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1.
J Endocrinol Invest ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913250

RESUMO

PURPOSE: Evidence-based guidelines for the management of polycystic ovary syndrome (PCOS) recommend clinical laboratories use liquid chromatography-tandem mass spectrometry (LC-MS/MS) for diagnosing biochemical hyperandrogenism. However, automated immunoassays are still mostly used in routine laboratories worldwide. Another hurdle for PCOS phenotyping in the clinical setting is ultrasound assessment of polycystic ovarian morphology. We address the impact of using state-of-the-art (LC-MS/MS) and of an anti-müllerian hormone (AMH) assay on the diagnosis of PCOS in routine practice. METHODS: In a cross-sectional study, we included 359 premenopausal women consecutively evaluated because of symptoms of functional androgen excess or hyperandrogenemia, and finally diagnosed with PCOS. Patients were submitted to routine phenotyping based on serum androgen measurements by immunoassays and an ovarian ultrasound when necessary. Samples of all patients were also assayed by LC-MS/MS for hyperandrogenemia and for circulating AMH. RESULTS: The observed agreement between immunoassays and LC-MS/MS in identifying hyperandrogenemia was poor [78.0%; k(95%CI): 0.366 (0.283;0.449)]. The observed agreement between ultrasound and increased AMH was 27.3% [(95%CI): 0.060 (0.005; 0.115)]. Using LC-MS/MS changed PCOS phenotypes in 60(15.8%) patients. Fifty-two (18.3%) individuals with hyperandrogenemia by routine immunoassays no longer presented with androgen excess by LC-MS/MS. Overall diagnostic agreement between routine assessment using immunoassays and ultrasound and that derived from LC-MS/MS and the addition of AMH to US was moderate [weighted κ (linear weights): 0.512 (0.416;0.608)]. CONCLUSIONS: Immunoassays used in routine practice are unacceptably inaccurate for phenotyping women with PCOS. Our data cast some doubts upon the interchangeability of serum AMH and ultrasound examination for the diagnosis of PCOS.

2.
J Dairy Sci ; 107(2): 1175-1196, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37730180

RESUMO

Recent studies indicate that heat stress pathophysiology is associated with intestinal barrier dysfunction, local and systemic inflammation, and gut dysbiosis. However, inconclusive results and a poor description of tissue-specific changes must be addressed to identify potential intervention targets against heat stress illness in growing calves. Therefore, the objective of this study was to evaluate components of the intestinal barrier, pro- and anti-inflammatory signals, and microbiota community composition in Holstein bull calves exposed to heat stress. Animals (mean age = 12 wk old; mean body weight = 122 kg) penned individually in temperature-controlled rooms were assigned to (1) thermoneutral conditions (constant room temperature at 19.5°C) and restricted offer of feed (TNR, n = 8), or (2) heat stress conditions (cycles of room temperatures ranging from 20 to 37.8°C) along with ad libitum offer of feed (HS, n = 8) for 7 d. Upon treatment completion, sections of the jejunum, ileum, and colon were collected and snap-frozen immediately to evaluate gene and protein expression, cytokine concentrations, and myeloperoxidase activity. Digesta aliquots of the ileum, colon, and rectum were collected to assess bacterial communities. Plasma was harvested on d 2, 5, and 7 to determine cytokine concentrations. Overall, results showed a section-specific effect of HS on intestinal integrity. Jejunal mRNA expression of TJP1 was decreased by 70.9% in HS relative to TNR calves. In agreement, jejunal expression of heat shock transcription factor-1 protein, a known tight junction protein expression regulator, decreased by 48% in HS calves. Jejunal analyses showed that HS decreased concentrations of IL-1α by 36.6% and tended to decrease the concentration of IL-17A. Conversely, HS elicited a 3.5-fold increase in jejunal concentration of anti-inflammatory IL-36 receptor antagonist. Plasma analysis of pro-inflammatory cytokines showed that IL-6 decreased by 51% in HS relative to TNR calves. Heat stress alteration of the large intestine bacterial communities was characterized by increased genus Butyrivibrio_3, a known butyrate-producing organism, and changes in bacteria metabolism of energy and AA. A strong positive correlation between the rectal temperature and pro-inflammatory Eggerthii spp. was detected in HS calves. In conclusion, this work indicates that HS impairs the intestinal barrier function of jejunum. The pro- and anti-inflammatory signal changes may be part of a broader response to restore intestinal homeostasis in jejunum. The changes in large intestine bacterial communities favoring butyrate-producing organisms (e.g., Butyrivibrio spp.) may be part of a successful response to maintain the integrity of the colonic mucosa of HS calves. The alteration of intestinal homeostasis should be the target for heat stress therapies to restore biological functions, and, thus highlights the relevance of this work.


Assuntos
Dieta , Resposta ao Choque Térmico , Animais , Bovinos , Masculino , Dieta/veterinária , Citocinas , Butiratos , Anti-Inflamatórios
3.
Vaccine ; 41(22): 3436-3445, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37120401

RESUMO

BACKGROUND: Procedural anxiety was anticipated in children 5-11 years during the COVID-19 vaccine rollout in Victoria, Australia, as children in this age group receive few routine vaccines. Therefore, the Victorian state government designed a tailored, child-friendly vaccine program. This study aimed to assess parental satisfaction with elements of the bespoke vaccination pathway. METHODS: The Victorian government and state-run vaccination hubs in Victoria facilitated an online immunisation plan to help parents identify their child's support needs, and utilised experienced paediatric staff and additional supports for children with severe needle distress and/or disability. All parents/guardians of children 5-11 years who received a COVID-19 vaccine in a vaccination hub were sent a 16-item feedback survey via text message. RESULTS: Between 9 February and 31 May 2022 there were 9203 responses; 865 children (9.4%) had a first language other than English, 499 (5.4%) had a disability or special needs, and 142 (1.5%) were Aboriginal or Torres Strait Islander. Most parents (94.4%; 8687/9203) rated their satisfaction with the program as very good or excellent. The immunisation plan was used by 13.5% (1244/9203) of respondents, with usage more common for Aboriginal or Torres Strait Islander children (26.1%; 23/88) or families with a first language other than English (23.5%; 42/179). The child-friendly staff (88.5%, 255/288) and themed environment (66.3%, 191/288) were the most valued measures for vaccination. Additional support measures were required by 1.6% (150/9203) of children in the general population and 7.9%, (17/261) of children with a disability and/or special needs. CONCLUSION: A tailored COVID-19 vaccination program for children 5-11 years, with additional support for children with severe needle distress and/or disability, had high parental satisfaction. This model could be utilised for COVID-19 vaccination in pre-school children and for routine childhood vaccination programs to provide optimal support to children and their families.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Criança , Pré-Escolar , Vitória/epidemiologia , Povos Aborígenes Australianos e Ilhéus do Estreito de Torres , COVID-19/prevenção & controle , Vacinação
4.
Calcif Tissue Int ; 112(1): 24-33, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36180602

RESUMO

Vertebral fractures (VF) are common in older men but data on VF prevalence in young men is limited. The aim of this study was to describe the prevalence of VF and non-fracture vertebral deformities (VD) in healthy young to middle-aged men, and compare the characteristics of men with normal vertebrae, VF and VD. In this cross-sectional study, vertebral fracture assessment by dual-energy X-ray absorptiometry was performed in 650 men, aged 32 to 60 years (mean 46.2), from the population-based SIBLOS-SIBEX cohort. For VF and VD assessment, both the modified algorithm-based qualitative approach (morphologic criteria) to discriminate VF from VD and the semi-quantitative (morphometric) grading system of Genant (GSQ) were used. We found 48 (0.6%) fractured vertebrae, of which 15 were classified grade 1, 29 grade 2 and 4 grade 3 VF. There were 378 (4.7%) VD, of which 296 were scored grade 1, 82 grade 2 and none grade 3 VD. Twenty-six participants (4%) had VF, 15 had one and 11 had 2 or more VF. Two hundred and twenty-eight (35.1%) men had VD. Femoral neck, total hip and lumbar spine areal bone mineral density (aBMD) were lower in men with VF than in those with normal vertebrae or VD. Men with VD, in turn, had aBMD values similar to men with normal vertebrae. Our results suggest that -even in young healthy men-using the GSQ without taking qualitative aspects into account overestimates VF prevalence, confirming the importance of morphologic criteria to correctly diagnose and distinguish VF from VD.


Assuntos
Fraturas da Coluna Vertebral , Coluna Vertebral , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Absorciometria de Fóton/métodos , Densidade Óssea , Estudos Transversais , Prevalência , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Coluna Vertebral/anormalidades , Coluna Vertebral/diagnóstico por imagem
5.
Vaccine X ; 12: 100240, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36438015

RESUMO

Objective: Women of childbearing age, including pregnant and breastfeeding women, report higher COVID-19 vaccine hesitancy, but reasons for this hesitancy are unknown. We explored factors influencing vaccine decision-making among women of childbearing age in Victoria, Australia to inform strategies to increase COVID-19 vaccine uptake. Methods: Twenty-four women aged 18-40 years were interviewed July-October 2021. Interview data were analyzed thematically using an inductive, constructivist approach. Results: Of 24 participants, 14 (57%) were vaccine-hesitant, of whom 10/14 pregnant or breastfeeding. Six key themes were identified: weighing up perceived risks for self and baby; availability of information; change and contradictions; vaccination above everything; practical issues - hurdles of inconvenience. Vaccine-hesitant women's concerns included safety in pregnancy, breastfeeding and fertility effects. Some participants expressed a loss of trust in healthcare providers following vaccine mandates. Conclusions: Public health campaigns and communication should be tailored to address specific concerns to increase COVID-19 vaccine uptake and prevent negative COVID-19 outcomes for women of childbearing age. Findings suggest that effective strategies to address hesitancy in this group may include providing robust short- and long-term safety data across fertility, birth outcomes and child development following COVID-19 vaccination. Other supportive strategies may include systemic changes like making childcare available at vaccination points (where practical), and using data linkage infrastructure to track post-vaccination outcomes.

6.
Sci Rep ; 12(1): 12655, 2022 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-35953699

RESUMO

Birds living in developed areas contend with numerous stressors, including human disturbance and light, noise, and air pollution. COVID-19 pandemic lockdowns presented a unique opportunity to disentangle these effects during a period of reduced human activity. We launched a community science project in spring 2020 to explore drivers of site use by and detection of common birds in cities under lockdown in the U.S. Pacific Northwest. Our goals were twofold: (1) consider how intensity of urbanization, canopy cover, and availability of bird feeders and bird baths influenced avian habitat use; and (2) quantify how daily changes in weather, air pollution, and human mobility influenced detection of birds. We analyzed 6,640 surveys from 367 volunteers at 429 monitoring sites using occupancy models for 46 study species. Neither land cover nor canopy cover influenced site use by 50% of study species, suggesting that backyard birds may have used a wider range of habitats during lockdowns. Human mobility affected detection of 76% of study species, suggesting that birds exhibited species-specific behavioral responses to day-to-day changes in human activity beginning shortly after initial lockdown restrictions were implemented. Our study also showcases how existing community science platforms can be leveraged to support local monitoring efforts.


Assuntos
Biodiversidade , COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis , Ecossistema , Humanos , Pandemias
7.
Sci Rep ; 12(1): 1587, 2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35091685

RESUMO

Increased ambient temperature causes heat stress in mammals, which affects physiological and molecular functions. We have recently reported that the dietary administration of a postbiotic from Aspergillus oryzae (AO) improves tolerance to heat stress in fruit flies and cattle. Furthermore, heat-induced gut dysfunction and systemic inflammation have been ameliorated in part by nutritional interventions. The objective of this study was to characterize the phenotypic response of growing calves to heat stress compared to thermoneutral ad libitum fed and thermoneutral feed-restricted counterparts and examining the physiologic alterations associated with the administration of the AO postbiotic to heat-stressed calves with emphasis on intestinal permeability. In this report, we expand previous work by first demonstrating that heat stress reduced partial energetic efficiency of growth in control (45%) but not in AO-fed calves (62%) compared to thermoneutral animals (66%). While heat stress increased 20% the permeability of the intestine, AO postbiotic and thermoneutral treatments did not affect this variable. In addition, AO postbiotic reduced fecal water content relative to thermoneutral and heat stress treatments. Heat stress increased plasma concentrations of serum amyloid A, haptoglobin and lipocalin-2, and administration of AO postbiotic did not ameliorate this effect. In summary, our findings indicated that heat stress led to reduced nutrient-use efficiency and increased systemic inflammation. Results suggest that the AO postbiotic improved energy-use efficiency, water absorption, and the intestinal permeability in heat stress-mediated increase in gut permeability but did not reduce heat stress-mediated rise in markers of systemic inflammation.


Assuntos
Aspergillus oryzae
9.
Sci Rep ; 11(1): 6407, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33742039

RESUMO

Heat stress is detrimental to food-producing animals and animal productivity remains suboptimal despite the use of heat abatement strategies during summer. Global warming and the increase of frequency and intensity of heatwaves are likely to continue and, thus, exacerbate the problem of heat stress. Heat stress leads to the impairment of physiological and cellular functions of ectothermic and endothermic animals. Therefore, it is critical to conceive ways of protecting animals against the pathological effects of heat stress. In experiments with endothermic animals highly sensitive to heat (Bos taurus), we have previously reported that heat-induced systemic inflammation can be ameliorated in part by nutritional interventions. The experiments conducted in this report described molecular and physiological adaptations to heat stress using Drosophila melanogaster and dairy cow models. In this report, we expand previous work by first demonstrating that the addition of a postbiotic from Aspergillus oryzae (AO) into the culture medium of ectothermic animals (Drosophila melanogaster) improved survival to heat stress from 30 to 58%. This response was associated with downregulation of genes involved in the modulation of oxidative stress and immunity, most notably metallothionein B, C, and D. In line with these results, we subsequently showed that the supplementation with the AO postbiotic to lactating dairy cows experiencing heat stress decreased plasma concentrations of serum amyloid A and lipopolysaccharide-binding protein, and the expression of interleukin-6 in white blood cells. These alterations were paralleled by increased synthesis of energy-corrected milk and milk components, suggesting enhanced nutrient partitioning to lactogenesis and increased metabolic efficiency. In summary, this work provides evidence that a postbiotic from AO enhances thermal tolerance likely through a mechanism that entails reduced inflammation.


Assuntos
Aspergillus oryzae/metabolismo , Produtos Biológicos/administração & dosagem , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Polissacarídeos Fúngicos/administração & dosagem , Transtornos de Estresse por Calor/dietoterapia , Transtornos de Estresse por Calor/veterinária , Resposta ao Choque Térmico/efeitos dos fármacos , Termotolerância/efeitos dos fármacos , Animais , Bovinos , Dieta/veterinária , Suplementos Nutricionais , Feminino , Expressão Gênica/efeitos dos fármacos , Temperatura Alta , Inflamação/dietoterapia , Inflamação/veterinária , Lactação/efeitos dos fármacos , Leite/química , Leite/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética
11.
Osteoporos Int ; 31(12): 2271-2286, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32642851

RESUMO

We provide an evidence base and guidance for the use of menopausal hormone therapy (MHT) for the maintenance of skeletal health and prevention of future fractures in recently menopausal women. Despite controversy over associated side effects, which has limited its use in recent decades, the potential role for MHT soon after menopause in the management of postmenopausal osteoporosis is increasingly recognized. We present a narrative review of the benefits versus risks of using MHT in the management of postmenopausal osteoporosis. Current literature suggests robust anti-fracture efficacy of MHT in patients unselected for low BMD, regardless of concomitant use with progestogens, but with limited evidence of persisting skeletal benefits following cessation of therapy. Side effects include cardiovascular events, thromboembolic disease, stroke and breast cancer, but the benefit-risk profile differs according to the use of opposed versus unopposed oestrogens, type of oestrogen/progestogen, dose and route of delivery and, for cardiovascular events, timing of MHT use. Overall, the benefit-risk profile supports MHT treatment in women who have recently (< 10 years) become menopausal, who have menopausal symptoms and who are less than 60 years old, with a low baseline risk for adverse events. MHT should be considered as an option for the maintenance of skeletal health in women, specifically as an additional benefit in the context of treatment of menopausal symptoms, when commenced at the menopause, or shortly thereafter, in the context of a personalized benefit-risk evaluation.


Assuntos
Terapia de Reposição de Estrogênios , Osteoporose Pós-Menopausa , Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios , Feminino , Terapia de Reposição Hormonal , Humanos , Menopausa , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico
12.
Drugs ; 80(15): 1537-1552, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32725307

RESUMO

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital.


Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Osteoporose/tratamento farmacológico , Placa Aterosclerótica/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Tromboembolia Venosa/epidemiologia , Conservadores da Densidade Óssea/administração & dosagem , Cálcio/administração & dosagem , Cálcio/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Difosfonatos/administração & dosagem , Difosfonatos/efeitos adversos , Terapia de Reposição Hormonal/efeitos adversos , Terapia de Reposição Hormonal/métodos , Humanos , Incidência , Menopausa/efeitos dos fármacos , Osteoporose/epidemiologia , Osteoporose/etiologia , Placa Aterosclerótica/induzido quimicamente , Placa Aterosclerótica/prevenção & controle , Vigilância de Produtos Comercializados , Medição de Risco/estatística & dados numéricos , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/prevenção & controle , Vitamina D/administração & dosagem , Vitamina D/efeitos adversos
13.
Maturitas ; 138: 14-25, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32631584

RESUMO

This narrative review discusses several aspects of the management of osteoporosis in patients under 50 years of age. Peak bone mass is genetically determined but can also be affected by lifestyle factors. Puberty constitutes a vulnerable period. Idiopathic osteoporosis is a rare, heterogeneous condition in young adults due in part to decreased osteoblast function and deficient bone acquisition. There are no evidence-based treatment recommendations. Drugs use can be proposed to elderly patients at very high risk. Diagnosis and management of osteoporosis in the young can be challenging, in particular in the absence of a manifest secondary cause. Young adults with low bone mineral density (BMD) do not necessarily have osteoporosis and it is important to avoid unnecessary treatment. A determination of BMD is recommended for premenopausal women who have had a fragility fracture or who have secondary causes of osteoporosis: secondary causes of excessive bone loss need to be excluded and treatment should be targeted. Adequate calcium, vitamin D, and a healthy lifestyle should be recommended. In the absence of fractures, conservative management is generally sufficient, but in rare cases, such as chemotherapy-induced osteoporosis, antiresorptive medication can be used. Osteoporosis in young men is most often of secondary origin and hypogonadism is a major cause; testosterone replacement therapy will improve BMD in these patients. Diabetes is characterized by major alterations in bone quality, implying that medical therapy should be started sooner than for other causes of osteoporosis. Primary hyperparathyroidism, hyperthyroidism, Cushing's syndrome and growth hormone deficiency or excess affect cortical bone more often than trabecular bone.


Assuntos
Osteoporose/tratamento farmacológico , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Fraturas Ósseas/etiologia , Humanos , Osteoporose/complicações , Osteoporose/diagnóstico , Pré-Menopausa
14.
Community Dent Health ; 37(1): 96-101, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32031348

RESUMO

OBJECTIVE: Laprise et al. (2019) observed a positive association between oral sex practices and oropharyngeal cancers (OPC) among HPV-negative individuals. Because oral HPV infections are likely to be transmitted through oral sex, these results are counterintuitive. We revisit Laprise et. al's analysis with the objective of estimating the impact of misclassification of HPV infection on the association between oral sex practices and OPC. METHODS: Data were drawn from the Head and Neck Cancer (HeNCe) Life study, a hospital-based case control study of head and neck cancer with frequency-matched controls by age and sex from 4 major referral hospitals in Montreal, Canada. We included only OPC cases (n = 188) and controls (n = 429) and used predictive value weighting, under differential and non-differential scenarios, to evaluate the misclassification. Subsequently, we used logistic regression and 95% confidence intervals to estimate the association between oral sex practice and OPC among HPV-negative individuals. RESULTS: Our results showed that the previously reported association between oral sex practices and OPC among HPV-negative individuals was attenuated or nullified both under differential and non-differential scenarios. CONCLUSION: The association between oral sex practice and OPC could be explained by biases in the data (e.g., HPV mediator misclassification). Our results highlight the need for widespread adoption of Quantitative Bias Analysis in oral health research.


Assuntos
Neoplasias Orofaríngeas , Papillomaviridae , Infecções por Papillomavirus , Viés , Canadá , Estudos de Casos e Controles , Humanos
15.
Osteoporos Int ; 30(11): 2155-2165, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31388696

RESUMO

Many patients at increased risk of fractures do not take their medication appropriately, resulting in a substantial decrease in the benefits of drug therapy. Improving medication adherence is urgently needed but remains laborious, given the numerous and multidimensional reasons for non-adherence, suggesting the need for measurement-guided, multifactorial and individualized solutions. INTRODUCTION: Poor adherence to medications is a major challenge in the treatment of osteoporosis. This paper aimed to provide an overview of the consequences, determinants and potential solutions to poor adherence and persistence to osteoporosis medication. METHODS: A working group was organized by the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) to review consequences, determinants and potential solutions to adherence and to make recommendations for practice and further research. A systematic literature review and a face-to-face experts meeting were undertaken. RESULTS: Medication non-adherence is associated with increased risk of fractures, leading to a substantial decrease in the clinical and economic benefits of drug therapy. Reasons for non-adherence are numerous and multidimensional for each patient, depending on the interplay of multiple factors, suggesting the need for multifactorial and individualized solutions. Few interventions have been shown to improve adherence or persistence to osteoporosis treatment. Promising actions include patient education with counselling, adherence monitoring with feedback and dose simplification including flexible dosing regimen. Recommendations for practice and further research were also provided. To adequately manage adherence, it is important to (1) understand the problem (initiation, implementation and/or persistence), (2) to measure adherence and (3) to identify the reason of non-adherence and fix it. CONCLUSION: These recommendations are intended for clinicians to manage adherence of their patients and to researchers and policy makers to design, facilitate and appropriately use adherence interventions.


Assuntos
Adesão à Medicação , Osteoporose/tratamento farmacológico , Consenso , Europa (Continente) , Fraturas Ósseas/etiologia , Processos Grupais , Humanos , Doenças Musculoesqueléticas , Osteoartrite/tratamento farmacológico , Osteoporose/complicações , Educação de Pacientes como Assunto , Guias de Prática Clínica como Assunto , Fatores de Risco , Sociedades Médicas
16.
Phys Rev Lett ; 121(22): 221301, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30547645

RESUMO

We present results from an analysis of all data taken by the bicep2/Keck CMB polarization experiments up to and including the 2015 observing season. This includes the first Keck Array observations at 220 GHz and additional observations at 95 and 150 GHz. The Q and U maps reach depths of 5.2, 2.9, and 26 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈400 square degrees. The 220 GHz maps achieve a signal to noise on polarized dust emission approximately equal to that of Planck at 353 GHz. We take auto and cross spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz. We evaluate the joint likelihood of the spectra versus a multicomponent model of lensed-ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and we impose priors on some of these using external information from Planck and WMAP derived from larger regions of sky. The model is shown to be an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.07 at 95% confidence, which tightens to r_{0.05}<0.06 in conjunction with Planck temperature measurements and other data. The lensing signal is detected at 8.8σ significance. Running a maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.020. These are the strongest constraints to date on primordial gravitational waves.

17.
J Dairy Sci ; 101(8): 7480-7486, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29729916

RESUMO

Hyperthermia alters utilization of AA in protein synthesis and cell-signaling activity in bovine mammary cells. Essential AA and insulin regulate translation of proteins by controlling the activity of mammalian target of rapamycin (mTOR) signaling pathway. The objectives of this study were to evaluate (1) the effects of incubation temperature on the mTOR signaling pathway and transcription of AA transporters in a bovine mammary alveolar cell line (MAC-T) and (2) the combined effects of incubation temperature and insulin on the mTOR signaling pathway in this cell line. Cells were cultured in medium with 10% fetal bovine serum at 37°C and 5% CO2. In experiment 1, cells were subjected to 37°C (control) or 41.5°C (high incubation temperature; HT) for 12 h. In experiment 2, cells were assigned to 1 of 4 treatments as a 2 × 2 factorial arrangement, including 2 cell culture temperatures (control and HT) and absence or presence of 1.0 µg/mL of insulin. Proteins were harvested and separated by gel electrophoresis. In experiment 1, gene expression of AA transporters (SLC1A1, SLC1A5, SLC3A2, SLC7A1, SLC7A5, and SLC36A1) were evaluated, and changes of ≥2 fold were deemed significantly different. In experiments 1 and 2, immunoblotting was used to identify total and site-specific phosphorylated forms of protein kinase B (Akt1; Ser473), p70 S6 kinase (S6K1; Thr389), ribosomal protein S6 (rpS6; Ser235/236), and eukaryotic elongation factor 2 (eEF2; Thr56). Phosphorylated and total forms of Akt1, S6K1, rpS6, and eEF2 were quantified and expressed as the ratio of phosphorylated to total protein. In experiment 1, HT resulted in a ≥2-fold increase expression of SLC1A1 and SLC3A2. High incubation temperature reduced the phosphorylated to total ratio of Akt1 and rpS6 and increased the phosphorylated to total ratio of eEF2. In experiment 2, we found no temperature by insulin interactions on phosphorylation state of the protein factors of interest. High incubation temperature reduced the phosphorylated to total ratio of Akt1. The addition of insulin increased the phosphorylated to total ratio of Akt1, S6K1, and rpS6. In summary, HT reduced the activity of the mTOR signaling pathway and increased the expression of AA transporters. High incubation temperature possibly reduced protein translation by reducing the mTOR signaling pathway activity in an effort to adapt to thermal stress. These results may help explain the direct effect of elevated temperature on AA metabolism and protein translation in heat-stressed animals.


Assuntos
Células Epiteliais/metabolismo , Glândulas Mamárias Animais/citologia , Sirolimo/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Bovinos , Feminino , Fosforilação , Temperatura
18.
J Dairy Sci ; 101(7): 6424-6429, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29605321

RESUMO

The objective of this study was to evaluate relationships between measurements of temperature-humidity index (THI) and rectal, vaginal, and udder surface temperatures in lactating cows exposed to heat stress (HS). In experiment 1, 12 multiparous and 8 primiparous Holstein cows experienced a THI ranging from 69 to 76 at 2000 to 1000 h and THI from 74 to 82 at 1000 to 2000 h (peaked at 82 from 1400 to 1800 h). Cows were exposed to HS 10 h daily for 21 d. Measurements of rectal temperature (RT) and udder surface temperature were collected at 1000 and 1500 h (±30 min). Vaginal temperature was monitored every 10 min using digital loggers, averaged over 1 h, and paired with corresponding rectal and udder surface temperature data. In experiment 2, 12 multiparous Holstein cows experienced a THI ranging from 60 to 76 at 2000 to 1000 h and THI from 69 to 83 at 1000 to 2000 h (peaked at 83 from 1600 and 1900 h), eliciting 10 h/d of HS for 7 d. Rectal and udder surface temperatures were analyzed at 0700 and 1500 h (±30 min). Vaginal temperature was recorded and analyzed as indicated in experiment 1. Afternoon THI showed weak correlations with surface temperature (r = 0.19, n = 420 in experiment 1; r = 0.23, n = 84 in experiment 2), weak to moderate correlations with RT (r = 0.34, n = 366 in experiment 1; r = 0.26, n = 84 in experiment 2), and moderate correlations with vaginal temperature (r = 0.34, n = 175 in experiment 1; r = 0.35, n = 40 in experiment 2). Moreover, vaginal temperature increased 0.10 and 0.22°C per unit of THI (R2 = 0.15 in experiment 1; R2 = 0.40 in experiment 2). Afternoon vaginal temperature strongly correlated with RT (r = 0.69, n = 131 in experiment 1; r = 0.63, n = 37 in experiment 2) and explained 57 (experiment 1) and 68% (experiment 2) of variation in RT. Surface temperature showed moderate to strong correlations with RT (r = 0.57, n = 84) and vaginal temperature (r = 0.74, n = 37) in experiment 2. In conclusion, THI showed a weak to moderate relationship with core body temperatures and explained the increase in rectal and vaginal temperatures experienced by HS cows. Compared with rectal temperature, vaginal temperature showed stronger relationships with THI and can be used to determine thermal load. Udder surface temperature showed a moderate to strong relationship with core body temperature, and this relationship may support the use of surface temperature data to manage thermal load in HS cows.


Assuntos
Temperatura Corporal/fisiologia , Bovinos , Temperatura Alta/efeitos adversos , Estresse Fisiológico , Animais , Feminino , Umidade , Lactação , Glândulas Mamárias Animais , Temperatura
20.
Clin Nutr ; 37(4): 1121-1132, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-28927897

RESUMO

There is a growing body of evidence that links nutrition to muscle mass, strength and function in older adults, suggesting that it has an important role to play both in the prevention and management of sarcopenia. This review summarises the discussions of a working group [ESCEO working group meeting 8th September 2016] that met to review current evidence and to consider its implications for preventive and treatment strategies. The review points to the importance of 'healthier' dietary patterns that are adequate in quality in older age, to ensure sufficient intakes of protein, vitamin D, antioxidant nutrients and long-chain polyunsaturated fatty acids. In particular, there is substantial evidence to support the roles of dietary protein and physical activity as key anabolic stimuli for muscle protein synthesis. However, much of the evidence is observational and from high-income countries. Further high-quality trials, particularly from more diverse populations, are needed to enable an understanding of dose and duration effects of individual nutrients on function, to elucidate mechanistic links, and to define optimal profiles and patterns of nutrient intake for older adults.


Assuntos
Fenômenos Fisiológicos da Nutrição/fisiologia , Sarcopenia , Adulto , Idoso , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Sarcopenia/fisiopatologia , Sarcopenia/prevenção & controle , Sarcopenia/terapia
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