Tag: pubmed

Genome Res. 2021 Jun 9. doi: 10.1101/gr.264465.120. Online ahead of print.

ABSTRACT

Neisseria meningitidis (the meningococcus) is a major human pathogen with a history of high invasive disease burden, particularly in sub-Saharan Africa. Our current understanding of the evolution of meningococcal genomes is limited by the rarity of large-scale genomic population studies and lack of in-depth investigation of the genomic events associated with routine pathogen transmission. Here, we fill this knowledge gap by a detailed analysis of 2839 meningococcal genomes obtained through a carriage study of over 50,000 samples collected systematically in Burkina Faso, West Africa, before, during, and after the serogroup A vaccine rollout, 2009-2012. Our findings indicate that the meningococcal genome is highly dynamic, with highly recombinant loci and frequent gene sharing across deeply separated lineages in a structured population. Furthermore, our findings illustrate how population structure can correlate with genome flexibility, as some lineages in Burkina Faso are orders of magnitude more recombinant than others. We also examine the effect of selection on the population, in particular how it is correlated with recombination. We find that recombination principally acts to prevent the accumulation of deleterious mutations, although we do also find an example of recombination acting to speed the adaptation of a gene. In general, we show the importance of recombination in the evolution of a geographically expansive population with deep population structure in a short timescale. This has important consequences for our ability to both foresee the outcomes of vaccination programs and, using surveillance data, predict when lineages of the meningococcus are likely to become a public health concern.

PMID:34108268 | DOI:10.1101/gr.264465.120

Sci Transl Med. 2021 Jun 9;13(597):eabe1376. doi: 10.1126/scitranslmed.abe1376.

ABSTRACT

Nitrous oxide at 50% inhaled concentration has been shown to improve depressive symptoms in patients with treatment-resistant major depression (TRMD). Whether a lower concentration of 25% nitrous oxide provides similar efficacy and persistence of antidepressant effects while reducing the risk of adverse side effects is unknown. In this phase 2 clinical trial (NCT03283670), 24 patients with severe TRMD were randomly assigned in a crossover fashion to three treatments consisting of a single 1-hour inhalation with (i) 50% nitrous oxide, (ii) 25% nitrous oxide, or (iii) placebo (air/oxygen). The primary outcome was the change on the Hamilton Depression Rating Scale (HDRS-21). Whereas nitrous oxide significantly improved depressive symptoms versus placebo (P = 0.01), there was no difference between 25 and 50% nitrous oxide (P = 0.58). The estimated differences between 25% and placebo were -0.75 points on the HDRS-21 at 2 hours (P = 0.73), -1.41 points at 24 hours (P = 0.52), -4.35 points at week 1 (P = 0.05), and -5.19 points at week 2 (P = 0.02), and the estimated differences between 50% and placebo were -0.87 points at 2 hours (P = 0.69), -1.93 points at 24 hours (P = 0.37), -2.44 points at week 1 (P = 0.25), and -7.00 points at week 2 (P = 0.001). Adverse events declined substantially with dose (P < 0.001). These results suggest that 25% nitrous oxide has comparable efficacy to 50% nitrous oxide in improving TRMD but with a markedly lower rate of adverse effects.

PMID:34108247 | DOI:10.1126/scitranslmed.abe1376

Occup Environ Med. 2021 Jun 9:oemed-2020-107197. doi: 10.1136/oemed-2020-107197. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate exposure-response between 1,3-butadiene, styrene and lymphohaematopoietic cancers in an updated cohort of workers at six North American plants that made synthetic rubber polymers.

METHODS: Employees were followed from 1943 through 2009 to determine mortality outcomes. Cox regression analyses estimated rate ratios (RRs) and 95% CIs by quartile of cumulative exposure to butadiene or styrene, measured in parts per million-years (ppm-years), and exposure-response trends for all leukaemia, lymphoid leukaemia, myeloid leukaemia, acute myeloid leukaemia, non-Hodgkin’s lymphoma (NHL), multiple myeloma and all B-cell malignancies.

RESULTS: Among 21 087 workers, adjusted RRs for butadiene and all leukaemia (132 deaths) rose with increasing exposure, with an RR of 2.53 (95% CI 1.37 to 4.67) in the highest exposure quartile (≥363.64 ppm-years), and the exposure-response trend was statistically significant for all leukaemia (p=0.014) and for lymphoid leukaemia (52 deaths, p=0.007). Styrene exposure-response trends for all leukaemia and lymphoid leukaemia were less consistent than those for butadiene. Cumulative exposures to butadiene and styrene were not associated consistently with myeloid leukaemias or the B-cell malignancies, NHL and multiple myeloma.

CONCLUSIONS: We confirmed a positive exposure-response relationship between butadiene and all leukaemia among workers, most of whom had coexposure to styrene. Results supported an association between butadiene and lymphoid leukaemia, but not myeloid leukaemia, and provided little evidence of any association of butadiene or styrene exposures with major subtypes of B-cell malignancies other than lymphoid leukaemia, including NHL and multiple myeloma.

PMID:34108254 | DOI:10.1136/oemed-2020-107197

Br J Ophthalmol. 2021 Jun 9:bjophthalmol-2021-319352. doi: 10.1136/bjophthalmol-2021-319352. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: To investigate retinal sensitivity and fixation stability using microperimetry in children with retinopathy of prematurity (ROP).

METHODS: Observational case series. Totally 51 preterm children who had been followed for ROP were examined in three groups (n=17 in each group). The groups were defined as children without ROP (group 1), children with spontaneously resolved ROP (group 2) and children who had laser treatment for ROP (group 3). All subjects underwent a detailed ophthalmic examination. Macular Analyzer Integrity Assessment Microperimetry was used to analyse macular light sensitivity and fixation stability. The results were compared between groups. The measurements were also analysed according to age, gender, birth weight and gestational age.

RESULTS: The mean age was 10.84±0.97 years, and 27 children were female. Mean average threshold (AT) for macular sensitivity was 25.5±2.1 decibel in group 1, 26.8±3.8 decibel in group 2 and 26.3±3.0 decibel in group 3. These differences were not statistically significant between the groups (p=0.067), but AT was abnormal in 29% of the whole study population. Outputs about fixation stability were similar between the three groups but fixation was unstable in 27% of the subjects. Mean AT was better in children ≥11 years old compared with the younger ones (p=0.022).

CONCLUSION: Preterm children may have some abnormalities in macular light sensitivity and fixation stability. These abnormalities may be more prominent in children less than 11 years old. ROP itself or the laser treatment seems not to affect macular light sensitivity and fixation stability.

PMID:34108227 | DOI:10.1136/bjophthalmol-2021-319352

RNA. 2021 Jun 9:rna.078707.121. doi: 10.1261/rna.078707.121. Online ahead of print.

ABSTRACT

Mammalian RNA interference (RNAi) is often linked to the regulation of gene expression in the cytoplasm. Synthetic RNAs, however, can also act through the RNAi pathway to regulate transcription and splicing. While nuclear regulation by synthetic RNAs can be robust, a critical unanswered question is whether endogenous functions for nuclear RNAi exist in mammalian cells. Using enhanced crosslinking immunoprecipitation (eCLIP), we mapped AGO2 binding sites within nuclear RNA. The strongest AGO2 binding sites were mapped to micro RNAs (miRNAs). The most abundant miRNAs were distributed similarly between cytoplasm and nucleus, providing no evidence for mechanisms that facilitate localization of miRNAs in one compartment versus the other. Beyond miRNAs, most statistically-significant AGO2 binding was within introns. Splicing changes were confirmed by RT-PCR and were recapitulated by synthetic duplex RNAs and miRNA mimics complementary to the sites of AGO2 binding. These data support the hypothesis that miRNAs can control gene splicing. While nuclear RNAi proteins have the potential to be a natural regulatory mechanism, careful study will be necessary to identify critical RNA drivers of normal physiology and disease.

PMID:34108230 | DOI:10.1261/rna.078707.121

Emerg Med J. 2021 Jun 9:emermed-2020-210693. doi: 10.1136/emermed-2020-210693. Online ahead of print.

ABSTRACT

BACKGROUND: A consistent approach to cervical spine injury (CSI) clearance for patients 65 and older remains a challenge. Clinical clearance algorithms like the National Emergency X-Radiography Utilisation Study (NEXUS) criteria have variable accuracy and the Canadian C-spine rule excludes older patients. Routine CT of the cervical spine is performed to rule out CSI but at an increased cost and low yield. Herein, we aimed to identify predictive clinical variables to selectively screen older patients for CSI.

METHODS: The University of Iowa’s trauma registry was interrogated to retrospectively identify all patients 65 years and older who presented with trauma from a ground-level fall from January 2012 to July 2017. The relationship between predictive variables (demographics, NEXUS criteria and distracting injuries) and presence of CSI was examined using the generalised linear modelling (GLM) framework. A training set was used to build the statistical models to identify clinical variables that can be used to predict CSI and a validation set was used to assess the reliability and consistency of the model coefficients estimated from the training set.

RESULTS: Overall, 2312 patients ≥65 admitted for ground-level falls were identified; 253 (10.9%) patients had a CSI. Using the GLM framework, the best predictive model for CSI included midline tenderness, focal neurological deficit and signs of trauma to the head/face, with midline tenderness highly predictive of CSI (OR=22.961 (15.178-34.737); p<0.001). The negative predictive value (NPV) for this model was 95.1% (93.9%-96.3%). In the absence of midline tenderness, the best model included focal neurological deficit (OR=2.601 (1.340-5.049); p=0.005) and signs of trauma to the head/face (OR=3.024 (1.898-4.815); p<0.001). The NPV was 94.3% (93.1%-95.5%).

CONCLUSION: Midline tenderness, focal neurological deficit and signs of trauma to the head/face were significant in this older population. The absence of all three variables indicates lower likelihood of CSI for patients≥65. Future observational studies are warranted to prospectively validate this model.

PMID:34108196 | DOI:10.1136/emermed-2020-210693

J Dr Nurs Pract. 2021 Jun 9:JDNP-D-20-00048. doi: 10.1891/JDNP-D-20-00048. Online ahead of print.

ABSTRACT

BACKGROUND: Learning depends not only upon how teachers have designed and structured their subjects and courses but also upon how their students perceive and understand this design and structure. Understanding student’s level of perception with their clinical education forms a basis of determining the quality of nursing education.

OBJECTIVE: Assess nursing students’ perception of their learning experience with community health nursing practical modules.

METHODS: Cross-sectional descriptive study, the convenience sample included 149 students studying a community health nursing practical course at the Faculty of Nursing affiliated to [Institution MASKED]. Three tools were used; (a) interviewing questionnaire regarding demographic characteristics. (b) Undergraduate modules experience questionnaire and (c) Student evaluation of clinical education environment inventory.

RESULTS: Students’ total perception mean scores regarding the practical modules experience questionnaire was (79.82%), and different community clinical learning environment, family health centers (82.01%), schools (76. 83%), and geriatric homes (79. 29%) with statistical significance differences p ≤ .042. Furthermore, significant relationship was found between students’ academic achievement and total perception of the Undergraduate Modules Experience Questionnaire (UMEQ) and its subscales, Good Teaching, Intellectual Motivation (p ≤ .01), Clear goals and standards and Generic Skills (p ≤ .04), Appropriate Assessment and Overall Satisfaction (p ≤ .05).

CONCLUSION: Nursing students revealed a higher positive perception of community health nursing practical modules experiences. However, there was few areas are required for improving quality of the practical modules.

IMPLICATIONS FOR NURSING EDUCATION: Increasing period of students’ clinical training exposure, teaching the skills of effective time management as well as increasing number of the academic staff in the community health nursing department are recommended strategies for improving quality of community health nursing practical modules.

PMID:34108197 | DOI:10.1891/JDNP-D-20-00048

BMJ Open. 2021 Jun 9;11(6):e045353. doi: 10.1136/bmjopen-2020-045353.

ABSTRACT

OBJECTIVE: Tourniquet use in total knee replacement (TKR) is believed to improve the bone-cement interface by reducing bleeding, potentially prolonging implant survival. This study aimed to compare the risk of revision for primary cemented TKR performed with or without a tourniquet.

DESIGN: We analysed data from the National Joint Registry (NJR) for all primary cemented TKRs performed in England and Wales between April 2003 and December 2003. Kaplan-Meier plots and Cox regression were used to assess the influence of tourniquet use, age at time of surgery, sex and American Society of Anaesthesiologists (ASA) classification on risk of revision for all-causes.

RESULTS: Data were available for 16 974 cases of primary cemented TKR, of which 16 132 had surgery with a tourniquet and 842 had surgery without a tourniquet. At 10 years, 3.8% had undergone revision (95% CI 2.6% to 5.5%) in the no-tourniquet group and 3.1% in the tourniquet group (95% CI 2.8% to 3.4%). After adjusting for age at primary surgery, gender and primary ASA score, the HR for all-cause revision for cemented TKR without a tourniquet was 0.82 (95% CI 0.57 to 1.18).

CONCLUSIONS: We did not find evidence that using a tourniquet for primary cemented TKR offers a clinically important or statistically significant reduction in the risk of all-cause revision up to 13 years after surgery. Surgeons should consider this evidence when deciding whether to use a tourniquet for cemented TKR.

PMID:34108163 | DOI:10.1136/bmjopen-2020-045353

BMJ Open. 2021 Jun 9;11(6):e050919. doi: 10.1136/bmjopen-2021-050919.

ABSTRACT

INTRODUCTION: Cardiothoracic surgical outcomes are poorer in people with diabetes compared with those without diabetes. There are two important uncertainties in the management of people with diabetes undergoing major surgery: (1) how to improve diabetes management in the weeks leading up to an elective procedure and (2) whether that improved management leads to better postoperative outcomes. We previously demonstrated the feasibility of delivering the Optimising Cardiac Surgery ouTcOmes in People with diabeteS (OCTOPuS) intervention, an outpatient intervention delivered by diabetes healthcare professionals for people with suboptimally managed diabetes over 8-12 weeks before elective cardiac surgery. The present study will assess the clinical and cost-effectiveness of the intervention in cardiothoracic centres across the UK.

METHODS AND ANALYSIS: A multicentre, parallel group, single-blinded 1:1 individually randomised trial comparing time from surgery until clinically fit for discharge in adults with suboptimally managed type 1 diabetes or type 2 diabetes undergoing elective surgery between the OCTOPuS intervention and usual care (primary endpoint). Secondary endpoints will include actual time from surgery to discharge from hospital; days alive and either out of hospital or judged as clinically fit for discharge; mortality; time on intensive therapy unit (ITU)/ventilator; infections; acute myocardial infarction; change in weight; effect on postoperative renal function and incidence of acute kidney injury; change in HbA_1c; frequency and severity of self-reported hypoglycaemia; operations permanently cancelled for suboptimal glycaemic levels; cost-effectiveness; psychosocial questionnaires. The target sample size will be 426 recruited across approximately 15 sites. The primary analysis will be conducted on an intention-to-treat population. A two-sided p value of 0.05 or less will be used to declare statistical significance for all analyses and results will be presented with 95% CIs.

ETHICS AND DISSEMINATION: The trial was approved by the South Central-Hampshire A Research Ethics Committee (20/SC/0271). Results will be disseminated through conferences, scientific journals, newsletters, magazines and social media.

TRIAL REGISTRATION NUMBER: ISRCTN10170306.

PMID:34108175 | DOI:10.1136/bmjopen-2021-050919

Zhonghua Gan Zang Bing Za Zhi. 2021 May 20;29(5):462-467. doi: 10.3760/cma.j.cn501113-20190520-00176.

ABSTRACT

Objective: To investigate the effect of baicalein in improving non-alcoholic fatty liver disease caused by high fat-induced oxidative damage in mice. Methods: Male C57BL/6J mice weighing 18-20 g were randomly divided into 4 groups: normal control group (C, 10% fat for energy), high-fat group (H, 60% fat for energy), high-fat + scutellaria baicalein group (H+B, baicalein: 400 mg·kg(-1)·bw(-1)), and baicalein control group (B, baicalein: 400 mg·kg(-1)·bw(-1)). After 12 weeks, mice were sacrificed, and the tissue samples were collected. Liver pathological changes were observed by hematoxylin and eosin staining. Mitochondrial morphology was examined by ultramicropathology. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and mitochondrial membrane potential (MMP) changing levels in the liver were determined by kit. Sestrin2 and protein carbonylation (PCOS) levels were detected by Western blotting. Small interfering RNA (siRNA) was used to knock-down the Sestrin2 protein expression in HepG2 cells. Intramyocellular lipid changes in HepG2 cells was detected by fluorescent dye BODIPY493/503. One way ANOVA was used LSD pairwise comparison method was used to test the statistical difference. Results: Compared with the normal control group, high-fat fed caused significant fatty degeneration, decreased GSH and SOD levels (P ​​< 0.05), increased MDA and protein carbonylation levels, and increased Sestrin2 expression (P < 0.05) in mice. Mitochondrial shape changes, swelling, lack of cristae, and MMP was down-regulated by 33.3% (t = 13.456, P ​​< 0.001). Baicalein intervention had effectively inhibited hepatic steatosis and oxidative damage caused by high-fat fed, and further up-regulated Sestrin2 expression, MMP (t = 10.104, P ​​< 0.001), and significantly alleviated liver damage in mice. Sestrin2 expression knock-down had further increased the intracellular lipid deposition and PCOs expression (P ​​< 0.05), and reduced baicalein ability to antagonize lipid deposition and antioxidant capacity in Hep2 cells. Conclusion: Baicalein alleviate non-alcoholic fatty liver by regulating Sestrin2 expression and high-fat fed-induced liver oxidative damage.

PMID:34107585 | DOI:10.3760/cma.j.cn501113-20190520-00176