Pure accelerated irradiation followed by intracavitary brachytherapy in selected cases of locally advanced carcinoma of cervix

INTRODUCTION: Carcinoma cervix is the most common gynaecological malignancy in women. Concurrent chemoradiation is the standard of care in locally advanced carcinoma cervix. However cytotoxic chemotherapy cannot be safely administered in elderly patients and those with pre-existing comorbid medical conditions. Hence pure accelerated radiotherapy with intracavitary brachytherapy has been tried in these patients. AIM OF THE STUDY: 1. To assess the immediate locoregional response rates of locally advanced carcinomas of cervix treated with pure accelerated EBRT followed by intracavitary brachytherapy. 2. To assess acute toxicities during treatment. MATERIAL AND METHODS: This is a single arm prospective study in which 30 patients with squamous cell and adenocarcinomas of cervix of stages IIB-IIIB, presenting in Department of Radiotherapy, MMC & RGGGH, who were not eligible for chemotherapy due to old age, comorbid medical conditions like renal disorders, cardiac diseases etc were treated with pure accelerated EBRT- 50 Gy (200 cGy/# in 25#/6 fractions per week) followed by intracavitary brachytherapy (7 Gy in 3# in HDR). The response both clinical and radiological, was assessed 6 weeks after completion of therapy, using RECIST criteria. Toxicity was assessed using RTOG Morbidity scoring. RESULTS: There was complete locoregional response in 23 patients (76.7%), partial response in 7 patients (23.3%) among whom 4 patients had adenocarcinoma histology. Complete response was seen in 85.7% (12/14) and in 62.5% (5/8) of stage IIB and IIIB respectively. Acute toxicities were observed but they were manageable. Diarrhoea presented as grade 1 in 6 patients (20%) and grade 2 in 3 patients (10%) respectively. Grade 1 haematological toxicity was seen in 7 patients (23.3%) during 3rd week of radiotherapy and no patients had grade 2 toxicity. Grade 1 and 2 skin reactions were seen in 12 patients (40%). The median treatment time for EBRT was 29 days. CONCLUSION: This study shows that pure accelerated EBRT alone followed by brachytherapy is a possible alternative in selected patients who are not fit for chemotherapy. The early responses are good and acute toxicities are lesser. However, the response of patients with adenocarcinoma was poor

Malpositioned dialysis catheters: A case series

Hemodialysis catheters (HDC) are the commonly used vascular access for hemodialysis. Functioning access is essential for adequate dialysis. Dialysis catheter insertion under ultrasound guidance is now standard practice and has reduced the incidence of mechanical complications during catheter insertion. However, complications such as tip misplacement and puncture of the mediastinum cannot be prevented by ultrasound-guided procedures alone. We report four cases of abnormal positioning of HDC insertion and emphasize the importance of fluoroscopy or radiography after the procedure to verify the position of the cathete

Reduction in Phencyclidine Induced Sensorimotor Gating Deficits in the Rat Following Increased System Xc − Activity in the Medial Prefrontal Cortex

Rationale: Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System xc −, a cystine–glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis. Objectives: Our goal was to determine whether increased system xc − activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating. Methods: In situ hybridization was used to map messenger RNA (mRNA) expression of xCT, the active subunit of system xc −, in the prefrontal cortex. Prepulse inhibition was used to measure sensorimotor gating; deficits in prepulse inhibition were produced using phencyclidine (0.3–3 mg/kg, sc). N-Acetylcysteine (10–100 μM) and the system xc − inhibitor (S)-4-carboxyphenylglycine (CPG, 0.5 μM) were used to increase and decrease system xc − activity, respectively. The uptake of 14C-cystine into tissue punches obtained from the prefrontal cortex was used to assay system xc − activity. Results: The expression of xCT mRNA in the prefrontal cortex was most prominent in a lateral band spanning primarily the prelimbic cortex. Although phencyclidine did not alter the uptake of 14C-cystine in prefrontal cortical tissue punches, intraprefrontal cortical infusion of N-acetylcysteine (10–100 μM) significantly reduced phencyclidine- (1.5 mg/kg, sc) induced deficits in prepulse inhibition. N-Acetylcysteine was without effect when coinfused with CPG (0.5 μM), indicating an involvement of system xc −. Conclusions: These results indicate that phencyclidine disrupts sensorimotor gating through system xc − independent mechanisms, but that increasing cystine–glutamate exchange in the prefrontal cortex is sufficient to reduce behavioral deficits produced by phencyclidine

Reproducibility of the mfERG between instruments

Purpose First, to examine both the reproducibility of the multifocal electroretinogram (mfERG) recorded on different versions of the same instrument, and the repeatability of the mfERG recorded on a single instrument using two different amplifiers. Second, to demonstrate a means by which multicenter and longitudinal studies that use more than one recording instrument can compare and combine data effectively. Methods Three different amplifiers and two mfERG setups, one using VERIS™ 4.3 software (mfERG1) and another using VERIS™ Pro 5.2 software (mfERG2), were evaluated. A total of 73 subjects with normal vision were tested in three groups. Group 1 (n = 42) was recorded using two amplifiers in parallel on mfERG1. Group 2 (n = 52) was recorded on mfERG2 using a single amplifier. Group 3 was a subgroup of 21 subjects from groups 1 and 2 that were tested sequentially on both instruments. A fourth group of 26 subjects with diabetes were also recorded using the two parallel amplifiers on mfERG1. P1 implicit times and N1-P1 amplitudes of the 103 local first order mfERGs were measured, and the differences between the instruments and amplifiers were evaluated as raw scores and Z-scores based on normative data. Measurements of individual responses and measurements averaged over the 103 responses were analyzed. Results Simultaneous recordings made on mfERG1 with the two different amplifiers showed differences in implicit times but similar amplitudes. There was a mean implicit time difference of 2.5 ms between the amplifiers but conversion to Z-scores improved their agreement. Recordings made on different days with the two instruments produced similar but more variable results, with amplitudes differing between them more than implicit times. For local response implicit times, the 95% confidence interval of the difference between instruments was approximately ±1 Z-score (±0.9 ms) in either direction. For local response amplitude, it was approximately ±1.6 Z-scores (±0.3 μV). Conclusions Different amplifiers can yield quite different mfERG P1 implicit times, even with identical band-pass settings. However, the reproducibility of mfERG Z-scores across recording instrumentation is relatively high. Comparison of data across systems and laboratories, necessary for multicenter or longitudinal investigations, is facilitated if raw data are converted into Z-scores based on normative data

2022 roadmap on low temperature electrochemical CO2 reduction

Electrochemical CO2 reduction (CO2R) is an attractive option for storing renewable electricity and for the sustainable production of valuable chemicals and fuels. In this roadmap, we review recent progress in fundamental understanding, catalyst development, and in engineering and scale-up. We discuss the outstanding challenges towards commercialization of electrochemical CO2R technology: energy efficiencies, selectivities, low current densities, and stability. We highlight the opportunities in establishing rigorous standards for benchmarking performance, advances in in operando characterization, the discovery of new materials towards high value products, the investigation of phenomena across multiple-length scales and the application of data science towards doing so. We hope that this collective perspective sparks new research activities that ultimately bring us a step closer towards establishing a low- or zero-emission carbon cycle.Catalysis and Surface Chemistr

Synaptic NMDA receptor activity is coupled to the transcriptional control of the glutathione system

How the brain’s antioxidant defenses adapt to changing demand is incompletely understood. Here we show that synaptic activity is coupled, via the NMDA receptor (NMDAR), to control of the glutathione antioxidant system. This tunes antioxidant capacity to reflect the elevated needs of an active neuron, guards against future increased demand and maintains redox balance in the brain. This control is mediated via a programme of gene expression changes that boosts the synthesis, recycling and utilization of glutathione, facilitating ROS detoxification and preventing <i>Puma</i>-dependent neuronal apoptosis. Of particular importance to the developing brain is the direct NMDAR-dependent transcriptional control of glutathione biosynthesis, disruption of which can lead to degeneration. Notably, these activity-dependent cell-autonomous mechanisms were found to cooperate with non-cell-autonomous Nrf2-driven support from astrocytes to maintain neuronal GSH levels in the face of oxidative insults. Thus, developmental NMDAR hypofunction and glutathione system deficits, separately implicated in several neurodevelopmental disorders, are mechanistically linked

A combination of ascorbic acid and α-tocopherol to test the effectiveness and safety in the fragile X syndrome: study protocol for a phase II, randomized, placebo-controlled trial

BACKGROUND: Fragile X syndrome (FXS) is an inherited neurodevelopmental condition characterised by behavioural, learning disabilities, phisical and neurological symptoms. In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms. Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of α-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment. Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children–Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment. METHODS/DESIGN: A phase II randomized, double-blind pilot clinical trial. Scope: male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria. Instrumentation: clinical data, blood analysis, Wechsler Intelligence Scale for Children–Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment. DISCUSSION: A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The results will provide evidence to improve hyperactivity control and reduce behavioural and learning problems using ascorbic acid (vitamin C) and α-tocopherol (vitamin E). The study protocol was approved by the Regional Government Committee for Clinical Trials in Andalusia and the Spanish agency for drugs and health products. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01329770 (29 March 2011

Preliminary phytochemical and antimicrobial studies on a spike-moss Selaginella inaequalifolia (hook. & grev.) Spring

AbstractObjectiveTo screen the anti-cancer spike-mosses for the presence of various bioactivities and to identify the important bioactive chemicals present in Selaginella inaequalifolia (S. inaequalifolia) (Hook. & Grev.) Spring.MethodsPreliminary phytochemical screening was done by following the method of Brindha et al. Antimicrobial study was carried out by disc diffusion method.ResultsResults of preliminary phytochemical screening on five different extracts (petroleum ether, benzene, chloroform, ethanol and distilled water) of the spike-moss S. inaequalifolia show the presence steroids, triterpenes, phenolic group, tannin, sugars and catechin. Alkaloids, amino acids, anthraquinone and reducing sugar did not show any positive result. Among the five different extracts, ethanol and chloroform extracts show the presence of maximum number (4 each) of compounds. The results on antimicrobial studies show that all the three microbes [Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and Candida albicans (C. albicans)] tested are resistant to the ethanol extract and susceptible to petroleum ether extract. The petroleum ether extract shows maximum inhibition with 45 mm of inhibition zone in C. albicans. The inhibition zone in S. aureus and E. coli are 26 mm and 22 mm respectively.ConclusionsThe present study shows S. inaequalifolia having potent antibacterial and anticandidal activities