A brief review of low-dose rate (LDR) and high-dose rate (HDR) brachytherapy boost for high-risk prostate

For patients with unfavorable or high-risk prostate cancer, dose escalated radiation therapy leads to improved progression free survival but attempts to deliver increased dose by external beam radiation therapy (EBRT) alone can be limited by late toxicities to nearby genitourinary and gastrointestinal organs at risk. Brachytherapy is a method to deliver dose escalation in conjunction with EBRT with a potentially improved late toxicity profile and improved prostate cancer related outcomes. At least three randomized controlled trials have demonstrated improved biochemical control with the addition of either low-dose rate (LDR) or high-dose rate (HDR) brachytherapy to EBRT, although only ASCENDE-RT compared brachytherapy to dose-escalated EBRT but did report an over 50% improvement in biochemical failure with a LDR boost. Multiple single institution and comparative research series also support the use of a brachytherapy boost in the DE-EBRT era and demonstrate excellent prostate cancer specific outcomes. Despite improved oncologic outcomes with a brachytherapy boost in the high-risk setting, the utilization of both LDR, and HDR brachytherapy use is declining. The acute genitourinary toxicities when brachytherapy boost is combined with EBRT, particularly a LDR boost, are of concern in comparison to EBRT alone. HDR brachytherapy boost has many physical properties inherent to its rapid delivery of a large dose which may reduce acute toxicities and also appeal to the radiobiology of prostate cancer. We herein review the evidence for use of either LDR or HDR brachytherapy boost for high-risk prostate cancer and summarize comparisons between the two treatment modalities

PART I: OPTIMIZATION OF HYDRALAZINE HYDROCHLORIDE IMMEDIATE RELEASE LAYER IN ANTIHYPERTENSIVE BILAYER TABLET

Objective: Aim of the present study was the optimization of the immediate release (IR) layer containing hydralazine hydrochloride (HHC) 25 mg and compressed with a sustained-release (SR) layer of isosorbide dinitrate (ISDN) 40 mg to decrease the dosing frequency. Methods: In this study, Drug-excipients compatibility study was carried out by FT-IR and a preliminary trial was conducted for screening of super disintegrating agents. The amount of sodium starch glycolate (SSG) (X1) and the amount of ac-di-sol® (X2) was chosen as independent variables in 32 full factorial design while wetting time (WT) (Y1), disintegration time (DT) (Y2) and In vitro drug release at 15 min (Q15) (Y3) were taken as dependent variables. Multiple linear regression analysis, ANOVA, and graphical representation of the influence of factor by 3D plots were performed by using sigma plot 13.0. In the present study, the following constraints were used for the selection of an optimized batch: WT<16 s, DT<25 s, and Q15>90%. To validate the evolved mathematical models, a checkpoint batch was selected from its desirability value. Results: FT-IR spectra show that the drug and excipients were compatible with each other. The calculated F values found for WT, DT, and Q15 were 045.559, 077.100 and 278.760, respectively. All Calculated F values are greater than tabulated values for all dependent variables. Prepared checkpoint was selected from its desirability value 0.935 and it gives a 100% drug release within 30 min. Conclusion: These results confirm that the prepared HHC 25 mg IR layer is used for rapid control of hypertension

Monoazo reactive dyes: Synthesis and application on cotton, silk and wool fibers

Mono azo reactive dyes are mostly used in textiles industries. The current study was developed to synthesize and apply mono azo reactive dyes. The primary goal of this research article is to highlight synthesized dyes with outstanding fixing properties for the dyeing and printing sectors to invent in future. Diazotized o-anisidine was coupled with several 4-amino-4ʼ-hydroxy benzilidene acetophenone cyanurated coupling component including H-acid, Gamma acid, J-acid, N-methyl J-acid, N-phenyl J-acid, K- acid and peri acid, to create a variety of monoazo reactive dyes. IR and elemental analyses were used to describe them. Moreover, the dyeing capabilities of each of these dyes on silk, wool, and cotton have been evaluated. The wet fastness properties also evaluated. Synthesized mono azo reactive dyes have excellent fixation values as well as fastness properties.Os corantes reativos monoazo são usados principalmente nas indústrias têxteis. O presente estudo foi desenvolvido para sintetizar e aplicar corantes reativos mono azo. O objetivo principal deste artigo de pesquisa é destacar corantes sintetizados com excelentes propriedades de fixação para os setores de tingimento e estamparia investirem ainda mais. A o-anisidina diazotizada foi acoplada a vários componentes de acoplamento cianuratados de 4-amino-4'-hidroxi benzlideno acetofenona, incluindo ácido H, ácido gama, ácido J, ácido N metil J, ácido N-fenil J, ácido K e peri ácido, para criar uma variedade de corantes reativos monoazo. Análises elementares de IR e nitrogênio foram usadas para descrevê-los. Além disso, as capacidades de tingimento de cada um desses corantes em seda, lã e algodão foram avaliadas. As propriedades de resistência à umidade também foram avaliadas. Os corantes reativos monoazo sintetizados têm excelentes valores de fixação, bem como propriedades de solidez

Tendências na síntese e aplicação de alguns corantes reativos: Uma revisão

From last 25 years that many researchers have developed the novel reactive dyes with modification in structure of reactive dyes. In the present review paper concentrated development of reactive dyes. The review paper is focused on the highlight such dyes have having excellent dyeing properties and wet-fastness properties. This review paper express the monstrous impression of reactive dyes on the textiles coloration industry. Particularized details are given regarding evolution in the chemistry of reactive structure systems. It is additionally mentioned pointed out that advance research is mandatory to enhance dye fixation and wet-fastness properties. Reactive dyes have been used for the past hundred years for dyeing of cellulosic fabrics. A reactive dye has a chromophore, which is a group or an atom that is responsible for the dye’s colour. It has a component which reacts with the fabric or substrate. They have excellent fastness features due to the presence of covalent bonds that takes place during dyeing. The dyeing industry is dominated by the parties who can create dyes having excellent dyeing efficiency, stable, can be resistant to chemical actions and be affordable. In this review on development of synthesis reactive dyes has been provided. This review paper concentrated on research of reactive groups type. En los últimos veinticinco años, muchos investigadores han desarrollado nuevos colorantes reactivos con modificaciones en la estructura de los colorantes reactivos. En este artículo de revisión, nos enfocamos en el desarrollo de colorantes reactivos. El artículo de revisión se centra en resaltar tales tintes con excelentes propiedades de teñido y propiedades de solidez a la humedad. Este artículo de revisión expresa la monstruosa impresión de los colorantes reactivos en la industria del teñido textil. Se dan detalles particulares sobre la evolución en la química de los sistemas de estructura reactiva. Además, se menciona que se necesita investigación avanzada para mejorar las propiedades de fijación del tinte y resistencia a la humedad. Los colorantes reactivos se han utilizado durante los últimos cien años para teñir tejidos celulósicos. Un tinte reactivo tiene un cromóforo, que es un grupo o átomo responsable del color del tinte. Tiene un componente que reacciona con el tejido o sustrato. Tienen excelentes características de solidez debido a la presencia de enlaces covalentes que se producen durante el teñido. La industria del teñido está dominada por partes que pueden crear tintes con excelente eficiencia de teñido, estables, resistentes a los químicos y asequibles. En esta revisión, se proporcionó el desarrollo de colorantes de síntesis reactiva. Este artículo de revisión se centró en la investigación de tipo de grupo reactivo.Nos últimos vinte e cinco anos, muitos pesquisadores desenvolveram novos corantes reativos com modificações na estrutura dos corantes reativos. No presente artigo de revisão, concentrou-se o desenvolvimento de corantes reativos. O artigo de revisão está focado no destaque que tais corantes têm com excelentes propriedades de tingimento e propriedades de resistência à umidade. Este artigo de revisão expressa a impressão monstruosa de corantes reativos na indústria de coloração têxtil. Detalhes particulares são dados sobre a evolução na química de sistemas de estrutura reativa. Além disso, é mencionado que pesquisas avançadas são necessárias para melhorar a fixação do corante e as propriedades de resistência à umidade. Os corantes reativos têm sido usados nos últimos cem anos para tingir tecidos celulósicos. Um corante reativo tem um cromóforo, que é um grupo ou átomo responsável pela cor do corante. Tem um componente que reage com o tecido ou substrato. Possuem excelentes características de solidez devido à presença de ligações covalentes que ocorrem durante o tingimento. A indústria de tingimento é dominada pelas partes que podem criar corantes com excelente eficiência de tingimento, estáveis, resistentes a ações químicas e acessíveis. Nesta revisão, o desenvolvimento de corantes reativos de síntese foi fornecido. Este artigo de revisão concentrou-se na pesquisa do tipo grupos reativos

Measurement of cervical length using transvaginal sonography for prediction of preterm labour

Background: Preterm labour and delivery cause major health burden to the society due to high perinatal morbidities and mortality and long-term health implications and also affects maternal. An effective and objective way for predicting preterm delivery is measurement of cervical length by transvaginal sonography as it allows better quality and accurate visualization of uterine cervix. Cervical length (<25 mm) is good and accurate cervical biometry for prediction of preterm birth. The objective of this study was to measure cervical length by transvaginal sonography for predicting preterm labour and fetal outcome.Methods: This prospective observational study was conducted in department of obstetrics and gynaecology, at SVPIMSR hospital, Ahmedabad from July 2018 to December 2019 in 150 antenatal women to assess cervical changes (cervical length, dilatation of internal OS, funnelling etc.) between 16 to 24 weeks of gestation and these cases followed till delivery and results were analysed.Results:150 antenatal women who fulfilled the selection criteria were studied using transvaginal ultrasound between 16-24 weeks of gestation, out of them 36 (24%) women delivered preterm babies. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) recorded in this study were 80.5%, 94.73%, 82.85% and 93.91% respectively.Conclusion: Transvaginal sonography is the most useful and better, safe, accurate, most effective, less expensive, objective and acceptable technique for assessing cervical length in all antenatal women and predicting the preterm labour when assessed between 16 -24 weeks of gestational age

A hospital based retrospective study of thyroid disorders on obstetric and perinatal outcomes

Background: The study was undertaken in pregnant women to understand and analyze the obstetric and foetal outcomes of thyroid disorders.Methods: TSH estimation was used as universal screening in their first visit to our hospital. Those patients with abnormal TSH values, i.e. above 2.5 mIU/ml in first trimester and above 3 mIU/ml in second and third trimesters were evaluated for free T3, free T4 and TPO Abs. They were treated accordingly and dosage adjustments made and the tests repeated once in 4-6 weeks. They were followed throughout pregnancy and delivery.Results: Total no of pregnant women screened were 904 over a period of 1 year from 15 March 2019 to 14 March 2020, of which 115 had abnormal thyroid functions, thereby the prevalence of thyroid disorders being 12.72%. Of the 115 patients with thyroid disorders, 112 were hypothyroid and 3 were hyperthyroid. Among the 112 hypothyroid cases, 48 were known cases and 64 were new cases. The total cases of subclinical hypothyroidism were 88, prevalence being 9.73% and overt cases were 24, prevalence being 2.65%; 3 cases were overt hyperthyroid, prevalence being 0.33%. 66% of subclinical hypothyroidism were TPO positive and 34% of overt hypothyroidism were TPO positive (p<0.05). Out of 115 abnormal thyroid function patients, 92 patients delivered in our hospital. There were 15 abortions, 13 spontaneous and 2 terminations of pregnancies; 7 patients have delivered outside and 1 patient lost follow up.Conclusions: The prevalence of thyroid disorders during pregnancy was significantly more in our study, hypothyroidism being the commonest. Significant numbers of cases were newly diagnosed on universal screening. The commonest disorder was subclinical hypothyroidism. Adverse maternal and foetal outcomes were almost similar in both subclinical and overt hypothyroidism. The common adverse outcomes noted were abortions, pre-eclampsia, gestational diabetes mellitus, preterm births and increased rates of caesarean sections. The adverse outcomes were significantly more in autoimmune antibody positive patients

Resolving the cofactor-binding site in the proline biosynthetic enzyme human pyrroline-5-carboxylate reductase 1

Pyrroline-5-carboxylate reductase (PYCR) is the final enzyme in proline biosynthesis, catalyzing the NAD(P)H-dependent reduction of [?]1-pyrroline-5-carboxylate (P5C) to proline. Mutations in the PYCR1 gene alter mitochondrial function and cause the connective tissue disorder cutis laxa. Furthermore, PYCR1 is overexpressed in multiple cancers, and the PYCR1 knock-out suppresses tumorigenic growth, suggesting that PYCR1 is a potential cancer target. However, inhibitor development has been stymied by limited mechanistic details for the enzyme, particularly in light of a previous crystallographic study that placed the cofactor-binding site in the C-terminal domain rather than the anticipated Rossmann fold of the N-terminal domain. To fill this gap, we report crystallographic, sedimentation- velocity, and kinetics data for human PYCR1. Structures of binary complexes of PYCR1 with NADPH or proline determined at 1.9 Å resolution provide insight into cofactor and substrate recognition.WeseeNADPHbound to the Rossmann fold, over 25 Å from the previously proposed site. The 1.85 Å resolution structure of a ternary complex containing NADPH and a P5C/proline analog provides a model of the Michaelis complex formed during hydride transfer. Sedimentation velocity shows that PYCR1 forms a concentration-dependent decamer in solution, consistent with the pentamer-of-dimers assembly seen crystallographically. Kinetic and mutational analysis confirmed several features seen in the crystal structure, including the importance of a hydrogen bond between Thr-238 and the substrate as well as limited cofactor discrimination

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Chemical intervention in plant sugar signalling increases yield and resilience

The pressing global issue of food insecurity due to population growth, diminishing land and variable climate can only be addressed in agriculture by improving both maximum crop yield potential and resilience. Genetic modification is one potential solution, but has yet to achieve worldwide acceptance, particularly for crops such as wheat. Trehalose-6-phosphate (T6P), a central sugar signal in plants, regulates sucrose use and allocation, underpinning crop growth and development. Here we show that application of a chemical intervention strategy directly modulates T6P levels in planta. Plant-permeable analogues of T6P were designed and constructed based on a ‘signalling-precursor’ concept for permeability, ready uptake and sunlight-triggered release of T6P in planta. We show that chemical intervention in a potent sugar signal increases grain yield, whereas application to vegetative tissue improves recovery and resurrection from drought. This technology offers a means to combine increases in yield with crop stress resilience. Given the generality of the T6P pathway in plants and other small-molecule signals in biology, these studies suggest that suitable synthetic exogenous small-molecule signal precursors can be used to directly enhance plant performance and perhaps other organism function

Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (Fludarabine/busulfan=166, Fludarabine/melphalan=327) and 379 using MAC (Fludarabine/busulfan=247, Busulfan/cyclophosphamide=132). In multivariable analysis with RIC, Fludarabine/melphalan was associated with inferior overall survival (HR 1.80, 95% CI 1.15-2.81, p=0.009), higher early non-relapse mortality (HR 1.81, 95% CI 1.12-2.91, p=0.01) and higher acute graft versus host disease (GVHD) (grade II-IV- HR 1.45, 95% CI 1.03-2.03, p=0.03; grade III-IV HR 2.21, 95%CI 1.28-3.83, p=0.004) compared to Fludarabine/busulfan. In the MAC setting, Busulfan/cyclophosphamide was associated with a higher acute GVHD (grade II-IV HR 2.33, 95% CI 1.67-3.25, p\u3c0.001; grade III-IV HR 2.31, 95% CI 1.52-3.52, p\u3c0.001) and inferior GVHD-free relapse-free survival (GRFS) (HR 1.94, 95% CI 1.49-2.53, p\u3c0.001) as compared to Fludarabine/busulfan. Hence, our study suggests that Fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lower early non-relapse mortality, lower acute GVHD) and MAC (lower acute GVHD and better GRFS) in myelofibrosis