Antiretroviral Treatment for HIV Elite Controllers?

In most HIV-infected persons, the natural history of untreated infection is one of sustained viremia, progressive CD4 T cell depletion with resultant morbidity and mortality. The advent of effective combination antiretroviral therapy (ART) that controls HIV replication has altered this landscape dramatically. Yet a rare population of HIV-infected persons-elite controllers (EC)-can control HIV replication such that plasma levels of virus are "undetectable" without ART. The EC phenotype is heterogeneous, with some subjects durably controlling the virus-persistent elite controllers-and some eventually losing viral control-transient elite controllers. Overall, EC tend to have robust HIV-specific T cell responses and in some cases, mainly in transient elite controllers, elevated activation and inflammation indices that diminish with ART suggesting that endogenous defenses against this persistent pathogen come at the cost of heightened activation/inflammation. A limited data set suggests that cardiovascular disease risk as well as the occur-rence of other morbid events may be greater in the overall EC population than in treated HIV infection. ART in EC decreases activation indices but does not appear to increase circulating CD4 T cell numbers nor do we know if it alters clinical outcomes. Thus, it is difficult to recommend or discourage a decision to start ART in the EC population but the authors lean toward treatment particularly in those EC whose activation indices are high and those who are progressively losing circulating CD4 T cell numbers. Biomarkers that can reliably predict loss of virologic control and immune failure are needed

Nephrotic syndrome caused by Babesia spp. in a dog: A case repor

P?ginas. 91-99Un canino, macho, entero, de raza Weimaraner, de dos a?os de edad, es presentado a consulta por adelgazamiento progresivo y distensi?n abdominal en el transcurso de cuatro semanas. Al realizar examen cl?nico y las pruebas de laboratorio, se confirm? la presencia de s?ndrome nefr?tico y enfermedad renal cr?nica, posiblemente desencadenada por Babesia spp. El tratamiento se enfoc? en el control del hemopar?sito y manejo sintom?tico de las afecciones asociadas al s?ndrome. El presente documento expone un caso cl?nico de s?ndrome nefr?tico, su diagn?stico y tratamiento.ABSTRACT. A two-years-old canine intact male Weimaraner is presented to the veterinary clinic with a record of progressive weight loss and abdominal distension since 4 weeks ago. Clinical examination and laboratory tests confirmed the presence of nephrotic syndrome and chronic kidney disease, suspected to be caused by Babesia spp. The treatment was focused on the hemoparasites and reduction of ascites. In this report we discuss the nephrotic syndrome, its diagnosis and treatment

Enhancement of spin orbit coupling at manganite surfaces

Spin orbit coupling in magnetic systems lacking inversion symmetry can give rise to nontrivial spin textures. Magnetic thin films and heterostructures are potential candidates for the formation of skyrmions and other noncollinear spin configurations as inversion symmetry is inherently lost at their surfaces and interfaces. However, manganites, in spite of their extraordinarily rich magnetic phase diagram, have not yet been considered of interest within this context as their spin orbit coupling is assumed to be negligible. We demonstrate here, by means of angular dependent x ray linear dichroism experiments and theoretical calculations, the existence of a noncollinear antiferromagnetic ordering at the surface of ferromagnetic La2 3Sr1 3MnO3 thin films whose properties can only be explained by an unexpectedly large enhancement of the spin orbit interaction. Our results reveal that spin orbit coupling, usually assumed to be very small in manganites, can be significantly enhanced at surfaces and interfaces adding a new twist to the possible magnetic orders that can arise in electronically reconstructed system

Impact of footwear and foot deformities in patients with Parkinson?s disease: A case-series study

Background: Parkinson's disease (PD) is a common and complex neurological problem. Gait abnormalities are frequent in PD patients, and this increases the risk of falls. However, little is known about foot deformities and footwear in this vulnerable population. Here we investigate whether patients with PD use an appropriate shoe size and know if they have foot deformities or alterations. Methodology: A study of a series of observational descriptive cases in a convenience sample (n = 53 patients) diagnosed with Parkinson's disease. One trained investigator evaluated foot and ankle health. The footwear and foot measurements were obtained using a Brannock device. Results: The podiatric examination and footwear examination detected a high presence of podiatric pathologies and inappropriate footwear. This has a negative impact on the quality of life of these patients. Conclusions: This research detected an elevated number of people with foot deformities or alterations. Moreover, a high proportion of participants with PD wear inadequate footwear (in length, width, or both)

ZrO2 Based materials as photocatalysts for 2-propanol oxidation by using UV and solar light irradiation and tests for CO2 reduction

Bare ZrO2, Ce doped ZrO2 and Er doped ZrO2 samples have been prepared by a hydrothermal process and have been used as photocatalysts for 2-propanol oxidation reaction in gas solid regime. Moreover, some preliminary tests have been carried out for CO2 reduction. The samples were physico-chemically characterized and both bare and doped ZrO2 based materials resulted active for oxidation and reduction reactions by using UV and solar irradiation. The reactivity results have been correlated with the compositional, structural and morphological features of the photocatalysts

Temperature but not leptin prevents semi-starvation induced hyperactivity in rats: implications for anorexia nervosa treatment

The hypothesis linking hyperactivity with weight loss associated hypoleptinemia in anorexia nervosa gained momentum after a study showing that leptin suppressed semi-starvation induced hyperactivity in rats. Alternatively, ambient temperature is a key modulating factor of activity in semi-starved rats. The aim of the study is to compare the efficacy of leptin with increased ambient temperature in the prevention of hyperactivity in semi-starved rats. 74 Sprague-Dawley male rats were employed in two experiments with the difference residing in the length of baseline. After an extended (28 days), or shorter (14 days) baseline with free access to food and the running wheel, housed at 21 degrees C, animals were either ad-lib feed or food restricted (60% of food ingested during previous week) and infused with same amount of leptin at 21 degrees C, 25 degrees C, or vehicle at 21 degrees C, 25 degrees C and 32 degrees C for a week. Animals housed at 32 degrees C significantly reduced wheel running and weight loss during food restriction while animals given leptin did not yield no differences in activity or weight loss. Moreover, unlike animals housed at 32 degrees C, body temperature of leptin infused animals housed at 21 degrees C was significantly reduced during food restriction. Furthermore, leptin treated rats without a preceding stable pattern of activity displayed a severe dysregulation of circadian rhythm in activity and a collapse of body temperature. Housing temperature plays a more critical role than leptin in the regulation of semi-starvation induced hyperactivity in rats, which may be of relevance for the management of hyperactivity in anorexia nervosa

Rapid Phenotype-Driven Gene Sequencing with the NeoSeq Panel: A Diagnostic Tool for Critically Ill Newborns with Suspected Genetic Disease

New genomic sequencing techniques have shown considerable promise in the field of neonatology, increasing the diagnostic rate and reducing time to diagnosis. However, several obstacles have hindered the incorporation of this technology into routine clinical practice. We prospectively evaluated the diagnostic rate and diagnostic turnaround time achieved in newborns with suspected genetic diseases using a rapid phenotype-driven gene panel (NeoSeq) containing 1870 genes implicated in congenital malformations and neurological and metabolic disorders of early onset (<2 months of age). Of the 33 newborns recruited, a genomic diagnosis was established for 13 (39.4%) patients (median diagnostic turnaround time, 7.5 days), resulting in clinical management changes in 10 (76.9%) patients. An analysis of 12 previous prospective massive sequencing studies (whole genome (WGS), whole exome (WES), and clinical exome (CES) sequencing) in newborns admitted to neonatal intensive care units (NICUs) with suspected genetic disorders revealed a comparable median diagnostic rate (37.2%), but a higher median diagnostic turnaround time (22.3 days) than that obtained with NeoSeq. Our phenotype-driven gene panel, which is specific for genetic diseases in critically ill newborns is an affordable alternative to WGS and WES that offers comparable diagnostic efficacy, supporting its implementation as a first-tier genetic test in NICUs

Identification of a novel synthetic lethal vulnerability in non-small cell lung cancer by co-targeting TMPRSS4 and DDR1

Finding novel targets in non-small cell lung cancer (NSCLC) is highly needed and identification of synthetic lethality between two genes is a new approach to target NSCLC. We previously found that TMPRSS4 promotes NSCLC growth and constitutes a prognostic biomarker. Here, through large-scale analyses across 5 public databases we identified consistent co-expression between TMPRSS4 and DDR1. Similar to TMPRSS4, DDR1 promoter was hypomethylated in NSCLC in 3 independent cohorts and hypomethylation was an independent prognostic factor of disease-free survival. Treatment with 5-azacitidine increased DDR1 levels in cell lines, suggesting an epigenetic regulation. Cells lacking TMPRSS4 were highly sensitive to the cytotoxic effect of the DDR1 inhibitor dasatinib. TMPRSS4/DDR1 double knock-down (KD) cells, but not single KD cells suffered a G0/G1 cell cycle arrest with loss of E2F1 and cyclins A and B, increased p21 levels and a larger number of cells in apoptosis. Moreover, double KD cells were highly sensitized to cisplatin, which caused massive apoptosis (~40%). In vivo studies demonstrated tumor regression in double KD-injected mice. In conclusion, we have identified a novel vulnerability in NSCLC resulting from a synthetic lethal interaction between DDR1 and TMPRSS4

Pass a Law, Any Law, Fast! State Legislative Responses to the Kelo Backlash

The Supreme Court in Kelo v. City of New London left protection of property against takings for economic development to the states. Since Kelo, thirty-seven states have enacted legislation to update their eminent domain laws. This paper is the first to theoretically and empirically analyze the factors that influence whether, in what manner, and how quickly states change their laws through new legislation. Fourteen of the thirty-seven new laws offer only weak protections against development takings. The legislative response to Kelo was responsive to measures of the backlash but only in the binary decision whether to pass any new law. The decision to enact a meaningful restriction was more a function of relevant political economy measures. States with more economic freedom, greater value of new housing construction, and less racial and income inequality are more likely to have enacted stronger restrictions, and sooner. Of the thirteen states that have not updated, Arkansas, Oklahoma and Mississippi are highly likely to do so in the future. Hawaii, Massachusetts and New York are unlikely to update ever if at all

Structural dynamics during laser induced ultrafast demagnetization

The mechanism underlying femtosecond laser pulse induced ultrafast magnetization dynamics remains elusive despite two decades of intense research on this phenomenon. Most experiments focused so far on characterizing magnetization and charge carrier dynamics, while first direct measurements of structural dynamics during ultrafast demagnetization were reported only very recently. We here present our investigation of the infrared laser pulse induced ultrafast demagnetization process in a thin Ni film, which characterizes simultaneously magnetization and structural dynamics. This is achieved by employing femtosecond time resolved X-ray resonant magnetic reflectivity (tr-XRMR) as probe technique. The experimental results reveal unambiguously that the sub-picosecond magnetization quenching is accompanied by strong changes in non-magnetic X-ray reflectivity. These changes vary with reflection angle and changes up to 30$\%$ have been observed. Modeling the X-ray reflectivity of the investigated thin film, we can reproduce these changes by a variation of the apparent Ni layer thickness of up to 1$\%$. Extending these simulations to larger incidence angles we show that tr-XRMR can be employed to discriminate experimentally between currently discussed models describing the ultrafast demagnetization phenomenon