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1.
  • DNA is the sequence that codes for proteins.
  • Messenger RNA is transcribed from the DNA sequence of genes and translated into protein.
  • It can be difficult to predict how a change in the DNA sequence will affect messenger RNA and protein quantity and quality.
  • DNA translocation changes can cause the joining of sequences from two different genes or different parts of the same gene.
  • DNA sequencing is often used clinically to predict how DNA changes might affect proteins.
  • Alternatively, RNA sequencing can be used as a more direct measure of the effect of DNA changes on the protein products.
  • This sequencing is important for identifying changes in cancer that may indicate response to targeted therapy, prognosis, or diagnosis.
  相似文献   
2.
Detailed contemporary knowledge of the characteristics of the surgical population, national anaesthetic workload, anaesthetic techniques and behaviours are essential to monitor productivity, inform policy and direct research themes. Every 3–4 years, the Royal College of Anaesthetists, as part of its National Audit Projects (NAP), performs a snapshot activity survey in all UK hospitals delivering anaesthesia, collecting patient-level encounter data from all cases under the care of an anaesthetist. During November 2021, as part of NAP7, anaesthetists recorded details of all cases undertaken over 4 days at their site through an online survey capturing anonymous patient characteristics and anaesthetic details. Of 416 hospital sites invited to participate, 352 (85%) completed the activity survey. From these, 24,177 reports were returned, of which 24,172 (99%) were included in the final dataset. The work patterns by day of the week, time of day and surgical specialty were similar to previous NAP activity surveys. However, in non-obstetric patients, between NAP5 (2013) and NAP7 (2021) activity surveys, the estimated median age of patients increased by 2.3 years from median (IQR) of 50.5 (28.4–69.1) to 52.8 (32.1–69.2) years. The median (IQR) BMI increased from 24.9 (21.5–29.5) to 26.7 (22.3–31.7) kg.m–2. The proportion of patients who scored as ASA physical status 1 decreased from 37% in NAP5 to 24% in NAP7. The use of total intravenous anaesthesia increased from 8% of general anaesthesia cases to 26% between NAP5 and NAP7. Some changes may reflect the impact of the COVID-19 pandemic on the anaesthetic population, though patients with confirmed COVID-19 accounted for only 149 (1%) cases. These data show a rising burden of age, obesity and comorbidity in patients requiring anaesthesia care, likely to impact UK peri-operative services significantly.  相似文献   
3.

Aims

Concomitant chemoradiation is the standard of care in patients with inoperable non-small cell lung cancer. The purpose of this study was to analyse the survival outcome and toxicity data of using hypofractionated chemoradiation.

Materials and methods

One hundred patients were treated from June 2011 to November 2016. Treatment consisted of 55 Gy in 20 daily fractions concurrently with split-dose cisplatin vinorelbine chemotherapy over 4 weeks followed by two cycles of cisplatin vinorelbine only. Survival was estimated using Kaplan–Meier and Cox regression was carried out for known prognostic factors. A systematic search of literature was conducted using Medline, Embase and Cochrane databases and relevant references included.

Results

In total, 97% of patients completed radiotherapy and 73% of patients completed all four cycles of chemotherapy. One patient died of a cardiac event during consolidative chemotherapy. There were two cases of grade 4 toxicities (one sepsis, one renal impairment). Grade 3 toxicities included nausea/vomiting (17%), oesophagitis (15%), infection with neutropenia (12%) and pneumonitis (4%). Clinical benefit was seen in 86%. Two-year progression-free survival and overall survival rates were 49% and 58%, respectively. The median progression-free survival and overall survival were 23.4 and 43.4 months, respectively. The only significant prognostic factor was the number of chemotherapy cycles received (P = 0.02). The systematic review identified 13 relevant studies; a variety of regimens were assessed with variable reporting of outcomes and toxicity but with overall an improvement in survival over time.

Conclusion

Our experience compared with the original phase II trial showed improved treatment completion rates and survival with acceptable morbidity. With appropriate patient selection this regimen is an effective treatment option for locally advanced non-small cell lung cancer. This study helps to benchmark efficacy and toxicity rates while considering the addition of new agents to hypofractionated concurrent chemoradiotherapy. The agreement of a standard regimen for assessment in future trials would be beneficial.  相似文献   
4.
5.
Our knowledge of the radiological spectrum of myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is growing rapidly. An update on the radiological features of the disease, and its evolution is thus necessary. Magnetic resonance imaging (MRI) has an increasingly important role in the differential diagnosis of MOGAD particularly from aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and multiple sclerosis (MS). Differentiating these conditions is of prime importance because the management is different between the three inflammatory diseases, and thus could prevent further attack-related disability. Therefore, identifying the MRI features suggestive of MOGAD has diagnostic and prognostic implications. We herein review optic nerve, spinal cord and the brain MRI findings from MOGAD adult patients, and compare them to AQP4-NMOSD and MS.  相似文献   
6.

Background

The Parkland Grading Scale for Cholecystitis (PGS) was developed as an intraoperative grading scale to stratify gallbladder (GB) disease severity during laparoscopic cholecystectomy (LC). We aimed to prospectively validate this scale as a measure of LC outcomes.

Methods

Eleven surgeons took pictures of and prospectively graded the initial view of 317?GBs using PGS while performing LC (LIVE) between 9/2016 and 3/2017. Three independent surgeon raters retrospectively graded these saved GB images (STORED). The Intraclass Correlation Coefficient (ICC) statistic assessed rater reliability. Fisher's Exact, Jonckheere-Terpstra, or ANOVA tested association between peri-operative data and gallbladder grade.

Results

ICC between LIVE and STORED PGS grades demonstrated excellent reliability (ICC?=?0.8210). Diagnosis of acute cholecystitis, difficulty of surgery, incidence of partial and open cholecystectomy rates, pre-op WBC, length of operation, and bile leak rates all significantly increased with increasing grade.

Conclusions

PGS is a highly reliable, simple, operative based scale that can accurately predict outcomes after LC.

Table of contents summary

The Parkland Grading Scale for Cholecystitis was found to be a reliable and accurate predictor of laparoscopic cholecystectomy outcomes. Diagnosis of acute cholecystitis, surgical difficulty, incidence of partial and open cholecystectomy rates, pre-op WBC, operation length, and bile leak rates all significantly increased with increasing grade.  相似文献   
7.

Introduction

The aim of this study was to evaluate the root canal shaping effect of instruments manufactured from nickel titanium, M-Wire, and Gold wire with different glide path preparation techniques.

Methods

One hundred thirty-five mesiobuccal canals of extracted human maxillary molars were randomly divided into 3 equal groups (N = 45) for glide path preparation with K-files (KF) (Dentsply Sirona, Ballaigues, Switzerland), One G (OG) files (Micro-Mega, Besançon, France), and ProGlider (PG) files (Dentsply Sirona). Specimens of each glide path group were further divided equally into 3 groups for instrumentation with ProTaper Next (PTN, Dentsply Sirona), One Shape (OS, Micro-Mega), and WaveOne Gold (WOG, Dentsply Sirona) systems (n = 15). Micro–computed tomographic imaging was used to scan teeth before instrumentation and after shaping to compare centering ratio and canal transportation values at the apical, midroot, and coronal levels and the overall changes in canal volume. Data sets were statistically analyzed (analysis of variance and Kruskal-Wallis H tests).

Results

The centering ratios for all groups were statistically similar at all levels. Apical canal transportation was significantly high for K/OS and K/PTN (P = .003). Midroot canal transportation was significantly high for K/PTN, K/OS, and OG/OS (P = .0003). Coronal canal transportation was significantly high for K/PTN and K/OS (P = .011). The highest change in canal volume was observed with all PTN groups and the lowest with PG/WOG (P = .06).

Conclusions

WOG manufactured from Gold wire combined with PG showed better root canal shaping ability and removed less dentin from the canal walls. The nickel-titanium (OS) and M-Wire (PTN) instruments used in combination with KF significantly transported more canals. PTN removed the most dentin from the canal walls regardless of the GPP technique.  相似文献   
8.

Background and Aims

Diet is known to play a decisive role in the development of coronary heart disease (CHD). One factor believed to decrease lifetime risk of CHD is the consumption of omega-3 fatty acids. Yet, conclusive evidence regarding the potential cardioprotective effects of fatty acids is far from being reached. The present study aimed to provide further evidence on the association of serum fatty acid profiles with CHD risk.

Methods and Results

The CARdio-vascular Disease, Living and Ageing in Halle study (CARLA study) is an observational cohort study comprising an older adult's general population with a high level of cardiovascular risk factors. In a matched case–control design the serum fatty acid concentrations of 73 subjects with an incident fatal or nonfatal CHD event were compared to 146 controls matched for sex and age. Our data show that the participants of the CARLA study are underserved in unsaturated fatty acids with respect to current dietary recommendations. In addition, the ratio of omega-6 to omega-3 fatty acids was determined to be 8:1 which underlines the consumption of a Western-style diet enriched in omega-6 fatty acids. There were no significant differences in fatty acid patterns between cases and controls. Thus, no clear association of particular serum fatty acid levels with cardiovascular risk was found.

Conclusion

Our results support the conclusion that in populations with a homogenous low level of omega-3 polyunsaturated fatty acids consumption, serum fatty acid levels are not associated with CHD risk.  相似文献   
9.

Background

The factors determining peak susceptibility of the developing brain to anaesthetics are unclear. It is unknown why postnatal day 7 (P7) male rats are more vulnerable to anaesthesia-induced memory deficits than littermate females. Given the precocious development of certain regions in the female brain during the neonatal critical period, we hypothesised that females are susceptible to anaesthetic brain injury at an earlier time point than previously tested.

Methods

Female rats were exposed to isoflurane (Iso) 1 minimum alveolar concentration or sham anaesthesia at P4 or P7. Starting at P35, rats underwent a series of behavioural tasks to test their spatial and recognition memory. Cell death immediately after anaesthesia was quantified by Fluoro-Jade C staining in select brain regions, and developmental expression of the chloride transporters KCC2 and NKCC1 was analysed by immunoblotting in male and female rats at P4 and P7.

Results

Female rats exposed to Iso at P4 displayed impaired spatial, object-place, -context, and social recognition memory, and increased cell death in the hippocampus and laterodorsal thalamus. Female rats exposed at P7 exhibited only decreased performance in object-context compared with control. The ratio of NKCC1/KCC2 expression in cerebral cortex was higher in P4 females than in P7 females, and similar to that in P7 males.

Conclusions

Female rats exposed to Iso at P4 are sensitive to anaesthetic injury historically observed in P7 males. This is consistent with a comparably immature developmental state in P4 females and P7 males. The window of anaesthetic vulnerability correlates with sex-specific cortical expression of chloride transporters NKCC1 and KCC2. These findings suggest that both sex and developmental age play important roles in determining the outcome after early anaesthesia exposure.  相似文献   
10.

Objective

Phlebolymphedema (chronic venous insufficiency-related lymphedema) is a common and costly condition. Nevertheless, there is a dearth of evidence comparing phlebolymphedema therapeutic interventions. This study sought to examine the medical resource utilization and phlebolymphedema-related cost associated with Flexitouch (FLX; Tactile Medical, Minneapolis, Minn) advanced pneumatic compression devices (APCDs) relative to conservative therapy (CONS) alone, simple pneumatic compression devices (SPCDs), and other APCDs in a representative U.S. population of phlebolymphedema patients.

Methods

This was a longitudinal matched case-control analysis of deidentified private insurance claims. The study used administrative claims data from Blue Health Intelligence for the complete years 2012 through 2016. Patients were continuously enrolled for at least 18 months, diagnosed with phlebolymphedema, and received at least one claim for CONS either alone or in addition to pneumatic compression (SPCDs or APCDs). The main outcomes included direct phlebolymphedema- and sequelae-related medical resource utilization and costs.

Results

After case matching, the study included 86 patients on CONS (87 on FLX), 34 on SPCDs (23 on FLX), and 69 on other APCDs (67 on FLX). Compared with CONS, FLX was associated with 69% lower per patient per year total phlebolymphedema- and sequelae-related costs net of any pneumatic compression device-related costs ($3839 vs $12,253; P = .001). This was driven by 59% fewer mean annual hospitalizations (0.13 vs 0.32; P < .001) corresponding to 82% lower inpatient costs and 55% lower outpatient hospital costs. FLX was also associated with 52% lower outpatient physical therapy and occupational therapy costs and 56% lower other outpatient-related costs. Compared with SPCDs, FLX was associated with 85% lower total costs ($1153 vs $7449; P = .008) driven by 93% lower inpatient costs ($297 vs $4215; P = .002), 84% lower outpatient hospital costs ($368 vs $2347; P = .020), and 85% lower other outpatient-related costs ($353 vs $2313; P = .023). Compared with APCDs, FLX was associated with 53% lower total costs ($3973 vs $8436; P = .032) because of lower outpatient costs and lower rates of cellulitis (22.4% vs 44.9% of patients; P = .02).

Conclusions

This analysis indicates significant benefits attributable to FLX compared with alternative compression therapies that can help reduce the notable economic burden of phlebolymphedema.  相似文献   
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