Th1-Th17 Cells Mediate Protective Adaptive Immunity against Staphylococcus aureus and Candida albicans Infection in Mice

We sought to define protective mechanisms of immunity to Staphylococcus aureus and Candida albicans bloodstream infections in mice immunized with the recombinant N-terminus of Als3p (rAls3p-N) vaccine plus aluminum hydroxide (Al(OH3) adjuvant, or adjuvant controls. Deficiency of IFN-γ but not IL-17A enhanced susceptibility of control mice to both infections. However, vaccine-induced protective immunity against both infections required CD4+ T-cell-derived IFN-γ and IL-17A, and functional phagocytic effectors. Vaccination primed Th1, Th17, and Th1/17 lymphocytes, which produced pro-inflammatory cytokines that enhanced phagocytic killing of both organisms. Vaccinated, infected mice had increased IFN-γ, IL-17, and KC, increased neutrophil influx, and decreased organism burden in tissues. In summary, rAls3p-N vaccination induced a Th1/Th17 response, resulting in recruitment and activation of phagocytes at sites of infection, and more effective clearance of S. aureus and C. albicans from tissues. Thus, vaccine-mediated adaptive immunity can protect against both infections by targeting microbes for destruction by innate effectors

Silencing Early Viral Replication in Macrophages and Dendritic Cells Effectively Suppresses Flavivirus Encephalitis

West Nile (WN) and St. Louis encephalitis (SLE) viruses can cause fatal neurological infection and currently there is neither a specific treatment nor an approved vaccine for these infections. In our earlier studies, we have reported that siRNAs can be developed as broad-spectrum antivirals for the treatment of infection caused by related viruses and that a small peptide called RVG-9R can deliver siRNA to neuronal cells as well as macrophages. To increase the repertoire of broad-spectrum antiflaviviral siRNAs, we screened 25 siRNAs targeting conserved regions in the viral genome. Five siRNAs were found to inhibit both WNV and SLE replication in vitro reflecting broad-spectrum antiviral activity and one of these was also validated in vivo. In addition, we also show that RVG-9R delivers siRNA to macrophages and dendritic cells, resulting in effective suppression of virus replication. Mice were challenged intraperitoneally (i.p.) with West Nile virus (WNV) and treated i.v. with siRNA/peptide complex. The peritoneal macrophages isolated on day 3 post infection were isolated and transferred to new hosts. Mice receiving macrophages from the anti-viral siRNA treated mice failed to develop any disease while the control mice transferred with irrelevant siRNA treated mice all died of encephalitis. These studies suggest that early suppression of viral replication in macrophages and dendritic cells by RVG-9R-mediated siRNA delivery is key to preventing the development of a fatal neurological disease

Immediate response of myocardium to pressure overload includes transient regulation of genes associated with mitochondrial bioenergetics and calcium availability

Ventricular hypertrophy is one of the major myocardial responses to pressure overload (PO). Most studies on early myocardial response focus on the days or even weeks after induction of hypertrophic stimuli. Since mechanotransduction pathways are immediately activated in hearts undergoing increased work load, it is reasonable to infer that the myocardial gene program may be regulated in the first few hours. In the present study, we monitored the expression of some genes previously described in the context of myocardial hypertrophic growth by using the Northern blot technique, to estimate the mRNA content of selected genes in rat myocardium for the periods 1, 3, 6, 12 and 48 h after PO stimuli. Results revealed an immediate switch in the expression of genes encoding alpha and beta isoforms of myosin heavy chain, and up-regulation of the cardiac isoform of alpha actin. We also detected transitory gene regulation as the increase in mitochondrial cytochrome c oxidase 1 gene expression, parallel to down-regulation of genes encoding sarco(endo)plasmic reticulum Ca+2 ATPase and sodium-calcium exchanger. Taken together, these results indicate that initial myocardial responses to increased work load include alterations in the contractile properties of sarcomeres and transitory adjustment of mitochondrial bioenergetics and calcium availability

Automated Analysis of Cryptococcal Macrophage Parasitism Using GFP-Tagged Cryptococci

The human fungal pathogens Cryptococcus neoformans and C. gattii cause life-threatening infections of the central nervous system. One of the major characteristics of cryptococcal disease is the ability of the pathogen to parasitise upon phagocytic immune effector cells, a phenomenon that correlates strongly with virulence in rodent models of infection. Despite the importance of phagocyte/Cryptococcus interactions to disease progression, current methods for assaying virulence in the acrophage system are both time consuming and low throughput. Here, we introduce the first stable and fully characterised GFP–expressing derivatives of two widely used cryptococcal strains: C. neoformans serotype A type strain H99 and C. gattii serotype B type strain R265. Both strains show unaltered responses to environmental and host stress conditions and no deficiency in virulence in the macrophage model system. In addition, we report the development of a method to effectively and rapidly investigate macrophage parasitism by flow cytometry, a technique that preserves the accuracy of current approaches but offers a four-fold improvement in speed

Subtidal macrozoobenthos communities from northern Chile during and post El Niño 1997–1998

Despite a large amount of climatic and oceanographic information dealing with the recurring climate phenomenon El Niño (EN) and its well known impact on diversity of marine benthic communities, most published data are rather descriptive and consequently our understanding of the underlying mechanisms and processes that drive community structure during EN are still very scarce. In this study, we address two questions on the effects of EN on macrozoobenthic communities: (1) how does EN affect species diversity of the communities in northern Chile? and (2) is EN a phenomenon that restarts community assembling processes by affecting species interactions in northern Chile? To answer these questions, we compared species diversity and co-occurrence patterns of soft-bottoms macrozoobenthos communities from the continental shelf off northern Chile during (March 1998) and after (September 1998) the strong EN event 1997–1998. The methods used varied from species diversity and species co-occurrence analyses to multivariate ordination methods. Our results indicate that EN positively affects diversity of macrozoobenthos communities in the study area, increasing the species richness and diversity and decreasing the species dominance. EN represents a strong disturbance that affects species interactions that rule the species assembling processes in shallow-water, sea-bottom environments

A systematic review and meta-analysis of bone metabolism in prostate adenocarcinoma

<p/> <p>Background</p> <p>Osteoporosis could be associated with the hormone therapy for metastatic prostate carcinoma (PCa) and with PCa <it>per se</it>. The objective of this review is to determine the incidence of bone loss and osteoporosis in patients with PCa who are or are not treated with hormone therapy (ADT).</p> <p>Methods</p> <p>The Medline, Embase, Cancerlit, and American Society of Clinical Oncology Abstract databases were searched for published studies on prostate cancer and bone metabolism. The outcomes assessed were: fracture, osteoporosis and osteopenia.</p> <p>Results</p> <p>Thirty-two articles (116,911 participants) were included in the meta-analysis. PCa patients under ADT had a higher risk of osteoporosis (RR, 1.30; <it>p </it>< 0.00001) and a higher risk of fractures (RR, 1.17; <it>p </it>< 0.00001) as compared to patients not under ADT. The total bone mineral density was lower in patients under ADT when compared with patients not under ADT (<it>p </it>= 0.031) but it was similar to bone mineral density found in healthy controls (<it>p </it>= 0.895). The time of androgen deprivation therapy correlated negatively with lumbar spine and total hip bone mineral density (Spearman's rho = -0.490 and -0.773; <it>p </it>= 0.028 and 0.001, respectively) and with total hip <it>t </it>score (Spearman's rho = -0.900; <it>p </it>= 0.037).</p> <p>Conclusion</p> <p>We found consistent evidence that the use of androgen deprivation therapy in patients with PCa reduces bone mineral density, increasing the risk of fractures in these patients.</p

Left atrial volume predicts adverse cardiac and cerebrovascular events in patients with hypertrophic cardiomyopathy

<p>Abstract</p> <p>Aims</p> <p>To prospectively evaluate the relationship between left atrial volume (LAV) and the risk of clinical events in patients with hypertrophic cardiomyopathy (HCM).</p> <p>Methods</p> <p>We enrolled a total of 141 HCM patients with sinus rhythm and normal pump function, and 102 patients (73 men; mean age, 61 ± 13 years) who met inclusion criteria were followed for 30.8 ± 10.0 months. The patients were divided into two groups with or without major adverse cardiac and cerebrovascular events (MACCE), a composite of stroke, sudden death, and congestive heart failure. Detailed clinical and echocardiographic data were obtained.</p> <p>Results</p> <p>MACCE occurred in 24 patients (18 strokes, 4 congestive heart failure and 2 sudden deaths). Maximum LAV, minimum LAV, and LAV index (LAVI) corrected for body surface area (BSA) were significantly greater in patients with MACCE than those without MACCE (maximum LAV: 64.3 ± 25.0 vs. 51.9 ± 16.0 ml, p = 0.005; minimum LAV: 33.9 ± 15.1 vs. 26.2 ± 10.9 ml, p = 0.008; LAVI: 40.1 ± 15.4 vs. 31.5 ± 8.7 ml/mm², p = 0.0009), while there were no differences in the other echocardiographic parameters.</p> <p>LAV/BSA of ≥ 40.4 ml/m²to identify patients with cardiovascular complications with a sensitivity of 73% and a specificity of 88%.</p> <p>Conclusion</p> <p>LAVI may be an effective marker for detecting the risk of MACCE in patients with HCM and normal pump function.</p

Hepatitis B and Hepatocellular Carcinoma Screening Among Asian Americans: Survey of Safety Net Healthcare Providers

BackgroundPhysician patterns of screening for hepatitis B (HBV) and hepatocellular carcinoma (HCC) among Asian Americans are not well described.AimsTo describe HBV and HCC screening practices among providers with large Asian American populations.MethodsProviders within San Francisco's safety net system were surveyed with respect to HBV and HCC screening practices as well as knowledge, attitudes, and barriers to HCC screening.ResultsAmong the 109 respondents (response rate = 72%), 62% were aged &gt;40, 65% female, 24% Asian, 87% primary care providers, and 48% had &gt;25% Asian patients. Only 76% had screened &gt;50% of their Asian patients for HBV and 43% had vaccinated &gt;50% of eligible patients against HBV. Although 94% knew Asians were disproportionately affected by HCC, only 79% had screened for HCC in &gt;50% of their Asian patients with chronic hepatitis B (CHB). A majority believed that HCC screening in CHB reduces HCC mortality (70%) and is cost-effective (57%). The most common HCC screening modality was AFP with abdominal ultrasound every 6-12 months (63%). Factors associated with HBV screening were familiarity with AASLD guidelines (OR 6.4, 95% CI 1.3-30.1, p = 0.02) and having vaccinated &gt;50% of eligible patients against HBV (OR 2.2, 95% CI 1.1-4.5, p = 0.03). Factors associated with HCC screening using abdominal ultrasound every 6-12 months were having &gt;25% Asian patients (OR = 4.5, 95% CI 1.3-15.3, p = 0.02) and higher HCC knowledge score (OR = 1.9 per item, 95% CI 1.01-3.6, p = 0.045).ConclusionsHBV and HCC screening rates and HBV vaccination among Asians from physician report is suboptimal. HCC screening is associated with having more Asian patients and higher provider knowledge. Provider education is essential in increasing rates of HBV and HCC screening among Asian Americans

Iterative Evolution of Sympatric Seacow (Dugongidae, Sirenia) Assemblages during the Past ∼26 Million Years

Extant sirenians show allopatric distributions throughout most of their range. However, their fossil record shows evidence of multispecies communities throughout most of the past ∼26 million years, in different oceanic basins. Morphological differences among co-occurring sirenian taxa suggest that resource partitioning played a role in structuring these communities. We examined body size and ecomorphological differences (e.g., rostral deflection and tusk morphology) among sirenian assemblages from the late Oligocene of Florida, early Miocene of India and early Pliocene of Mexico; each with three species of the family Dugongidae. Although overlapping in several ecomorphological traits, each assemblage showed at least one dominant trait in which coexisting species differed. Fossil sirenian occurrences occasionally are monotypic, but the assemblages analyzed herein show iterative evolution of multispecies communities, a phenomenon unparalleled in extant sirenian ecology. As primary consumers of seagrasses, these communities likely had a strong impact on past seagrass ecology and diversity, although the sparse fossil record of seagrasses limits direct comparisons. Nonetheless, our results provide robust support for previous suggestions that some sirenians in these extinct assemblages served as keystone species, controlling the dominance of climax seagrass species, permitting more taxonomically diverse seagrass beds (and sirenian communities) than many of those observed today

Species Interactions during Diversification and Community Assembly in an Island Radiation of Shrews

Closely related, ecologically similar species often have adjacent distributions, suggesting competitive exclusion may contribute to the structure of some natural communities. In systems such as island archipelagos, where speciation is often tightly associated with dispersal over oceanic barriers, competitive exclusion may prevent population establishment following inter-island dispersal and subsequent cladogenesis.) species in the Philippines are the result of competitive exclusion preventing secondary invasion of occupied islands. We first compare ecological niche models between two widespread, allopatric species and find statistical support for their ecological similarity, implying that competition for habitat between these species is possible. We then examine dispersion patterns among sympatric species and find some signal for overdispersion of body size, but not for phylogenetic branch length. Finally, we simulate the process of inter-island colonization under a stochastic model of dispersal lacking ecological forces. Results are dependent on the geographic scope and colonization probability employed. However, some combinations suggest that the number of inter-island dispersal events necessary to populate the archipelago may be much higher than the minimum number of colonization events necessary to explain current estimates of species richness and phylogenetic relationships. If our model is appropriate, these results imply that alternative factors, such as competitive exclusion, may have influenced the process of inter-island colonization and subsequent cladogenesis.We interpret the combined results as providing tenuous evidence that similarity in body size may prevent co-occurrence in Philippine shrews and that competitive exclusion among ecologically similar species, rather than an inability to disperse among islands, may have limited diversification in this group, and, possibly other clades endemic to island archipelagos