Out-reach Colposcopy Clinics and HPV Self-Sampling Decreases Loss to Follow up in a Community based Cervical Cancer Screening Programme.

OBJECTIVE: To introduce HPV self-sampling and out-reach colposcopy clinic as interventions to improve the follow-up of HPV positive women in a community based cervical cancer screening programme. METHODS: This was a prospective observational study conducted during October 2017 to August 2019 and 2977 women underwent cervical cancer screening using CareHPV test. Follow up colposcopy for HPV positive women were conducted at the rural health center and alternatively as out-reach clinics in their own villages and default rates were compared. HPV positive women were followed up at one-year. They were given an option of either having a follow-up HPV test performed by a health care worker (HCW) or by self-sampling. Compliance to follow up in these two modalities were compared. A validated questionnaire was given to women who had given an HPV self-sample to assess their awareness about HPV and cervical cancer. RESULTS: During our initial round of cervical cancer screening using HPV as a primary screening modality, our HPV screen positive rate was 7.05% (210 out of 2977 women screened).  Our colposcopy rates following an initial invitation at the rural health centre was only 28.5%. Following this, we initiated out-reach colposcopy clinics at their own villages for HPV positive women and this increased colposcopy rates from 28.5% to 45.2%. The participation rate at one-year follow-up was increased from 40.5% to 60% by the introduction of self-sampling as a follow up option and 16.2% of women who were initially positive remained HPV positive at 12-14 months follow up. All women who were offered the option of self-sampling preferred it over a HCW collected sample. CONCLUSION: Our study showed that self-sampling could also be used effectively in the follow up of HPV positive women in the community. Outreach colposcopy clinics in their own villages enabled better follow up of HPV positive women.

Combined Effects of Low-Dose Proton Radiation and Simulated Microgravity on the Mouse Retina and the Hematopoietic System.

The purpose of the current study was to characterize the effects of simulated microgravity and radiation-induced changes in retina and retinal vasculature, and to assess the accompanying early changes in immune cells and hematological parameters. To better understand the effects of spaceflight, we used a combination of treatments designed to simulate both the radiation and low-gravity aspects of space conditions. To simulate the broad energy spectrum of a large solar particle event (SPE) and galactic cosmic ray (GCR) radiation, male C57BL/6J mice were exposed to whole-body irradiation using fully modulated beams of 150-MeV protons containing particles of energy from 0 to 150 MeV and a uniform dose-vs.-depth profile. The mice were also hindlimb-unloaded (HLU) by tail suspension. Mice were unloaded for 7 days, exposed to 50 cGy, unloaded for an additional 7 days and then sacrificed for tissue isolation at days 4 and 30 after the combined treatments. Increases in the number of apoptotic cells were observed in the endothelial cells of mice that received radiation alone or with HLU compared to controls at both days 4 and 30 (P < 0.05). Endothelial nitric oxide synthase (eNOS) levels were significantly elevated in the retina after irradiation only or combined with HLU compared to controls at the 30-day time point (P < 0.05). The most robust changes were observed in the combination group, suggesting a synergistic response to radiation and unloading. For hematopoietic parameters, our analysis indicated the main effects for time and radiation at day 4 after treatments (day 11 postirradiation) (P < 0.05), but a smaller influence of HLU for both white blood cell and lymphocyte counts. The group treated with both radiation and HLU showed greater than 50% reduction in lymphocyte counts compared to controls. Radiation-dependent differences were also noted in specific lymphocyte subpopulations (T, B, natural killer cells). This study shows indications of an early effect of low-dose radiation and spaceflight conditions on retina and immune populations.

Acute Effect of Low-Dose Space Radiation on Mouse Retina and Retinal Endothelial Cells.

There is concern that degradation of vision as a result of space flight may compromise both mission goals and long-term quality of life after space travel. The visual disturbances may be due to a combination of intracerebral pressure changes and exposure to ionizing radiation. The retina and the retinal vasculature play important roles in vision, yet have not been studied extensively in relationship to space travel and space radiation. The goal of the current study was to characterize oxidative damage and apoptosis in retinal endothelial cells after whole-body gamma-ray, proton and oxygen (16O) ion radiation exposure at 0.1 to 1 Gy. Six-month-old male C57Bl/6J mice were whole-body irradiated with 600 MeV/n 16O ions (0, 0.1, 0.25, 1 Gy), solar particle event (SPE)-like protons (0, 0.1, 0.25, 0.5 Gy) or 60Co gamma rays (0, 0.1, 0.25, 0.5 Gy). Eyes were isolated for examining endothelial nitric oxide synthase (eNOS) expression and characterization of apoptosis in retina and retinal endothelial cells at two weeks postirradiation. The expression of eNOS was significantly increased in the retina after proton and 16O ion exposure. 16O ions induced over twofold increase in eNOS expression compared to proton exposure at two weeks postirradiation ( P < 0.05). TUNEL assays showed dose-dependent increases in apoptosis in the retina after irradiation. Low doses of 16O ions elicited apoptosis in the mouse retinal endothelial cells with the most robust changes observed after 0.1 Gy irradiation ( P < 0.05) compared to controls. Data also showed that 16O ions induced a higher frequency of apoptosis in retinal endothelial cells compared to protons ( P < 0.05). In summary, our study revealed that exposure to low-dose ionizing radiation induced oxidative damage and apoptosis in the retina. Significant changes in retinal endothelial cells occur at doses as low as 0.1 Gy. There were significant differences in the responses of endothelial cells among the radiation types examined here.

Development of a biofilm inhibitor molecule against multidrug resistant Staphylococcus aureus associated with gestational urinary tract infections.

Urinary Tract Infection (UTI) is a globally widespread human infection caused by an infestation of uropathogens. Eventhough, Escherichia coli is often quoted as being the chief among them, Staphylococcus aureus involvement in UTI especially in gestational UTI is often understated. Staphylococcal accessory regulator A (SarA) is a quorum regulator of S. aureus that controls the expression of various virulence and biofilm phenotypes. Since SarA had been a focussed target for antibiofilm agent development, the study aims to develop a potential drug molecule targeting the SarA of S. aureus to combat biofilm associated infections in which it is involved. In our previous studies, we have reported the antibiofilm activity of SarA based biofilm inhibitor, (SarABI) with a 50% minimum biofilm inhibitory concentration (MBIC50) value of 200 µg/mL against S. aureus associated with vascular graft infections and also the antibiofilm activity of the root ethanolic extracts of Melia dubia against uropathogenic E. coli. In the present study, in silico design of a hybrid molecule composed of a molecule screened from M. dubia root ethanolic extracts and a modified SarA based inhibitor (SarABI(M)) was undertaken. SarABI(M) is a modified form of SarABI where the fluorine groups are absent in SarABI(M). Chemical synthesis of the hybrid molecule, 4-(Benzylamino)cyclohexyl 2-hydroxycinnamate (henceforth referred to as UTI Quorum-Quencher, UTI(QQ)) was then performed, followed by in vitro and in vivo validation. The MBIC50 and MBIC90 of UTI(QQ) were found to be 15 and 65 µg/mL, respectively. Confocal laser scanning microscopy (CLSM) images witnessed biofilm reduction and bacterial killing in either UTI(QQ) or in combined use of antibiotic gentamicin and UTI (QQ) . Similar results were observed with in vivo studies of experimental UTI in rat model. So, we propose that the drug UTI(QQ) would be a promising candidate when used alone or, in combination with an antibiotic for staphylococcal associated UTI.

Structural, magnetic, and dielectric studies on Gd0.7Y0.3MnO3.

Structural, magnetic, specific heat, and dielectric studies were carried out on Y substituted (30 at. %) GdMnO(3) compound as a function of temperature. Anomalies occur at ~41 and 18 K, in the specific heat measurements and are ascribed to paramagnetic, to sinusoidal incommensurate antiferromagnetic transition (ICAFM) and ICAFM to commensurate antiferromagnetic transitions, respectively. Changes in the lattice parameters across these temperatures indicate magneto-elastic coupling present in the compound. However, in the dielectric measurements, an anomaly at 18 K alone is observed and is ascribed to a ferroelectric transition, giving rise to spontaneous ferroelectric ordering at low temperatures. This observation is supported by an anomaly in lattice parameters, across the transition temperature. From the frequency dependent dielectric studies, a strong coupling between Gd(3+) and Mn(3+) magnetic sublattices is inferred and Y substitution results in substantial changes in the relaxation process compared to that of GdMnO(3).

Local structural studies of the cubic Cd1-xCaxO system through Cd K-edge extended X-ray absorption spectroscopic studies.

Cd K-edge extended X-ray absorption fine-structure spectroscopic studies were carried out on Cd(1-x)Ca(x)O (0 ≤ x ≤0.9) solid solutions and the first and second nearest neighbour (NN) distances and their mean square relative displacement σ(2) were estimated. The first NN distance, d(Cd-O)(x), was found to be smaller than its expected value, a(x)/2, obtained from the X-ray diffraction measurements. It increases monotonically and non-linearly with a negative curvature, comparable with that of the a(x) value variation. The variation σ(2) of the 1NN with x is consistent with a disordered solid solution model. The 2NN distances d(Cd-Cd)(x) and d(Cd-Ca)(x) are found to follow the average values obtained by X-ray diffraction with d(Cd-Ca)(x) > d(Cd-Cd)(x). From detailed analysis it is argued that the solid solution exhibits a bimodal distribution of the 1NN distances, d(Cd-O)(x) and d(Ca-O)(x), and that the system belongs to a persistent type.

Prolyl hydroxylase inhibitor treatment confers whole-animal hypoxia tolerance.

AIM: Recently a family of O(2)-dependent prolyl hydroxylase domain-containing enzymes (PHD) has been identified as a cellular oxygen-sensing mechanism. Reduced prolyl hydroxylase activity initiates a signalling cascade that includes the accumulation, as well as the activation, of hypoxia-inducible factor (HIF-1alpha). In turn the transcription factor HIF-1alpha, and other targets of the PHD, elicit a myriad of incompletely understood cellular responses. In these studies we have tested: (1) whether a small-molecule prolyl hydroxylase inhibitor (PHI) can effectively activate the oxygen-sensing pathway when administered systemically to mice, and (2) whether the activation of the PHD signalling pathway at the cellular level results in whole-animal hypoxic tolerance. METHODS: Mice received daily injections of the PHI, ethyl-3,4 dihydroxybenzoate (EDHB, 100-250 mg kg(-1)) or vehicle. Tissue levels of HIF-1alpha and the serum levels of the HIF-inducible gene, erythropoietin (EPO), were measured to evaluate PHD-pathway activation. To evaluate hypoxic tolerance, the endurance and survival ability of these animals was tested in sublethal (8% O(2)) and lethal hypoxia (5% O(2)) respectively. RESULTS: Systemic treatment of mice with the PHD inhibitor, EDHB, leads to elevated levels of HIF-1alpha in liver and HIF-inducible EPO in serum, indicating activation of the cellular oxygen-sensing pathway. Animals treated with EDHB display significantly increased viability and enhanced exercise performance in hypoxia. CONCLUSION: These results demonstrate a novel pharmacological strategy to induce hypoxic tolerance and are the first to demonstrate that the activation of the PHD oxygen-sensing pathway at the cellular level is sufficient to produce a hypoxic-tolerant phenotype at the physiological level of the whole animal.

Isoindolones and related N-heterocycles via palladium nanoparticle-catalyzed 3-component cascade reactions.

Non-phosphine-containing cyclopalladated N-heterocycles possessing either sp2 C-Pd(II) or sp3 C-Pd(II) bonds and simple Pd(II) salts are precursors of Pd(0) nanoparticles whose initial morphology is dependent on the nature of the precursor. Addition of polyvinylpyrrolidone (pvp) dramatically increases catalyst lifetime. Nanoparticle generation can be achieved at ambient temperature in the presence of carbon monoxide by a process akin to the water-gas shift reaction. Allene also lowers the temperature required for nanoparticle generation. 3-Component catalytic cascades employing one or both of these substrates provide access to a variety of 5- and 6-membered N-heterocycles including isoindolones, N-aminoisoindolones, phthalazones, dihydroisoquinolines, and isoquinolones.

Double MITs and magnetoresistance: an intrinsic feature of Ru substituted La(0.67)Ca(0.33)MnO(3).

In this paper, we examine the possible influence of extrinsic factors on the electrical and magnetotransport of La(0.67)Ca(0.33)Mn(1-x)Ru(x)O(3) (x≤0.10). Ru substitution results in double metal-insulator transitions (MITs) at T(MI1) and T(MI2), both exhibiting magnetoresistance (MR). No additional magnetic signal corresponding to a second low-temperature maximum (LTM) at T(MI2) could be observed, either in ac susceptibility (χ(')) or in specific heat (C(p)). Typical grain sizes of ∼18 000-20 000 nm, as estimated from the scanning electron microscope (SEM) micrographs, are not so small as to warrant an LTM. The absence of additional peaks in the high statistics powder x-ray diffraction (XRD), a linear systematic increase of the unit cell parameters, close matching of the transition temperatures in resistivity, χ(') and C(p) and their linear systematic decrease with x, and an homogeneous distribution of Mn, Ru and O at arbitrarily selected regions within and across the grains exclude chemical inhomogeneity in the samples. The insensitivity of grain boundary MR at 5 K to Ru composition indicates that the grain boundary is not altered to result in an LTM. Oxygen stoichiometry of all the compounds is close to the nominal value of 3. These results not only exclude the extrinsic factors, but also establish that double MITs, both exhibiting MR, are intrinsic to Ru substituted La(0.67)Ca(0.33)MnO(3).

NMR investigation of hydrogen bonding and 1,3-tautomerism in 2-(2-hydroxy-5-substituted-aryl) benzimidazoles.

The 1,3-tautomerism associated with 2-(2-hydroxy-5-substituted-aryl)benzimidazoles was studied in different solvents. The effect of hydrogen bonding involving the hydroxyl group of the 2-aryl ring on the tautomerism was investigated using NMR spectroscopy. The influence of the solvent concentration on 2-(2-hydroxy-5-chloroaryl)benzimidazole was studied in acetone-d6 and DMSO-d6.

A novel route to substituted 4-methylene-4,5-dihydroisoxazoles mediated by hafnium(IV) chloride.

Heating alkyl vinyl ketones and N-tert-butylarylmethylideneamine N-oxides in the presence of HfCl4 results in the formation of 4-methylene-4,5-dihydroisoxazoles in good yield.

Tuberculosis control programme in rural area: experiences from the field.

PIP: According to the Indian National Tuberculosis Program (NTP), only 30% of tuberculosis (TB) patients receiving conventional treatment and 52% of those receiving short-course chemotherapy (SCC) complete the treatment. Incompletely cured patients return to the community, and each sputum-positive case can infect 10-14 people in the course of a year. Direct monitoring of chemotherapy is a must for success, especially if rifampicin is used after accurate diagnosis based on bacteriological examination. The National Leprosy Eradication Program, which has involved voluntary organizations, provides an example to be followed by NTP. This example was considered when the Karuna Trust, a voluntary organization, launched a TB control program on January 1, 1992, for Yelandur taluk, covering a population of 69,484 in 40 villages. A staff consisting of a medical officer, a supervisor, a smear technician, and paramedical workers had undergone training at the National TB Institute in Bangalore. Detection of cases was carried out by house-to-house visits, which could detect about 65% of cases. It was also found that TB treatment had been started without a sputum examination, sputum-positive cases had been on rifampicin, and data recording was incomplete. Up to October 1994, a total of 231 cases were registered and compliance was ensured by home visits. Private practitioners were carrying out harmful activities by not enforcing full patient compliance and thereby contributing to the increasing number of drug-resistant cases. In contrast, this program had a default of only 19.1% among sputum-positive cases, but even these can be recovered with an interaction with private practitioners. Treatment failure amounted to 10.1%, all having been on rifampicin. Retreatment requires more expensive second-line drugs. Drug collection will be decentralized for the convenience of patients; and an adequate supply of drugs was secured. Some suggestions were also made concerning adequate resources, integration of the program, monitoring, and involving nongovernmental organizations in implementation and evaluation.^ieng

Strategies for the management and control of antibiotic resistant organisms on a spinal cord injury unit.

Individuals with a spinal cord injury (SCI) are at an increased risk of infection and colonization. Frequent lengthy hospitalizations, invasive procedures, and skin breakdown contribute to this risk. Intermittent antibiotic use influences the emergence of antibiotic resistance in these organisms. As a result, there is risk of transmission of these antibiotic resistant organisms (ARO). This article describes the application of a continuous quality improvement model to evaluate ARO management strategies in a SCI unit. A conservative, labor intensive, crisis management approach to the control of ARO was replaced with a more cost effective prospective plan. The new strategies were aimed at control rather than eradication and included collaborative, multidisciplinary planning and improved resource utilization. Efforts have been successful and have resulted in the control of ARO.