RESUMO
Latiné people differ markedly in our lived experiences in ways that are underappreciated. Meanwhile, variations in social experiences are known to be associated with differential health outcomes. We test whether immigration history is associated with health differences among U.S.-based Cuban refugees. Cubans from the circum-1980 Mariel Boatlift migration wave reported significantly higher instances of disability than Early Cuban Exiles, Freedom Flight refugees, and Special Period refugees. We also interviewed Miami-based Cubans. Participants described heightened discrimination in 1980s Cuba and U.S., which we hypothesize contributed to higher instances of disability refugees of that era. By understanding how differential social experiences shape health, we aim to provide a nuanced understanding of the social determinants of health and the ways adverse experiences can be combated.
RESUMO
Pregnancy detection has evolved over the last few decades and the importance of early pregnancy detection is critical to minimize the amount of time a cow spends not pregnant. Embryonic mortality (EM) is generally considered to be the primary factor limiting pregnancy rates in cattle and occurs early (Assuntos
Feminino
, Animais
, Gravidez
, Bovinos
, Bovinos/embriologia
, Desenvolvimento Embrionário
, MicroRNAs/análise
, Testes de Gravidez
, Testes de Gravidez/veterinária
, Mortalidade
RESUMO
The objectives of the present study were to evaluate factors associated with estrous synchronization responses and pregnancy per insemination (P/AI) in Bos indicus beef cows submitted to progesterone-based fixed-time artificial insemination (FTAI) protocols. A total of 2388 cows (1869 Nellore and 519 crossbred NellorexAngus) from 10 commercial farms were evaluated to determine the relationships among breed, body condition score (BCS) on the first day of the FTAI protocol, the occurrence of estrus between progesterone device removal and FTAI, and diameter of largest ovarian follicle (LF) at FTAI on estrous synchronization responses and P/AI. Cows (n=412 primiparous; 1976 multiparous) received an intravaginal device containing progesterone or an ear implant containing norgestomet (a progestin), and an injection of estradiol at the beginning of the estrous synchronization protocol. Body condition was scored using a 1-5 scale on the first day of the FTAI protocol and at 30-60 days postpartum. Females received 300IU of equine chorionic gonadotropin (eCG) and PGF(2alpha) on the day the progesterone device/implant was removed and were inseminated 48-60h later. At insemination, cows (n=2388) were submitted to an ultrasonographic exam to determine the diameter of the LF. Follicles were classified into four categories based on mean and standard deviation (SD) of the LF (LF1=two SD below the mean; LF2=mean minus one SD; LF3=mean plus one SD; LF4=two SD above the mean). Ovulation rate was determined in a subset of cows (n=813) by three consecutive ultrasonographic exams: (1) at time of progesterone device/implant removal, (2) at time of FTAI and (3) 48h after FTAI. Ovulation was defined as the disappearance of a large follicle (>or=8.0mm) that was previously recorded. Estrus was determined in a subset of the cows (n=445) by the activation of a detection of estrous patch placed on the tail head on the day of progesterone device/implant removal. Pregnancy was diagnosed 30 days after FTAI. Pregnancy was influenced (P=0.001) by follicle diameter [LF1=27.5% (81/295), LF2=46.6% (328/705), LF3=57.9% (647/1118), LF4=63.3% (171/270)] and the occurrence of estrus [estrus=67.7% (174/257) and no estrus=36.2% (68/188)]. Follicle diameter at FTAI influenced ovulation rate [LF1=42.5% (34/80), LF2=73.9% (161/218), LF3=95.8% (407/425), LF4=97.8% (88/90)], the occurrence of estrus [LF1=54.8% (51/93), LF2=33.6% (43/128), LF3=68.9% (126/183), LF4=90.2% (37/41)] and P/AI among cows that had ovulations [LF1=32.4% (11/34), LF2=50.3% (81/161), LF3=60.0% (244/407), LF4=68.2% (60/88)]. Improving estrous responses between progesterone device withdrawal and FTAI and increasing the diameter of the LF at FTAI may be important aspects to achieve improved estrous synchronization responses and P/AI following progesterone/progestin and estradiol based FTAI protocols in suckled Bos indicus cows.
Assuntos
Ciclo Estral/fisiologia , Sincronização do Estro/métodos , Inseminação Artificial/veterinária , Folículo Ovariano/citologia , Previsão da Ovulação/métodos , Prenhez , Animais , Animais Lactentes , Bovinos , Tamanho Celular/efeitos dos fármacos , Protocolos Clínicos , Combinação de Medicamentos , Ciclo Estral/efeitos dos fármacos , Sincronização do Estro/fisiologia , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Lactação/fisiologia , Folículo Ovariano/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Ovulação/fisiologia , Gravidez , Testes de Gravidez/veterinária , Progesterona/administração & dosagem , Progestinas/administração & dosagem , Fatores de TempoRESUMO
Neuronal protein inclusions are a common feature in Alzheimer disease (AD) and Pick disease. Even though the inclusions are morphologically different, flame-shape structure for AD vs. spherical structure for Pick disease, both have filaments mainly composed of tau protein. In AD, a well-defined pattern of conformational changes and truncation has been described. In this study, we used laser scanning confocal microscopy to characterize and compare the processing of tau protein during Pick disease with that found in AD. We found that tau protein of Pick disease preserves most of the relevant epitopes found in AD, the conformational foldings labelled by Alz-50 and Tau-66, the cleavage sites D(421) and E(391), as well as many phosphorylated sites, such as Ser(199/202), Thr(205) and Ser(396/404). We found a strong pattern of association between phosphorylation and cleavage at site D(421), as well as the phosphorylation and the conformational Alz-50 epitope. When we used late AD markers such as the conformational Tau-66 epitope and MN423 (cleavage at site E(391)) in Pick bodies (PBs), the overlap was significantly less. Furthermore, following morphological quantification, we found significantly higher numbers of phosphorylated tau in PBs. Overall, our findings suggest that phosphorylation is an early event, likely preceding the cleavage of tau at D(421). Despite this consistency with AD, we found a major distinction, namely that PBs lack beta-sheet conformation. We propose a scheme of early tau processing in these structures, similar to neurofibrillary tangles of AD.
Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Doença de Pick/metabolismo , Proteínas tau/química , Proteínas tau/metabolismo , Idoso , Doença de Alzheimer/patologia , Encéfalo/patologia , Imunofluorescência , Humanos , Imuno-Histoquímica , Microscopia Confocal , Pessoa de Meia-Idade , Fosforilação , Doença de Pick/patologiaRESUMO
In this paper, we review experimental advances in molecular neurobiology of Alzheimer's disease (AD), with special emphasis on analysis of neural function of proteins involved in AD pathogenesis, their relation with several signaling pathways and with oxidative stress in neurons. Molecular genetic studies have found that mutations in APP, PS1 and PS2 genes and polymorphisms in APOE gene are implicated in AD pathogenesis. Recent studies show that these proteins, in addition to its role in beta-amyloid processing, are involved in several neuroplasticity-signaling pathways (NMDA-PKA-CREB-BDNF, reelin, wingless, notch, among others). Genomic and proteomic studies show early synaptic protein alterations in AD brains and animal models. DNA damage caused by oxidative stress is not completely repaired in neurons and is accumulated in the genes of synaptic proteins. Several functional SNPs in synaptic genes may be interesting candidates to explore in AD as genetic correlates of this synaptopathy in a "synaptogenomics" approach. Thus, experimental evidence shows that proteins implicated in AD pathogenesis have differential roles in several signaling pathways related to neuromodulation and neurotransmission in adult and developing brain. Genomic and proteomic studies support these results. We suggest that oxidative stress effects on DNA and inherited variations in synaptic genes may explain in part the synaptic dysfunction seen in AD.
Assuntos
Doença de Alzheimer/metabolismo , Estresse Oxidativo , Amiloide/metabolismo , Animais , Apolipoproteínas E/metabolismo , Dano ao DNA , Genômica/métodos , Humanos , Modelos Biológicos , Modelos Moleculares , Neurônios/metabolismo , Presenilinas/metabolismo , Proteômica/métodos , Proteína Reelina , Transdução de SinaisRESUMO
Alzheimer disease, the most prevalent dementia of the aged, is defined by the concurrence of two filamentous brain lesions: neurofibrillary tangles and senile plaques. The lesions are temporally and spatially correlated to each other and to cognitive impairment suggesting that is a interaction between neurofibrillary tangles and senile plaques that might play a role in disease pathogenesis. Here we present findings demonstrating specific interactions between the major protein components of the lesions. Such an interaction is likely important to lesion genesis and to the overall cognitive deficits seen clinically. Also important are forces that stabilize and cement abnormal interactions and protect them form removal. Oxidative post-translational modifications is probably one of the major mediators that by disrupting cellular homeostatic balance both promotes abnormal interactions and makes them resistant to proteolytic removal. Overall, these findings support the view that the lesions of Alzheimer disease are intimately involved in neuronal destructions.
Assuntos
Doença de Alzheimer/etiologia , Proteínas de Neurofilamentos/metabolismo , Estresse Oxidativo/fisiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Proteínas do Citoesqueleto/metabolismo , Humanos , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologiaRESUMO
Information was collected on 301 cases of the Wiskott-Aldrich syndrome in the United States and Canada Examination of available medical records, death certificates and published case reports on these patients showed that they came from a wide geographic area and many diverse ethnic and racial groups. No significant difference was found in the incidence of cases born between 1947 and 1976; the overall rate was 4.0 per million live male births in the United States. Median survival has increased with time from eight months for patients born before 1935 to 6.5 years for those born after 1964. Seventy-six of the 301 patients (25%) were still alive at last follow-up and ranged in age from 1 to 36 years with a median of 10 years. Causes of death were primarily limited to infections or bleeding, but malignancy represented a significant problem. Twelve percent of the group (36 of 301) developed malignancy, the predominant types being lymphorecticular tumors (23 of 36) and leukemia (7 of 36). The overall relative risk for malignancy was found to be greater than 100 times that of the general population and was found to increase with increasing age.