Effect of antiretroviral therapy on progression of endothelial dysfunction in acquired immune deficiency syndrome patients

Background: Though the natural history of Human Immunodeficiency Virus (HIV) infection in many patients has been dramatically altered through the use of antiretroviral therapy, this treatment paradigm of chronic chemotherapy may not be sustainable given the short and long-term toxicities of these medications. Currently, there is lack of data in the Indian literature regarding study of endothelial dysfunction in HIV patients. The purpose of our research was to study the effect of anti-retroviral therapy on the progression of endothelial dysfunction in HIV/AIDS patients.Methods: The study comprises a total number of 30 adult HIV positive patients of both sex with confirmed HIV seropositivity and CD 4+T cell count < 200/µl. None of these patients had ever received anti retroviral therapy (ART). These patients were subjected to detailed clinical examination and markers of endothelial dysfunction - Flow mediated vasodilatation (FMD) of brachial artery, S. Nitrite and C-reactive protein (CRP) were performed before starting ART. Study group patients were started on ART, they received triple drug ART (Lamivudine 150 mg BD, Stavudine 30 mg BD, Nevirapine 200 mg BD). In patients on ART after a period of 6 months, markers of endothelial dysfunction - FMD, S. Nitrite and CRP tests were reassessed.Results: FMD (4.08±3.58) and S. Nitrite (20.83±13.75) were also depressed after six months of anti retroviral therapy. Also, patients showed more CRP positivity and higher titres after ART. CD 4+T cell count before ART (124.16±84.46) and after ART (186.63±70.96). This rise in count was statistically significant.Conclusions: HIV patients who are receiving ART demonstrate a number of metabolic abnormalities with more severe depression in markers of endothelial function

Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts

We thank the Peggy and Charles Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK, for funding, who received an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20 GM103639 for the use of the Histology and Immunohistochemistry Core for providing immunohistochemistry and photographic services. This work was also supported by Oklahoma State University, Center of Veterinary Health Science (Support Grant AE-1-50060 to P.C.S.), the Musella Foundation (R.A.T.), and the Childhood Brain Tumor Foundation (R.A.T.).Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals (Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05), as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients.Yeshttp://www.plosone.org/static/editorial#pee

The DUNE far detector vertical drift technology. Technical design report

DUNE is an international experiment dedicated to addressing some of the questions at the forefront of particle physics and astrophysics, including the mystifying preponderance of matter over antimatter in the early universe. The dual-site experiment will employ an intense neutrino beam focused on a near and a far detector as it aims to determine the neutrino mass hierarchy and to make high-precision measurements of the PMNS matrix parameters, including the CP-violating phase. It will also stand ready to observe supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector implements liquid argon time-projection chamber (LArTPC) technology, and combines the many tens-of-kiloton fiducial mass necessary for rare event searches with the sub-centimeter spatial resolution required to image those events with high precision. The addition of a photon detection system enhances physics capabilities for all DUNE physics drivers and opens prospects for further physics explorations. Given its size, the far detector will be implemented as a set of modules, with LArTPC designs that differ from one another as newer technologies arise. In the vertical drift LArTPC design, a horizontal cathode bisects the detector, creating two stacked drift volumes in which ionization charges drift towards anodes at either the top or bottom. The anodes are composed of perforated PCB layers with conductive strips, enabling reconstruction in 3D. Light-trap-style photon detection modules are placed both on the cryostat's side walls and on the central cathode where they are optically powered. This Technical Design Report describes in detail the technical implementations of each subsystem of this LArTPC that, together with the other far detector modules and the near detector, will enable DUNE to achieve its physics goals

Performance of a modular ton-scale pixel-readout liquid argon time projection chamber

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations

Intensified tuberculosis and HIV surveillance in a prison in Northeast India: Implementation research.

Structural and individual level factors in prisons create challenges towards detection and management of HIV/tuberculosis. WHO and India's HIV/tuberculosis control programs recommend intensified case finding in prisons. Low HIV and tuberculosis detection rates suggest poor implementation of existing surveillance strategies within the prison healthcare system in Mizoram's capital city of Aizawl. We explored the operational feasibility of implementing the intensified case finding strategy in Aizawl central prison. We implemented the intensified screening through entry screening of new inmates, mass screening of resident inmates and exit screening at release. We set up digital chest radiography, sputum smear microscopy and HIV testing facilities within the prison and referral to external facility for Cartridge Based Nucleic Acid Amplification Test (CBNAAT). We screened 738 inmates (Male: 626; Female: 112). Of 53% inmates having presumptive tuberculosis symptoms, 37% underwent sputum microscopy. We detected 14 new tuberculosis cases; overall tuberculosis positivity 1.9%. We tested 65% of 657 inmates for HIV, of which 41 new cases were detected; overall HIV positivity 16.5%. Three male inmates had HIV-tuberculosis co-infection. It is feasible to implement intensified case detection for tuberculosis/HIV in the prison with inter-departmental coordination, albeit with certain challenges

Effect of age and season on the thyroid hormone activity of Mizoram strain female mithun (Bos frontalis)

Aim: The aim of the present study was to generate baseline data on the normal values of the thyroidhormone (TH) activity as well as their correlation with age and season. Materials and Methods: Blood samples (10 ml) were collected from jugular vein of 30 female mithun’s of three different age groups viz. Calves (6 months to 1 year), heifer (1-3 years) and adult (above 3 years) during the three season’s viz. Monsoon, winter and spring of a year. The serum was analyzed for thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) activity. Result: The result showed a significantly (p<0.05) a higher T3 level in heifers followed by adults and calves and higher T4 level in adults followed by heifers and calves in all the seasons. The TSH level was higher in heifers in all the seasons. The winter season recorded higher level of T3, T4, and TSH as compared to the other seasons of a year. Conclusion: The TSH and T3 level were the highest for aheifer, whereas T4 level was the highest for adults inall the season. Furthermore, the higher level of TH was observed in winter season. The increased level of the TH during the winter season signifies their calorigenic effect. Similarly in heifers, the increased T3 concentrations show its importance in reproductive physiology and its association with ovarian activity. This indicates that age and season have aprofound effect on TH activity of Mizoram strain female mithun

Dicationic Alkylidene−, Olefin−, and Alkoxyalkenylcarbene−Osmium Complexes Stabilized by a NHC Ligand

7 páginas, 3 figuras, 5 esquemas.Complex [Os(═CHPh)(CH3CN)4(IPr)](OTf)2 (1) (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazolylidene; OTf = CF3SO3) exchanges the alkylidene group with propylene to give styrene and [Os(═CHCH3)(CH3CN)4(IPr)](OTf)2 (2). The reaction of 1 with ethylene leads to [Os(η2-CH2═CH2)(CH3CN)4(IPr)](OTf)2 (3) via the propylene intermediate [Os(η2-CH2═CHCH3)(CH3CN)4(IPr)](OTf)2 (4). Acetonitrile displaces the olefin ligand of both 3 and 4 to generate the pentakis (solvento) derivative [Os(CH3CN)5(IPr)](OTf)2 (5). In 2-propanol and methanol, complex 5 reacts with 1,1-diphenyl-2-propyn-1-ol and 2-methyl-3-butyn-2-ol to yield the corresponding alkoxyalkenylcarbene compounds [Os{═C(OR)CH═CR′2}(CH3CN)4(IPr)](OTf)2 (R = CH(CH3)2; R′ = Ph (6), CH3 (7); R = CH3; R′ = Ph (8), CH3 (9)). The X-ray structures of 4, 5, and 6 are also reported.Peer reviewe

C−C Bond Activation of the NHC Ligand of an Osmium−Amido Complex

Treatment of (η6-p-cymene)OsCl2(IPr) (1, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazolylidene) with AgBF4 in acetonitrile leads to [(η6-p-cymene)Os(CH3CN)2(IPr)][BF4]2 (2), which reacts with aniline and cyclohexylamine to afford [(η6-p-cymene)Os(dNHR)(IPr)]BF4 (R = Ph (3), Cy (4)). Complexes 3 and 4 have also been prepared by addition of nBuLi to tetrahydrofuran solutions of the amine compounds [(η6-p-cymene)OsCl(NH2R)(IPr)]BF4 (R = Ph (6), Cy (7)). Complex 4 decomposes in tetrahydrofuran at 100 _C and in the presence of H2O to give cyclohexanone, propane, and [η6-p-cymene)Os{CCHCHCHC(iPr)CNCHCHN(C6H3iPr2)C}(NH3)]BF4 (8). In dichloromethane at 50 _C, 4 evolves to [(η6-p-cymene)OsH(NHdCCH2CH2CH2CH2CH2)(IPr)]BF4 (9), which also gives 8 in tetrahydrofuran at 100ºC and in the presence of H2O. On the basis of these transformations, a mechanism for the formation of 8 is proposed.Financial support from the Spanish MICINN (project number CTQ2008-00810 and Consolider Ingenio 2010 CSD2007-00006), the Diputación General de Aragón (E35), and the European Social Fund is acknowledged.Peer Reviewe