Comparison of Visual Inspection Methods with Pap Smear as Screening Test for Premalignant Lesions of the Cervix.

Aim and Objectives: The present study was done to compare the visual inspection methods with Pap smear as a screening test for premalignant lesions of the cervix. Materials and Methods: The present observational prospective study was done at the Department of Obstetrics and Gynecology at Teerthanker Mahaveer Medical College and Research Center for 18 months. All study subjects were subjected to Papanicolaou smear, VIA, and VILI examination. If any of these tests were found positive, then a colposcopy and cervical biopsy were done. Results: The sensitivity of Pap, VIA, VILI, and colposcopy was 52.63%, 84.21%, 73.68%, and 84.21%, respectively. The specificity of Pap, VIA, VILI, and colposcopy was 60.0%, 80.0%, 60.0%, and 80.0%, respectively. The accuracy of Pap, VIA, VILI, and colposcopy was 54.17%, 83.33%, 70.83%, and 83.33%, respectively. Conclusion: It is well known that VIA and VILI are very easy to carry out and apply. Even technically they do not cost much, consume less tax and can be applied to all the patients. Even the results are calculated in a faster manner which helps in chalking out the plan in an easy way.

Combined effect of myofascial release and passive stretching on plantar pressure in individual with hamstring tightness- an experimental study.

INTRODUCTION: The lower kinetic chain is known to be affected by hamstring tightness which causes biomechanical alterations. As per the literature, short hamstring might cause prolonged forefoot loading, which can cause higher repeated stress on the plantar fascia. There is evidence supporting the use of various stretching and myofascial release techniques for hamstring tightness, further research is needed to investigate their impact on plantar pressure. Hence the study aims to determine combined effect of myofascial release and passive stretching on plantar pressure in individual with hamstring tightness. METHODS: This was an experimental pre-post study design with 67 randomised screenings from asymptomatic health care science students aged 18 to 25. From this scientific survey, a sample size of 47 students having HMS tightness based on the popliteal angle were recruited using a universal goniometer. An intervention was proposed that included MFR and passive stretching in 3 sessions on alternate days. Plantar pressure of these individuals was noted by using the "Harris and Beath foot printing mat" before and after the intervention. RESULT: Significant pressure changes were observed after intervention: great toe of right side (p = 0.001), toes 2 to 5 of right side (p = 0.010) and left side (p = 0.008), first metatarsal of left side (p = 0.010), lateral forefoot of right side (p = 0.019) and left (p = 0.018), medial heel (p = 0.044), and lateral heel of right side (p = 0.025). These values substantiate the enhancement in plantar pressure. CONCLUSION: The combined effect of Myofascial release and passive stretching in an individual with hamstring tightness resulted in a significant increase in popliteal angle and plantar pressure.

Synthesis, characterization and thermoluminescence of MgO:Li,Tb,Sm phosphor for high dose gamma dosimetry applications.

A detailed TL investigation on MgO:Li,Tb,Sm phosphor has been carried out by studying several TL characteristics - TL glow curve structure, dose response, linearity dose behaviour, fading and reproducibility. TL glow curve structure of the phosphor reveals the presence of two TL glow peaks. The main TL glow peak of high intensity is observed at high temperature side i.e. at 162 °C and another peak of low intensity is observed at 316 °C. Further, the effect of dose on TL response of the phosphor has been studied and a new behaviour is noticed. With increasing doses, the position of main TL glow peak is similar while the second TL glow peak vanishes at higher doses. A linear TL response is observed from 10 Gy-700 Gy and becomes sublinear above 700 Gy. Low TL fading characteristics and good reproducibility have also been observed. Encouraging results suggest the applicability of doped MgO phosphor for the detection of gamma rays.

Molecular signature of excessive female aggression: study of stressed mice with genetic inactivation of neuronal serotonin synthesis.

Aggression is a complex social behavior, critically involving brain serotonin (5-HT) function. The neurobiology of female aggression remains elusive, while the incidence of its manifestations has been increasing. Yet, animal models of female aggression are scarce. We previously proposed a paradigm of female aggression in the context of gene x environment interaction where mice with partial genetic inactivation of tryptophan hydroxylase-2 (Tph2+/- mice), a key enzyme of neuronal 5-HT synthesis, are subjected to predation stress resulting in pathological aggression. Using deep sequencing and the EBSeq method, we studied the transcriptomic signature of excessive aggression in the prefrontal cortex of female Tph2+/- mice subjected to rat exposure stress and food deprivation. Challenged mutants, but not other groups, displayed marked aggressive behaviors. We found 26 genes with altered expression in the opposite direction between stressed groups of both Tph2 genotypes. We identified several molecular markers, including Dgkh, Arfgef3, Kcnh7, Grin2a, Tenm1 and Epha6, implicated in neurodevelopmental deficits and psychiatric conditions featuring impaired cognition and emotional dysregulation. Moreover, while 17 regulons, including several relevant to neural plasticity and function, were significantly altered in stressed mutants, no alteration in regulons was detected in stressed wildtype mice. An interplay of the uncovered pathways likely mediates partial Tph2 inactivation in interaction with severe stress experience, thus resulting in excessive female aggression.

Manufacturing and characterization of whey and stevia-based popsicles enriched with concentrated beetroot juice.

The beet-root (Beta vulgaris) and whey powder together, can potentially use as a multifunctional ingredient in the manufacturing of the "Popsicles", due to their biochemical composition that can enhance the concentration of bioactive compounds. In the present study, beet-root juice concentrates were prepared at different time/temperature treatments viz 45 °C, 55 °C, and 65 °C for 120, 80 and 45 min. The effect of different time/temperature treatments on physicochemical composition, colour, antioxidant activity (%), bioactive compounds, spectral data and sensory acceptance were evaluated. The physicochemical parameters of popsicles (PTI, PT2, PT3) including protein, total phenols, betalain, radical scavenging activity %, colour and melting values were significantly affected (p ≤ 0.05) by the different time/temperature treatments. The concentration of betalain and protein in all the popsicles ranged from 1134 to 1299 mg/L and 1.92 to 1.54 g/100 g respectively. The reduction of bioactive components viz betacyanins, betaxanthins, betanin, oxalic and syringic acid was also observed in popsicle (PTI) as compared to control. Furthermore, popsicle (PT1) was prepared with beet-root juice concentrated at 45 °C showed maximum sensory acceptance. The physicochemical and organoleptic attributes of processed popsicles encourage the commercial usage of whey powder and concentrated beetroot juice.

Investigations of thermoluminescence characteristics of CaSiO3:Yb phosphor irradiated with gamma rays and carbon ion beam.

In the present work, the thermoluminescence (TL) properties of Yb doped CaSiO3 phosphor exposed to gamma rays and carbon (C) ion beam have been reported. The phosphor has been synthesized using solid-state reaction method. The formation and surface morphology of the phosphor have been studied using X-ray diffraction (XRD) and field emission scanning electron microscopy (FE-SEM) respectively. The optical band gap of the phosphor is determined using UV-Visible spectroscopy. TL properties on Yb doped CaSiO3 phosphor irradiated with carbon ion beam has been reported first time. Different TL properties like TL glow curve, dose response, fading etc. have been investigated in detail. The TL glow curve of CaSiO3:Yb phosphor consists of two prominent glow peaks. Under gamma irradiation, the main dosimetric peak is centered at 141 °C and other peak is centered at 265 °C. The dose response behaviour has been studied in the range 10 Gy-1000 Gy. However, C ion beam irradiated phosphor also consists similar TL glow curve structure with glow peaks shifted towards high temperature side (approx. 50 °C). The dose response behaviour of C ion beam irradiated phosphor has been examined in the ion fluence range varying from 5 × 109-5 × 1012 ions/cm2. A track interaction model is used to explain the sublinearity at higher fluences of carbon ion beam. Different ion beam parameters have been analyzed using Monte-Carlo simulation-based SRIM code. A comparative TL study of the phosphor irradiated with gamma rays and carbon ion beam suggests that gamma irradiated phosphor has shown better TL properties such as high TL sensitivity, good linear dose response (10 Gy-500 Gy), stable TL glow curve structure and low fading. Various TL trapping parameters i.e. order of kinetics, activation energy and frequency factor have been calculated using Chen's peak shape method to analyze the nature of TL traps responsible for showing different behaviour of the phosphor towards both the radiations. Good TL properties of CaSiO3:Yb phosphor supports its possible use in gamma dosimetry.

S-adenosylmethionine biosynthesis is a targetable metabolic vulnerability of cancer stem cells.

PURPOSE: Many transformed cells and embryonic stem cells are dependent on the biosynthesis of the universal methyl-donor S-adenosylmethionine (SAM) from methionine by the enzyme MAT2A to maintain their epigenome. We hypothesized that cancer stem cells (CSCs) rely on SAM biosynthesis and that the combination of methionine depletion and MAT2A inhibition would eradicate CSCs. METHODS: Human triple (ER/PR/HER2)-negative breast carcinoma (TNBC) cell lines were cultured as CSC-enriched mammospheres in control or methionine-free media. MAT2A was inhibited with siRNAs or cycloleucine. The effects of methionine restriction and/or MAT2A inhibition on the formation of mammospheres, the expression of CSC markers (CD44hi/C24low), MAT2A and CSC transcriptional regulators, apoptosis induction and histone modifications were determined. A murine model of metastatic TNBC was utilized to evaluate the effects of dietary methionine restriction, MAT2A inhibition and the combination. RESULTS: Methionine restriction inhibited mammosphere formation and reduced the CD44hi/C24low CSC population; these effects were partly rescued by SAM. Methionine depletion induced MAT2A expression (mRNA and protein) and sensitized CSCs to inhibition of MAT2A (siRNAs or cycloleucine). Cycloleucine enhanced the effects of methionine depletion on H3K4me3 demethylation and suppression of Sox9 expression. Dietary methionine restriction induced MAT2A expression in mammary tumors, and the combination of methionine restriction and cycloleucine was more effective than either alone at suppressing primary and lung metastatic tumor burden in a murine TNBC model. CONCLUSIONS: Our findings point to SAM biosynthesis as a unique metabolic vulnerability of CSCs that can be targeted by combining methionine depletion with MAT2A inhibition to eradicate drug-resistant CSCs.

Structural and mechanistic insights into ATRX-dependent and -independent functions of the histone chaperone DAXX.

The ATRX-DAXX histone chaperone complex incorporates the histone variant H3.3 at heterochromatic regions in a replication-independent manner. Here, we present a high-resolution x-ray crystal structure of an interaction surface between ATRX and DAXX. We use single amino acid substitutions in DAXX that abrogate formation of the complex to explore ATRX-dependent and ATRX-independent functions of DAXX. We find that the repression of specific murine endogenous retroviruses is dependent on DAXX, but not on ATRX. In support, we reveal the existence of two biochemically distinct DAXX-containing complexes: the ATRX-DAXX complex involved in gene repression and telomere chromatin structure, and a DAXX-SETDB1-KAP1-HDAC1 complex that represses endogenous retroviruses independently of ATRX and H3.3 incorporation into chromatin. We find that histone H3.3 stabilizes DAXX protein levels and can affect DAXX-regulated gene expression without incorporation into nucleosomes. Our study demonstrates a nucleosome-independent function for the H3.3 histone variant.

Molecular approaches to potentiate cisplatin responsiveness in carcinoma therapeutics.

INTRODUCTION: Cisplatin has been considered as the crucial regimen of widely prescribed chemotherapy treatment for cancer. The advancing treatment of cancers has reached the border line, where tumors show resistance to cisplatin and may thwart its use. Other than issues of drug resistance, cisplatin has been reported to evince side effects such as nephrotoxicity and ototoxicity. Therefore, there is a compelling need to untangle the problems associated with cisplatin treatment in carcinoma. Areas covered: In this review, we summarize the current status of combinatorial options to bring about better pre-clinical and clinical cisplatin drug responses in carcinoma. We begin with problems associated with cisplatin drugs and current avenues such as depicting molecular modulation of enhanced influx and reduced efflux. We also discuss the scope of the DNA damage response landscape and contribution of regulatory small RNAs towards potentiation of cisplatin responses. Expert commentary: The extensive use of cisplatin and incessant high drug dose have prompted the scientific community to limit the burden of cisplatin without compromising therapeutic success. Currently, there are reports on the potential use of other non-toxic small molecule inhibitors, interference RNAs and peptide mimetics to get rid of cellular adversities responsible for cisplatin resistance and high dose effects.

Localization of Low Copy Number Plasmid pRC4 in Replicating Rod and Non-Replicating Cocci Cells of Rhodococcus erythropolis PR4.

Rhodococcus are gram-positive bacteria, which can exist in two different shapes rod and cocci. A number of studies have been done in the past on replication and stability of small plasmids in this bacterium; however, there are no reports on spatial localization and segregation of these plasmids. In the present study, a low copy number plasmid pDS3 containing pRC4 replicon was visualized in growing cells of Rhodococcus erythropolis PR4 (NBRC100887) using P1 parS-ParB-GFP system. Cells were initially cocci and then became rod shaped in exponential phase. Cocci cells were found to be non-replicating as evident by the presence of single fluorescence focus corresponding to the plasmid and diffuse fluorescence of DnaB-GFP. Rod shaped cells contained plasmid either present as one fluorescent focus observed at the cell center or two foci localized at quarter positions. The results suggest that the plasmid is replicated at the cell center and then it goes to quarter position. In order to observe the localization of plasmid with respect to nucleoid, plasmid segregation was also studied in filaments where it was found to be replicated at the cell center in a nucleoid free region. To the best of our knowledge, this is the first report on segregation of small plasmids in R. erythropolis.

Export of microRNAs: A Bridge between Breast Carcinoma and Their Neighboring Cells.

Breast cancer is a leading type of cancer among women in India as well as worldwide. According to the WHO 2015 report, it has been anticipated that there would be a twofold rise in the death due to breast cancer among women. The heterogeneous property of breast carcinoma has been suggested to be linked with dedicated set of communication and signaling pathway with their surroundings, which culminate into progression and development of the cancer. Among the plethora of communication tools in the hand of breast carcinoma cells is the recently appreciated exocytosis of the tightly packed short non-coding RNA molecules, predominantly the microRNAs (miRNAs). Recent studies suggest that miRNAs may work as courier messengers to participate in endocrine and paracrine signaling to facilitate information transfer between breast carcinoma and their neighboring cells. Evidence suggests that breast tumor cells communicate via packaged miRNAs in the tumor-released microvesicles, which enrich the tumor microenvironment. There is a strong view that dissecting out the mechanistic and regulatory aspects of miRNA export and role may uncover many prospects for overcoming the signaling defects and thereby controlling aberrant cell division. The detection of circulating miRNAs associated with breast carcinoma can also be used as biomarkers for early diagnosis. This review article is an attempt to provide updated knowledge on implications of short RNAs and their transport in the breast cancer pathophysiology.

Broad host range plasmids.

Plasmids are and will remain important cloning vehicles for biotechnology. They have also been associated with the spread of a number of diseases and therefore are a subject of environmental concern. With the advent of sequencing technologies, the database of plasmids is increasing. It will be of immense importance to identify the various bacterial hosts in which the plasmid can replicate. The present review article describes the features that confer broad host range to the plasmids, the molecular basis of plasmid host range evolution, and applications in recombinant DNA technology and environment.