850 resultados para Perinatal Morbidity And Mortality
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In many regions of Asia and Africa, consanguineous marriages currently account for approximately 20 to 50% of all unions, and preliminary observations indicate that migrants from these areas continue to contract marriages with close relatives when resident in North America and Western Europe. Consanguinity is associated with increased gross fertility, due at least in part to younger maternal age at first livebirth. Morbidity and mortality also may be elevated, resulting in comparable numbers of surviving offspring in consanguineous and nonconsanguineous families. With advances in medicine and public health, genetic disorders will account for an increased proportion of disease worldwide. Predictably, this burden will fall more heavily on countries and communities in which consanguinity is strongly favored, as the result of the expression of deleterious recessive genes. However, studies conducted in such populations indicate that the adverse effects associated with inbreeding are experienced by a minority of families.
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Mycobacterium tuberculosis, an etiological agent of pulmonary tuberculosis, causes significant morbidity and mortality worldwide. Pathogenic mycobacteria survive in the host by subverting host innate immunity. Dendritic cells (DCs) are professional antigen-presenting cells that are vital for eliciting immune responses to infectious agents, including pathogenic mycobacteria. DCs orchestrate distinct Th responses based on the signals they receive. In this perspective, deciphering the interactions of the proline-glutamic acid/proline-proline-glutamic acid (PE/PPE) family of proteins of M. tuberculosis with DCs assumes significant pathophysiological attributes. In this study, we demonstrate that Rv1917c (PPE34), a representative member of the proline-proline-glutamic-major polymorphic tandem repeat family, interacts with TLR2 and triggers functional maturation of human DCs. Signaling perturbations implicated a critical role for integrated cross-talk among PI3K-MAPK and NF-kappa B signaling cascades in Rv1917c-induced maturation of DCs. However, this maturation of DCs was associated with a secretion of high amounts of anti-inflammatory cytokine IL-10, whereas Th1-polarizing cytokine IL-12 was not induced. Consistent with these results, Rv1917c-matured DCs favored secretion of IL-4, IL-5, and IL-10 from CD4(+) T cells and contributed to Th2-skewed cytokine balance ex vivo in healthy individuals and in patients with pulmonary tuberculosis. Interestingly, the Rv1917c-skewed Th2 immune response involved induced expression of cyclooxygenase-2 (COX-2) in DCs. Taken together, these results indicate that Rv1917c facilitates a shift in the ensuing immunity toward the Th2 phenotype and could aid in immune evasion by mycobacteria.
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Introduction: Combination antiretroviral therapy (cART) has decreased morbidity and mortality of individuals infected with human immunodeficiency virus type 1 (HIV-1). Its use, however, is associated with adverse effects which increase the patients risk of conditions such as diabetes and coronary heart disease. Perhaps the most stigmatizing side effect is lipodystrophy, i.e., the loss of subcutaneous adipose tissue (SAT) in the face, limbs and trunk while fat accumulates intra-abdominally and dorsocervically. The pathogenesis of cART-associated lipodystrophy is obscure. Nucleoside reverse transcriptase inhibitors (NRTI) have been implicated to cause lipoatrophy via mitochondrial toxicity. There is no known effective treatment for cART-associated lipodystrophy during unchanged antiretroviral regimen in humans, but in vitro data have shown uridine to abrogate NRTI-induced toxicity in adipocytes. Aims: To investigate whether i) cART or lipodystrophy associated with its use affect arterial stiffness; ii) lipoatrophic SAT is inflamed compared to non-lipoatrophic SAT; iii) abdominal SAT from patients with compared to those without cART-associated lipoatrophy differs with respect to mitochondrial DNA (mtDNA) content, adipose tissue inflammation and gene expression, and if NRTIs stavudine and zidovudine are associated with different degree of changes; iv) lipoatrophic abdominal SAT differs from preserved dorsocervical SAT with respect to mtDNA content, adipose tissue inflammation and gene expression in patients with cART-associated lipodystrophy and v) whether uridine can revert lipoatrophy and the associated metabolic disturbances in patients on stavudine or zidovudine based cART. Subjects and methods: 64 cART-treated patients with (n=45) and without lipodystrophy/-atrophy (n=19) were compared cross-sectionally. A marker of arterial stiffness, heart rate corrected augmentation index (AgIHR), was measured by pulse wave analysis. Body composition was measured by magnetic resonance imaging and dual-energy X-ray absorptiometry, and liver fat content by proton magnetic resonance spectroscopy. Gene expression and mtDNA content in SAT were assessed by real-time polymerase chain reaction and microarray. Adipose tissue composition and inflammation were assessed by histology and immunohistochemistry. Dorsocervical and abdominal SAT were studied. The efficacy and safety of uridine for the treatment of cART-associated lipoatrophy were evaluated in a randomized, double-blind, placebo-controlled 3-month trial in 20 lipoatrophic cART-treated patients. Results: Duration of antiretroviral treatment and cumulative exposure to NRTIs and protease inhibitors, but not the presence of cART-associated lipodystrophy, predicted AgIHR independent of age and blood pressure. Gene expression of inflammatory markers was increased in SAT of lipodystrophic as compared to non-lipodystrophic patients. Expression of genes involved in adipogenesis, triglyceride synthesis and glucose disposal was lower and of those involved in mitochondrial biogenesis, apoptosis and oxidative stress higher in SAT of patients with than without cART-associated lipoatrophy. Most changes were more pronounced in stavudine-treated than in zidovudine-treated individuals. Lipoatrophic SAT had lower mtDNA than SAT of non-lipoatrophic patients. Expression of inflammatory genes was lower in dorsocervical than in abdominal SAT. Neither depot had characteristics of brown adipose tissue. Despite being spared from lipoatrophy, dorsocervical SAT of lipodystrophic patients had lower mtDNA than the phenotypically similar corresponding depot of non-lipodystrophic patients. The greatest difference in gene expression between dorsocervical and abdominal SAT, irrespective of lipodystrophy status, was in expression of homeobox genes that regulate transcription and regionalization of organs during embryonal development. Uridine increased limb fat and its proportion of total fat, but had no effect on liver fat content and markers of insulin resistance. Conclusions: Long-term cART is associated with increased arterial stiffness and, thus, with higher cardiovascular risk. Lipoatrophic abdominal SAT is characterized by inflammation, apoptosis and mtDNA depletion. As mtDNA is depleted even in non-lipoatrophic dorsocervical SAT, lipoatrophy is unlikely to be caused directly by mtDNA depletion. Preserved dorsocervical SAT of patients with cART-associated lipodystrophy is less inflamed than their lipoatrophic abdominal SAT, and does not resemble brown adipose tissue. The greatest difference in gene expression between dorsocervical and abdominal SAT is in expression of transcriptional regulators, homeobox genes, which might explain the differential susceptibility of these adipose tissue depots to cART-induced toxicity. Uridine is able to increase peripheral SAT in lipoatrophic patients during unchanged cART.
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Trypanosoma evansi is a causative agent of `surra', a common haemoprotozoan disease of livestock in India causing high morbidity and mortality in disease endemic areas. The proteinases released by live and dead trypanosomes entail immunosuppression in the infected host, which immensely contribute in disease pathogenesis. Cysteine proteinases are identified in the infectious cycle of trypanosomes such as cruzain from Trypanosoma cruzi, rhodesain or brucipain from Trypanosoma brucei rhodesiense and congopain from Trypanosoma congelense. These enzymes localised in lysosome-like organelles, flagellar pocket and on cell surface, which play a critical role in the life cycle of protozoan parasites, viz. in host invasion, nutrition and alteration of the host immune response. The paper describes the identification of cysteine proteinases of T. evansi lysate, activity profile at different pH optima and inhibition pattern using a specific inhibitor, besides the polypeptide profile of an antigen. Eight proteinases of T. evansi were identified in the molecular weight (MW) ranges of 28-170 kDa using gelatin substrate-polyacrylamide gel electrophoresis (GS-PAGE), and of these proteinases, six were cysteine proteinases, as they were inhibited by L-3-carboxy-2,3-transepoxypropionyl-lecuylamido (4-guanidino)-butane (E-64), a specific inhibitor. These proteolytic enzymes were most reactive in acidic pH between 3.0 and 5.5 in the presence of dithiothreitol and completely inactive at alkaline pH 10.0. Similarly, the GS-PAGE profile of the serum samples of rats infected with T. evansi revealed strong proteolytic activity only at the 28-kDa zone at pH 5.5, while no proteolytic activity was observed in serum samples of uninfected rats. Further, the other zones of clearance, which were evident in T. evansi antigen zymogram, could not be observed in the serum samples of rats infected with T. evansi. The polypeptide pattern of the whole cell lysate antigen revealed 12-15 polypeptide bands ranging from 28 to 81 kDa along with five predominant polypeptides bands (MW of 81, 66, 62, 55 and 45 kDa), which were immunoreactive with hyperimmune serum (HIS) and serum of experimentally infected rabbits with T. evansi infection. The immunoblot recognised antibodies in experimentally infected rabbits and against HIS as well, corresponding to the zone of clearances at lower MW ranges (28-41 kDa), which may be attributed to the potential of these proteinases in the diagnosis of T. evansi infection. Since these thiol-dependent enzymes are most active in acidic pH and considering their inhibition characteristics, these data suggest that they resemble to the mammalian lysosomal cathepsin B and L.
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ENGLISH: Age composition of catch, and growth rate, of yellowfin tuna have been estimated by Hennemuth (1961a) and Davidoff (1963). The relative abundance and instantaneous total mortality rate of yellowfin tuna during 1954-1959 have been estimated by Hennenmuth (1961b). It is now possible to extend this work, because more data are available; these include data for 1951-1954, which were previously not available, and data for 1960-1962, which were collected subsequent to Hennemuth's (1961b) publication. In that publication, Hennemuth estimated the total instantaneous mortality rate (Z) during the entire time period a year class is present in the fishery following full recruitment. However, this method may lead to biased estimates of abundance, and hence mortality rates, because of both seasonal migrations into or out of specific fishing areas and possible seasonal differences in availability or vulnerability of the fish to the fishing gear. Schaefer, Chatwin and Broadhead (1961) and Joseph etl al. (1964) have indicated that seasonal migrations of yellowfin occur. A method of estimating mortality rates which is not biased by seasonal movements would be of value in computations of population dynamics. The method of analysis outlined and used in the present paper may obviate this bias by comparing the abundance of an individual yellowfin year class, following its period of maximum abundance, in an individual area during a specific quarter of the year with its abundance in the same area one year later. The method was suggested by Gulland (1955) and used by Chapman, Holt and Allen (1963) in assessing Antarctic whale stocks. This method, and the results of its use with data for yellowfin caught in the eastern tropical Pacific from 1951-1962 are described in this paper. SPANISH: La composición de edad de la captura, y la tasa de crecimiento del atún aleta amarilla, han sido estimadas por Hennemuth (1961a) y Davidoff (1963). Hennemuth (1961b), estimó la abundancia relativa y la tasa de mortalidad total instantánea del atún aleta amarilla durante 1954-1959. Se puede ampliar ahora, este trabajo, porque se dispone de más datos; éstos incluyen datos de 1951 1954, de los cuales no se disponía antes, y datos de 1960-1962 que fueron recolectados después de la publicación de Hennemuth (1961b). En esa obra, Hennemuth estimó la tasa de mortalidad total instantánea (Z) durante todo el período de tiempo en el cual una clase anual está presente en la pesquería, consecutiva al reclutamiento total. Sin embargo, este método puede conducir a estimaciones con bias (inclinación viciada) de abundancia, y de aquí las tasas de mortalidad, debidas tanto a migraciones estacionales dentro o fuera de las áreas determinadas de pesca, como a posibles diferencias estacionales en la disponibilidad y vulnerabilidad de los peces al equipo de pesca. Schaefer, Chatwin y Broadhead (1961) y Joseph et al. (1964) han indicado que ocurren migraciones estacionales de atún aleta amarilla. Un método para estimar las tasas de mortalidad el cual no tuviera bias debido a los movimientos estacionales, sería de valor en los cómputos de la dinámica de las poblaciones. El método de análisis delineado y usado en el presente estudio puede evitar este bias al comparar la abundancia de una clase anual individual de atún aleta amarilla, subsecuente a su período de abundancia máxima en un área individual, durante un trimestre específico del año, con su abundancia en la misma área un año más tarde. Este método fue sugerido por Gulland (1955) y empleado por Chapman, Holt y Allen (1963) en la declaración de los stocks de la ballena antártica. Este método y los resultados de su uso, en combinación con los datos del atún aleta amarilla capturado en el Pacífico oriental tropical desde 1951-1962, son descritos en este estudio.
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The epidemic of HIV/AIDS in the United States is constantly changing and evolving, starting from patient zero to now an estimated 650,000 to 900,000 Americans infected. The nature and course of HIV changed dramatically with the introduction of antiretrovirals. This discourse examines many different facets of HIV from the beginning where there wasn't any treatment for HIV until the present era of highly active antiretroviral therapy (HAART). By utilizing statistical analysis of clinical data, this paper examines where we were, where we are and projections as to where treatment of HIV/AIDS is headed.
Chapter Two describes the datasets that were used for the analyses. The primary database utilized was collected by myself from an outpatient HIV clinic. The data included dates from 1984 until the present. The second database was from the Multicenter AIDS Cohort Study (MACS) public dataset. The data from the MACS cover the time between 1984 and October 1992. Comparisons are made between both datasets.
Chapter Three discusses where we were. Before the first anti-HIV drugs (called antiretrovirals) were approved, there was no treatment to slow the progression of HIV. The first generation of antiretrovirals, reverse transcriptase inhibitors such as AZT (zidovudine), DDI (didanosine), DDC (zalcitabine), and D4T (stavudine) provided the first treatment for HIV. The first clinical trials showed that these antiretrovirals had a significant impact on increasing patient survival. The trials also showed that patients on these drugs had increased CD4+ T cell counts. Chapter Three examines the distributions of CD4 T cell counts. The results show that the estimated distributions of CD4 T cell counts are distinctly non-Gaussian. Thus distributional assumptions regarding CD4 T cell counts must be taken, into account when performing analyses with this marker. The results also show the estimated CD4 T cell distributions for each disease stage: asymptomatic, symptomatic and AIDS are non-Gaussian. Interestingly, the distribution of CD4 T cell counts for the asymptomatic period is significantly below that of the CD4 T cell distribution for the uninfected population suggesting that even in patients with no outward symptoms of HIV infection, there exists high levels of immunosuppression.
Chapter Four discusses where we are at present. HIV quickly grew resistant to reverse transcriptase inhibitors which were given sequentially as mono or dual therapy. As resistance grew, the positive effects of the reverse transcriptase inhibitors on CD4 T cell counts and survival dissipated. As the old era faded a new era characterized by a new class of drugs and new technology changed the way that we treat HIV-infected patients. Viral load assays were able to quantify the levels of HIV RNA in the blood. By quantifying the viral load, one now had a faster, more direct way to test antiretroviral regimen efficacy. Protease inhibitors, which attacked a different region of HIV than reverse transcriptase inhibitors, when used in combination with other antiretroviral agents were found to dramatically and significantly reduce the HIV RNA levels in the blood. Patients also experienced significant increases in CD4 T cell counts. For the first time in the epidemic, there was hope. It was hypothesized that with HAART, viral levels could be kept so low that the immune system as measured by CD4 T cell counts would be able to recover. If these viral levels could be kept low enough, it would be possible for the immune system to eradicate the virus. The hypothesis of immune reconstitution, that is bringing CD4 T cell counts up to levels seen in uninfected patients, is tested in Chapter Four. It was found that for these patients, there was not enough of a CD4 T cell increase to be consistent with the hypothesis of immune reconstitution.
In Chapter Five, the effectiveness of long-term HAART is analyzed. Survival analysis was conducted on 213 patients on long-term HAART. The primary endpoint was presence of an AIDS defining illness. A high level of clinical failure, or progression to an endpoint, was found.
Chapter Six yields insights into where we are going. New technology such as viral genotypic testing, that looks at the genetic structure of HIV and determines where mutations have occurred, has shown that HIV is capable of producing resistance mutations that confer multiple drug resistance. This section looks at resistance issues and speculates, ceterus parabis, where the state of HIV is going. This section first addresses viral genotype and the correlates of viral load and disease progression. A second analysis looks at patients who have failed their primary attempts at HAART and subsequent salvage therapy. It was found that salvage regimens, efforts to control viral replication through the administration of different combinations of antiretrovirals, were not effective in 90 percent of the population in controlling viral replication. Thus, primary attempts at therapy offer the best change of viral suppression and delay of disease progression. Documentation of transmission of drug-resistant virus suggests that the public health crisis of HIV is far from over. Drug resistant HIV can sustain the epidemic and hamper our efforts to treat HIV infection. The data presented suggest that the decrease in the morbidity and mortality due to HIV/AIDS is transient. Deaths due to HIV will increase and public health officials must prepare for this eventuality unless new treatments become available. These results also underscore the importance of the vaccine effort.
The final chapter looks at the economic issues related to HIV. The direct and indirect costs of treating HIV/AIDS are very high. For the first time in the epidemic, there exists treatment that can actually slow disease progression. The direct costs for HAART are estimated. It is estimated that the direct lifetime costs for treating each HIV infected patient with HAART is between $353,000 to $598,000 depending on how long HAART prolongs life. If one looks at the incremental cost per year of life saved it is only $101,000. This is comparable with the incremental costs per year of life saved from coronary artery bypass surgery.
Policy makers need to be aware that although HAART can delay disease progression, it is not a cure and HIV is not over. The results presented here suggest that the decreases in the morbidity and mortality due to HIV are transient. Policymakers need to be prepared for the eventual increase in AIDS incidence and mortality. Costs associated with HIV/AIDS are also projected to increase. The cost savings seen recently have been from the dramatic decreases in the incidence of AIDS defining opportunistic infections. As patients who have been on HAART the longest start to progress to AIDS, policymakers and insurance companies will find that the cost of treating HIV/AIDS will increase.
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Ichthyoplankton surveys were conducted in shelf and slope waters of the northern Gulf of Mexico during the months of May–September in 2005 and 2006 to investigate the potential role of this region as spawning and nursery habitat of sailfish (Istiophorus platypterus). During the two-year study, 2426 sailfish larvae were collected, ranging in size from 2.0 to 24.3 mm standard length. Mean density for all neuston net collections (n=288) combined was 1.5 sailfish per 1000 m2, and maximum density was observed within frontal features created by hydrodynamic convergence (2.3 sailfish per 1000 m2). Sagittal otoliths were extracted from 1330 larvae, and otolith microstructure analysis indicated that the sailfish ranged in age from 4 to 24 days after hatching (mean=10.5 d, standard deviation [SD]=3.2 d). Instantaneous growth coefficients (g) among survey periods (n=5) ranged from 0.113 to 0.127, and growth peaked during July 2005 collections when density within frontal features was highest. Daily instantaneous mortality rates (Z) ranged from 0.228 to 0.381, and Z was indexed to instantaneous weight-specific growth (G) to assess stage-specific production potential of larval cohorts. Ratios of G to Z were greater than 1.0 for all but one cohort examined, indicating that cohorts were gaining biomass during the majority of months investigated. Stage-specific production potential, in combination with catch rates and densities of larvae, indicates that the Gulf of Mexico likely represents important spawning and nursery habitat for sailfish.
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The western butterfish (Pentapodus vitta) is numerous in the bycatch of prawn trawling and recreational fishing in Shark Bay, Western Australia. We have thus determined crucial aspects of its biological characteristics and the potential impact of fishing on its abundance within this large subtropical marine embayment. Although both sexes attained a maximum age of 8 years, males grow more rapidly and to a larger size. Maturity is attained at the end of the first year of life and spawning occurs between October and January. The use of a Bayesian approach to combine independent estimates for total mortality, Z, and natural mortality, M, yielded slightly higher point estimates for Z than M. This result indicates that P. vitta is lightly impacted by fishing. It is relevant that, potentially, the individuals can spawn twice before recruitment into the fishery and that 73% of recreationally caught individuals are returned live to the water.
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Growth parameters and mortality rates were estimated from length-frequency data sampled in 1982, using the FiSAT software, for three coral reef fish species, the surgeon fish (Ctenochaetus striatus), the damselfish (Stegastes nigricans) and the squirrel fish (Sargocentron microstoma) in Tiahura Reef, Moorea Island, French Polynesia.
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A brief description of fisheries development in Djibouti is given, with emphasis on the major constraints that have to date limited the increase of fishing effort. Estimates of L sub( infinity ) obtained through Wetherall plots are presented for three important demersal species caught off northern Somalia and landed in Djibouti: the groupers Cephalopholis sonnerati, Epinephelus chlorostigma and E. areolatus (Fam. Serranidae). These are combined with estimates of the growth performance index O' to calculate K values, subsequently used for the construction of length-converted catch curves. The estimate of mortality thus obtained suggests that these stocks are lightly fished.
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Growth and mortality parameters of the small Lake Victoria cyprinid Rastrineobola argentea were determined from length-frequency analysis, using the ELEFAN I and II programs. The results of two sampling programs, both performed during 1988, one in Uganda (mosquito seine) and the other in Tanzania (pelagic trawl), were highly corresponding, In comparison with previously published data on the growth of dagaa and some similar species, low values for L sub( infinity ) (65 mm standard length) and K (1 year super(-1)) were found. Total mortality (Z) amounted to 3.9-4.4 year super(-1). A single annual breeding peak was observed both in Uganda (October/November) and in Tanzania (February/March).
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Age estimates for striped trumpeter (Latris lineata) from Tasmanian waters were produced by counting annuli on the transverse section of sagittal otoliths and were validated by comparison of growth with known-age individuals and modal progression of a strong recruitment pulse. Estimated ages ranged from one to 43 years; fast growth rates were observed for the first five years. Minimal sexual dimorphism was shown to exist between length, weight, and growth characteristics of striped trumpeter. Seasonal growth variability was strong in individuals up to at least age four, and growth rates peaked approximately one month after the observed peak in sea surface temperature. A modified two-phase von Bertalanffy growth function was fitted to the length-at-age data, and the transition between growth phases was linked to apparent changes in physiological and life history traits, including offshore movement as fish approach maturity. The two-phase curve was found to represent the mean length at age in the data better than the standard von Bertalanffy growth function. Total mortality was estimated by using catch curve analysis based on the standard and two-phase von Bertalanffy growth functions, and estimates of natural mortality were calculated by using two empirical models, one based on longevity and the other based on the parameters L∞ and k from both growth functions. The interactions between an inshore gillnet fishery targeting predominately juveniles and an offshore hook fishery targeting predominately adults highlight the need to use a precautionary approach when developing harvest strategies.
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Background: The rising temperature of the world’s oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. Methodology/Principal Findings: Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers’ field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. Conclusions/Significance: Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch’s Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate