Detection of Human Papillomavirus among Cervical Cancer Patients by Qualitative Polymerase Chain Reaction on Formalin- fixed, Paraffin-embedded Tissue: A Retrospective Observational Analysis

Introduction: Cervical cancer is second most commonly diagnosed and third most common cause for cancer death among women in the developing countries. It is now-established that Human Papillomavirus (HPV) infection is responsible for pathogenesis of cervical cancer. HPV Deoxyribonucleic Acid (DNA) detection is generally done on cytology specimens to triage women undergoing cervical cancer screening, but testing of Formalin-fixed, Paraffin- embedded tissue (FFPE) is not yet widely used. Aim: To study the detection of HPV by Qualitative PCR by extraction of DNA from FFPE. Materials and Methods: This retrospective observational analysis was carried out at Department of Pathology, Armed Forces Medical College, Pune, Maharashtra, India, managed at the centre from 2008 to 2015. The data analysis was done Aug 2013-Oct 2015 on 35 patients of cervical cancer which were reconfirmed by histopatholgical study of sections. Tissue blocks were obtained from the selected subjects and 3-5 micron sections were taken and prepared for Haematoxylin and Eosin (H&E) staining. Qualitative PCR was run on DNA extracted from FFPE tissue for evaluation of HPV. The amplified DNA varied between 230-270 base pairs (bp) and was analysed for oncogenic HPV type 16, 18, 31, 33, 35, 45, 52b and 58 by gel electrophoresis. Data was tabulated in Microsoft excel and mean, frequency and percentages were calculated. Pearson’s Chi-square test was used to calculate the significance. Results: Out of the total 35 samples analysed (mean age: 51.08±10.6 years),15 cases were large cell non keratinising carcinoma, 12 cases of keratinising squamous cell carcinoma, 5 cases of carcinoma in-situ and 3 cases were adenocarcinoma. A total of 13 cases out of 35 showed the bands of HPV genomes, indicating either of the HPV strain. Conclusion: Although molecular diagnostics on FFPE tissue is need of hour, stringent protocols for timing of fixation, technical expertise for extraction of DNA or Ribonucleic Acid (RNA), careful handling of the sample and quality control is of paramount importance. Fragmentation is a problem in DNA extracted from FFPE tissue, so primers having small base pairs should be used to maximise the yield

Audit of short term outcomes of surgical and medical second trimester termination of pregnancy

<p>Abstract</p> <p>Background</p> <p>As comparisons of modern medical and surgical second trimester termination of pregnancy (TOP) are limited, and the optimum method of termination is still debated, an audit of second trimester TOP was undertaken, with the objective of comparing the outcomes of modern medical and surgical methods.</p> <p>Methods</p> <p>All cases of medical and surgical TOP between the gestations of 13 and 20 weeks from 1st January 2007 to 30th June 2008, among women residing in the local health board district, a tertiary teaching hospital in an urban setting, were identified by a search of ICD-10 procedure codes (surgical terminations) and from a ward database (medical terminations). Retrospective review of case notes was undertaken. A total of 184 cases, 51 medical and 133 surgical TOP, were identified. Frequency data were compared using Chi-squared or Fischer's Exact tests as appropriate and continuous data are presented as mean and standard deviation if normally distributed or median and interquartile range if non-parametric.</p> <p>Results</p> <p>Eighty-one percent of surgical terminations occurred between 13 to 16 weeks gestation, while 74% of medical terminations were performed between 17 to 20 weeks gestation. The earlier surgical TOP occurred in younger women and were more often indicated for maternal mental health. Sixteen percent of medical TOP required surgical delivery of the placenta. Evacuation of retained products was required more often after medical TOP (10%) than after surgical TOP (1%). Other serious complications were rare.</p> <p>Conclusion</p> <p>Both medical and surgical TOP are safe and effective for second trimester termination. Medical TOP tend to be performed at later gestations and are associated with a greater likelihood of manual removal of the placenta and delayed return to theatre for retained products. This case series does not address long term complications.</p

The 2019 review of IPBES and future priorities: Reaching beyond assessment to enhance policy impact

The Intergovernmental Science–Policy Platform on Biodiversity and Ecosystem Services (IPBES) is an independent scientific body focused on assessing the state of the world's ecosystem services and biodiversity. IPBES members agreed in 2017 that a review of the Platform's first work programme should be undertaken by an independent panel examining all aspects of IPBES' work – including implementation of the four functions of IPBES; policies, operating principles and procedures; governance structure and arrangements; communication, stakeholder engagement and partnerships; and funding mechanisms. The review found that for IPBES to have its anticipated transformative impact: All four functions of IPBES (i.e. assessment, knowledge generation, policy support, capacity building), with better communication, must be significantly strengthened, integrated and delivered together; The policy aspects of IPBES work need to be strengthened and greater emphasis needs to be placed on the co-design and co-production of assessments; A more strategic and collaborative approach to stakeholders is needed; and IPBES must develop a more sustainable financial base. Given those changes, IPBES, as an embryonic boundary organization, can become the key influencing organization in the global landscape of biodiversity and ecosystem services organizations, helping thus to catalyze transformative change in the relationship between people and the rest of nature

Antiprogestins reduce epigenetic field cancerization in breast tissue of young healthy women

Background: Breast cancer is a leading cause of death in premenopausal women. Progesterone drives expansion of luminal progenitor cells, leading to the development of poor-prognostic breast cancers. However, it is not known if antagonising progesterone can prevent breast cancers in humans. We suggest that targeting progesterone signalling could be a means of reducing features which are known to promote breast cancer formation. Methods: In healthy premenopausal women with and without a BRCA mutation we studied (i) estrogen and progesterone levels in saliva over an entire menstrual cycle (n = 20); (ii) cancer-free normal breast-tissue from a control population who had no family or personal history of breast cancer and equivalently from BRCA1/2 mutation carriers (n = 28); triple negative breast cancer (TNBC) biopsies and healthy breast tissue taken from sites surrounding the TNBC in the same individuals (n = 14); and biopsies of ER+ve/PR+ve stage T1–T2 cancers and healthy breast tissue taken from sites surrounding the cancer in the same individuals (n = 31); and (iii) DNA methylation and DNA mutations in normal breast tissue (before and after treatment) from clinical trials that assessed the potential preventative effects of vitamins and antiprogestins (mifepristone and ulipristal acetate; n = 44). Results: Daily levels of progesterone were higher throughout the menstrual cycle of BRCA1/2 mutation carriers, raising the prospect of targeting progesterone signalling as a means of cancer risk reduction in this population. Furthermore, breast field cancerization DNA methylation signatures reflective of (i) the mitotic age of normal breast epithelium and (ii) the proportion of luminal progenitor cells were increased in breast cancers, indicating that luminal progenitor cells with elevated replicative age are more prone to malignant transformation. The progesterone receptor antagonist mifepristone reduced both the mitotic age and the proportion of luminal progenitor cells in normal breast tissue of all control women and in 64% of BRCA1/2 mutation carriers. These findings were validated by an alternate progesterone receptor antagonist, ulipristal acetate, which yielded similar results. Importantly, mifepristone reduced both the TP53 mutation frequency as well as the number of TP53 mutations in mitotic-age-responders. Conclusions: These data support the potential usage of antiprogestins for primary prevention of poor-prognostic breast cancers

Bedaquiline, Delamanid, Linezolid and Clofazimine for Treatment of Pre-extensively Drug-Resistant Tuberculosis.

BACKGROUND Treatment success rates for multidrug-resistant tuberculosis (MDR-TB) remain low globally. Availability of newer drugs has given scope to develop regimens that can be patient-friendly, less toxic, with improved outcomes. We proposed to determine the effectiveness of an entirely oral, short-course regimen with Bedaquiline and Delamanid in treating MDR-TB with additional resistance to fluoroquinolones (MDR-TBFQ+) or second-line injectable (MDR-TBSLI+). METHODS We prospectively determined the effectiveness and safety of combining two new drugs with two repurposed drugs - Bedaquiline, Delamanid, Linezolid, and Clofazimine for 24-36 weeks in adults with pulmonary MDR-TBFQ+ or/and MDR-TBSLI+. The primary outcome was a favorable response at end of treatment, defined as two consecutive negative cultures taken four weeks apart. The unfavorable outcomes included bacteriologic or clinical failure during treatment period. RESULTS Of the 165 participants enrolled, 158 had MDR-TBFQ+. At the end of treatment, after excluding 12 patients due to baseline drug susceptibility and culture negatives, 139 of 153 patients (91%) had a favorable outcome. Fourteen patients (9%) had unfavorable outcomes: four deaths, seven treatment changes, two bacteriological failures, and one withdrawal. During treatment, 85 patients (52%) developed myelosuppression, 69 (42%) reported peripheral neuropathy, and none had QTc(F) prolongation >500msec. At 48 weeks of follow-up, 131 patients showed sustained treatment success with the resolution of adverse events in the majority. CONCLUSION After 24-36 weeks of treatment, this regimen resulted in a satisfactory favorable outcome in pulmonary MDR-TB patients with additional drug resistance. Cardiotoxicity was minimal, and myelosuppression, while common, was detected early and treated successfully

Ultrafast Sampling using Low Temperature Grown GaAs MSM Switches Integrated with CMOS Amplifier for Photonic A/D Conversion

Within the past few years, various photonic A/D conversion systems have achieved speed and resolution performance far surpassing conventional mixed signal technology, lending merit to this hybrid approach [1,2]. In our system, we utilize an optically triggered, electrical sample and hold scheme with low temperature (LT) grown GaAs MSM switches. The switch is attached to a transmission line and samples the input electrical signal onto a hold capacitor when optically activated by a short-pulse laser. An electrical A/D converter then digitizes the held signal. By time-interleaving a number of these channels, the aggregate sampling rate of the system is increased, with the larger bandwidth requirements being placed on the input sample and hold. The short carrier trapping time and relatively high mobility of the LT GaAs material provide broadband sampling capability with good optical sensitivity [3]. Previously, we demonstrated a sample and hold test circuit with 5.7 effective number of bits (ENOB) accuracy under dc input conditions and a sampling gate width of less than 2 ps [4]. The sample and hold process exhibits good linearity for up to 20 GHz input frequency and a&gt;50 GHz 3 dB bandwidth [5]. In this work, we demonstrate LT GaAs MSM switches integrated with the front-end silicon-CMOS buffer amplifier stage with linear sampling capability from dc to 20 GHz input frequency. To our knowledge, this represents the highest bandwidth of any integrated system with CMOS technology

Effect of Cow Urine-Based Bioformulations on Growth and Physiological Responses in Mungbean Under Soil Moisture Stress Conditions

Not AvailableExperiments were conducted to evaluate the influence of cow urine-based bio formulations on the morphological, physiological growth response and expression of stress responsive genes under drought stress in mung-bean [Vigna radiata (L.) Wilczek] plants. An initial in vitro evaluation and three separate pot experiments were carried out by treating mungbean with varying concentrations of bioformulations under different soil moisture conditions(well watered and water stressed). The application of bio-formulations (BR and SH) led to an increase in number of nodules (22.41 in R3 stage under stress; 12.17 in R5 stage under stress recovery) and total plant dry weight (1.12 g inR3 stage under stress; 1.22 g in R5 stage under stress recovery) at different growth stages and soil moisture conditions. Least decrease or no change in photo chemical efficiency of PS-II (Fv/Fm) in the bioformulations-treated plants under stress-imposed conditions indicated that bio-formulations used in this experiment have potential role inmitigating soil moisture stress in crops like mungbean. The enhanced expression of genes of membrane-integrated protein like aquaporins (Nodulin 26-like Intrinsic Proteins—NIP) in the treated plants under low soil moisture conditions further accentuated the efficacy of these bio-formulations to alleviate the drought stress in crops.ICAR-NIAS