Gender Bias and Organ Transplantation in Nepal

Women in Nepal are less likely to receive proper, high quality medical care than their male relatives. Live-donor kidney transplantation provides a compelling example of such disparities, as 84% of recipients are male, 75% of donors are female and most kidneys are transferred from mother to son and from wife to husband. In the case of transplantation, women are not just denied healthcare, they are also responsible for the health of their male kin. Based on semi-structured ethnographic interviews with transplant patients, organ donors, dialysis patients and relatives, this paper elaborates on the social and economic factors that have created an extreme gender bias in transplantation. We argue that women, whose livelihoods largely depend on their husbands, donate kidneys out of self-protection and a sense of duty. Conversely, men receive kidneys but rarely donate them to women, because the health of men is a more productive economic investment than the health of women. We reject the notion that wives are directly coerced or pressured into donating kidneys to their husbands. Rather, we argue that female kidney donors make thoughtful, independent decisions that serve their best interests, and allow them to assert some control over their lives. It is, however, Nepal’s patriarchal society that both necessitates and limits such assertions of power

Origin of X-rays in the low state of the FSRQ 3C 273: Evidence of inverse Compton emission

We analyze the 2.5--10 keV X-ray spectra of the luminous quasar 3C 273 and simultaneous observations in UV wavelengths from XMM--Newton between 2000 and 2015. The lowest flux level ever was observed in 2015. The continuum emission from 3C 273 is generally best described by an absorbed power-law but during extremely low states the addition of fluorescence from the K-shell iron line improves the fit. We study the spectral evolution of the source during its extended quiescent state and also examine connections between the X-ray and ultraviolet emissions, which have been seen in some, but not all, previous work. We detect a possible anti-correlation between these two bands during the low state that characterized 3C 273 for most of this period; however, this was not present during a flaring state. A harder-when-brighter trend for the X-ray spectrum was observed in these long-term observations of 3C 273 for the first time. We suggest that the X-ray emission in 3C 273 is the result of inverse Compton scattering of soft UV seed photons (emitted from the local environment of the AGN), most likely in a thermal corona. We can explain the significant temporal variation of the spectral continuum as an outcome of changing optical depth of the comptonizing medium, along the lines of the wind-shock model proposed by Courvoisier and Camenzind (1989).Comment: 17 pages, 8 figures, 3 tables; Accepted for publication in MNRA

Squeezing in Multivariate Spin Systems

In contrast to the canonically conjugate variates $q$,$p$ representing the position and momentum of a particle in the phase space distributions, the three Cartesian components, $J_{x}$,$J_{y}$, $J_{z}$ of a spin-$j$ system constitute the mutually non-commuting variates in the quasi-probabilistic spin distributions. It can be shown that a univariate spin distribution is never squeezed and one needs to look into either bivariate or trivariate distributions for signatures of squeezing. Several such distributions result if one considers different characteristic functions or moments based on various correspondence rules. As an example, discrete probability distribution for an arbitrary spin-1 assembly is constructed using Wigner-Weyl and Margenau-Hill correspondence rules. It is also shown that a trivariate spin-1 assembly resulting from the exposure of nucleus with non-zero quadrupole moment to combined electric quadrupole field and dipole magnetic field exhibits squeezing in cerain cases.Comment: 13 pages, 1 Table, Presented at ICSSUR-05, Franc

Uterine Endoplasmic Reticulum Stress and Its Unfolded Protein Response May Regulate Caspase 3 Activation in the Pregnant Mouse Uterus

We have previously proposed that uterine caspase-3 may modulate uterine contractility in a gestationally regulated fashion. The objective of this study was to determine the mechanism by which uterine caspase-3 is activated and consequently controlled in the pregnant uterus across gestation. Utilizing the mouse uterus as our gestational model we examined the intrinsic and extrinsic apoptotic signaling pathways and the endoplasmic reticulum stress response as potential activators of uterine caspase-3 at the transcriptional and translational level. Our study revealed robust activation of the uterine myocyte endoplasmic reticulum stress response and its adaptive unfolded protein response during pregnancy coinciding respectively with increased uterine caspase-3 activity and its withdrawal to term. In contrast the intrinsic and extrinsic apoptotic signaling pathways remained inactive across gestation. We speculate that physiological stimuli experienced by the pregnant uterus likely potentiates the uterine myocyte endoplasmic reticulum stress response resulting in elevated caspase-3 activation, which is isolated to the pregnant mouse myometrium. However as term approaches, activation of an elevated adaptive unfolded protein response acts to limit the endoplasmic reticulum stress response inhibiting caspase-3 resulting in its decline towards term. We speculate that these events have the capacity to regulate gestational length in a caspase-3 dependent manne

Protective effect of Pisonia aculeata on Rifampicin and Isoniazid induced hepatotoxicity in rats

Pisonia aculeata is traditionally used in treatment of liver disorder and thought to have a protective effect which may be beneficial to reduce symptoms of hepatotoxicity. The current study aimed to evaluate the scientific merit of these anecdotal claims in an in vivo model. Methanolic extract of leaves of Pisonia aculeata (250 and 500 mg/kg, p.o.) showed a remarkable hepatoprotective and antioxidant activity against　 Rifampicin and Isoniazid induced hepatotoxicity as judged from the serum marker enzymes and　antioxidant levels in liver tissues. Acetaminophen induced a significant rise in aspartate　amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP),　total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO) with a reduction of total protein, superoxide dismutase (SOD), catalase, glutathione peroxidase　(GPx), reduced glutathione (GSH), Glutathione reductase (GR), Vitamin C and E. Treatment of rats with different doses of　plant extract (200 and 300 mg/kg) significantly (P<0.001) altered serum marker　enzymes and antioxidant levels to near normal against acetaminophen treated rats. Also the extract was effectively altered the drug metabolizing enzymes such as Cytochrome P450, NADPH   Cytochrome C reductase and glutathione S transferase. The activity of the extract at dose of 500 mg/kg was comparable to the standard drug, silymarin (50 mg/kg, p.o.). Histopathological changes of liver sample were compared with respective control. Results indicate the hepatoprotective and antioxidant properties of Pisonia aculeata against rifampicin and isoniazid -induced hepatotoxicity in rats. Keywords: Pisonia aculeata; Rifampicin; Isoniazid; Biochemical parameters;　Antioxidants; Lipid peroxidation; Histopathology

Generic drugs: a study on awareness among medical students and interns

Background: Use of generic drugs and its availability is one of the less discussed topics in the medical education but at the same time holds a lot of importance in providing affordable health care to the general public.Methods: All 150 II MBBS students and 80 interns who were willing were included in the study. After explaining the aims and objectives and obtaining the informed consent, a set of 14 semi structured questionnaire were given to the students through an online link. A total duration of 15 minutes was given to complete the questionnaire and submit to prevent bias.Results: Most of the students 98 (75.4%) believe that generic drugs are non-inferior to branded drugs compared to interns 33 (49.3%) who are still doubtful about its efficacy (p=0.0003). Most of the students 101 (77.7%) and interns 52 (77.6%) think that composition, dose and indications are same as branded drugs (p=0.987). 75 (57.7%) students and 25 (37.3%) of interns know that generic medicines are marketed only after the expiry of patent period of innovator drug (p=0.005). About 102 (78.5%) students and 44 (65.7%) interns prefer to prescribe generic drugs to their patients (p=0.061). Only 34 (26.2%) students and few interns 19 (28.4%) knew about jan aushadhi sugam app (p=0.744).Conclusions: Lack of awareness about the jan aushadhi sugam app and location of nearby generic stores was acting as the main hindrance in optimal utilization of generic drugs

Delays in Antiretroviral Therapy Initiation Among HIV-Positive Individuals: Results of the Positive Living with HIV Study

Background: Lack of early initiation of antiretroviral therapy (ART) remains a major health concern due to increased risk of premature mortality and further HIV transmission. This study explored CD4+ cell count monitoring in relation to delays in ART initiation among HIV-positive individuals in the Kathmandu Valley, Nepal, where ART coverage was only 23.7% in 2011. Design: We recruited a total of 87 ART-naïve, HIV-positive individuals aged 18 to 60 years through the networks of five non-government organizations working with HIV-positive individuals. We collected data on the history of ART initiation, CD4+ cell count monitoring, socio-demographic variables, perceived family support (measured with 10-item Nepali Family Support and Difficulty Scale), depression, and HIV symptom burden. Correlates of ART eligibility were examined using multivariable logistic regression analysis. Results: A total of 72 of the 87 ART-naïve participants (82.8%) had monitored their CD4+ cell count in the past 6 months. Of these, 36 (50%) participants were eligible for ART initiation with CD4+ cell count /mm3. A total of 12 participants had CD4+ cell count /mm3. Lower level of perceived family support was associated with 6.05-fold higher odds (95% confidence interval =1.95 to 18.73) of being ART eligible with a CD4+ cell count /mm3. Conclusions: High rate of delays in ART initiation and the strong association of low perceived family support with ART eligibility in our study participants suggest that HIV service providers should consider the role and impact of family support in influencing individual decisions to initiate ART among eligible HIV-positive individuals

In vitro activities of novel 4-HPR derivatives on a panel of rhabdoid and other tumor cell lines

<p>Abstract</p> <p>Background</p> <p>Rhabdoid tumors (RTs) are aggressive pediatric malignancies with poor prognosis. N-(4-hydroxy phenyl) retinamide (4-HPR or fenretinide) is a potential chemotherapeutic for RTs with activity correlated to its ability to down-modulate Cyclin D1. Previously, we synthesized novel halogen-substituted and peptidomimetic-derivatives of 4-HPR that retained activity in MON RT cells. Here we analyzed the effect of 4-HPR in inhibiting the growth of several RT, glioma, and breast cancer cell lines and tested their effect on cell cycle, apoptosis and Cyclin D1 expression.</p> <p>Methods</p> <p>Effect of compounds on RT cell cycle profiles, and cell death were assessed by MTS cell survival assays and FACS analysis. The effects of treatment on Cyclin D1 expression were determined by immunoblotting. The efficacy of these compounds on glioma and breast cancer cell lines was also determined using MTS assays.</p> <p>Results</p> <p>Low micromolar concentrations of 4-HPR derivatives inhibited cell survival of all RT cells tested. The 4-HPR derivatives altered RT cell cycle profiles and induced high levels of cell death that was correlated with their potency. ATRA exhibited high IC₅₀values in all cell lines tested and did not cause cell death. In MON RT cells, the iodo-substituted compounds were more active than 4-HPR in inducing cell cycle arrest and apoptosis. Additionally, the activity of the compounds correlated with their ability to down-modulate Cyclin D1: while active compounds reduced Cyclin D1 levels, inactive ATRA did not. In glioma and breast cancer cell lines, 4-HPR and 4-HPR derivatives showed variable efficacy.</p> <p>Conclusions</p> <p>Here we demonstrate, for the first time, that the inhibitory activities of novel halogen-substituted and peptidomimetic derivatives of 4-HPR are correlated to their ability to induce cell death and down-modulate Cyclin D1. These 4-HPR derivatives showed varied potencies in breast cancer and glioma cell lines. These data indicate that further studies are warranted on these derivatives of 4-HPR due to their low IC₅₀s in RT cells. These derivatives are of general interest, as conjugation of halogen radioisotopes such as ¹⁸F, ¹²⁴I, or ¹³¹I to 4-HPR will allow us to combine chemotherapy and radiotherapy with a single drug, and to perform PET/SPECT imaging studies in the future.</p

Serum 25-Hydroxyvitamin D Levels and C-Reactive Protein in Persons with Human Immunodeficiency Virus Infection

Human immunodeficiency virus (HIV) infection has frequently been associated with vitamin D deficiency as well as chronic inflammatory response. We tested the hypothesis of an independent relationship between serum concentrations of 25-hydroxyvitamin D [25(OH)D] and high-sensitivity C-reactive protein (CRP) in a cohort of HIV-positive people. A cross-sectional survey was conducted among 316 HIV-positive people (181 men and 135 women) aged 16 to 60 years residing in the Kathmandu Valley, Nepal. Serum high-sensitivity CRP concentrations and serum 25(OH)D levels were measured by the latex agglutination nephelometry method and the competitive protein-binding assay, respectively. The relationship between serum CRP concentrations and 25(OH)D serum level was assessed using multiple logistic regression analysis with adjustment of potential cardiovascular and HIV-related factors. The proportions of participants with 25(OH)D serum levels \u3c 20 ng/ml, 20–30 ng/ml, and ‡ 30 ng/ml were 83.2%, 15.5%, and 1.3%, respectively. The mean 25(OH)D serum levels in men and women were 15.3 ng/ml and 14.4 ng/ml, respectively. Participants with a 25(OH)D serum level of \u3c 20 ng/ml had a 3.2-fold higher odds of high CRP ( \u3e 3mg/liter) compared to those with a 25(OH)D serum level of ‡ 20 ng/ml ( p = 0.005). Men and women with a 25(OH)D serum level of \u3c 20 ng/ml had 3.2- and 2.7-fold higher odds of high CRP ( \u3e 3mg/liter), respectively, compared to those with a 25(OH)D serum level of ‡ 20 ng/ml. The relationships remained significant only in men ( p = 0.02) but not in women ( p = 0.28). The risk of having a high level of inflammation (CRP \u3e 3mg/liter) may be high among HIV-positive men and women with a 25(OH)D serum level of \u3c 20 ng/ml

Knowing the Consequences of Unprotected Sex with Seroconcordant Partner Is Associated with Increased Safer Sex Intentions among HIV-positive Men in Kathmandu, Nepal

Unprotected sexual intercourse among HIV-positive people can adversely affect their own health by increasing their exposure to multiple strains of HIV-1 or other sexually transmitted infections (STIs). The study explored the relationship between knowledge of Nepalese HIV-positive men about the consequences of having unprotected sex with seroconcordant partners and their intention to practise safer sex with such partners. In total, 166 participants recruited conveniently in the Kathmandu Valley, Nepal, were interviewed. Each participant reported intention to practise safer sex with seroconcordant partners, know-ledge about the consequences of having unprotected sex with seroconcordant partners, perceived partner-related barriers to condom-use, belief that condoms interfere with sex, and condom-use self-efficacy. Of the 166 participants, 50.6% intended to practise safer sex every time they have sex with seroconcordant partners. Results of multiple logistic regression analysis showed that the participants who were aware of the possibility of HIV superinfection [adjusted odds ratio (AOR)=2.93, 95% confidence interval (CI) 1.16-7.34, p=0.022)] or that the presence of STIs in HIV-positive persons increases progression of HIV disease (AOR=2.80, 95% CI 1.08-7.26, p=0.033) were more likely to intend to practise safer sex with seroconcordant partners. Similarly, the participants who were employed or who had lower levels of belief that condoms interfere with sex were more likely to intend to practise safer sex. The findings suggest that improving the knowledge of HIV-positive persons about the consequences of having unprotected sex with seroconcordant partners might improve their intention to practise safer sex with such partners