Thioredoxin-Interacting Protein Deficiency Protects against Diabetic Nephropathy

Expression of thioredoxin-interacting protein (TxNIP), an endogenous inhibitor of the thiol oxidoreductase thioredoxin, is augmented by high glucose (HG) and promotes oxidative stress. We previously reported that TxNIP-deficient mesangial cells showed protection from HG-induced reactive oxygen species, mitogen-activated protein kinase phosphorylation, and collagen expression. Here, we investigated the potential role of TxNIP in the pathogenesis of diabetic nephropathy (DN) in vivo. Wild-type (WT) control, TxNIP^−/−, and TxNIP^+/− mice were rendered equally diabetic with low-dose streptozotocin. In contrast to effects in WT mice, diabetes did not increase albuminuria, proteinuria, serum cystatin C, or serum creatinine levels in TxNIP^−/− mice. Whereas morphometric studies of kidneys revealed a thickened glomerular basement membrane and effaced podocytes in the diabetic WT mice, these changes were absent in the diabetic TxNIP^−/− mice. Immunohistochemical analysis revealed significant increases in the levels of glomerular TGF-β1, collagen IV, and fibrosis only in WT diabetic mice. Additionally, only WT diabetic mice showed significant increases in oxidative stress (nitrotyrosine, urinary 8-hydroxy-2-deoxy-guanosine) and inflammation (IL-1β mRNA, F4/80 immunohistochemistry). Expression levels of Nox4-encoded mRNA and protein increased only in the diabetic WT animals. A significant loss of podocytes, assessed by Wilms’ tumor 1 and nephrin staining and urinary nephrin concentration, was found in diabetic WT but not TxNIP^−/− mice. Furthermore, in cultured human podocytes exposed to HG, TxNIP knockdown with siRNA abolished the increased mitochondrial O₂⁻ generation and apoptosis. These data indicate that TxNIP has a critical role in the progression of DN and may be a promising therapeutic target.     

Disclosure of Microbicide Gel Use to Sexual Partners: Influence on Adherence in the CAPRISA 004 Trial

Young women in sub-Saharan Africa are disproportionately affected by HIV, making the development of women initiated and controlled methods of prevention, including microbicides, a priority. Adherence is pivotal to microbicide efficacy and partner related factors are known to impact adherence. An analysis of disclosure of gel use to sexual partners and adherence in CAPRISA 004 women was conducted to better understand this relationship. Partner disclosure was significantly associated with a modest 4.2 % increased adherence (71.0 vs. 66.8 %, p = 0.03). Most women rated the experience of disclosure as positive, despite 6.7 % of partners expressing a negative reaction.Participants who disclosed were more likely to reside with their regular partner (14.4 vs. 8.4 %; p = 0.01) and reported consistent condom use at baseline (32.9 vs. 20.9 %; p < 0.01). Partner disclosure needs to be better understood as a potential facilitator or barrier to microbicide adherence.     

Exploiting sensitization windows of opportunity in hyper and hypo-fractionated radiation therapy

In contrast to the conventional radiotherapy/chemoradiotherapy paradigms used in the treatment of majority of cancer types, this review will describe two areas of radiobiology, hyperfractionated and hypofractionated radiation therapy, for cancer treatment focusing on application of novel concepts underlying these treatment modalities. The initial part of the review discusses the phenomenon of hyper-radiation sensitivity (HRS) at lower doses (0.1 to 0.6 Gy), describing the underlying mechanisms and how this could enhance the effects of chemotherapy, particularly, in hyperfractionated settings. The second part examines the radiobiological/physiological mechanisms underlying the effects of high-dose hypofractionated radiation therapy that can be exploited for tumor cure. These include abscopal/bystander effects, activation of immune system, endothelial cell death and effect of hypoxia with re-oxygenation. These biological properties along with targeted dose delivery and distribution to reduce normal tissue toxicity may make high-dose hypofractionation more effective than conventional radiation therapy for treatment of advanced cancers. The novel radiation physics based methods that take into consideration the tumor volume to be irradiated and normal tissue avoidance/tolerance can further improve treatment outcome and post-treatment quality of life. In conclusion, there is enough evidence to further explore novel avenues to exploit biological mechanisms from hyper-fractionation by enhancing the efficacy of chemotherapy and hypo-fractionated radiation therapy that could enhance tumor control and use imaging and technological advances to reduce toxicity.KEYWORDS : Low Doses Fractionated Radiation Therapy (LDFRT), hyper-radiation sensitivity (HRS), induced radiation resistance (IRR), hyperfractionation, chemopotentiation, stereotactic body radiation therapy (SBRT), stereotactic ablative radiosurgery (SARS), stereotactic ablative radiotherapy (SABR), stereotactic radiosurgery (SRS), spatially fractionated GRID radiotherapy (SFGRT), lattice     

A case report of cecal plasmablastic lymphoma in a HIV-negative patient

Plasmablastic lymphoma (PBL) is a unique type of diffuse proliferation of large neoplastic lymphoid cells most of which resemble B immunoblasts, but all tumor cells show the immunophenotype of plasma cells. It has a strong predilection for jaw and oral cavity in HIV-positive patients. Incidences of extraoral location of this tumor is increasingly being recognized especially in HIV-negative patients for example, stomach, jejunum, omentum, anorectum, lungs, testes, soft tissues, lymph nodes, bone marrow, skin, and central nervous system. We present a case of PBL found in cecum in an HIV-negative patient. It was accompanied by lung and lymph node involvement and presented as abdominal mass. This is only the second reported case of PBL originating in cecum.     

Cross-sectional assessment of prevalence and correlates of blood-borne and sexually-transmitted infections among Afghan National Army recruits

ABSTRACT: BACKGROUND: Few data are available in Afghanistan to shape national military force health practices, particularly with regard to sexually-transmitted infections (STIs). We measured prevalence and correlates of HIV, syphilis, herpes simplex 2 virus (HSV-2), and hepatitis C virus (HCV) among Afghan National Army (ANA) recruits. METHODS: A cross-sectional sample of male ANA recruits aged 18--35 years were randomly selected at the Kabul Military Training Center between February 2010 and January 2011. Participants completed an interviewer-administered questionnaire and serum-based rapid testing for syphilis, hepatitis C virus antibody on-site; HIV and HSV-2 screening, and confirmatory testing were performed off-site. Prevalence of each infection was calculated and logistic regression analysis performed to identify correlates. RESULTS: Of 5313 recruits approached, 4750 consented to participation. Participants had a mean age of 21.8 years (SD[PLUS-MINUS SIGN]3.8), 65.5% had lived outside Afghanistan, and 44.3% had no formal education. Few reported prior marijuana (16.3%), alcohol (5.3%), or opium (3.4%) use. Of sexually active recruits (58.7%, N = 2786), 21.3% reported paying women for sex and 21.3% reported sex with males. Prevalence of HIV (0.063%, 95% CI: 0.013- 0.19), syphilis (0.65%, 95% CI: 0.44 -- 0.93), and HCV (0.82%, 95% CI: 0.58 -- 1.12) were quite low. Prevalence of HSV-2 was 3.03% (95% CI: 2.56 - 3.57), which was independently associated with age (Adjusted Odds Ratio (AOR) = 1.04, 95% CI: 1.00 - 1.09) and having a television (socioeconomic marker) (AOR = 1.46, 95% CI: 1.03 -- 2.05). CONCLUSION: Though prevalence of HIV, HCV, syphilis, and HSV-2 was low, sexual risk behaviors and intoxicant use were present among a substantial minority, indicating need for prevention programming. Formative work is needed to determine a culturally appropriate approach for prevention programming to reduce STI risk among Afghan National Army troops.     

Development of hydrophobic reduced graphene oxide as a new efficient approach for photochemotherapy

Nowadays, chemotherapy is one of the crucial and common therapies in the world. So far, it has been revealed to be highly promising, yet patients suffer from the consequences of severe negative medical dosages. In order to overcome these issues, the enhancement of photothermal chemotherapy with reduced graphene oxide (rGO) as a photothermal agent (PTA) is widely utilised in current medical technologies. This is due to its high near-infrared region (NIR) response, in vitro or in vivo organism biocompatibility, low risk of side effects, and effective positive results. Moreover, rGO not only has the ability to ensure that selective cancer cells have a higher mortality rate but can also improve the growth rate of recovering tissues that are untouched by necrosis and apoptosis. These two pathways are specific diverse modalities of cell death that are distinguished by cell membrane disruption and deoxyribonucleic acid (DNA) disintegration of the membrane via phosphatidylserine exposure in the absence of cell membrane damage. Therefore, this review aimed to demonstrate the recent achievements in the modification of rGO nanoparticles as a PTA as well as present a new approach for performing photochemotherapy in the clinical setting.

rGO of QD-rGO nanocomposite could absorb and convert into heat when harvested under NIR radiation, resulting cell death with reduction of fluorescence.