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1.
Cancer Radiother ; 24(6-7): 559-566, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32753240

RESUMO

PURPOSE: Patients with synchronous metastatic head and neck squamous cell carcinomas often present associated locoregional symptoms and a risk of life-threatening primary tumour progression. Few data have been published about the use of radiation therapy in the management of newly diagnosed metastatic disease associated with advanced locoregional disease. In this article, we aim to determine the role of radiation therapy of the primary tumour in the overall therapeutic strategy for these diseases. We further address radiation therapy modalities (technique, volumes, and fractionation) in such a context. MATERIAL AND METHODS: We conducted a literature survey on locoregional radiotherapy for newly diagnosed metastatic head and neck squamous cell carcinomas. RESULTS: Several retrospective studies have reported that locoregional radiotherapy is associated with improved overall survival of patients with synchronous metastatic head and neck squamous cell carcinomas. However, data about modalities such as timing of radiotherapy in the overall strategy, dose, fractionation and delineation volumes are scarce. Two schematic situations can be distinguished with respect to prognosis and treatment adaptations: polymetastatic/bulky or oligometastatic disease. In polymetastic/bulky disease associated with poor prognosis, standard-of-care is systemic therapy, but locoregional radiotherapy can be discussed either upfront, mainly for symptomatic palliation, or as consolidation after downsizing obtained by systemic therapy. As for oligometastatic disease, with the rise in use of efficacious and well-tolerated local ablative treatments of metastases, aggressive curative-intent locoregional radiotherapy can be considered with or without systemic therapy. CONCLUSION: Because locoregional disease is a major cause of disease failure in patients with synchronous metastatic head and neck squamous cell carcinomas, aggressive locoregional radiation therapy to the primary tumour may be discussed in the initial management of the disease where systemic therapy alone may not induce sufficient primary tumour reduction. With recent technological advances in radiotherapy, the delivery of radiotherapy is safe and feasible even in metastatic setting. Clinical trials assessing radiotherapy use for metastatic head and neck squamous cell carcinomas are warranted.


Assuntos
Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Algoritmos , Humanos , Metástase Neoplásica/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
2.
Osteoporos Int ; 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32789607

RESUMO

Using decision curve analysis on 2188 women and 1324 men, we found that an osteogenomic profile constructed from 62 genetic variants improved the clinical net benefit of fracture risk prediction over and above that of clinical risk factors and BMD. INTRODUCTION: Genetic profiling is a promising tool for assessing fracture risk. This study sought to use the decision curve analysis (DCA), a novel approach to determine the impact of genetic profiling on fracture risk prediction. METHODS: The study involved 2188 women and 1324 men, aged 60 years and above, who were followed for up to 23 years. Bone mineral density (BMD) and clinical risk factors were obtained at baseline. The incidence of fracture and mortality were recorded. A weighted individual genetic risk score (GRS) was constructed from 62 BMD-associated genetic variants. Four models were considered: CRF (clinical risk factors); CRF + GRS; Garvan model (GFRC) including CRF and femoral neck BMD; and GFRC + GRS. The DCA was used to evaluate the clinical net benefit of predictive models at a range of clinically reasonable risk thresholds. RESULTS: In both women and men, the full model GFRC + GRS achieved the highest net benefits. For 10-year risk threshold > 18% for women and > 15% for men, the GRS provided net benefit above those of the CRF models. At 20% risk threshold, adding the GRS could help to avoid 1 additional treatment per 81 women or 1 per 24 men compared with the Garvan model. At lower risk thresholds, there was no significant difference between the four models. CONCLUSIONS: The addition of genetic profiling into the clinical risk factors can improve the net clinical benefit at higher risk thresholds of fracture. Although the contribution of genetic profiling was modest in the presence of BMD + CRF, it appeared to be able to replace BMD for fracture prediction.

3.
Osteoporos Int ; 31(11): 2077-2081, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32561953

RESUMO

Asia Pacific Consortium on Osteoporosis (APCO) comprises of clinical experts from across the Asia Pacific region, uniting to develop solutions to problems facing osteoporosis management and care. The vision of APCO is to reduce the burden of osteoporosis and fragility fractures in the Asia Pacific region. INTRODUCTION: The Asia Pacific (AP) region comprises 71 countries with vastly different healthcare systems. It is predicted that by 2050, more than half the world's hip fractures will occur in this region. The Asia Pacific Consortium on Osteoporosis (APCO) was set up in May 2019 with the vision of reducing the burden of osteoporosis and fragility fractures in the AP region. METHODS: APCO has so far brought together 39 clinical experts from countries and regions across the AP to develop solutions to challenges facing osteoporosis management and fracture prevention in this highly populous region of the world. APCO aims to achieve its vision by engaging with relevant stakeholders including healthcare providers, policy makers and the public. The initial APCO project is to develop and implement a Framework of pan-AP minimum clinical standards for the screening, diagnosis and management of osteoporosis. RESULTS AND CONCLUSIONS: The Framework will serve as a platform upon which new national clinical guidelines can be developed or existing guidelines be revised, in a standardised fashion. The Framework will also facilitate benchmarking for provision of quality of care. It is hoped that the principles underlying the formation and functioning of APCO can be adopted by other regions and that every health care facility and progressively every country in the world can follow our aspirational path and progress towards best practice.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32460374

RESUMO

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that severely impairs patients' quality of life. It is characterized by recurrent painful nodules, abscesses and draining sinus tracts in primarily intertriginous areas. We aimed to review the most up-to-date information regarding the epidemiology, clinical presentation, diagnostic studies, pathogenesis, comorbidities and quality of life of patients with hidradenitis suppurativa. We performed a systematic search of Medline, Embase database (from inception to September 2019) and review of bibliographies without restrictions on year or language. HS has an estimated global prevalence of 0.00033-4.1% (but most likely 0.7-1.2% in the European-US population). Patients still experience a significant diagnostic delay, up to several years. In the absence of pathognomonic tests, the diagnosis of HS is made from clinical observation and the disease narrative. Phenotypic variation renders diagnosis and severity assessment difficult. Ultrasound imaging is an emerging assessment tool for deep-seated lesions. The Hurley Staging System is still widely used in severity rating. Follicular hyperkeratosis and dilatation, follicular rupture and chronic inflammation with architectural tissue changes have been implicated in the pathogenesis of HS. HS has been associated with metabolic syndrome and other risk factors for cardiovascular disease, diabetes mellitus type II, polycystic ovarian syndrome, depression, suicide and substance use disorders. It has been linked to other immune-mediated diseases such as inflammatory bowel disease and spondyloarthropathy. Pain, pruritus, malodour, low self-esteem, sleep and sexual dysfunctions, and poor mental health are chronic symptoms or consequences of uncontrolled disease. HS is an under-diagnosed and under-treated disease with a profound negative impact on patients' quality of life. In the light of its associated comorbidities, an interdisciplinary management approach may be needed to ensure the best outcomes.

5.
J Environ Manage ; 264: 110440, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32217320

RESUMO

For decades, there has been a strong interest in mitigating greenhouse gas (GHG) emissions from wastewater treatment plants (WWTPs). Numerous models were developed to measure the emissions and propose the quantification. Existing studies looked at the relationship between GHG emissions and operational cost (OCI), which is one of the most important indicators for decision-makers. Other parameters that can influence the control strategies include the effluent quality (EQI) and total environmental impacts. Plant-wide models are reliable methods to examine the OCI, EQI and GHG emissions while Life cycle assessment (LCA) works to assess the potential environmental impacts. A combined LCA and plant-wide model proved to be a valuable tool evaluating and comparing strategies for the best performance of WWTPs. For this study involving a WWTP, the benchmark model is used while LCA is the decision tool to find the most suitable treatment strategy. LCA adds extra criteria that complement the existing criteria provided by such models. Complementing the cost/performance criteria is proposed for plant-wide models, including environmental evaluation, based on LCA, which provides an overall better assessment of WWTPs. It can capture both the dynamic effects and potential environmental impacts. This study provides an overview of the integration between plant-wide models and LCA.


Assuntos
Gases de Efeito Estufa , Águas Residuárias , Meio Ambiente , Efeito Estufa
6.
Osteoporos Int ; 30(10): 2079-2085, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31214749

RESUMO

Patients with type 2 diabetes have an increased risk of fracture despite having a higher areal bone mineral density. This meta-analysis showed that compared with controls, diabetic patients had a lower trabecular bone score (TBS) than non-diabetic individuals, suggesting that TBS can be a useful measurement for the assessment of fracture risk in diabetic patients. INTRODUCTION: The association between type 2 diabetes and trabecular bone score (TBS) has not been clear. The present study sought to answer the specific question of whether patients with type 2 diabetes have a lower TBS than those without diabetes. METHODS: Using electronic and manual search, we identified 12 studies that had examined the association between type 2 diabetes and TBS between 2013 and 2019. These studies involved 35,546 women and 4962 men aged 30 years and older. We extracted the mean and standard deviation of TBS for patients with and without diabetes. The synthesis of effect sizes was done by the random effects meta-analysis model. RESULTS: Patients with diabetes had significantly lower TBS than those without diabetes, with standardized mean difference being - 0.31 (95% CI, - 0.45 to - 0.16). The difference was greater in women (- 0.50; 95% CI, - 0.69 to - 0.32) than in men (- 0.04; 95% CI, - 0.17 to 0.10). Compared with normal individuals, those with prediabetes had significantly lower TBS (d = - 0.13; 95% CI, - 0.23 to - 0.04; P = 0.005). There was heterogeneity between the studies, with the index of inconsistency (I2) ranging from 92% (in women) to 69.5% (in men). CONCLUSION: Patients with type 2 diabetes have a lower TBS than non-diabetic individuals, suggesting that TBS can be a useful measurement for the assessment of fracture risk in diabetic patients.


Assuntos
Osso Esponjoso/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Absorciometria de Fóton , Densidade Óssea/fisiologia , Medicina Baseada em Evidências , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/fisiopatologia , Masculino , Estado Pré-Diabético/fisiopatologia , Fatores Sexuais
7.
J Dev Orig Health Dis ; 10(5): 578-586, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30898182

RESUMO

Prenatal sex steroid exposure plays an important role in determining child development. Yet, measurement of prenatal hormonal exposure has been limited by the paucity of newborn/infant data and the invasiveness of fetal hormonal sampling. Here we provide descriptive data from the MIREC-ID study (n=173 girls; 162 boys) on a range of minimally invasive physical indices thought to reflect prenatal exposure to androgens [anogenital distances (AGDs); penile length/width, scrotal/vulvar pigmentation], to estrogens [vaginal maturation index (VMI) - the degree of maturation of vaginal wall cells] or to both androgens/estrogens [2nd-to-4th digit ratio (2D:4D); areolar pigmentation, triceps/sub-scapular skinfold thickness, arm circumference]. VMI was found to be associated with triceps skinfold thickness (ß=0.265, P=0.005), suggesting that this marker may be sensitive to estrogen levels produced by adipose tissue in girls. Both estrogenic and androgenic markers (VMI: ß=0.338, P=0.031; 2D:4D - right: ß=-0.207, P=0.040; left: ß=-0.276, P=0.006; AGD-fourchette - ß=0.253, P=0.036) were associated with areolar pigmentation in girls, supporting a role for the latter as an index of both androgen and estrogen exposure. We also found AGD-penis (distance from the anus to the penis) to be associated with scrotal pigmentation (ß=0.290, P=0.048), as well as right arm circumference (ß=0.462, P<0.0001), supporting the notion that these indices may be used together as markers of androgen exposure in boys. In sum, these findings support the use of several physical indices at birth to convey a more comprehensive picture of prenatal exposure to sex hormones.


Assuntos
Androgênios/efeitos adversos , Estrogênios/efeitos adversos , Genitália Feminina/patologia , Genitália Masculina/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Adolescente , Estudos de Coortes , Feminino , Genitália Feminina/efeitos dos fármacos , Genitália Masculina/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
8.
Plant Dis ; 103(4): 721-728, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30777802

RESUMO

Panama disease caused by Fusarium oxysporum f. sp. cubense has devastated banana production worldwide. This work aimed to determine effective disinfectants against two races of F. oxysporum f. sp. cubense, race 1 and tropical race 4 (TR4), for implementation with on-farm biosecurity procedures against this disease following the outbreak of TR4 in North Queensland in 2015. A total of 32 commercial disinfectants were screened and their activity was assessed after ≤30 s, 5 min, 30 min, and 24 h of contact with an F. oxysporum f. sp. cubense suspension containing 105 chlamydospores/ml without and with soil added (0.05 g/ml). Of the disinfectants tested, the quaternary ammonium compounds containing ≥10% active ingredient were found to be the most effective against both F. oxysporum f. sp. cubense races. These products, when used at a 1:100 dilution, completely inhibited the survival of all F. oxysporum f. sp. cubense propagules across all the contact times regardless of the absence or presence of soil. The bioflavonoid product EvoTech 213 and bleach (10% sodium hypochlorite) used at a 1:10 dilution also eliminated all F. oxysporum f. sp. cubense propagules across all the contact times. None of the detergent-based or miscellaneous products tested were completely effective against both F. oxysporum f. sp. cubense races even used at a 1:10 dilution. Soil decreases the efficacy of disinfectants and therefore must be removed from contaminated items before treatments are applied.


Assuntos
Desinfetantes , Microbiologia de Alimentos , Fusarium , Desinfetantes/farmacologia , Desinfetantes/normas , Microbiologia de Alimentos/métodos , Fusarium/efeitos dos fármacos , Musa/microbiologia , Doenças das Plantas/prevenção & controle , Queensland
9.
Osteoporos Int ; 30(4): 817-828, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30607457

RESUMO

In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. INTRODUCTION: Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. METHODS: A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. RESULTS: There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate]. CONCLUSION: Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Idoso , Alendronato/uso terapêutico , Canadá/epidemiologia , Ácido Etidrônico/uso terapêutico , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Osteoporose/mortalidade , Fraturas por Osteoporose/mortalidade , Estudos Prospectivos , Ácido Risedrônico/uso terapêutico , Fatores de Risco , Comportamento de Redução do Risco
10.
Chem Commun (Camb) ; 54(92): 12970-12973, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30383065

RESUMO

The retro-Claisen reaction is frequently used in organic synthesis to access ester derivatives from 1,3-dicarbonyl precursors. The C-C bond cleavage in this reaction is usually promoted by a number of transition-metal Lewis acid catalysts or organic Brønsted acids/bases. Herein we report a new convenient and efficient method utilizing the tropylium ion as a mild and environmentally friendly organocatalyst to mediate retro-Claisen-type reactions. Using this method, a range of synthetically valuable substances can be accessed via solvolysis of 1,3-dicarbonyl compounds.

11.
Osteoporos Int ; 29(12): 2739-2744, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30196375

RESUMO

The present cross-sectional study constructed reference ranges for bone resorption marker beta isomerized form of C-terminal crosslinking telopeptides of type I collagen (beta-CTX) and bone formation marker procollagen type 1 N-terminal propeptide (PINP) for the Vietnamese population. We have further shown that for a given age and weight, higher levels of beta-CTX were significantly associated with bone mineral density in men and women. INTRODUCTION: Normal bone is constantly renewed by two opposing processes of resorption and formation which can be reflected by bone turnover markers (BTMs). This study sought to define the contribution of BTMs to the variation in bone mineral density (BMD) in normal individuals. METHODS: The study involved 205 men and 432 women aged between 18 and 87, who were randomly selected from various districts within Ho Chi Minh City, Vietnam. Fasting serum levels of PINP and beta-CTX were determined by electrochemiluminescence (Roche, ECLIA). BMD at the lumbar spine (LS) and femoral neck (FN) was measured by dual-energy x-ray absorptiometry (Hologic, Waltham, MA, USA). RESULTS: Among those aged < 50 years, women had lower PINP and beta-CTX levels than men, but among those aged > 50 years, women had higher PINP and beta-CTX levels than men. In the multiple linear regression analysis, beta-CTX-but not PINP-was significantly associated with both femoral neck (P = 0.008) and lumbar spine BMD (P = 0.008) and the association was independent of gender, age, and body weight. The proportion of variance in BMD attributable to beta-CTX was 1% for femoral neck BMD and 2% for lumbar spine BMD. CONCLUSION: The elevation in bone formation marker PINP and bone resorption marker beta-CTX in postmenopausal women was greater than in elderly men. However, only beta-CTX was modestly but significantly associated with BMD.


Assuntos
Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Absorciometria de Fóton/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Envelhecimento/fisiologia , Biomarcadores/sangue , Colágeno Tipo I/sangue , Estudos Transversais , Feminino , Colo do Fêmur/fisiologia , Humanos , Vértebras Lombares/fisiologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue , Caracteres Sexuais , Adulto Jovem
12.
Osteoporos Int ; 29(9): 2059-2067, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29967929

RESUMO

It is not clear why type 2 diabetes (T2D) has an increased risk of fracture despite higher areal bone mineral density. This study showed that compared with controls, T2D patients had higher trabecular bone density but lower cortical bone density, resulting in a lower bone strength. INTRODUCTION: To define the association between type 2 diabetes and bone architecture and measures of bone strength. METHODS: The study was part of the Vietnam Osteoporosis Study, in which 1115 women and 614 men aged ≥ 30 were randomly recruited from Ho Chi Minh City. HbA1c levels were measured with analyzers ADAMS™ A1c HA-8160 (Arkray, Kyoto, Japan). The diagnosis of T2D was made if HbA1c was ≥ 6.5%. Trabecular and cortical volumetric bone density (vBMD) was measured in the forearm and leg by a pQCT XCT2000 (Stratec, Germany). Polar stress strain index (pSSI) was derived from the pQCT measurements. Difference in bone parameters between T2D and non-diabetic individuals was assessed by the number of standard deviations (effect size [ES]) by the propensity score analysis. RESULTS: The prevalence of T2D was ~ 8%. The results of propensity score matching for age, sex, and body mass index in 137 pairs of diabetic and non-diabetic individuals showed that T2D patients had significantly higher distal radius trabecular vBMD (ES 0.26; 95% CI, 0.02 to 0.50), but lower cortical vBMD (ES - 0.22; - 0.46 to 0.00) and reduced pSSI (ES - 0.23; - 0.47 to - 0.02) compared with non-diabetic individuals. Multiple linear regression analysis based on the entire sample confirmed the results of the propensity score analysis. CONCLUSION: Compared with non-diabetic individuals, patients with T2D have greater trabecular but lower cortical vBMD which leads to lower bone strength.


Assuntos
Densidade Óssea/fisiologia , Osso Esponjoso/fisiopatologia , Osso Cortical/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/etiologia , Osteoporose/fisiopatologia , Prevalência , Pontuação de Propensão , Estudos Prospectivos , Rádio (Anatomia)/fisiopatologia , Tíbia/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Vietnã/epidemiologia , Adulto Jovem
13.
Cryo Letters ; 39(2): 131-136, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29734422

RESUMO

BACKGROUND: Short-term storage is valuable method to reuse manipulated embryos. OBJECTIVE: The present study evaluated the effects of antifreeze protein (AFP) supplementation on the quality and development of in vitro-produced porcine morulae after short-term storage (24 h). MATERIALS AND METHODS: The morulae were stored with various concentrations of AFP type III for 24 h at 5, 15 and 25C. RESULTS: Supplementation of AFP type III (1.0 microgram per mL) improved the developmental competence of embryos stored at 25C. The proportions of DNA-fragmented nuclei in the blastocysts did not differ between the embryos stored at 25C and the control embryos without storage treatment. However, the developmental competence of embryos stored at hypothermic temperatures decreased relative to that of the control embryos. CONCLUSION: Supplementation of AFP type III (1.0 microgram per mL) maintained the quality of embryos stored at 25C, but did not have beneficial effects on the development of embryos stored at hypothermic temperatures.


Assuntos
Proteínas Anticongelantes/farmacologia , Blastocisto/efeitos dos fármacos , Criopreservação/métodos , Crioprotetores/farmacologia , Animais , Fragmentação do DNA/efeitos dos fármacos , Feminino , Suínos
14.
Ned Tijdschr Geneeskd ; 162: D2078, 2018.
Artigo em Holandês | MEDLINE | ID: mdl-29328012

RESUMO

A 31-year-old man visited the outpatient clinic Dermatology with an exacerbation of his atopic eczema. Since a few day vesicles and crusts had appeared and his eyelids were swollen. He was known to have eczema, for which he was treated with ciclosporin 200 mg 2 times a day (4 mg/kg per day) since four months. Under this treatment the eczema used to be under control. There were no neurological symptoms or vision problems. At physical examination we saw erythematous papules, vesicles, superficial erosions and crusts on all body regions, but especially on the trunk and in the main neck region. The patient was diagnosed with eczema herpeticum and he was treated with intravenous aciclovir 1000 mg 3 times a day (10 mg/kg 3 dd) and flucloxacillin 1000 mg 4 times a day for seven days.


Assuntos
Aciclovir/administração & dosagem , Antivirais/administração & dosagem , Dermatite Atópica/virologia , Exantema/tratamento farmacológico , Floxacilina/administração & dosagem , Erupção Variceliforme de Kaposi/tratamento farmacológico , Adulto , Quimioterapia Combinada , Exantema/virologia , Humanos , Masculino
15.
J Neuroendocrinol ; 30(2)2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28489322

RESUMO

Neuroendocrine theories of brain development posit that androgens play a crucial role in sex-specific cortical growth, although little is known about the differential effects of testosterone and dehydroepiandrosterone (DHEA) on cortico-limbic development and cognition during adolescence. In this context, the National Institutes of Health Study of Normal Brain Development, a longitudinal study of typically developing children and adolescents aged 4-24 years (n=433), offers a unique opportunity to examine the developmental effects of androgens on cortico-limbic maturation and cognition. Using data from this sample, our group found that higher testosterone levels were associated with left-sided decreases in cortical thickness (CTh) in post-pubertal boys, particularly in the prefrontal cortex, compared to right-sided increases in CTh in somatosensory areas in pre-pubertal girls. Prefrontal-amygdala and prefrontal-hippocampal structural covariance (considered to reflect structural connectivity) also varied according to testosterone levels, with the testosterone-related brain phenotype predicting higher aggression levels and lower executive function, particularly in boys. By contrast, DHEA was associated with a pre-pubertal increase in CTh of several regions involved in cognitive control in both boys and girls. Covariance within several cortico-amygdalar structural networks also varied as a function of DHEA levels, with the DHEA-related brain phenotype predicting improvements in visual attention in both boys and girls. DHEA-related cortico-hippocampal structural covariance, on the other hand, predicted higher scores on a test of working memory. Interestingly, there were significant interactions between testosterone and DHEA, such that DHEA tended to mitigate the anti-proliferative effects of testosterone on brain structure. In sum, testosterone-related effects on the developing brain may lead to detrimental effects on cortical functions (ie, higher aggression and lower executive function), whereas DHEA-related effects may optimise cortical functions (ie, better attention and working memory), perhaps by decreasing the influence of amygdalar and hippocampal afferents on cortical functions.


Assuntos
Androgênios/metabolismo , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Neurônios/metabolismo , Caracteres Sexuais , Adolescente , Agressão/fisiologia , Criança , Pré-Escolar , Função Executiva/fisiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Maturidade Sexual/fisiologia , Adulto Jovem
16.
Reprod Domest Anim ; 53(2): 313-318, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29135047

RESUMO

This study was conducted to determine suitable conditions for an experimental method in which the CRISPR/Cas9 system is introduced into in vitro-produced porcine zygotes by electroporation. In the first experiment, when putative zygotes derived from in vitro fertilization (IVF) were electroporated by either unipolar or bipolar pulses, keeping the voltage, pulse duration and pulse number fixed at 30 V/mm, 1 msec and five repeats, respectively, the rate of blastocyst formation from zygotes electroporated by bipolar pulses decreased compared to zygotes electroporated by unipolar pulses. In the second experiment, the putative zygotes were electroporated by electroporation voltages ranging from 20 V/mm-40 V/mm with five 1-msec unipolar pulses. The rate of cleavage and blastocyst formation of zygotes electroporated at 40 V/mm was significantly lower (p < .05) than that of zygotes electroporated at less than 30 V/mm. Moreover, the apoptotic nuclei indices of blastocysts derived from zygotes electroporated by voltages greater than 30 V/mm significantly increased compared with those from zygotes electroporated by voltages less than 25 V/mm (p < .05). When zygotes were electroporated with Cas9 mRNA and single-guide RNA (sgRNA) targeting site in the FGF10 exon 3, the proportions of blastocysts with targeted genomic sequences were 7.7% (2/26) and 3.6% (1/28) in the embryos derived from zygotes electroporated at 25 V/mm and 30 V/mm, respectively. Our results indicate that electroporation at 25 V/mm may be an acceptable condition for introducing Cas9 mRNA and sgRNA into pig IVF zygotes under which the viability of the embryos is not significantly affected.


Assuntos
Eletroporação/veterinária , Embrião de Mamíferos/citologia , Sus scrofa , Animais , Apoptose , Sistemas CRISPR-Cas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Eletroporação/métodos , Desenvolvimento Embrionário/fisiologia , Feminino , Fertilização In Vitro/veterinária , Edição de Genes/métodos , Edição de Genes/veterinária , RNA Guia/genética , RNA Mensageiro/genética
17.
Transl Psychiatry ; 7(8): e1193, 2017 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-28786978

RESUMO

Clinical evidence suggests that symptoms in premenstrual dysphoric disorder (PMDD) reflect abnormal responsivity to ovarian steroids. This differential steroid sensitivity could be underpinned by abnormal processing of the steroid signal. We used a pharmacometabolomics approach in women with prospectively confirmed PMDD (n=15) and controls without menstrual cycle-related affective symptoms (n=15). All were medication-free with normal menstrual cycle lengths. Notably, women with PMDD were required to show hormone sensitivity in an ovarian suppression protocol. Ovarian suppression was induced for 6 months with gonadotropin-releasing hormone (GnRH)-agonist (Lupron); after 3 months all were randomized to 4 weeks of estradiol (E2) or progesterone (P4). After a 2-week washout, a crossover was performed. Liquid chromatography/tandem mass spectrometry measured 49 steroid metabolites in serum. Values were excluded if >40% were below the limit of detectability (n=21). Analyses were performed with Wilcoxon rank-sum tests using false-discovery rate (q<0.2) for multiple comparisons. PMDD and controls had similar basal levels of metabolites during Lupron and P4-derived neurosteroids during Lupron or E2/P4 conditions. Both groups had significant increases in several steroid metabolites compared with the Lupron alone condition after treatment with E2 (that is, estrone-SO4 (q=0.039 and q=0.002, respectively) and estradiol-3-SO4 (q=0.166 and q=0.001, respectively)) and after treatment with P4 (that is, allopregnanolone (q=0.001 for both PMDD and controls), pregnanediol (q=0.077 and q=0.030, respectively) and cortexone (q=0.118 and q=0.157, respectively). Only sulfated steroid metabolites showed significant diagnosis-related differences. During Lupron plus E2 treatment, women with PMDD had a significantly attenuated increase in E2-3-sulfate (q=0.035) compared with control women, and during Lupron plus P4 treatment a decrease in DHEA-sulfate (q=0.07) compared with an increase in controls. Significant effects of E2 addback compared with Lupron were observed in women with PMDD who had significant decreases in DHEA-sulfate (q=0.065) and pregnenolone sulfate (q=0.076), whereas controls had nonsignificant increases (however, these differences did not meet statistical significance for a between diagnosis effect). Alterations of sulfotransferase activity could contribute to the differential steroid sensitivity in PMDD. Importantly, no differences in the formation of P4-derived neurosteroids were observed in this otherwise highly selected sample of women studied under controlled hormone exposures.


Assuntos
Estradiol/farmacologia , Leuprolida/farmacologia , Metaboloma/efeitos dos fármacos , Transtorno Disfórico Pré-Menstrual/metabolismo , Progesterona/farmacologia , Adulto , Estudos Cross-Over , Desoxicorticosterona/sangue , Estradiol/análogos & derivados , Estradiol/sangue , Estrona/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Pregnanodiol/sangue , Pregnanolona/sangue , Adulto Jovem
18.
Reprod Domest Anim ; 52(6): 969-975, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28660662

RESUMO

Chlorogenic acid (CGA) is a quinic acid conjugate of caffeic acid, and a phytochemical found in many fruits and beverages that acts as an antioxidant. The present study investigated the effects of CGA supplementation during in vitro maturation (IVM), on in vitro development of porcine oocytes, to improve the porcine in vitro production (IVP) system. Oocytes were matured either without (control) or with CGA (10, 50, 100 and 200 µM). Subsequently, the matured oocytes were fertilized and cultured in vitro for 7 day. The rates of maturation, fertilization and blastocyst formation of oocytes matured with 50 µM CGA were significantly (p < .05) higher than those of the control oocytes. Hydrogen peroxide (H2 O2 ) is one of the reactive oxygen species and induces DNA damage in porcine oocytes. When oocytes were matured with 1 mM H2 O2 to assess the protective effect of CGA, 50 µM CGA supplementation improved the maturation rate and the proportion of DNA-fragmented nuclei in oocytes compared with control oocytes matured without CGA. Moreover, when oocytes were matured with either 50 µM CGA (control) or caffeic acid (10, 50 and 100 µM), the rates of maturation, fertilization and the blastocyst formation of oocytes matured with 50 µM CGA were similar to those of oocytes matured with 10 and 50 µM caffeic acid. Our results suggest that CGA has comparable effects to caffeic acid, and IVM with 50 µM CGA is particularly beneficial to IVP of porcine embryos and protects oocytes from DNA damage induced by oxidative stress. Supplementation of CGA to the maturation medium has a potential to improve porcine IVP system.


Assuntos
Ácido Clorogênico/farmacologia , Oócitos/citologia , Oócitos/efeitos dos fármacos , Suínos , Animais , Ácidos Cafeicos/farmacologia , Dano ao DNA , Feminino , Fertilização In Vitro/veterinária , Peróxido de Hidrogênio , Técnicas de Maturação in Vitro de Oócitos/métodos , Técnicas de Maturação in Vitro de Oócitos/veterinária , Masculino , Interações Espermatozoide-Óvulo/efeitos dos fármacos , Espermatozoides
19.
Physiol Biochem Zool ; 90(3): 407-414, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28384425

RESUMO

We examined ionoregulatory characteristics of two species of characiform fish and two species of cichlids that are not native to the Rio Negro, an extremely ion-poor, acidic tributary of the Amazon River, in order to gain insight into the origin of the specializations possessed by Rio Negro fish. The two characiform species examined, Congo tetras (Phenacogrammus interruptus) and black neon tetras (Hyphessobrycon herbertaxelrodi), had high-affinity/high-capacity transporters that produce high rates of uptake in dilute water. Na+ uptake for both was pH insensitive (down to pH 3.5). Exposure to 100 µmol L-1 phenamil had no effect on Na+ uptake in either species, while exposure to 1 mmol L-1 NH4Cl- (high external ammonia [HEA]) slightly stimulated Na+ uptake in Congo tetras. Exposure to "Na+-free" water significantly inhibited Na+ uptake (by 65%-85%) but had no effect on net ammonia flux. The two cichlid species examined, convict cichlids (Amatitlania siquia) and red point cichlids (Archocentrus sp.), had high-affinity but low-capacity transporters that yield low rates of uptake in dilute media. Sodium transport was pH sensitive and completely inhibited at pH 3.5. Phenamil exposure inhibited Na+ uptake by 60% in convict cichlids but had no effect on red point cichlids, and exposure to HEA reduced Na+ uptake in both species by 70%-85%. Exposure to "Na+-free" water reduced Na+ uptake by 80%-85%, and in convict cichlids it also reduced net ammonia flux by about 50%. The ionoregulatory characteristics described for both groups are strikingly similar to those for Rio Negro species, and we suggest that they may be ancestral physiological traits for these two groups. Further, if this is the case, it seems likely that these traits existed before the Rio Negro and may explain the great success of these species-rich groups in colonizing the river despite its challenging chemistry.


Assuntos
Caraciformes/fisiologia , Ciclídeos/fisiologia , Rios/química , Equilíbrio Hidroeletrolítico/fisiologia , Distribuição Animal , Animais , Especificidade da Espécie
20.
Chem Commun (Camb) ; 53(36): 4950-4953, 2017 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-28422202

RESUMO

The construction of C(sp3)-C(sp3) bond is an essential chemical transformation in synthetic chemistry due to its abundance in organic scaffolds. Here we demonstrate a valuable adaptation of the Wittig-type chemical procedure to efficiently facilitate C(sp3)-C(sp3) bond formation utilizing a range of alkyl building blocks. Additionally the method is amenable with flow synthesis to afford coupled products in good to excellent yields without laborious purification process.

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