Microglia refine developing retinal astrocytic and vascular networks through the complement C3/C3aR axis.

Microglia, a resident immune cell of the central nervous system (CNS), play a pivotal role in facilitating neurovascular development through mechanisms that are not fully understood. Previous reports indicate a role for microglia in regulating astrocyte density. This current work resolves the mechanism through which microglia facilitate astrocyte spatial patterning and superficial vascular bed formation in the neuroretina during development. Ablation of microglia increased astrocyte density and altered spatial patterning. Mechanistically, we show that microglia regulate the formation of the spatially organized astrocyte template required for subsequent vascular growth, through the complement C3/C3aR axis during neuroretinal development. Lack of C3 or C3aR hindered the developmental phagocytic removal of astrocyte bodies and resulted in increased astrocyte density. In addition, increased astrocyte density was associated with elevated proangiogenic extracellular matrix gene expression in C3- and C3aR-deficient retinas, resulting in increased vascular density. These data demonstrate that microglia regulate developmental astrocyte and vascular network spatial patterning in the neuroretina via the complement axis.

Internal and external adenomyosis phenotypes: ultrasound features and association with clinical outcomes.

STUDY QUESTION: What are the sonographic and clinical findings in women diagnosed with external and internal adenomyosis by ultrasound? SUMMARY ANSWER: Patients with external and internal adenomyosis phenotypes, diagnosed by ultrasound, present differences in sonographic features of the disease and demographic characteristics including age, parity, and association with deep endometriosis (DE) and leiomyomas. WHAT IS KNOWN ALREADY: Two different phenotypes of adenomyosis have been described based on the anatomical location of adenomyotic lesions in the myometrium, suggesting that adenomyosis affecting the inner myometrium and that affecting the external myometrial layer may have distinct origins. STUDY DESIGN, SIZE, DURATION: A cross-sectional study including 505 patients with a sonographic diagnosis of adenomyosis was performed between January 2021 and December 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women sonographically diagnosed with adenomyosis in a tertiary referral hospital that serves as a national reference center for endometriosis were included over a 2-year period. Patients were divided into two groups (internal and external adenomyosis) according to the myometrial layer affected by adenomyosis. We compared sonographic and clinical outcomes including a multivariate analysis between the two groups. MAIN RESULTS AND THE ROLE OF CHANCE: According to ultrasound findings, 353 (69.9%) patients presented with internal adenomyosis, while 152 (30.1%) presented with external adenomyosis. Women with internal adenomyosis were significantly older and less frequently nulliparous compared to those with external adenomyosis. Sonographically, internal adenomyosis appeared diffusely, it had a greater number of adenomyosis features, it presented a globular morphology of the uterus more frequently, and it coexisted with leiomyomas more frequently, compared to external adenomyosis. Conversely, the presence of translesional vascularity and associated DE were more common among the external adenomyosis group. No significant differences were found between internal and external adenomyosis groups regarding pain, heavy menstrual bleeding, spotting, or infertility. In the multivariate analysis, nulliparity, the presence of leiomyomas, and the presence of DE were independently associated with adenomyosis phenotypes (the presence of DE and nulliparity increased the risk of external adenomyosis, whereas the presence of leiomyomas was a risk factor for internal adenomyosis). Considering the impact of hormonal treatment, we found that the number of ultrasound adenomyosis criteria was significantly greater in patients without hormonal treatment. Non-treated patients more commonly presented dysmenorrhea or bleeding-associated pain and heavy menstrual bleeding than women on hormonal treatment, although there were no significant differences according to adenomyosis phenotypes. LIMITATIONS, REASONS FOR CAUTION: As the population was selected from the Endometriosis Unit of a tertiary center, there may be patient selection bias, given the high prevalence of individuals with associated endometriosis, previous endometriosis-related surgery, and/or receiving hormonal treatment. WIDER IMPLICATIONS OF THE FINDINGS: Transvaginal ultrasound is the most available and cost-effective tool for the diagnosis of adenomyosis. Adenomyosis phenotypes based on ultrasound findings may be key in achieving an accurate diagnosis and in decision-making regarding the most adequate therapeutic strategy for the management of patients with adenomyosis. Determination of the sonographic features associated with symptoms could help in the evaluation of treatment response. STUDY FUNDING/COMPETING INTEREST(S): No funding was obtained for this study and there are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Do preschoolers trust a competent robot pointer?

How young children learn from different informants has been widely studied. However, most studies investigate how children learn verbally conveyed information. Furthermore, most studies investigate how children learn from humans. This study sought to investigate how 3-year-old children learn from, and come to trust, a competent robot versus an incompetent human when competency is established using a pointing paradigm. During an induction phase, a robot informant pointed at a toy inside a transparent box, whereas a human pointed at an empty box. During the test phase, both agents pointed at opaque boxes. We found that young children asked the robot for help to locate a hidden toy more than the human (ask questions) and correctly identified the robot to be accurate (judgment questions). However, children equally endorsed the locations pointed at by both the robot and the human (endorse questions). This suggests that 3-year-olds are sensitive to the epistemic characteristics of the informant even when its displayed social properties are minimal.

Neuroendoscopic access to the third ventricle in patients with narrow foramen of monro without stenosis/obstruction: role of foraminoplasty.

OBJECT: One of the critical steps for the success of intraventricular neuroendoscopic procedures is the entry into the third ventricle and passage of the endoscopy system through the foramen of Monro (FM). A diameter larger than that of the instrument used is considered a prerequisite for safely performing the technique, as damage to this structure can lead to alterations in the fornix and vascular structures. When the foramen diameter is narrow and there is no obstruction/stenosis, the role of foraminoplasty in reducing the risk of complications has not been adequately assessed in the literature. METHODS: A review of endoscopic procedures conducted at our center since 2018 was undertaken. Cases in which preoperative imaging indicated a FM diameter < 6 mm and foraminoplasty technique was applied were examined to determine the technical and functional success of the procedure. The technical success was determined by completing the neuroendoscopic procedure with the absence of macroscopic lesions in the various structures comprising the foramen and without complications in the follow-up imaging tests. Functional success was defined as the absence of cognitive/memory alterations during the 3-month postoperative follow-up. Additionally, a review of the various forms of foraminoplasty described in the literature is conducted. RESULTS: In our cohort, six patients were identified with a preoperative FM diameter < 6 mm without obstruction or stenosis. Foraminoplasty was planned for these cases to facilitate various intraventricular neuroendoscopic procedures. In all instances, the technique was successfully performed without causing macroscopic damage to the structures comprising the foramen. Follow-up visits included various cognitive tests to assess potential sequelae related to microscopic damage to the fornix. None of the patients exhibited anomalies. CONCLUSION: Foraminoplasty in patients with a narrow FM without signs of stenosis/obstruction is a useful technique to reduce the risk of complications during the passage of the endoscopy system through this structure, enabling the safe performance of neuroendoscopic procedures.

Use of autologous tooth-derived material as a graft in the post-extraction socket. Split-mouth study with radiological and histological analysis.

BACKGROUND: The healing process after tooth removal involves bone remodelling which implies some loss of alveolar bone volume. Among materials proposed for minimising this remodelling and preserving the bone, autologous dental tissue is a promising option, but more data are needed. In this context, we evaluated size and density changes using cone beam computed tomography in autologous dental material (ADM)-preserved sockets compared to controls, and assessed biological responses by histological analysis. METHODS: A split-mouth study was conducted including 22 patients, who underwent removal of ≥ 2 single-rooted teeth with intact sockets, assigning one socket to the experimental group which received ADM for alveolar preservation and another to the control group, which only underwent blood clot stabilisation. Cone beam computed tomography was performed postoperatively (week 0) and at weeks 8 and 16 to assess socket size and bone density. Histological analysis was carried out on trephine biopsies taken (Ø4 × 4.5 mm) from the experimental group. RESULTS: Less horizontal shrinkage was observed in the ADM group, especially at week 16 considering the group-by-time interaction for the following variables: difference in height between the lingual and buccal alveolar crests (-1.00; p < .01; 95% CI: -0.28 - -1.73), and half-widths, measured as the distance from the long axis of the missing tooth to the buccal alveolar crest at 1 mm (-0.61; p < .01; 95% CI: -0.18 - -1.04) and at 3 mm (-0.56; p < .01; 95% CI: -0.15 - -0.97) below the crest, with mean decreases of 1.07 and 2.14 mm in height difference, 0.66 and 1.32 mm in half-width at 1 mm and 0.43 and 1.02 mm in half-width at 3 mm in ADM and control groups respectively. Densitometry analysis showed higher bone densities in Hounsfield units in the ADM group considering all factors analysed regardless of time point and socket third (coronal, middle, or apical). Histologically, there were no signs of inflammation or foreign body reaction, and dentin particles were surrounded by and in close contact with bone tissue. CONCLUSION: These results add to the evidence that dentin can be used successfully as a material for alveolar socket preservation, given its desirable mechanical and biological properties, and warrant larger studies.

High-risk Opioid Prescribing Associated with Postoperative New Persistent Opioid Use in Adolescents and Young Adults.

OBJECTIVE: In this study, we explored which postoperative opioid prescribing practices were associated with persistent opioid use among adolescents and young adults. BACKGROUND: Approximately 5% of adolescents and young adults develop postoperative new persistent opioid use. The impact of physician prescribing practices on persistent use among young patients is unknown. METHODS: We identified opioid-naïve patients aged 13 to 21 who underwent 1 of 13 procedures (2008-2016) and filled a perioperative opioid prescription using commercial insurance claims (Optum Deidentified Clinformatics Data Mart Database). Persistent use was defined as ≥ 1 opioid prescription fill 91 to 180 days after surgery. High-risk opioid prescribing included overlapping opioid prescriptions, co-prescribed benzodiazepines, high daily prescribed dosage, long-acting formulations, and multiple prescribers. Logistic regression modeled persistent use as a function of exposure to high-risk prescribing, adjusted for patient demographics, procedure, and comorbidities. RESULTS: High-risk opioid prescribing practices increased from 34.9% to 43.5% over the study period; the largest increase was in co-prescribed benzodiazepines (24.1%-33.4%). High-risk opioid prescribing was associated with persistent use (aOR 1.235 [1.12,1.36]). Receipt of prescriptions from multiple opioid prescribers was individually associated with persistent use (aOR 1.288 [1.16,1.44]). The majority of opioid prescriptions to patients with persistent use beyond the postoperative period were from nonsurgical prescribers (79.6%). CONCLUSIONS: High-risk opioid prescribing practices, particularly receiving prescriptions from multiple prescribers across specialties, were associated with a significant increase in adolescent and young adult patients' risk of persistent opioid use. Prescription drug monitoring programs may help identify young patients at risk of persistent opioid use.

Long-term secondary prevention of cardiovascular disease with a Mediterranean diet and a low-fat diet (CORDIOPREV): a randomised controlled trial.

BACKGROUND: Mediterranean and low-fat diets are effective in the primary prevention of cardiovascular disease. We did a long-term randomised trial to compare the effects of these two diets in secondary prevention of cardiovascular disease. METHODS: The CORDIOPREV study was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive a Mediterranean diet or a low-fat diet intervention, with a follow-up of 7 years. Clinical investigators (physicians, investigators, and clinical endpoint committee members) were masked to treatment assignment; participants were not. A team of dietitians did the dietary interventions. The primary outcome (assessed by intention to treat) was a composite of major cardiovascular events, including myocardial infarction, revascularisation, ischaemic stroke, peripheral artery disease, and cardiovascular death. This study is registered with ClinicalTrials.gov, NCT00924937. FINDINGS: From Oct 1, 2009, to Feb 28, 2012, a total of 1002 patients were enrolled, 500 (49·9%) in the low-fat diet group and 502 (50·1%) in the Mediterranean diet group. The mean age was 59·5 years (SD 8·7) and 827 (82·5%) of 1002 patients were men. The primary endpoint occurred in 198 participants: 87 in the Mediterranean diet group and 111 in the low-fat group (crude rate per 1000 person-years: 28·1 [95% CI 27·9-28·3] in the Mediterranean diet group vs 37·7 [37·5-37·9] in the low-fat group, log-rank p=0·039). Multivariable-adjusted hazard ratios (HRs) of the different models ranged from 0·719 (95% CI 0·541-0·957) to 0·753 (0·568-0·998) in favour of the Mediterranean diet. These effects were more evident in men, with primary endpoints occurring in 67 (16·2%) of 414 men in the Mediterranean diet group versus 94 (22·8%) of 413 men in the low-fat diet group (multiadjusted HR 0·669 [95% CI 0·489-0·915], log-rank p=0·013), than in 175 women for whom no difference was found between groups. INTERPRETATION: In secondary prevention, the Mediterranean diet was superior to the low-fat diet in preventing major cardiovascular events. Our results are relevant to clinical practice, supporting the use of the Mediterranean diet in secondary prevention. FUNDING: Fundacion Patrimonio Comunal Olivarero; Fundacion Centro para la Excelencia en Investigacion sobre Aceite de Oliva y Salud; local, regional, and national Spanish Governments; European Union.

Divergent pathways of liver fat accumulation, oxidation, and secretion in lipodystrophy versus obesity-associated NAFLD.

BACKGROUND AND AIMS: Fatty liver is common in obesity as well as in partial lipodystrophy (PL) syndromes, characterized by deficient adipose tissue. Insulin resistance is key to fatty liver pathogenesis in both entities. We aimed to compare the contributions of insulin resistance and adipose tissue to hepatic steatosis in PL and non-syndromic, obesity-associated non-alcoholic fatty liver disease (NS-NAFLD). METHODS: In a cross-sectional comparison of people with NS-NAFLD (N = 73) and PL (N = 27), liver fat was measured by FibroScan® controlled attenuation parameter (CAP) and insulin resistance by HOMA-IR, Adipo-IR, and NMR-based LP-IR. RESULTS: Insulin resistance was greater in PL versus NS-NAFLD by HOMA-IR (p = 0.005), Adipo-IR (p = 0.01) and LP-IR (p = 0.05) while liver fat was comparable (304 vs. 324 dB/m, p = 0.12). Liver fat correlated with HOMA-IR in both groups, but CAP values were lower by 32 dB/m in PL compared with NS-NAFLD for any given HOMA-IR. In contrast, Adipo-IR and LP-IR correlated with CAP only in the NS-NAFLD group, suggesting different pathways for fat accumulation. Plasma free fatty acids, reflecting substrate input from the adipose tissue, were comparable between groups. However, the levels of ß-hydroxybutyrate, a marker of ß-oxidation, and large triglyceride-rich lipoprotein particles, a marker of VLDL secretion, were both higher in PL (p < 0.001 for both). CONCLUSION: Liver fat content was comparable in subjects with PL-associated NAFLD and NS-NAFLD, despite worse insulin resistance in partial lipodystrophy. Our data demonstrate higher triglyceride oxidation and export in PL, suggesting a compensatory shift of fat from liver storage into the circulation that does not occur in NS-NAFLD.

Changes in quantity plant-based protein intake on type 2 diabetes remission in coronary heart disease patients: from the CORDIOPREV study.

PURPOSE: Diabetes remission is a phenomenon described in the context of drastic weight loss due to bariatric surgery or low-calorie diets. Evidence suggests that increasing the intake of plant protein could reduce the risk of type 2 diabetes. We sought for association between changes in plant protein intake in the context of 2 healthy diets without weight loss nor glucose-lowering medication, and diabetes remission in coronary heart disease patients from the CORDIOPREV study. METHODS: Newly diagnosed type 2 diabetes participants without glucose-lowering treatment were randomized to consume a Mediterranean or a low-fat diet. Type 2 diabetes remission was assessed with a median follow-up of 60 months according to the ADA recommendation. Information on patient's dietary intake was collected using food-frequency questionnaires. At first year of intervention, 177 patients were classified according to changes in plant protein consumption into those who increased or decreased its intake, in order to perform an observational analysis on the association between protein intake and diabetes remission. RESULTS: Cox regression showed that patients increasing plant protein intake were more likely to remit from diabetes than those who decreased its intake (HR = 1.71(1.05-2.77)). The remission occurred mainly at first and second year of follow-up with diminished number of patients achieving remission in the third year onwards. The increase in plant protein was associated with lower intake of animal protein, cholesterol, saturated fatty acids, and fat, and with higher intake of whole grains, fibre, carbohydrates, legumes, and tree nuts. CONCLUSION: These results support the need to increase protein intake of vegetal origin as dietary therapy to reverse type 2 diabetes in the context of healthy diets without weight loss.

Psychological symptoms in difficult-to-sedate critical care survivors.

BACKGROUND: Critical care survivors often experience symptoms of anxiety, depression, or post-traumatic stress disorder (PTSD). AIMS: To determine the prevalence and severity of psychological symptoms during the first 6 months after discharge from the intensive care unit (ICU) and to evaluate its association with patients who are difficult to sedate during admission. DESIGN: Descriptive, prospective analysis of psychological symptoms in survivors from medicosurgical ICU over a 2-year period. METHODS: All ICU survivors who required mechanical ventilation (MV) for more than 24 hours were followed for 6 months after their ICU discharge. ICU outcome and complications as well as the presence of psychological symptoms, 1 to 3 to 6 months after discharge were prospectively evaluated through phone interviews comparing the incidence and intensity of patients who were difficult to sedate during their ICU stay with those who were not. Descriptive analysis and multivariate logistic regression were performed. RESULTS: Data were obtained for 195 patients, of whom 30% experienced difficult sedation (DS). Difficult-to-sedate patients were younger (P = .001), less critically ill (APACHE II score P = .002), and more likely to engage in harmful use of alcohol (P = .001) and psychoactive/psychotropic drug abuse. They also spent longer times on MV and in the ICU (P = .001). Anxiety incidence at 1 to 3 to 6 months post-discharge was significantly higher in DS patients than in those who were not (87.7% vs 45.4%, 75.5% vs 29.0%, and 70.8% vs 23.7%; P < .01), respectively. Depression incidence was also significantly higher in the DS group (82.4% vs 43.1%, 66% vs 33.9%, and 60.4% vs 27.2%; [P = .001]) at 1 to 3 to 6 months, respectively. A higher percentage of patients in the DS group reported symptoms of PTSD at 1 month (28.1% vs 11.5%) (P = .007) when compared with non-DS group. CONCLUSIONS: Critical care survivors who are difficult to sedate during their ICU stay are more likely to present psychological sequelae. Early identification of at-risk patients is necessary to implement appropriate preventive strategies. RELEVANCE TO CLINICAL PRACTICE: Patients who are difficult to sedate in the ICU may develop psychological disorders upon discharge, which may negatively affect their recovery. The prevention of DS and the early detection of psychological disorders are essential to minimize its subsequent impact.

Long-term effect of a dietary intervention with two-healthy dietary approaches on food intake and nutrient density in coronary patients: results from the CORDIOPREV trial.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of disease burden in the world by non-communicable diseases. Nutritional interventions promoting high-quality dietary patterns with low caloric intake value and high nutrient density (ND) could be linked to a better control of CVD risk and recurrence of coronary disease. This study aims to assess the effects of a dietary intervention based on MedDiet or Low-Fat dietary intervention over changes in ND and food intake after 1 and 7 years of follow-up of the CORDIOPREV study. METHODS: We prospectively analyzed the results of the 802 coronary patients randomized to two healthy dietary patterns (MedDiet = 425, Low-Fat Diet = 377) who completed the 7 years of follow-up and had all the dietary data need. Dietary intake information obtained from a validated 137-item Food Frequency Questionnaire was used to calculate 1- and 7-year changes in dietary intake and ND (measured as nutrient intake per 1000 kcal). T test was used to ascertain differences in food intake and ND between groups across follow-up time. Within-subject (dietary allocation group) differences were analyzed with ANOVA repeated measures. RESULTS: From baseline to 7 years of follow-up, significant increases of vegetables, fruits, and whole cereals within groups (p < 0.001) was found. We found a higher increase in dietary intake of certain food groups with MedDiet in comparison with Low-Fat Diet for vegetables (46.1 g/day vs. 18.1 g/day, p < 00.1), fruits (121.3 g/day vs. 72.9 g/day), legumes (4.3 g/day vs. 0.16 g/day) and nuts (7.3 g/day vs. - 3.7 g/day). There was a decrease in energy intake over time in both groups, slightly higher in Low-Fat Diet compared to MedDiet group (- 427.6 kcal/day vs. - 279.8 kcal/day at 1st year, and - 544.6 kcal/day vs. - 215.3 kcal/day after 7 years of follow-up). ND of all the nutrients increased within group across follow-up time, except for Saturated Fatty Acids (SFA), cholesterol and sodium (p < 0.001). CONCLUSIONS: A comprehensive dietary intervention improved quality of diet, reducing total energy intake and increasing the intake of healthy food groups and overall ND after 1 year and maintaining this trend after 7 years of follow-up. Our results reinforce the idea of the participation in trials, enhance nutrition literacy and produces better nutritional outcomes in adult patients with established CVD. CLINICAL TRIAL REGISTRY: The trial was registered in 2009 at ClinicalTrials.gov (number NCT00924937).

Can Patient Expectations Modulate the Short-Term Effects of Dry Needling on Sensitivity Outcomes in Patients with Mechanical Neck Pain? A Randomized Clinical Trial.

OBJECTIVE: Dry needling is commonly used for the management of patients with musculoskeletal pain. However, the effects of patient expectations are uncertain. Our aim was to determine the effect of patient expectations on short-term clinical outcomes after the application of a single session of dry needling in individuals with neck pain. METHODS: We conducted a randomized, placebo-controlled clinical trial including 50 patients with mechanical neck pain. Participants received a single session of dry needling or sham needling in a blinded design. Predicted patient expectation was categorized as positive, neutral, or negative. Outcomes including neck pain intensity (visual analog scale, 0-100), pressure pain thresholds, and self-perceived improvement (Global Rating of Change, -7 to +7) were assessed at baseline, 1 day after the intervention (immediately after), and 7 days after the intervention (1 week after) by a blinded assessor. Repeated-measures analyses of covariance were conducted to assess the effects of real/sham needling adjusted by patient expectations. RESULTS: Individuals receiving dry needling exhibited better outcomes immediately and 1 week after the intervention than did those receiving sham needling (all P < 0.01). No general effects of patient expectations, either related to pain recovery or functional improvement, were observed on the clinical outcomes, except for a small association of questionable clinical relevance between positive expectations and localized pressure pain thresholds in the dry needling group. CONCLUSION: This study did not find a significant effect of predicted patient expectations on the short-term effects of dry needling on pain intensity and pressure pain thresholds in people with mechanical neck pain.

Stakeholder engagement in developing a father-inclusive early life obesity prevention intervention: First Heroes.

BACKGROUND: Although paternal involvement in the perinatal period is associated with benefits for maternal-child health and reduced obesity risk, fathers are seldom included in perinatal or obesity prevention efforts. Engaging community leaders and fathers as stakeholders in intervention development is a critical step in designing a father-inclusive intervention that is efficacious and responsive to their needs. METHODS: We conducted a structured engagement study, including community stakeholder engagement and qualitative interviews with new fathers, to inform the development of a prospective randomized controlled trial that includes mothers and fathers as equal partners in infant obesity prevention. We interpreted stakeholder feedback through the Consolidated Framework for Implementation Research (CFIR) framework. RESULTS: Between September 2019 and April 2020, we held a Community Engagement meeting, formed a Community Advisory Board, and conducted 16 qualitative interviews with new fathers. Stakeholder engagement revealed insights across CFIR domains including intervention characteristics (relative advantage, complexity, design quality & packaging), outer setting factors (cosmopolitanism and culture), individual characteristics (including self-efficacy, state of change, identification with the organization) and process (engagement and adaptation). Stakeholders discussed the diverse challenges and rewards of fatherhood, as well as the intrinsic paternal motivation to be a loving, supportive father and partner. Both community leaders and fathers emphasized the importance of tailoring program delivery and content to meet specific parental needs, including a focus on the social-emotional needs of new parents. CONCLUSIONS: A structured process of multidimensional stakeholder engagement was successful in improving the design of a father-inclusive perinatal obesity prevention interventions. Father engagement was instrumental in both reinforcing community ties and increasing our understanding of fathers' needs, resulting in improvements to program values, delivery strategies, personnel, and content. This study provides a practical approach for investigators looking to involve key stakeholders in the pre-implementation phase of intervention development. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04477577 . Registered 20 July 2020.

Mediterranean Diet Reduces Atherosclerosis Progression in Coronary Heart Disease: An Analysis of the CORDIOPREV Randomized Controlled Trial.

Background and Purpose: Lifestyle and diet affect cardiovascular risk, although there is currently no consensus about the best dietary model for the secondary prevention of cardiovascular disease. The CORDIOPREV study (Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention) is an ongoing prospective, randomized, single-blind, controlled trial in 1002 coronary heart disease patients, whose primary objective is to compare the effect of 2 healthy dietary patterns (low-fat rich in complex carbohydrates versus Mediterranean diet rich in extra virgin olive oil) on the incidence of cardiovascular events. Here, we report the results of one secondary outcome of the CORDIOPREV study. Thus, to evaluate the efficacy of these diets in reducing cardiovascular disease risk. Intima-media thickness of both common carotid arteries (IMT-CC) was ultrasonically assessed bilaterally. IMT-CC is a validated surrogate for the status and future cardiovascular disease risk. Methods: From the total participants, 939 completed IMT-CC evaluation at baseline and were randomized to follow a Mediterranean diet (35% fat, 22% monounsaturated fatty acids, <50% carbohydrates) or a low-fat diet (28% fat, 12% monounsaturated fatty acids, >55% carbohydrates) with IMT-CC measurements at 5 and 7 years. We also analyzed the carotid plaque number and height. Results: The Mediterranean diet decreased IMT-CC at 5 years (−0.027±0.008 mm; P<0.001), maintained at 7 years (−0.031±0.008 mm; P<0.001), compared to baseline. The low-fat diet did not modify IMT-CC. IMT-CC and carotid plaquemax height were higher decreased after the Mediterranean diet, compared to the low-fat diet, throughout follow-up. Baseline IMT-CC had the strongest association with the changes in IMT-CC after the dietary intervention. Conclusions: Long-term consumption of a Mediterranean diet rich in extravirgin olive oil, if compared to a low-fat diet, was associated with decreased atherosclerosis progression, as shown by reduced IMT-CC and carotid plaque height. These findings reinforce the clinical benefits of the Mediterranean diet in the context of secondary cardiovascular prevention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00924937.

Bowel preparation prior to transvaginal ultrasound improves detection of rectosigmoid deep infiltrating endometriosis and is well tolerated: prospective study of women with suspected endometriosis without surgical criteria.

OBJECTIVES: To analyze the effect of bowel preparation prior to transvaginal ultrasound (TVS) examination on the detection of bowel involvement and the description of rectosigmoid nodules of deep infiltrating endometriosis (DIE), and to evaluate patient tolerance of bowel preparation. METHODS: This was a prospective study of paired data obtained between September 2015 and March 2016 from a cohort of women referred, on suspicion of DIE but without surgical criteria, to the endometriosis unit of a tertiary university hospital. In all patients, the wall of the rectum and lower sigmoid colon was evaluated by two TVS examinations: the first was performed without bowel preparation and the second was done after the patient had followed a 3-day low-residue diet and received two 250-mL enemas, one the night before TVS and the second 1-3 h before the examination. The presence of adhesions, number and size of rectosigmoid nodules, deepest layer of the rectum affected, percentage of the circumference of the bowel affected and distance from the most caudal part of the bowel nodule to the anal verge were determined. Patient tolerance to bowel preparation was assessed using a 5-point Likert scale, in which 1 represented 'very well tolerated' and 5 represented 'very poorly tolerated'. RESULTS: The mean ± SD age of the 110 patients included in the study was 36.8 ± 5.07 years. As many as 55% of those identified during the first examination (TVS alone) as having adhesions were identified at the second examination (TVS with prior bowel preparation) as having rectosigmoid nodules, and 22 additional nodules were observed on TVS following bowel preparation. These newly detected rectosigmoid nodules, initially assessed mainly as adhesions, were smaller and more superficial compared with the nodules detected on TVS alone, or located in the anterior sigmoid wall. Patient tolerance overall to bowel preparation scored a mean of 1.81 on the 5-point Likert scale. CONCLUSIONS: Bowel preparation is well tolerated by patients. When bowel preparation is performed before TVS, the detection of small and superficial nodules and those in the anterior sigmoid wall is improved, allowing more detailed description of these nodules in patients with suspected endometriosis. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Transvaginal ultrasound for diagnosis of deep endometriosis involving uterosacral ligaments, torus uterinus and posterior vaginal fornix: prospective study.

OBJECTIVE: To evaluate the accuracy of transvaginal ultrasound (TVS) in diagnosing deep endometriosis (DE) involving the uterosacral ligaments (USLs), torus uterinus (TU) or posterior vaginal fornix (PVF) in women with suspected endometriosis scheduled for laparoscopic surgery. METHODS: In this prospective study, consecutive women with clinically suspected pelvic endometriosis who were scheduled for laparoscopic surgery were invited to participate. TVS was performed before surgery. TVS findings were compared with those obtained at laparoscopy and confirmed histologically. The accuracy of TVS for diagnosing DE involving the USLs, TU or PVF was assessed. Additionally, the association of DE involving the USLs, TU or PVF on TVS with symptoms and with DE affecting other pelvic locations was assessed. RESULTS: In total, 172 patients were included. The global sensitivity and specificity of TVS in diagnosing DE affecting the USLs, TU and/or PVF were 92% and 87%, respectively. For DE involving the USLs, the accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio and negative likelihood ratio of TVS were 89.5%, 96.6%, 82.1%, 85.0%, 95.8%, 5.41 and 0.04, respectively; the respective values for DE involving the TU were 86.6%, 83.9%, 89.4%, 89.0%, 84.4%, 7.92 and 0.18, and the respective values for DE involving the PVF were 93.6%, 87.0%, 94.6%, 71.4%, 97.9%, 16.20 and 0.14. Logistic regression analysis showed a significant association between DE affecting the USLs, TU and/or PVF and DE affecting the rectosigmoid (odds ratio, 5.43; P < 0.001). Dyschezia was associated strongly with DE involving the USLs, TU and PVF, while dysmenorrhea was associated significantly with DE involving the TU. CONCLUSION: TVS has high accuracy, sensitivity, specificity, PPV and NPV for the detection of DE involving the USLs, TU and PVF in women with suspected endometriosis scheduled for laparoscopic surgery. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

A Sequential Inspection Procedure for Fault Detection in Multistage Manufacturing Processes.

Fault diagnosis in multistage manufacturing processes (MMPs) is a challenging task where most of the research presented in the literature considers a predefined inspection scheme to identify the sources of variation and make the process diagnosable. In this paper, a sequential inspection procedure to detect the process fault based on a sequential testing algorithm and a minimum monitoring system is proposed. After the monitoring system detects that the process is out of statistical control, the features to be inspected (end of line or in process measurements) are defined sequentially according to the expected information gain of each potential inspection measurement. A case study is analyzed to prove the benefits of this approach with respect to a predefined inspection scheme and a randomized sequential inspection considering both the use and non-use of fault probabilities from historical maintenance data.

Asynchronous Testing of 2 Specimen-Diversion Devices to Reduce Blood Culture Contamination: A Single-Site Product Supply Quality Improvement Project.

OBJECTIVE: Blood culture contamination above the national threshold has been a consistent clinical issue in the ED setting. Two commercially available devices were examined that divert an initial small volume of the specimen before the collection of blood culture to reduce skin contamination. METHODS: Prospectively, 2 different blood culture-diversion devices were made available in the unit supplies to ED clinicians at a single site during 2 different periods of time as a follow-up strategy to an ongoing quality improvement project. Blood samples were collected in the emergency department over a period of 16 months. A retrospective record review study was conducted comparing the use of the 2 specimen-diversion devices with no device (control group) for blood culture contamination rates. The main outcome of monthly blood culture contamination per device was tested using a Bayesian Poisson multilevel regression model. RESULTS: A total of 4030 blood samples were collected and analyzed from November 2017 to February 2019. The model estimated that the mean incidence of contaminated blood draws in the device A group was 0.29 (0.14-0.55) times the incidence of contaminated draws in the control group. The mean incidence of contaminated blood draws in the device B group was 0.23 (0.13-0.37) times the incidence of contaminated draws in the control group, suggesting that initial-diversion methods reduced blood culture contamination. CONCLUSION: Initial specimen-diversion devices supplement present standard phlebotomy protocols to bring down the blood culture contamination rate.

[Laparoscopic surgery in the COVID-19 era]. / Cirugía laparoscópica en tiempos de COVID-19.

Coexistence with COVID-19 infection (coronavirus disease 2019) in all hospital and health care settings is a current challenge of adaptation, as well as the creation of new protocols and care models. At present, there are still many unknowns about this infection, and much more unknown is the impact into the surgical field. Although evidence regarding the effect of SARS-CoV-2 and laparoscopic surgery is scarce, laparoscopy has been considered the method of choice by different scientific societies for most indications in gynaecology during the COVID-19 pandemic. This is due to the advantages over the open route. There is less morbidity and hospital stay, and in addition, as it involves autonomous and contained surgical procedures with respect to smoke release. Moreover, the instruments and the setting in the operating room mean that there can be safe distance from the surgeon and other staff to the patient. Overall, the main recommendations in laparoscopic surgery during the COVID era include: the use of Personal Protective Equipment for operating room personnel, and the adoption of safety measures to reduce CO2 exposure and surgical smoke release.

Fine-tuning of the flowering time control in winter barley: the importance of HvOS2 and HvVRN2 in non-inductive conditions.

BACKGROUND: In winter barley plants, vernalization and photoperiod cues have to be integrated to promote flowering. Plant development and expression of different flowering promoter (HvVRN1, HvCO2, PPD-H1, HvFT1, HvFT3) and repressor (HvVRN2, HvCO9 and HvOS2) genes were evaluated in two winter barley varieties under: (1) natural increasing photoperiod, without vernalization, and (2) under short day conditions in three insufficient vernalization treatments. These challenging conditions were chosen to capture non-optimal and natural responses, representative of those experienced in the Mediterranean area. RESULTS: In absence of vernalization and under increasing photoperiods, HvVRN2 expression increased with day-length, mainly between 12 and 13 h photoperiods in our latitudes. The flowering promoter gene in short days, HvFT3, was only expressed after receiving induction of cold or plant age, which was associated with low transcript levels of HvVRN2 and HvOS2. Under the sub-optimal conditions here described, great differences in development were found between the two winter barley varieties used in the study. Delayed development in 'Barberousse' was associated with increased expression levels of HvOS2. Novel variation for HvCO9 and HvOS2 is reported and might explain such differences. CONCLUSIONS: The balance between the expression of flowering promoters and repressor genes regulates the promotion towards flowering or the maintenance of the vegetative state. HvOS2, an ortholog of FLC, appears as a strong candidate to mediate in the vernalization response of barley. Natural variation found would help to exploit the plasticity in development to obtain better-adapted varieties for current and future climate conditions.