a) expression that is crucial to skeletal muscle mitochondrial function. The expression of type 2 deiodinase (D2), which activates thyroid hormone in skeletal muscle is upregulated by acute treadmill exercise through a ß-adrenergic receptor-dependent mechanism. Pharmacological block of D2 or disruption of the Dio2 gene in skeletal muscle fibres impaired acute exercise-induced PGC-1a expression. Dio2 disruption also impaired muscle PGC-1a expression and mitochondrial citrate synthase activity in chronically exercised mice. ABSTRACT: Thyroid hormone promotes expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1a), which mediates mitochondrial biogenesis and oxidative capacity in skeletal muscle (SKM). Skeletal myocytes express the type 2 deiodinase (D2), which generates 3,5,3'-triiodothyronine (T3 ), the active thyroid hormone. To test whether D2-generated T3 plays a role in exercise-induced PGC-1a expression, male rats and mice with SKM-specific Dio2 inactivation (SKM-D2KO or MYF5-D2KO) were studied. An acute treadmill exercise session (20 min at 70-75% of maximal aerobic capacity) increased D2 expression/activity (1.5- to 2.7-fold) as well as PGC-1a mRNA levels (1.5- to 5-fold) in rat soleus muscle and white gastrocnemius muscle and in mouse soleus muscle, which was prevented by pretreatment with 1 mg (100 g body weight)(-1) propranolol or 6 mg (100 g body weight)(-1) iopanoic acid (5.9- vs. 2.8-fold; P < 0.05), which blocks D2 activity . In the SKM-D2KO mice, acute treadmill exercise failed to induce PGC-1a fully in soleus muscle (1.9- vs. 2.8-fold; P < 0.05), and in primary SKM-D2KO myocytes there was only a limited PGC-1a response to 1 µm forskolin (2.2- vs. 1.3-fold; P < 0.05). Chronic exercise training (6 weeks) increased soleus muscle PGC-1a mRNA levels (∼25%) and the mitochondrial enzyme citrate synthase (∼20%). In contrast, PGC-1a expression did not change and citrate synthase decreased by ∼30% in SKM-D2KO mice. The soleus muscle PGC-1a response to chronic exercise was also blunted in MYF5-D2KO mice. In conclusion, acute treadmill exercise increases SKM D2 expression through a ß-adrenergic receptor-dependent mechanism. The accelerated conversion of T4 to T3 within myocytes mediates part of the PGC-1a induction by treadmill exercise and its downstream effects on mitochondrial function.

Does low serum TSH within the normal range have negative impact on physical exercise capacity and quality of life of healthy elderly people?

Objective Investigate the differences in cardiopulmonary (CP) capacity and Quality of Life (QOL) between healthy elderly (≥ 65 years) with different TSH levels (< 1.0 and ≥ 1.0 μIU/mL) both within the normal range. Also, evaluate the effects of TSH elevation on CP test and QOL, by administering methimazole to subjects with initial lower-normal TSH, in order to elevate it to superior-normal limit. Materials and methods Initially, a cross-sectional study was performed to compare CP capacity at peak exercise and QOL (using WHOQOL-OLD questionnaire) between healthy seniors (age ≥ 65 years) with TSH < 1.0 μIU/mL vs. TSH ≥1.0 μIU/mL. In the second phase, participants with TSH < 1.0 μIU/mL were included in a non-controlled-prospective-interventional study to investigate the effect of TSH elevation, using methimazole, on QOL and CP capacity at peak exercise. Results From 89 elderly evaluated, 75 had TSH ≥ 1 μIU/mL and 14 TSH < 1 μIU/mL. The two groups had similar basal clinical characteristics. No difference in WHOQOL-OLD scores was observed between groups and they did not differ in terms of CP function at peak exercise. QOL and CP variables were not correlated with TSH levels. Twelve of 14 participants with TSH < 1.0 μIU/mL entered in the prospective study. After one year, no significant differences in clinical caracteristics, QOL, and CP variables were detected in paired analysis before and after methimazole intervention. Conclusions We found no differences in CP capacity and QOL between health elderly with different TSH levels within normal range and no impact after one year of methimazole treatment. More prospective-controlled-randomized studies are necessary to confirm or not the possible harm effect in normal low TSH.

Does low serum TSH within the normal range have negative impact on physical exercise capacity and quality of life of healthy elderly people?

OBJECTIVE: Investigate the differences in cardiopulmonary (CP) capacity and Quality of Life (QOL) between healthy elderly (≥ 65 years) with different TSH levels (< 1.0 and ≥ 1.0 µIU/mL) both within the normal range. Also, evaluate the effects of TSH elevation on CP test and QOL, by administering methimazole to subjects with initial lower-normal TSH, in order to elevate it to superior-normal limit. MATERIALS AND METHODS: Initially, a cross-sectional study was performed to compare CP capacity at peak exercise and QOL (using WHOQOL-OLD questionnaire) between healthy seniors (age ≥ 65 years) with TSH < 1.0 µIU/mL vs. TSH ≥1.0 µIU/mL. In the second phase, participants with TSH < 1.0 µIU/mL were included in a non-controlled-prospective-interventional study to investigate the effect of TSH elevation, using methimazole, on QOL and CP capacity at peak exercise. RESULTS: From 89 elderly evaluated, 75 had TSH ≥ 1 µIU/mL and 14 TSH < 1 µIU/mL. The two groups had similar basal clinical characteristics. No difference in WHOQOL-OLD scores was observed between groups and they did not differ in terms of CP function at peak exercise. QOL and CP variables were not correlated with TSH levels. Twelve of 14 participants with TSH < 1.0 µIU/mL entered in the prospective study. After one year, no significant differences in clinical caracteristics, QOL, and CP variables were detected in paired analysis before and after methimazole intervention. CONCLUSIONS: We found no differences in CP capacity and QOL between health elderly with different TSH levels within normal range and no impact after one year of methimazole treatment. More prospective-controlled-randomized studies are necessary to confirm or not the possible harm effect in normal low TSH.

Thyroid hormone and estrogen regulate exercise-induced growth hormone release.

Growth hormone (GH) regulates whole body metabolism, and physical exercise is the most potent stimulus to induce its secretion in humans. The mechanisms underlying GH secretion after exercise remain to be defined. The aim of this study was to elucidate the role of estrogen and pituitary type 1 deiodinase (D1) activation on exercise-induced GH secretion. Ten days after bilateral ovariectomy, animals were submitted to 20 min of treadmill exercise at 75% of maximum aerobic capacity and tissues were harvested immediately or 30 min after exercise. Non-exercised animals were used as controls. A significant increase in D1 activity occurred immediately after exercise (~60%) in sham-operated animals and GH was higher (~6-fold) 30 min after exercise. Estrogen deficient rats exhibited basal levels of GH and D1 activity comparable to those found in control rats. However, after exercise both D1 activity and serum GH levels were blunted compared to sedentary rats. To understand the potential cause-effect of D1 activation in exercise-induced GH release, we pharmacologically blocked D1 activity by propylthiouracil (PTU) injection into intact rats and submitted them to the acute exercise session. D1 inhibition blocked exercise-induced GH secretion, although basal levels were unaltered. In conclusion, estrogen deficiency impairs the induction of thyroid hormone activating enzyme D1 in the pituitary, and GH release by acute exercise. Also, acute D1 activation is essential for exercise-induced GH response.

Potential risks of glucagon stimulation test in elderly people.

UNLABELLED: The glucagon stimulation test (GST) is a reliable measure for assessing growth hormone (GH) and adrenocorticotropic hormone (ACTH) secretion. The GST is considered to be a safe test, with few mild side effects, especially in adults and in the elderly in whom underlying co-morbidities may be present. OBJECTIVE: To describe the side effects of the GST in elderly people. DESIGN AND SETTING: The study was performed with patients of the geriatric ambulatory of our hospital who were recruited to voluntarily participate in a research study concerning the GH and ACTH axis in the elderly people. Forty-two subjects (n=5 males and 37 females) aged 67-88 years, without hypothalamic-pituitary disease, were submitted to the GST. The GST was performed by intramuscular injection of 1mg of glucagon. Blood samples were collected at baseline, and 90, 120, 150, and 180 min after glucagon injection for GH and cortisol measurements. RESULTS: During the test, 9 subjects (21.4%) had side effects, which included: nausea (14.2%), indisposition (11.9%), hypotension (9.5%), vomiting (7.1%), sweating (4.7%), and dizziness (2.3%). There were four cases of severe symptomatic hypotension, with inaudible blood pressure in two cases. In one case of severe hypotension, the subject suffered two episodes of generalized tonic seizures. Patients who had side effects at GST had statistically higher peak of cortisol (28.9 ± 6.67 µg/dL) and a statistical trend to higher GH peak (8.74 ± 5.96 µg/L). In the group of patients who did not have side effects, the mean cortisol and GH peak were 19.05 ± 5.36 µg/dL and 5.32 ± 3.52 µg/L, respectively. CONCLUSION: Although the GST is a reliable alternative test to the ITT, it should be cautiously used in the elderly because this population may have co-morbidities including vascular and cardiac diseases that could be potentiated with side effects of the test, such as severe hypotension.