Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study).

OBJECTIVES: Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis. METHODS: We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes. RESULTS: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified. CONCLUSIONS: LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.

Effect of cabergoline alginate nanocomposite on the transgenic Drosophila melanogaster model of Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. Dopamine agonists help the patients with PD by reversing the dopamine depletion and related motor deficits. In the present work, cabergoline, a potent ergot dopamine agonist, was given in the form of cabergoline alginate nanocomposite (CANC) to the PD model flies to study its effects on climbing ability, activity pattern, life span, lipid peroxidation, glutathione (GSH) content, glutathione-S-transferase (GST) activity, dopamine content, protein carbonyl content, mean gray-scale values, and caspase-3 and caspase-9 activities. Cabergoline alginate nanocomposite was synthesized by adding the cabergoline solution in the warm aqueous solution of sodium alginate; The synthesized CANC was characterized using fourier transform (FTIR) infrared spectroscopy, transmission electron microscopy (TEM), and UV-Visible spectroscopic techniques. The synthesized CANC having the final doses of 1, 2, and 3 µM was supplemented with diet and the flies were allowed to feed on it for 24 days. Cabergoline alginate nanocomposite significantly increases climbing ability, reduces lipid peroxidation, GST activity, protein carbonyl content, caspase 3/9 activity, mean gray-scale values, and increases the GSH as well as dopamine content in a dose-dependent manner. The results of this study suggest that CANC is potent in delaying and reducing the symptoms of PD.

Quercetin sensitizes fluconazole-resistant candida albicans to induce apoptotic cell death by modulating quorum sensing.

Quorum sensing (QS) regulates group behaviors of Candida albicans such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by C. albicans, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of C. albicans infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (Usnea longissima), can be implemented as a sensitizing agent for FCZ-resistant C. albicans NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons-biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZ-mediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of C. albicans infections.

Silver nanoparticles embedded mesoporous SiO2 nanosphere: an effective anticandidal agent against Candida albicans 077.

Candida albicans is a diploid fungus that causes common infections such as denture stomatitis, thrush, urinary tract infections, etc. Immunocompromised patients can become severely infected by this fungus. Development of an effective anticandidal agent against this pathogenic fungus, therefore, will be very useful for practical application. In this work, Ag-embedded mesoporous silica nanoparticles (mSiO2@AgNPs) have successfully been synthesized and their anticandidal activities against C. albicans have been studied. The mSiO2@AgNPs nanoparticles (d ∼ 400 nm) were designed using pre-synthesized Ag nanoparticles and tetraethyl orthosilicate (TEOS) as a precursor for SiO2 in the presence of cetyltrimethyl ammonium bromide (CTAB) as an easily removable soft template. A simple, cost-effective, and environmentally friendly approach has been adopted to synthesize silver (Ag) nanoparticles using silver nitrate and leaf extract of Azadirachta indica. The mesopores, with size-equivalent diameter of the micelles (d = 4-6 nm), were generated on the SiO2 surface by calcination after removal of the CTAB template. The morphology and surface structure of mSiO2@AgNPs were characterized through x-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), particle size analysis (PSA), atomic force microscopy (AFM), field emission scanning electron microscopy (FESEM), Brunauer-Emmett-Teller (BET) and high-resolution transmission electron microscopy (HRTEM). The HRTEM micrograph reveals the well-ordered mesoporous structure of the SiO2 sphere. The antifungal activities of mSiO2@AgNPs on the C. albicans cell have been studied through microscopy and are seen to increase with increasing dose of mSiO2@AgNPs, suggesting mSiO2@AgNPs to be a potential antifungal agent for C. albicans 077.

MiRNA-181a regulates Toll-like receptor agonist-induced inflammatory response in human fibroblasts.

MicroRNAs (miRNAs) regulate the synthesis of cytokines in response to Toll-like receptor (TLR) activation. Our recent microarray study comparing normal and inflamed human dental pulps showed that miRNA-181 (miR-181) family is differentially expressed in the presence of inflammation. Prior studies have reported that the dental pulp, which is composed primarily of TLR4/2+ fibroblasts, expresses elevated levels of cytokines including interleukin-8 (IL-8) when inflamed. In this study, we employed an in-vitro model to determine the role of the miRNA-181 family in the TLR agonist-induced response in human fibroblasts. TLR4/2+ primary human dental pulp fibroblasts were stimulated with lipopolysaccharide from Porphyromonas gingivalis (Pg LPS), a known oral pathogen, and IL-8 and miR-181 expression measured. An inversely proportional relationship between IL-8 and miR-181a was observed. In-silico analysis identified a miR-181a-binding site on the 3' untranslated region (UTR) of IL-8, which was confirmed by dual-luciferase assays. MiR-181a directly binds to the 3'UTR of IL-8, an important inflammatory component of the immune response, and modulates its levels. This is the very first report demonstrating miR-181a regulation of IL-8.

Detection of carcinogenic chromium in synthetic hair dyes using laser induced breakdown spectroscopy.

A laser induced breakdown spectroscopic (LIBS) system, consisting of a pulsed 266 nm laser radiation, in conjunction with a high-resolution spectrograph, a gated intensified charge coupled device camera, and a built-in delay generator were used to develop a sensitive detector to quantify the concentration of toxic substances such as chromium in synthetic hair dyes available on the local market. The strong atomic transition line of chromium (Cr I) at 427.5 nm wavelength was used as a fingerprint wavelength to calibrate the detection system and also to quantify the levels of chromium in the hair dye samples. The limit of detection achieved by our LIBS detection system for chromium was 1.2 ppm, which enabled us to detect chromium concentration in the range of 5-11 ppm in the commercial hair dyes available on the local market. The concentrations of chromium in the hair dyes measured using our system were validated using a standard analytical technique such as inductively coupled plasma mass spectrometry (ICPMS), and acceptable agreement (nearly 8%) was found between the results obtained by the two methods (LIBS and ICPMS). This study is highly significant for human health, specifically for people using synthetic hair dyes for changing the color of their hair.

Economic evaluation of treatment for acute lymphoblastic leukaemia in childhood.

Berlin-Frankfurt-Munster (BFM) and Dana-Farber Cancer Institute (DFCI) consortia's treatment strategies for acute lymphoblastic leukaemia (ALL) in children are widely used. We compared the health effects and monetary costs of hospital treatments for these two strategies. Parents of children treated at seven centres in Canada, Italy and the USA completed health-related quality of life (HRQL) assessments during four active treatment phases and at 2 years after treatment. Mean HRQL scores were used to calculate quality-adjusted life years (QALYs) for a period of 5 years following diagnosis. Total costs of treatment were determined from variables in administrative databases in a universally accessible and publicly funded healthcare system. Valid HRQL assessments (n = 1200) were collected for 307 BFM and 317 DFCI patients, with costs measured for 66 BFM and 28 DFCI patients. QALYs per patient were <1.0% greater for BFM than DFCI. Median HRQL scores revealed no difference in QALYs. The difference in mean total costs for BFM (US$88 480) and DFCI (US$93 026) was not significant (P = 0.600). This study provides no evidence of superiority for one treatment strategy over the other. Current BFM or DFCI strategies should represent conventional management for the next economic evaluation of treatments for ALL in childhood.

The fraction of recombinant factor VIII:Ag unable to bind von Willebrand factor has no FVIII coagulant activity: studies in vitro.

A fraction of FVIII:Ag in commercial recombinant FVIII (rFVIII) cannot bind VWF whereas all the FVIII:Ag in plasma-derived FVIII (pd-FVIII) concentrates does. To compare the FVIII:C activities of the fractions of rFVIII:Ag that can and cannot bind VWF. The FVIII:Ag contents of the rFVIII Kogenate, and Advate and a pd-FVIII-pd-VWF (Fanhdi) were measured by ELISA. The FX activation was initiated by adding 1.0 IU of FVIII:C of each FVIII-containing product to a coagulant phospholipids suspension containing 1.0 nm FIXa, 100 nm FX, 1 µm hirudin and 2 mm calcium chloride and measured after 1, 5 and 10 min. The same approach was followed after adding 2.0 IU of pd-VWF to 1.0 IU of FVIII:C of Kogenate or Advate. The FVIII:Ag content/IU of FVIII:C of Kogenate, Advate and Fanhdi were 1.80 ± 0.05, 1.31 ± 0.9 and 0.84 ± 1.5 IU respectively. Only Kogenate and Advate effectively enhanced FX activation 1 min after adding each FVIII:C to the coagulant suspension containing FIXa and FX. Thus, the FXa initially generated by FIXa readily activated FVIII:C in control Kogenate and Advate to thereby effectively enhance FX activation while the VWF in Fanhdi continued to suppress FX activation for up to 10 min. Addition of pd-VWF to Kogenate or Advate effectively decreased their enhancements of FX activation to the same level as Fanhdi over 10 min. The FVIII:Ag fraction in Kogenate and Advate that cannot bind VWF appears to be inactive as it has no measureable FVIII:C activity in the presence of added VWF in vitro.

Global assessment of tropospheric and ground air pollutants and its correlation with COVID-19.

The declaration of COVID-19 pandemic by the WHO initiated a series of lockdowns globally that varied in stringency and duration; however, the spatiotemporal effects of these lockdowns on air quality remain understudied. This study evaluates the global impact of lockdowns on air pollutants using tropospheric and ground-level indicators over a five-month period. Moreover, the relationship between air pollution and COVID-19 cases and mortalities was examined. Changes in the global tropospheric (NO2, aerosols, and O3) and ground-level (PM2.5, PM10, NO2, and O3) pollutants were observed, and the maximum air quality improvement was observed immediately after lockdown. Except for a few countries, a decline in air pollutants correlated with a reduction in Land Surface Temperature (LST). Notably, regions with higher tropospheric NO2 and aerosol concentrations were also COVID-19 hotspots. Our analysis showed moderate positive correlation for NO2 with COVID-19 cases (R2 = 0.33; r = 0.57, P = 0.006) and mortalities (R2 = 0.40; r = 0.63, P = 0.015), while O3 showed a weak-moderate positive correlation with COVID-19 cases (R2 = 0.22; r = 0.47, P = 0.003) and mortalities (R2 = 0.12; r = 0.35, P = 0.012). However, PM2.5, and PM10 showed no significant correlation with either COVID-19 cases or mortality. This study reveals that humans living under adverse air pollution conditions are at higher risk of COVID-19 infection and mortality.

Variation in chicken populations may affect the enzymatic activity of lysozyme.

The chicken lysozyme gene encodes a hydrolase that has a key role in defence, especially in ovo. This gene was resequenced in global chicken populations [red, grey, Ceylon and green jungle fowl (JF)] and related bird species. Networks, summary statistics and tests of neutrality indicate that although there is extensive variation at the gene, little is present at coding sites, with the exception of one non-synonymous site. This segregating site and a further fixed non-synonymous change between red JF and domestic chicken populations are spatially close to the catalytic sites of the enzyme and so might affect its activity.

Evidence of balanced diversity at the chicken interleukin 4 receptor alpha chain locus.

BACKGROUND: The comparative analysis of genome sequences emerging for several avian species with the fully sequenced chicken genome enables the genome-wide investigation of selective processes in functionally important chicken genes. In particular, because of pathogenic challenges it is expected that genes involved in the chicken immune system are subject to particularly strong adaptive pressure. Signatures of selection detected by inter-species comparison may then be investigated at the population level in global chicken populations to highlight potentially relevant functional polymorphisms. RESULTS: Comparative evolutionary analysis of chicken (Gallus gallus) and zebra finch (Taeniopygia guttata) genes identified interleukin 4 receptor alpha-chain (IL-4Ralpha), a key cytokine receptor as a candidate with a significant excess of substitutions at nonsynonymous sites, suggestive of adaptive evolution. Resequencing and detailed population genetic analysis of this gene in diverse village chickens from Asia and Africa, commercial broilers, and in outgroup species red jungle fowl (JF), grey JF, Ceylon JF, green JF, grey francolin and bamboo partridge, suggested elevated and balanced diversity across all populations at this gene, acting to preserve different high-frequency alleles at two nonsynonymous sites. CONCLUSION: Haplotype networks indicate that red JF is the primary contributor of diversity at chicken IL-4Ralpha: the signature of variation observed here may be due to the effects of domestication, admixture and introgression, which produce high diversity. However, this gene is a key cytokine-binding receptor in the immune system, so balancing selection related to the host response to pathogens cannot be excluded.

The specialist management of non-temporomandibular orofacial pain: maxillofacial surgery's known unknown?

The management of orofacial pain is considered to be within the remit of oral and maxillofacial surgery (OMFS). In this study we aimed to provide an overview of the healthcare "journey" of a group of patients referred to a specialist unit with "complex" non-temporomandibular orofacial pain. We retrospectively reviewed all those who were referred over a six-month period and followed for up to three years. A total of 133 were included, 69% were female, and the mean (SD) duration of symptoms before assessment was 66.4 (88.8) months. Patients were treated for seven different conditions by a mean (SD) of 2.6 (1.2) specialties, and 3.2 (2.5) medications had been tried before assessment at the unit. A mean (SD) of 3.9 (3.3) appointments were attended over the three years, and 80% of patients were prescribed at least one medication. Patients were under the care of the unit for a mean (SD) of 11.9 (14.0) months, and 38% were still being seen at three years. Those with trigeminal neuralgia were most likely to remain in care at three years (p=<0.001), and those with burning mouth syndrome (p=<0.001) or persistent idiopathic facial pain (p=0.005) were most likely to be discharged. In the current NHS climate, the lack of resources to treat facial pain and the focus on a mix of skills, mean that OMF surgeons are likely to have an increasing role in the treatment of these patients. This paper provides an important insight into these conditions.

Antagonism of p66shc by melanoma inhibitory activity.

The p66shc protein governs oxidant stress and mammalian lifespan. Here, we identify melanoma inhibitory activity (MIA), a protein secreted by melanoma cells, as a novel binding partner and antagonist of p66shc. The N-terminal collagen homology-2 (CH2) domain of p66shc binds to the Src Homology-3 (SH3)-like domain of MIA in vitro. In cells, ectopically expressed MIA and p66shc colocalize and co-precipitate. MIA also co-precipitates with the CH2 domain of p66shc in vivo. MIA expression in vivo suppresses p66shc-stimulated increase in endogenous hydrogen peroxide (H(2)O(2)), and inhibits basal and H(2)O(2)-induced phosphorylation of p66shc on serine 36 and H(2)O(2)-induced death. In human melanoma cells expressing MIA, endogenous MIA and p66shc co-precipitate. Downregulation of MIA in melanoma cells increases basal and ultraviolet radiation (UVR)-induced phosphorylation of p66shc on serine 36, augments endogenous H(2)O(2) levels, and increases their susceptibility to UVR-induced death. These findings show that MIA binds to p66shc, and suggest that this interaction antagonizes phosphorylation and function of p66shc.

Chemotherapeutic Response and Survival for Patients With an Anal Squamous Cell Carcinoma and Low Hemoglobin Levels.

PURPOSE: Anemia is associated with poor treatment results for a variety of cancers. The effect of low hemoglobin levels on long-term outcomes after the treatment of patients with an anal squamous cell carcinoma (SCC) remains unclear. For that reason, this study aimed to investigate the effect of anemia on treatment outcomes following chemoradiation for an anal SCC. METHODS: This was a retrospective study of all patients who underwent curative treatment for an anal SCC between 2009 and 2015 at 2 trusts in the United Kingdom. Data were collated from prospectively collected cancer databases and were cross-checked with operating-room records and records in the hospitals' patient management systems. RESULTS: We identified 103 patients with a median age of 63 years (range, 36-84 years). The median overall survival was 39 months (range, 9-90 months), and the disease-free survival was 36 months (range, 2-90 months). During the follow-up period, 16.5% patients died and 13.6% patients developed recurrence. Twenty-two people were anemic prior to treatment, with a female preponderance (20 of 22). No differences in disease-free survival (P = 0.74) and overall survival (P = 0.12) were noted between patients with anemia and those with normal hemoglobin levels. On regression the analysis, the combination of anemia, the presence of a defunctioning colostomy, lymph-node involvement and higher tumor stage correlated with poor overall survival. CONCLUSION: In this study, anemia did not influence disease-free survival or overall survival. We suggest that the interaction between anemia and survival is more complex than previously demonstrated and potentially reliant on other coexisting factors.

Anastomosing hemangioma of the kidney: radiologic and pathologic distinctions of a kidney cancer mimic.

Anastomosing hemangioma (ah) is a rare subtype of primary vascular tumour that can, clinically and radiologically, present similarly to malignant renal tumours such as renal cell carcinoma (rcc) and angiosarcoma. Rarely seen in the genitourinary system, the ah we report here occurred in a 40-year-old male patient diagnosed initially with rcc based on imaging and successfully treated by laparoscopic left radical nephrectomy, with adrenal sparing and perihilar lymph node dissection. The pathologic diagnosis of ah can be challenging on small biopsy specimens; we therefore opine that it is appropriate to excise these lesions to facilitate diagnosis and definitively exclude common renal cancers. However, in this review, we describe some radiologic and pathologic distinctions between ah and malignant tumours.

Scaffold of Selenium Nanovectors and Honey Phytochemicals for Inhibition of Pseudomonas aeruginosa Quorum Sensing and Biofilm Formation.

Honey is an excellent source of polyphenolic compounds that are effective in attenuating quorum sensing (QS), a chemical process of cell-to-cell communication system used by the opportunistic pathogen Pseudomonas aeruginosa to regulate virulence and biofilm formation. However, lower water solubility and inadequate bioavailability remains major concerns of these therapeutic polyphenols. Its therapeutic index can be improved by using nano-carrier systems to target QS signaling potently. In the present study, we fabricated a unique drug delivery system comprising selenium nanoparticles (SeNPs; non-viral vectors) and polyphenols of honey (HP) for enhancement of anti-QS activity of HP against P. aeruginosa PAO1. The developed selenium nano-scaffold showed superior anti-QS activity, anti-biofilm efficacy, and anti-virulence potential in both in-vitro and in-vivo over its individual components, SeNPs and HP. LasR is inhibited by selenium nano-scaffold in-vitro. Using computational molecular docking studies, we have also demonstrated that the anti-virulence activity of selenium nano-scaffold is reliant on molecular binding that occurs between HP and the QS receptor LasR through hydrogen bonding and hydrophobic interactions. Our preliminary investigations with selenium-based nano-carriers hold significant promise to improve anti-virulence effectiveness of phytochemicals by enhancing effective intracellular delivery.

Data collection using open access technology in multicentre operational research involving patient interviews.

Conducting multicentre operational research is challenging due to issues related to the logistics of travel, training, supervision, monitoring and troubleshooting support. This is even more burdensome in resource-constrained settings and if the research includes patient interviews. In this article, we describe an innovative model that uses open access tools such as Dropbox, TeamViewer and CamScanner for efficient, quality-assured data collection in an ongoing multicentre operational research study involving record review and patient interviews. The tools used for data collection have been shared for adaptation and use by other researchers.

Conduire des recherches opérationnelles multicentriques est un défi, particulièrement dans les contextes de ressources limitées, en tenant compte des questions de logistique de déplacement, de formation, de supervision, de suivi et de soutien à la résolution des problèmes; encore plus si cette recherche implique des entretiens avec des patients. Dans cet article, nous décrivons un modèle innovant qui utilise des outils à accès ouvert comme Dropbox, TeamViewer et CamScanner pour un recueil de données efficace et de qualité assurée dans le cadre d'une recherche opérationnelle continue multicentrique impliquant des revues de dossiers et des entretiens avec des patients. Les outils utilisés pour le recueil de données ont été partagés pour l'adaptation et l'utilisation par d'autres chercheurs.

La realización de investigaciones operativas multicéntricas puede ser problemática, sobre todo en los entornos con restricción de los recursos, habida cuenta de las dificultades en la organización de los desplazamientos, la capacitación, la supervisión, el seguimiento y el apoyo a la resolución de problemas; más aun, cuando la investigación precisa entrevistas a los pacientes. En el presente artículo se describe un modelo innovador que utiliza herramientas de libre acceso como las plataformas Dropbox, TeamViewer y CamScanner, con el fin de lograr una obtención de datos eficiente y de calidad garantizada, en una investigación operativa multicéntrica en curso que comporta el examen de las historias clínicas y entrevistas a los pacientes. Se comunican las herramientas utilizadas en la recogida de datos, con la finalidad de que otros investigadores puedan adaptarlas y las apliquen.

Efficacy of isoniazid prophylaxis in renal allograft recipients.

The efficacy of isoniazid (INH) prophylaxis in renal allograft recipients who are on long-term immunosuppression in a region highly prevalent for tuberculosis (TB) was studied. INH (300 mg/d in patients weighing more than 35 kg and 5 mg/kg/d in patients with <35 kg body weight) together with Pyridoxine 50 mg/d for 1 year was started in randomly assigned renal allograft recipients. Occurrence of clinical tuberculosis during the initial 2 years posttransplantation was observed in the risk group and patients at no risk. Risks were defined as acute rejection episodes and exposure to antirejection therapy, past history of TB completely or incompletely treated, radiological evidence of past tuberculosis, history of tuberculosis in close contacts. Among 480 patients registered in the study, INH prophylaxis was given to 219 randomly assigned renal allograft recipients. Results were compared among patients developing TB during the initial 2 years posttransplantation in both the groups. Risk factors were analyzed for comparison in both groups. No significant difference was observed in terms of past history of TB, TB in close contacts, episodes of acute rejection during the initial 3 months, and comorbidities such as cytomegalovirus infection, hepatitis C virus infection, and posttransplant diabetes. One patient from the INH group and 10 patients from the non-INH group developed TB during the initial 2 years posttransplantation (P < .0001). None of patients required discontinuation of INH. INH was observed to be safe and effective as a chemoprophylactic agent in renal allograft recipients.

Outcome of pregnancy in renal allograft recipients: SIUT experience.

The course of pregnancy and its outcome was studied in renal allograft recipients. Between November 1985 and November 2005, a total of 1481 renal transplants were carried out at the Sindh Institute of Urology and Transplantation (SIUT); among them were 348 females, with 73 potential females for pregnancy. All patients received cyclosporine and prednisolone, with 82% also receiving azathioprine and 4 patients mycophenolate mofetil as a third immunosuppressant drug. We evaluated incidence of hypertension, diabetes, pre-eclampsia, urinary tract infection (UTI), rejection during pregnancy and during 3 months' postdelivery as well as outcomes of pregnancy. Among 73 potential candidates, 31 had 47 pregnancies, after an average of 31 months (8-86 months). Of 31 subjects, 21 subjects were hypertensive on one or two drugs prior to conception. A rise in blood pressure during pregnancy was noticed in 7 patients. Albuminuria from trace to 3+ appeared in 13 patients and glycosuria in one other. Blood sugar levels remained within normal range in all subjects. UTIs occurred during pregnancy in 7 patients. Among 47 pregnancies, 9 had abortions (7 spontaneous, 2 therapeutic) and 6 had preterm deliveries. The others were full-term deliveries: 12 via a lower segment caesarean section and 20 were normal vaginal deliveries. Average birth weight was 4.8 lbs. At an average follow-up of 38 months the serum creatinine values ranged from 0.94 to 2.3 mg %. One patient developed acute irreversible graft dysfunction soon after delivery. Our study demonstrated that pregnancy did not reduce renal graft survival, but newborns are at greater risk of premature birth and low birth weight.

Performance improvement of keV Neutrons-based PGNAA setups.

The performance of keV neutrons based Prompt Gamma Ray Neutron Activation Analysis (PGNAA) setups have been observed to improve by enclosing its neutron source inside the moderator. The keV neutrons were produced via (7)Li(p,n) reaction and (3)H(p,n) reactions. For the two PGNAA setups, the maximum intensity of the prompt gamma-ray yield was observed for a 5cm long moderator with the neutron source positioned at a distance of 0.5cm from the moderator-end facing the sample. Due to enclosing the source inside the moderator, the prompt gamma-ray yield from the (7)Li(p,n) reaction and (3)H(p,n) reaction based PGNAA setups have increased by a factor of three as compared to that achieved from these setups with the source outside the moderator. This study provides a theoretical basis for the measurement of performance of (7)Li(p,n) reaction and the (3)H(p,n) reaction based PGNAA setups.