Tag: pubmed

Cancer Commun (Lond). 2021 Jun 10. doi: 10.1002/cac2.12164. Online ahead of print.

ABSTRACT

BACKGROUND: Y-box binding protein 1 (YB1 or YBX1) plays a critical role in tumorigenesis and cancer progression. However, whether YB1 affects malignant transformation by modulating non-coding RNAs remains largely unknown. This study aimed to investigate the relationship between YB1 and microRNAs and reveal the underlying mechanism by which YB1 impacts on tumor malignancy via miRNAs-mediated regulatory network.

METHODS: The biological functions of YB1 in hepatocellular carcinoma (HCC) cells were investigated by cell proliferation, wound healing, and transwell invasion assays. The miRNAs dysregulated by YB1 were screened by microarray analysis in HCC cell lines. The regulation of YB1 on miR-205 and miR-200b was determined by quantitative real-time PCR, dual-luciferase reporter assay, RNA immunoprecipitation, and pull-down assay. The relationships of YB1, DGCR8, Dicer, TUT4, and TUT1 were identified by pull-down and coimmunoprecipitation experiments. The cellular co-localization of YB1, DGCR8, and Dicer were detected by immunofluorescent staining. The in vivo effect of YB1 on tumor metastasis was determined by injecting MHCC97H cells transduced with YB1 shRNA or shControl via the tail vein in nude BALB/c mice. The expression levels of epithelial to mesenchymal transition markers were detected by immunoblotting and immunohistochemistry assays.

RESULTS: YB1 promoted HCC cell migration and tumor metastasis by regulating miR-205/200b-ZEB1 axis partially in a Snail-independent manner. YB1 suppressed miR-205 and miR-200b maturation by interacting with the microprocessors DGCR8 and Dicer as well as TUT4 and TUT1 via the conserved cold shock domain. Subsequently, the downregulation of miR-205 and miR-200b enhanced ZEB1 expression, thus leading to increased cell migration and invasion. Furthermore, statistical analyses on gene expression data from HCC and normal liver tissues showed that YB1 expression was positively associated with ZEB1 expression and remarkably correlated with clinical prognosis.

CONCLUSION: This study reveals a previously undescribed mechanism by which YB1 promotes cancer progression by regulating the miR-205/200b-ZEB1 axis in HCC cells. Furthermore, these results highlight that YB1 may play biological functions via miRNAs-mediated gene regulation, and it can serve as a potential therapeutic target in human cancers.

PMID:34110104 | DOI:10.1002/cac2.12164

Cancer Sci. 2021 Jun 10. doi: 10.1111/cas.15020. Online ahead of print.

ABSTRACT

Despite immune checkpoint inhibitors(ICIs) have achieved unprecedented success in dMMR tumours, pMMR tumors accounting for 85% of colorectal cancer(CRC) cases remains unresponsive. Lactate dehydrogenase A(LDH-A) is the rate-limiting enzyme that catalyses the transformation of pyruvate to lactate in the process of glycolysis. We investigate the relationship between LDH-A and dMMR with the purpose of exploring the treatment strategy for pMMR CRC patients . We herein show that LDH-A can promote the proliferation of dMMR and pMMR CRC cells by positively regulating MMR proteins both in vitro and in vivo. LDH-A inhibition can improve the efficacy of PD-1 blockade in pMMR CRC xenograft model.. A statistical analysis of 186 CRC specimens showed a significant correlation between LDH-A and dMMR status. Moreover, patients with both low LDH-A expression and dMMR exhibited better disease free survival than patients with other combinations. The close correlation of LDH-A and dMMR may offer the promising therapeutic strategy that combination of LDH-A inhibitor and ICIs may improve the clinical benefit for pMMR CRC patients.

PMID:34110068 | DOI:10.1111/cas.15020

Wound Repair Regen. 2021 Jun 10. doi: 10.1111/wrr.12948. Online ahead of print.

ABSTRACT

Complex surgery of abdominal wall hernia continues to bear the major concern of wound healing disorders. Technical modifications have not been able to sufficiently prevent wound healing impairments or infections, even in clean elective cases, especially when dealing with large-scale hernia defects. Incisional negative pressure wound therapy (iNPWT) in its intentional use as a preventive tool has recently found its way from theoretical and experimental advantages to the clinical routine. Different indications have been defined but evidence is lacking. We performed a retrospective analysis (1/2014-5/2019) of all ventral hernia repairs (n = 386) done in our institution as open sublay mesh reinforcement, partially requiring component separation (CS), receiving iNPWT in selected cases based on single surgeon experience. Pre- and perioperative data included patient and hernia characteristics as well as the employed mesh sizes. Postoperative follow-up (median 38.5 months [interquartile range: 23.4, 53.3]) extended beyond patient dismissal and included the rate of re-admission due to wound healing disorders. The primary outcome was the incidence of surgical site occurrences (SSO). Secondary endpoints included wound-related readmissions, reoperations and recurrences. Patients were matched based on propensity scores in a 1:1 ratio. Propensity scores were calculated based on five preoperative variables, including sex, body-mass-index, American Society of Anesthesiology classification, recurrent hernia repair and operation technique, to identify significant parameters. The rate of SSO was 12% (n = 46) for all operated cases, and the rate of surgical site infection (SSI) was 8.8% (n = 34). In the subgroup of CS (n = 40), the rate increased to 15% (n = 6). The usage of iNPWT (n = 54) led to an in-hospital SSO rate of 14.8% (n = 8) but increased to 33.3% (n = 18) when including the re-admission rate. The SSI rate for the iNPWT cohort was 14.8% (n = 8) with a consecutive need for reoperation (Clavien-Dindo IIIb) in 87.5% (n = 7). In the matched-pair analysis, the hernia-size and mesh-size were the main risk factors for SSO. The use of iNPWT significantly reduced this statistical effect (p = 0.405). In a large and representative patient cohort, we were able to demonstrate that the advantage of iNPWT used after complex abdominal wall repair does not come first hand. Especially in the follow-up, we found a relevant increase in wound healing problems after dismissal. To proof the benefit of iNPWT in these heterogeneous patients, we could identify hernia size and mesh size as individual risk factors that were nihilated by the use of iNPWT. We found it to be favourable to use iNPWT when mesh-size exceeded 450 cm² .

PMID:34110077 | DOI:10.1111/wrr.12948

Indoor Air. 2021 Jun 10. doi: 10.1111/ina.12867. Online ahead of print.

ABSTRACT

Although solid fuel use has been increasingly linked to cardiovascular events (CVEs), conclusions have been inconsistent. We systematically searched 3 databases (PubMed, Embase, and Web of Science) up to July 3, 2020, to identify English language reports that assessed the association of solid fuel use with CVEs. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated with a random-effects model. Subgroup analyses and sensitivity analyses were conducted to explore the potential sources of heterogeneity and to test the stability of the results. We finally included 13 observational studies (8 cohort, 3 cross-sectional, and 2 case-control studies comprising 791,220 participants) in the meta-analysis. The risk of CVEs was increased 21% with the highest versus the lowest solid fuel use (highest/lowest, RR_pooled = 1.21, 95% CI: 1.10-1.34). As for the subgroup analyses on study design, the pooled RR for cohort studies, case-control studies, and cross-sectional studies were 1.11 (95%CI: 1.03-1.19), 4.80 (95%CI: 2.22-10.39), and 1.46 (95%CI: 0.82-2.62), respectively. The results of this study suggested that high solid fuel use was associated with increased CVE risk, and that reducing the use of solid fuel will be important for improving the health of the populations in developing countries.

PMID:34110043 | DOI:10.1111/ina.12867

J Anim Physiol Anim Nutr (Berl). 2021 Jun 10. doi: 10.1111/jpn.13588. Online ahead of print.

ABSTRACT

The objectives of this study were to investigate the relationship between the in vitro ruminal ammonia nitrogen (NH₃ -N) concentration and the Cornell Net Carbohydrate and Protein System (CNCPS) N-fractions of feeds for cattle and further compare the performance of developing multiple linear regression (MLR) and artificial neural network (ANN) models in estimating the NH₃ -N concentration in rumen fermentation. Two data sets were established, of which the training data set containing forty-five rations for cattle with concentrate/roughage ratios of 50:50, 40:60, 30:70, 20:80 and 10:90 used for developing models and the test data set containing ten other rations with the same concentrate/roughage ratios with the training data set were used for validating of models. The NH₃ -N concentrations of feed samples were measured using an in vitro incubation technique. The CNCPS N-fractions (g), for example PB₁ (rapidly degraded true protein), PB₂ (neutral detergent soluble nitrogen), PB₃ (acid detergent soluble nitrogen) of rations, were calculated based on chemical analysis. Statistical analysis indicated that the NH₃ -N concentration (mg) was significantly correlated with the CNCPS N-fractions (g) PB₁ , PB₂ and PB₃ in a multiple linear pattern: NH₃ -N = (130.70±33.80) PB₁ + (155.83±17.89) PB₂ – (85.44±37.69) PB₃ + (42.43±1.05), R² = 0.77, p < 0.0001, n = 45. The results indicated that both MLR and ANN models were suitable for predicting in vitro NH₃ -N concentration of rations using CNCPS N-fractions PB₁ , PB₂ , and PB₃ as independent variables while the neural network model showed better performance in terms of greater r² , CCC and lower RMSPE between the observed and predicted values.

PMID:34110053 | DOI:10.1111/jpn.13588

Aust J Rural Health. 2021 Jun 10. doi: 10.1111/ajr.12685. Online ahead of print.

ABSTRACT

OBJECTIVE: To measure the effect of depression awareness and management training on the attitudes of rural primary health care workers.

DESIGN: A repeated measures design in which participants acted as their own controls.

SETTING: The training program occurred in 6 locations across rural South Australia.

PARTICIPANTS: The study enrolled primary care workers in general practitioner surgeries, Aboriginal Community Controlled Health Organisations, community health centres, public hospitals, regional health services and non-government organisations.

INTERVENTION: A six-session training workshop that was informed by the National Institute for Health and Care Excellence guidelines for the treatment and care of people with depression.

MAIN OUTCOME MEASURE: The 22-item Revised Depression Attitude Questionnaire comprised the main outcome measure. Participants were assessed 12 weeks before the training, again on the day of commencement of the training and after the training.

RESULTS: Seventy-two primary health workers completed the training program in depression awareness, building therapeutic relationships, working with ambivalence, and goal setting. Between the 2 pre-training assessments mean scores showed no significant difference. There were statistically significant improvements on the overall attitudes and the subscales therapeutic optimism and professional confidence between pre-training and post-training.

CONCLUSION: Training rural primary health care workers in depression may improve their attitudes to working with people living with depression.

PMID:34110058 | DOI:10.1111/ajr.12685

Cochrane Database Syst Rev. 2021 Jun 10;6:CD009517. doi: 10.1002/14651858.CD009517.pub4.

ABSTRACT

BACKGROUND: Implantation of an embryo within the endometrial cavity is a critical step in the process of in vitro fertilisation (IVF). Previous research has suggested that endometrial injury (also known as endometrial scratching), defined as intentional damage to the endometrium, can increase the chance of pregnancy in women undergoing IVF.

OBJECTIVES: To assess the effectiveness and safety of endometrial injury performed before embryo transfer in women undergoing in vitro fertilisation (IVF) including intracytoplasmic sperm injection (ICSI) and frozen embryo transfer.

SEARCH METHODS: In June 2020 we searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, LILACS, DARE and two trial registries. We also checked the reference sections of relevant studies and contacted experts in the field for any additional trials.

SELECTION CRITERIA: Randomised controlled trials comparing intentional endometrial injury before embryo transfer in women undergoing IVF, versus no intervention or a sham procedure.

DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Two independent review authors screened studies, evaluated risk of bias and assessed the certainty of the evidence by using GRADE (Grading of Recommendation, Assessment, Development and Evaluation) criteria. We contacted and corresponded with study investigators as required. Due to the high risk of bias associated with many of the studies, the primary analyses of all review outcomes were restricted to studies at a low risk of bias for selection bias and other bias. Sensitivity analysis was then performed including all studies. The primary review outcomes were live birth and miscarriage.

MAIN RESULTS: Endometrial injury versus control (no procedure or a sham procedure) A total of 37 studies (8786 women) were included in this comparison. Most studies performed endometrial injury by pipelle biopsy in the luteal phase of the cycle before the IVF cycle. The primary analysis was restricted to studies at low risk of bias, and included eight studies. The effect of endometrial injury on live birth is unclear as the result is consistent with no effect, or a small reduction, or an improvement (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.98 to 1.28; participants = 4402; studies = 8; I² = 15%, moderate-certainty evidence). This suggests that if the chance of live birth with IVF is usually 27%, then the chance when using endometrial injury would be somewhere between < 27% and 32%. Similarly, the effect of endometrial injury on clinical pregnancy is unclear (OR 1.08, 95% CI 0.95 to 1.23; participants = 4402; studies = 8; I² = 0%, moderate-certainty evidence). This suggests that if the chance of clinical pregnancy from IVF is normally 32%, then the chance when using endometrial injury before IVF is between 31% and 37%. When all studies were included in the sensitivity analysis, we were unable to conduct meta-analysis for the outcomes of live birth and clinical pregnancy due to high risk of bias and statistical heterogeneity. Endometrial injury probably results in little to no difference in chance of miscarriage (OR 0.88, 95% CI 0.68 to 1.13; participants = 4402; studies = 8; I² = 0%, moderate-certainty evidence), and this result was similar in the sensitivity analysis that included all studies. The result suggests that if the chance of miscarriage with IVF is usually 6.0%, then when using endometrial injury it would be somewhere between 4.2% and 6.8%. Endometrial injury was associated with mild to moderate pain (approximately 4 out of 10), and was generally associated with some minimal bleeding. The evidence was downgraded for imprecision due to wide confidence intervals and therefore all primary analyses were graded as moderate certainty. Higher versus lower degree of injury Only one small study was included in this comparison (participants = 129), which compared endometrial injury using two different instruments in the cycle prior to the IVF cycle: a pipelle catheter and a Shepard catheter. This trial was excluded from the primary analysis due to risk of bias. In the sensitivity analysis, all outcomes reported for this study were graded as very-low certainty due to risk of bias, and as such we were not able to interpret the study results.

AUTHORS’ CONCLUSIONS: The effect of endometrial injury on live birth and clinical pregnancy among women undergoing IVF is unclear. The results of the meta-analyses are consistent with an increased chance, no effect and a small reduction in these outcomes. We are therefore uncertain whether endometrial injury improves the chance of live birth or clinical pregnancy in women undergoing IVF. Endometrial injury does not appear to affect the chance of miscarriage. It is a somewhat painful procedure associated with a small amount of bleeding. In conclusion, current evidence does not support the routine use of endometrial injury for women undergoing IVF.

PMID:34110001 | DOI:10.1002/14651858.CD009517.pub4

Biomed Chromatogr. 2021 Jun 10:e5194. doi: 10.1002/bmc.5194. Online ahead of print.

ABSTRACT

The current work describes development and validation of a stability-indicating UPLC method for the determination of Olmesaratan Medoxomil (OLM), Amlodipine Besylate (AMB), Hydrochlorothiazide (HCT) and their degradation products in the triple-combination tablet dosage form. The separation was achieved using Zorbax Eclipse plus C8 RRHD (100mm x 3.0 mm), 1.8μm column with gradient elution of mobile phase-A containing 0.02M of sodium phosphate buffer (pH 3.35) and mobile phase B as acetonitrile and water (90:10, v/v). The detector signal was monitored at UV 250 nm. Analytical performance of the optimized UPLC method was validated as per ICH guidelines. The linearity ranges for OLM, AMB and HCT were 0.59-240 μg/mL, 0.30-60 μg/mL and 0.37-150 μg/mL respectively with correlation coefficients >0.999. The dosage form was subjected to forced-degradation conditions of neutral, acidic, and alkaline hydrolysis, oxidation, thermal and photo degradation. The method is proved to be stability-indicating by demonstrating the specificity of the drugs from degradation products. Robustness of the method was evaluated through 2-level, 3-factorial design with multivariate approach. Statistical data analysis with best model fit p-value<0.05 from ANOVA test indicated that the individual factors influence is relatively higher than the interaction effects. The method was for the analysis of drug product.

PMID:34110035 | DOI:10.1002/bmc.5194

J Vet Diagn Invest. 2021 Jun 10:10406387211021865. doi: 10.1177/10406387211021865. Online ahead of print.

ABSTRACT

Estimation of the postmortem interval (PMI) is a poorly studied field in veterinary pathology. The development of field-applicable methods is needed given that animal cruelty investigations are increasing continually. We evaluated various histologic criteria in equine brain, liver, and muscle tissue to aid the estimation of PMI in horses, which is central to forensic investigations of suspicious death. After death, autolysis proceeds predictably, depending on environmental conditions. Currently, no field-applied methods exist that accurately estimate the PMI using histology in animals or humans through quantification of autolysis. Brain, liver, and skeletal muscle from 12 freshly euthanized horses were held at 22°C and 8°C for 72 h. Tissues were sampled at T0h, T1h, T2h, T4h, T6h, T12h, T24h, T36h, T48h, T60h, and T72h. For each tissue, we quantified 5 to 7 criteria associated with autolysis, based on the percentage of microscopic field involved. Each criterion was modeled, with temperature and time as independent variables. Changes were most predictable in liver and muscle over the first 72 h postmortem. The criteria for autolysis that were present most extensively at both temperatures were hepatocyte individualization and the separation of bile duct epithelium from the basement membrane. The changes that were present next most extensively were disruption of myofiber continuity, hypereosinophilia, and loss of striation. Brain changes were highly variable. The high statistical correlation between the parameter “autolysis” and the variables “time/temperature”, indicates that autolysis is progressive and predictable. Further investigation of these criteria is needed to establish histologic algorithms for PMI.

PMID:34109897 | DOI:10.1177/10406387211021865

Rev Neurol. 2021 Jun 16;72(12):411-418. doi: 10.33588/rn.7212.2020595.

ABSTRACT

AIM: The aim of this study is to determine whether there are any differences in the dream content in different sleep disorders and to describe their characteristics.

PATIENTS AND METHODS: We studied four sleep disorders: sleep apnoea and hypopnoea syndrome (SAHS), primary insomnia (PI), idiopathic REM sleep behaviour disorder (IRBD) and narcolepsy type I. Each patient was asked to keep a dream diary for two weeks. The content of the diaries was transcribed and analysed for length, mental content, complexity and threat. The results were compared to establish differences.

RESULTS: Eighty-nine patients were studied: 23 with SAHS without continuous positive airway pressure (CPAP) who had the highest number of dreams involving threats (32.5%); 19 with SAHS treated with CPAP who had the highest number of dreams involving objects (64.8%), descriptive elements (38%) and higher complexity (9.5%); 22 with primary insomnia who had the highest number of dreams with threatening events in the social sphere (57.7%); 12 with IRBD who had the highest number of dreams with failures (14%) and lower complexity (71.7%); and 13 with narcolepsy type I who had the highest number of dreams related to activities (84.3%) and threats to life (41.4%) These differences were statistically significant (p <0.05).

CONCLUSIONS: Different sleep disorders are associated with different dream contents, which would be translating different underlying neurological processes. These findings should be replicated in studies that analyse more patients and add a control group without sleep disorders.

PMID:34109996 | DOI:10.33588/rn.7212.2020595