Field experience with the 8-HPV-type oncoprotein test for cervical cancer screening among HPV-positive women living with and without HIV in LMICs.

Overexpression of HPV-oncoproteins E6 and E7 is necessary for HPV-driven cervical carcinogenesis. Hence, these oncoproteins are promising disease-specific biomarkers. We assessed the technical and operational characteristics of the 8-HPV-type OncoE6/E7 Cervical Test in different laboratories using cervical samples from HPV-positive women living with (WLWH) and without HIV. The 8-HPV-type OncoE6/E7 Test (for short: "OncoE6/E7 test") was performed in 2833 HIV-negative women and 241 WLWH attending multicentric studies in Latin America (ESTAMPA study), and in Africa (CESTA study). Oncoprotein positivity were evaluated at each testing site, according to HIV status as well as type-specific agreement with HPV-DNA results. A feedback questionnaire was given to the operators performing the oncoprotein test to evaluate their impression and acceptability regarding the test. The OncoE6/E7 test revealed a high positivity rate heterogeneity across all testing sites (I2: 95.8%, p < .01) with significant lower positivity in WLWH compared to HIV-negative women (12% vs 25%, p < .01). A similar HPV-type distribution was found between HPV DNA genotyping and oncoprotein testing except for HPV31 and 33 (moderate agreement, k = 0.57). Twenty-one laboratory technicians were trained on oncoprotein testing. Despite operators' concerns about the time-consuming procedure and perceived need for moderate laboratory experience, they reported the OncoE6/E7 test as easy to perform and user-friendly for deployment in resource-limited settings. The high positivity rate variability found across studies and subjectivity in test outcome interpretation could potentially results in oncoprotein false positive/negative, and thus the need for further refinements before implementation of the oncoprotein testing in screen-triage-and-treat approaches is warranted.

Neuropathological Findings in Short-Chain enoyl-CoA Hydratase 1 Deficiency (ECHS1D): Case Report and Differential Diagnosis.

Short-chain enoyl-CoA hydratase 1 (ECHS1) is an enzyme that participates in the metabolism of valine, transforming methacrylyl-CoA in ß-hydroxy-isobutyryl-CoA. There is an accumulation of intermediate acids and ammonium as a consequence of its deficit. This background generates a harmful environment for the brain causing neuronal death and severe brain lesions. We present a case of a 39 weeks newborn that died at 31 hours old. We found vacuolization in basal areas, brain stem, cerebellum and spinal cord white matter (spongiform myelinopathy). These vacuoles were periodic acid-Schiff stain negative, there were neither acompanion gliosis nor macrophagic reaction. These findings were suggestive of metabolism acid disorders. The final diagnosis was confirmed by genetic study by massive parallel sequencing, showing 2 previously described pathogenic variants (c.160C > T and c.394G > A) of short-chain enoyl-CoA hydratase 1 gene. To our knowledge, this is the first case reporting the histological changes in short-chain enoyl-CoA hydratase 1 deficiency. Histological study provides useful information to orientate the diagnostic and clarify the clinical manifestations, especially in hospitals where urine or blood samples are not taking routinely or where genetic studies may not be performed.Synopsis: The main neuropathological findings in Short-chain enoyl-CoA hydratase 1 deficiency are the presence of whitte matter vacuoles in basal areas, brain stem and spinal cord.

Association of Visiting the Physiotherapist with Mortality in the Spanish General Population: A Population-Based Cohort Study.

Background and Objectives: The purpose of this retrospective population-based cohort study was to analyse the association between attendance of physiotherapy with mortality in the Spanish general population and describe the profile of people who do not visit a physiotherapist in Spain. Material and Methods: The data sources were the 2011/2012 National Health Survey (ENSE11) and the national database of death in Spain, and the participants were all adult respondents in the ENSE11. Results: Of 20,397 people, 1101 (5.4%) visited the physiotherapist the previous year, and the cumulative incidence of total mortality was 5.4% (n = 1107) at a mean follow-up of 6.2 years. Visiting the physiotherapist was associated with lower all-cause mortality in the population residing in Spain, quantified at 30.1% [RR = 0.699; 95% CI (0.528-0.927); p = 0.013]. The factors associated with not visiting a physiotherapist were the following: rating one's health as good (9.8%; n = 1017; p < 0.001), not having any hospital admission in the previous year (9.6%; n = 1788; p < 0.001), not having visited the general practitioner in the previous month (9.6%; n = 1408; p < 0.001), and not having attended a day hospital in the previous year (9.7%; n = 1836; p < 0.001). Conclusions: Visiting a physiotherapist was associated with a lower mortality from all causes in the population living in Spain.

Redundancy Analysis to Reduce the High-Dimensional Near-Infrared Spectral Information to Improve the Authentication of Olive Oil.

The high price of marketing of extra virgin olive oil (EVOO) requires the introduction of cost-effective and sustainable procedures that facilitate its authentication, avoiding fraud in the sector. Contrary to classical techniques (such as chromatography), near-infrared (NIR) spectroscopy does not need derivatization of the sample with proper integration of separated peaks and is more reliable, rapid, and cost-effective. In this work, principal component analysis (PCA) and then redundancy analysis (RDA)─which can be seen as a constrained version of PCA─are used to summarize the high-dimensional NIR spectral information. Then PCA and RDA factors are contemplated as explanatory variables in models to authenticate oils from qualitative or quantitative analysis, in particular, in the prediction of the percentage of EVOO in blended oils or in the classification of EVOO or other vegetable oils (sunflower, hazelnut, corn, or linseed oil) by the use of some machine learning algorithms. As a conclusion, the results highlight the potential of RDA factors in prediction and classification because they appreciably improve the results obtained from PCA factors in calibration and validation.

Effect of rowing on mobility, functionality, and quality of life in women with and without breast cancer: a 4-month intervention.

PURPOSE: Of the different modalities of rowing, dragon boat training is the most analyzed in breast cancer (BC). However, other types of boats, such as the felucca, use different biomechanical techniques, which have not been studied in the scientific literature. Consequently, in this study, we sought to determine the benefits of felucca rowing on the physical, psychological, and emotional well-being of patients with BC and healthy persons. METHODS: A pre- and post-intervention, single-arm study without a control group with a 4-month intervention was carried out in Spain in 2019. The study sample included six women with BC and 15 healthy women. The following questionnaires were administered before and after the intervention: Disabilities of the Arm, Shoulder, and Hand (DASH), Constant-Murley score (CMS), and the European Quality of Life 5 Dimensions (EQ-5D, rate your health today). Differences were determined before and after the intervention using the paired t test. RESULTS: Significant differences (p < 0.05) were found in the results of all the questionnaires for the women with BC and for the healthy women: DASH (- 13.8 BC and - 6.7 healthy), CMS (+ 12.0 BC and 9.2 healthy), and EQ-5D (+ 8.5 BC and 10.5 healthy). CONCLUSION: Felucca rowing showed benefits in health and quality of life in both women with BC and healthy women. In future studies with controlled design, values regarding clinical relevance, such as effect sizes/confidence intervals, are needed to corroborate our results.

The Victorian Institute of Sport Assessment Scale for Patellar Tendinopathy (VISA-P): A Reliability Generalization Meta-analysis.

OBJECTIVE: The Victorian Institute of Sport Assessment-Patella (VISA-P) is a questionnaire to assess the severity of patellar tendinopathies. Its use requires good reliability indicators: internal consistency, test-retest and parallel forms. Several studies have been published examining this question, but to date the reliability of this questionnaire (meta-analysis) has not been generalized. The aim of this study was to perform a meta-analysis to generalize the reliability of the VISA-P. DATA SOURCES: MEDLINE, EMBASE, and Scopus. STUDY SELECTION: Studies included were those examining the reliability coefficients of the VISA-P: Cronbach alpha, intraclass correlation coefficient (ICC), and parallel-forms (correlation coefficients compared with other scales). DATA EXTRACTION: All coefficients were extracted and the mean reliability was obtained using fixed- or random-effects models. Sensitivity (leave-one-out analysis) was analyzed. Quality assessment was performed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. DATA SYNTHESIS: Of 364 scientific articles, 12 fulfilled meta-analysis criteria. The summary statistic was 0.86 [95% confidence interval (CI): 0.78-0.92] for Cronbach alpha and 0.94 (95% CI: 0.89-0.97) for the ICC. Parallel forms depended on the comparative test used, ranging from -0.83 to 0.68. The sensitivity analysis found an influential study for the parallel-forms reliability in the Blazina score. We were unable to analyze the asymmetry of funnel plots and meta-regression models because of the number of studies. CONCLUSIONS: The reliability of VISA-P for assessing the severity of patellar tendinopathies requires greater evaluation with more scientific evidence before it can be implemented in clinical practice.

Mutations in TIMM50 cause severe mitochondrial dysfunction by targeting key aspects of mitochondrial physiology.

3-Methylglutaconic aciduria (3-MGA-uria) syndromes comprise a heterogeneous group of diseases associated with mitochondrial membrane defects. Whole-exome sequencing identified compound heterozygous mutations in TIMM50 (c.[341 G>A];[805 G>A]) in a boy with West syndrome, optic atrophy, neutropenia, cardiomyopathy, Leigh syndrome, and persistent 3-MGA-uria. A comprehensive analysis of the mitochondrial function was performed in fibroblasts of the patient to elucidate the molecular basis of the disease. TIMM50 protein was severely reduced in the patient fibroblasts, regardless of the normal mRNA levels, suggesting that the mutated residues might be important for TIMM50 protein stability. Severe morphological defects and ultrastructural abnormalities with aberrant mitochondrial cristae organization in muscle and fibroblasts were found. The levels of fully assembled OXPHOS complexes and supercomplexes were strongly reduced in fibroblasts from this patient. High-resolution respirometry demonstrated a significant reduction of the maximum respiratory capacity. A TIMM50-deficient HEK293T cell line that we generated using CRISPR/Cas9 mimicked the respiratory defect observed in the patient fibroblasts; notably, this defect was rescued by transfection with a plasmid encoding the TIMM50 wild-type protein. In summary, we demonstrated that TIMM50 deficiency causes a severe mitochondrial dysfunction by targeting key aspects of mitochondrial physiology, such as the maintenance of proper mitochondrial morphology, OXPHOS assembly, and mitochondrial respiratory capacity.

Design and Development of a Low-Cost Wearable Glove to Track Forces Exerted by Workers in Car Assembly Lines.

Wearables are gaining widespread use and technologies are making it possible to monitor human physical activity and behaviour as part of connected infrastructures. Many companies see wearables as an opportunity to enhance worker safety since they can monitor their workers' activity in real life scenarios. One of the goals of this technology is to integrate existing electronic components, such as sensors or conductors, in order to create fully wearable systems. This integration is constrained not only by technical factors but also by user requirements and internal company standards. This paper considers such constraints and presents preliminary research for the design of a wearable glove as a new tool to track forces exerted by workers in car assembly lines. The objective of the glove is to measure forces and compare these to maximum forces already identified by the company. Thus, the main objectives are to: (1) integrate the components based on the requirements of the users and the context of application, and (2) provide a new tool that can be used "in situ" to track workers. This study was carried out in close collaboration with Volkswagen through a human-centred iterative design process. Thus, this paper presents the development of a wearable device glove based on a specific design methodology where both the human and technological aspects are considered.

A personalized intervention to prevent depression in primary care: cost-effectiveness study nested into a clustered randomized trial.

BACKGROUND: Depression is viewed as a major and increasing public health issue, as it causes high distress in the people experiencing it and considerable financial costs to society. Efforts are being made to reduce this burden by preventing depression. A critical component of this strategy is the ability to assess the individual level and profile of risk for the development of major depression. This paper presents the cost-effectiveness of a personalized intervention based on the risk of developing depression carried out in primary care, compared with usual care. METHODS: Cost-effectiveness analyses are nested within a multicentre, clustered, randomized controlled trial of a personalized intervention to prevent depression. The study was carried out in 70 primary care centres from seven cities in Spain. Two general practitioners (GPs) were randomly sampled from those prepared to participate in each centre (i.e. 140 GPs), and 3326 participants consented and were eligible to participate. The intervention included the GP communicating to the patient his/her individual risk for depression and personal risk factors and the construction by both GPs and patients of a psychosocial programme tailored to prevent depression. In addition, GPs carried out measures to activate and empower the patients, who also received a leaflet about preventing depression. GPs were trained in a 10- to 15-h workshop. Costs were measured from a societal and National Health care perspective. Qualityadjustedlife years were assessed using the EuroQOL five dimensions questionnaire. The time horizon was 18 months. RESULTS: With a willingness-to-pay threshold of €10,000 (£8568) the probability of cost-effectiveness oscillated from 83% (societal perspective) to 89% (health perspective). If the threshold was increased to €30,000 (£25,704), the probability of being considered cost-effective was 94% (societal perspective) and 96%, respectively (health perspective). The sensitivity analysis confirmed these results. CONCLUSIONS: Compared with usual care, an intervention based on personal predictors of risk of depression implemented by GPs is a cost-effective strategy to prevent depression. This type of personalized intervention in primary care should be further developed and evaluated. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01151982. Registered on June 29, 2010.

Effectiveness of Psychological and Educational Interventions to Prevent Depression in Primary Care: A Systematic Review and Meta-Analysis.

PURPOSE: Although evidence exists for the efficacy of psychosocial interventions to prevent the onset of depression, little is known about its prevention in primary care. We aimed to evaluate the effectiveness of psychological and educational interventions to prevent depression in primary care. METHODS: We conducted a systematic review and meta-analysis of relevant randomized controlled trials (RCTs) examining the effect of psychological and educational interventions to prevent depression in nondepressed primary care attendees. We searched MEDLINE, PsycINFO, Web of Science, OpenGrey Repository, Cochrane Central Register of Controlled Trials, and other sources up to May 2016. At least 2 reviewers independently evaluated the eligibility criteria, extracted data, and assessed the risk of bias. We calculated standardized mean differences (SMD) using random-effects models. RESULTS: We selected 14 studies (7,365 patients) that met the inclusion criteria, 13 of which were valid to perform a meta-analysis. Most of the interventions had a cognitive-behavioral orientation, and in only 4 RCTs were the intervention clinicians primary care staff. The pooled SMD was -0.163 (95%CI, -0.256 to -0.070; P = .001). The risk of bias and the heterogeneity (I2 = 20.6%) were low, and there was no evidence of publication bias. Meta-regression detected no association between SMD and follow-up times or SMD and risk of bias. Subgroup analysis suggested greater effectiveness when the RCTs used care as usual as the comparator compared with those using placebo. CONCLUSIONS: Psychological and educational interventions to prevent depression had a modest though statistically significant preventive effect in primary care. Further RCTs using placebo or active comparators are needed.

Intervention to Prevent Major Depression in Primary Care: A Cluster Randomized Trial.

BACKGROUND: Not enough is known about universal prevention of depression in adults. OBJECTIVE: To evaluate the effectiveness of an intervention to prevent major depression. DESIGN: Multicenter, cluster randomized trial with sites randomly assigned to usual care or an intervention. (ClinicalTrials.gov: NCT01151982). SETTING: 10 primary care centers in each of 7 cities in Spain. PARTICIPANTS: Two primary care physicians (PCPs) and 5236 nondepressed adult patients were randomly sampled from each center; 3326 patients consented and were eligible to participate. INTERVENTION: For each patient, PCPs communicated individual risk for depression and personal predictors of risk and developed a psychosocial program tailored to prevent depression. MEASUREMENTS: New cases of major depression, assessed every 6 months for 18 months. RESULTS: At 18 months, 7.39% of patients in the intervention group (95% CI, 5.85% to 8.95%) developed major depression compared with 9.40% in the control (usual care) group (CI, 7.89% to 10.92%) (absolute difference, -2.01 percentage points [CI, -4.18 to 0.16 percentage points]; P = 0.070). Depression incidence was lower in the intervention centers in 5 cities and similar between intervention and control centers in 2 cities. LIMITATION: Potential self-selection bias due to nonconsenting patients. CONCLUSION: Compared with usual care, an intervention based on personal predictors of risk for depression implemented by PCPs provided a modest but nonsignificant reduction in the incidence of major depression. Additional study of this approach may be warranted. PRIMARY FUNDING SOURCE: Institute of Health Carlos III.

PARP-1 regulates metastatic melanoma through modulation of vimentin-induced malignant transformation.

PARP inhibition can induce anti-neoplastic effects when used as monotherapy or in combination with chemo- or radiotherapy in various tumor settings; however, the basis for the anti-metastasic activities resulting from PARP inhibition remains unknown. PARP inhibitors may also act as modulators of tumor angiogenesis. Proteomic analysis of endothelial cells revealed that vimentin, an intermediary filament involved in angiogenesis and a specific hallmark of EndoMT (endothelial to mesenchymal transition) transformation, was down-regulated following loss of PARP-1 function in endothelial cells. VE-cadherin, an endothelial marker of vascular normalization, was up-regulated in HUVEC treated with PARP inhibitors or following PARP-1 silencing; vimentin over-expression was sufficient to drive to an EndoMT phenotype. In melanoma cells, PARP inhibition reduced pro-metastatic markers, including vasculogenic mimicry. We also demonstrated that vimentin expression was sufficient to induce increased mesenchymal/pro-metastasic phenotypic changes in melanoma cells, including ILK/GSK3-ß-dependent E-cadherin down-regulation, Snail1 activation and increased cell motility and migration. In a murine model of metastatic melanoma, PARP inhibition counteracted the ability of melanoma cells to metastasize to the lung. These results suggest that inhibition of PARP interferes with key metastasis-promoting processes, leading to suppression of invasion and colonization of distal organs by aggressive metastatic cells.

Deciphering the insights of poly(ADP-ribosylation) in tumor progression.

Poly (ADP-ribose) polymerase (PARP) inhibitors are particularly efficient against tumors with defects in the homologous recombination repair pathway. Nonetheless poly(ADP-ribosylation) (PARylation) modulates prometastasic activities and adaptation of tumor to a hostile microenvironment. Modulation of metastasis-promoting traits is possible through the alteration of key transcription factors involved in the regulation of the hypoxic response, the recruitment of new vessels (or angiogenesis), and the stimulation of epithelial to mesenchymal transition (EMT). In this review, we summarized some of the findings that focalize on PARP-1's action on tumor aggressiveness, suggesting new therapeutic opportunities against an assembly of tumors not necessarily bearing DNA repair defects. Metastasis accounts for the vast majority of mortality derived from solid cancer. PARP-1 is an active player in tumor adaptation to metastasis and PARP inhibitors, recognized as promising therapeutic agents against homologous recombination deficient tumors, has novel properties responsible for the antimetastatic actions in different tumor settings.

Medical abortion and manual vacuum aspiration for legal abortion protect women's health and reduce costs to the health system: findings from Colombia.

The majority of abortions in Colombia continue to take place outside the formal health system under a range of conditions, with the majority of women obtaining misoprostol from a thriving black market for the drug and self-administering the medication. We conducted a cost analysis to compare the costs to the health system of three approaches to the provision of abortion care in Colombia: post-abortion care for complications of unsafe abortions, and for legal abortions in a health facility, misoprostol-only medical abortion and vacuum aspiration abortion. Hospital billing records from three institutions, two large maternity hospitals and one specialist reproductive health clinic, were analysed for procedure and complication rates, and costs by diagnosis. The majority of visits (94%) were to the two hospitals for post-abortion care; the other 6% were for legal abortions. Only one minor complication was found among the women having legal abortions, a complication rate of less than 1%. Among the women presenting for post-abortion care, 5% had complications during their treatment, mainly from infection or haemorrhage. Legal abortions were associated not only with far fewer complications for women, but also lower costs for the health system than for post-abortion care. We calculated based on our findings that for every 1,000 women receiving post-abortion care instead of a legal abortion within the health system, 16 women experienced avoidable complications, and the health system spent US $48,000 managing them. Increasing women's access to safe abortion care would not only reduce complications for women, but would also be a cost-saving strategy for the health system.

Modeling and partial least squares approaches in OODA.

This is a discussion of the following paper: "Overview of object oriented data analysis" by J. Steve Marron and Andrés M. Alonso.

Preventing the onset of major depression based on the level and profile of risk of primary care attendees: protocol of a cluster randomised trial (the predictD-CCRT study).

BACKGROUND: The 'predictD algorithm' provides an estimate of the level and profile of risk of the onset of major depression in primary care attendees. This gives us the opportunity to develop interventions to prevent depression in a personalized way. We aim to evaluate the effectiveness, cost-effectiveness and cost-utility of a new intervention, personalized and implemented by family physicians (FPs), to prevent the onset of episodes of major depression. METHODS/DESIGN: This is a multicenter randomized controlled trial (RCT), with cluster assignment by health center and two parallel arms. Two interventions will be applied by FPs, usual care versus the new intervention predictD-CCRT. The latter has four components: a training workshop for FPs; communicating the level and profile of risk of depression; building up a tailored bio-psycho-family-social intervention by FPs to prevent depression; offering a booklet to prevent depression; and activating and empowering patients. We will recruit a systematic random sample of 3286 non-depressed adult patients (1643 in each trial arm), nested in 140 FPs and 70 health centers from 7 Spanish cities. All patients will be evaluated at baseline, 6, 12 and 18 months. The level and profile of risk of depression will be communicated to patients by the FPs in the intervention practices at baseline, 6 and 12 months. Our primary outcome will be the cumulative incidence of major depression (measured by CIDI each 6 months) over 18 months of follow-up. Secondary outcomes will be health-related quality of life (SF-12 and EuroQol), and measurements of cost-effectiveness and cost-utility. The inferences will be made at patient level. We shall undertake an intention-to-treat effectiveness analysis and will handle missing data using multiple imputations. We will perform multi-level logistic regressions and will adjust for the probability of the onset of major depression at 12 months measured at baseline as well as for unbalanced variables if appropriate. The economic evaluation will be approached from two perspectives, societal and health system. DISCUSSION: To our knowledge, this will be the first RCT of universal primary prevention for depression in adults and the first to test a personalized intervention implemented by FPs. We discuss possible biases as well as other limitations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01151982.

Exploring the relationship between frailty and executive dysfunction: the role of frontal white matter hyperintensities.

Introduction: Frailty is a geriatric syndrome frequently associated with executive dysfunction and white matter hyperintensities (WMH). But the relation between executive dysfunction and brain changes is poorly understood in frail subjects. Our hypothesis is that frontal-WMH mediates the association between frailty and executive dysfunction. Methods: A convenience sample of 113 subjects older than 65 years without dementia was studied with neuropsychological test, a structured clinical interview, physical examination and brain MRI. They were classified as robust or pre-frail and frail using the frailty phenotype score (0-5). The frontal WMH (F-WMH) were manually graduated (0-6) using the "Age-Related White Matter Changes score" from FLAIR sequences at a 3 Tesla brain MRI. A mediation analysis was done for testing whether F-WMH could act as a link factor between frailty phenotype score and executive dysfunction. Results: The group's mean age was 74 ± 6 years, subjects with higher frailty score had more depressive symptoms and worse performance in executive function tests. A regression analysis that explained 52% of the variability in executive functions, revealed a significant direct effect of frailty score (Standardized ßcoeff [95% CI] -0.201, [-0.319, -0.049], and F-WMH (-0.152[-0.269, -0.009]) on executive functions, while the F-WMH showed a small partial mediation effect between frailty and executive functions (-0.0395, [-0.09, -0.004]). Discussion: Frontal matter hyperintensities had a small mediation effect on the association between frailty and executive dysfunction, suggesting that other neuropathological and neurofunctional changes might also be associated with executive dysfunction in frail subjects.

BCL7A is silenced by hypermethylation to promote acute myeloid leukemia.

BACKGROUND: Recent massive sequencing studies have revealed that SWI/SNF complexes are among the most frequently altered functional entities in solid tumors. However, the role of SWI/SNF in acute myeloid leukemia is poorly understood. To date, SWI/SNF complexes are thought to be oncogenic in AML or, at least, necessary to support leukemogenesis. However, mutation patterns in SWI/SNF genes in AML are consistent with a tumor suppressor role. Here, we study the SWI/SNF subunit BCL7A, which has been found to be recurrently mutated in lymphomas, but whose role in acute myeloid malignancies is currently unknown. METHODS: Data mining and bioinformatic approaches were used to study the mutational status of BCL7A and the correlation between BCL7A expression and promoter hypermethylation. Methylation-specific PCR, bisulfite sequencing, and 5-aza-2'-deoxycytidine treatment assays were used to determine if BCL7A expression was silenced due to promoter hypermethylation. Cell competition assays after BCL7A expression restoration were used to assess the role of BCL7A in AML cell line models. Differential expression analysis was performed to determine pathways and genes altered after BCL7A expression restoration. To establish the role of BCL7A in tumor development in vivo, tumor growth was compared between BCL7A-expressing and non-expressing mouse xenografts using in vivo fluorescence imaging. RESULTS: BCL7A expression was inversely correlated with promoter methylation in three external cohorts: TCGA-LAML (N = 160), TARGET-AML (N = 188), and Glass et al. (2017) (N = 111). The AML-derived cell line NB4 silenced the BCL7A expression via promoter hypermethylation. Ectopic BCL7A expression in AML cells decreased their competitive ability compared to control cells. Additionally, restoration of BCL7A expression reduced tumor growth in an NB4 mouse xenograft model. Also, differential expression analysis found that BCL7A restoration altered cell cycle pathways and modified significantly the expression of genes like HMGCS1, H1-0, and IRF7 which can help to explain its tumor suppressor role in AML. CONCLUSIONS: BCL7A expression is silenced in AML by promoter methylation. In addition, restoration of BCL7A expression exerts tumor suppressor activity in AML cell lines and xenograft models.

Cross-Cultural Adaptation and Validation of the Perceptions of Empowerment in Midwifery Scale in the Spanish Context (PEMS-e).

Midwifery empowerment is an important topic. The most widely used instrument to measure the perceived empowerment of midwives is the Perceptions of Empowerment in Midwifery Scale (PEMS), which has not been validated in Spain. The aim of this study was to translate and adapt the PEMS to the Spanish context. This research was carried out in two phases; Phase 1: Methodological study; translation, backtranslation and cross-cultural adaptation of the PEMS and pilot study on the target population (10 midwives) for evaluation of face validity. Phase 2: Cross-sectional observational study to obtain a sample for construct validation by Exploratory Factor Analysis and measurement of PEMS-e reliability. Additionally, an inferential analysis was carried out to study the possible association between several collected variables and PEMS-e subscale-scores. A total of 410 midwives from 18 Spanish regions participated in the study through an online questionnaire. An initial Spanish version of the PEMS scale was produced, demonstrating adequate face validity. A final model was produced for the PEMS-e, which included 17 items classified into two subscales ("Organizational support" and "Own skills and teamwork") with fit indexes RMSEA = 0.062 (95%CI: 0.048-0.065) and AGFI = 0.985 (95%CI: 0.983-0.989) and Cronbach's alpha 0.922 for the total scale. Results showed that one in four midwives had considered abandoning the profession in the last 6 months (p ≤ 0.001). This research suggests that Spanish midwives perceive their empowerment level as low. The PEMS-e is a valid tool with solid psychometric properties that can be used in future research to identify factors that contribute to increased empowerment among Spanish midwives and inform strategies to improve job satisfaction and retention in the profession.

Availability of Pharmacist-Prescribed Contraception in Hawai'i.

In 2017, the state of Hawai'i passed Act 067 which allows trained pharmacists to prescribe hormonal contraceptives in an effort to expand access to contraception. The extent to which this policy has been implemented is not known. This study aimed to determine the proportion of Hawai'i pharmacies that currently provide pharmacist-prescribed hormonal contraceptives. In June 2020, a list of retail pharmacies was compiled using Google and Google Maps searches and pharmacy directories from major health insurance providers. Between June 23, 2020, and July 2, 2020, two trained interviewers called pharmacies and inquired about the availability of pharmacist-prescribed contraceptives using a "secret shopper" technique. Of the 175 pharmacies included in our analysis, 54 (31%) offered pharmacist-prescribed contraceptives. Kaua'i (40%) had the highest proportion of pharmacies offering pharmacist-prescribed contraceptives, followed by Maui (35%), O'ahu (30%), and Hawai'i Island (29%) (P=.88). Among pharmacies located in rural communities, 20 of 63 (32%) prescribed contraceptives, compared to 34 of 112 (30 %) pharmacies located in urban communities (P=.85). Of the 118 pharmacies that did not prescribe contraceptives and provided a reason for not doing so 33% cited lack of training and 28% lack of knowledge about Act 067. Thirty-one pharmacies provided information on the cost of pharmacist-prescribed contraceptives with 71% (22) stating that the patient would have to pay extra for the consultation (mean cost = $34.6, range $30-$45). Findings from this study can help inform future public health policies and implementation strategies aimed at improving contraceptive access in Hawai'i.