Modulation of neuronal activity in human centromedian nucleus during an auditory attention and working memory task.

Centromedian nucleus (CM) is one of several intralaminar nuclei of the thalamus and is thought to be involved in consciousness, arousal, and attention. CM has been suggested to play a key role in the control of attention, by regulating the flow of information to different brain regions such as the ascending reticular system, basal ganglia, and cortex. While the neurophysiology of attention in visual and auditory systems has been studied in animal models, combined single unit and LFP recordings in human have not, to our knowledge, been reported. Here, we recorded neuronal activity in the CM nucleus in 11 patients prior to insertion of deep brain stimulation electrodes for the treatment of epilepsy while subjects performed an auditory attention task. Patients were requested to attend and count the infrequent (p = 0.2) odd or "deviant" tones, ignore the frequent standard tones and report the total number of deviant tones at trial completion. Spikes were discriminated, and LFPs were band pass filtered (5-45 Hz). Average peri­stimulus time histograms and spectra were constructed by aligning on tone onsets and statistically compared. The firing rate of CM neurons showed selective, multi-phasic responses to deviant tones in 81% of the tested neurons. Local field potential analysis showed selective beta and low gamma (13-45 Hz) modulations in response to deviant tones, also in a multi-phasic pattern. The current study demonstrates that CM neurons are under top-down control and participate in the selective processing during auditory attention and working memory. These results, taken together, implicate the CM in selective auditory attention and working memory and support a role of beta and low gamma oscillatory activity in cognitive processes. It also has potential implications for DBS therapy for epilepsy and non-motor symptoms of PD, such as apathy and other disorders of attention.

Effectiveness of the Use of the Human Recombinant Epidermal Growth Factor in the Subsidized Regime vs The Contributive Regime in Patients with Venous Ulcers in Bogotá.

Introduction: Vascular ulcers constitute a serious global public health problem, responsible for causing a significant social and economic impact due to their recurrent, disabling nature and the need for prolonged therapies to cure them. Objective: To evaluate the use and efficacy of the rhEGF in the epithelialization of patients with a diagnosis of CEAP stage 6 venous insufficiency, in the two regimes of the health system in Colombia, the contributive (equivalent to a health system where citizens with payment capacity contribute a percentage of their salary) and the subsidized (equivalent to a health system where the state covers the vulnerable population and low socioeconomic level) versus the other treatments used. Methodology: Observational, descriptive, retrospective, multicenter study, in which 105 medical records with 139 ulcers were reviewed, in 2 centers, one belonging to the subsidized system and the other to the contributive system in Colombia. Results: The association with the epithelialization variable of the different treatment groups for ulcers according to the application of the mixed effect model test, for both regimes was for the Biologicals (EC 34.401/p = 0.000), Bioactive Agents (Hydrogels) (EC 24.735/p = 0.005) groups; for the rest of the treatment groups, the results were neither associated nor statistically significant. Conclusion: Intra- and perilesional therapy with rhEGF expands the therapeutic spectrum in patients with venous ulcers, regardless of the type of health system in which it will be applied, shortening the healing time and reaching a possible therapeutic goal, which according to this study there is an association with epithelialization regardless of the regime applied.

Increasing precision during neuromodulator injections for frontal rhytids-Using ultrasound imaging to identify the line of convergence.

BACKGROUND: Recent research introduced the concept of the "line of convergence" as a guide for injectors to enhance precision and avoid complications when treating the frontalis muscle with toxins. However, currently, no pre-injection ultrasound scanning is employed to increase precision and reduce adverse events when searching for the line of convergence. OBJECTIVE: To explore the feasibility and practicality of implementing pre-injection ultrasound scanning into aesthetic neuromodulator treatments of the forehead. METHODS: The sample of this study consisted of n = 55 volunteers (42 females and 13 males), with a mean age of 42.24 (10.3) years and a mean BMI of 25.07 (4.0) kg/m2. High-frequency ultrasound imaging was utilized to measure the thickness, length, and contractility of the frontal soft tissue and to determine the precise location of the line of convergence during maximal frontalis muscle contraction. RESULTS: The results revealed that the line of convergence was located at 58.43% (8.7) of the total forehead height above the superior border of the eyebrow cilia without a statistically significant difference between sex, age, or BMI. With frontalis muscle contraction, the forehead shortens in males by 25.90% (6.5), whereas in females it shortens only by 21.74% (5.1), with p < 0.001 for sex differences. CONCLUSION: This study demonstrated the feasibility and practicality of pre-injection ultrasound scanning for facial aesthetic neuromodulator treatments. Knowing the location of the line of convergence, injectors can determine precisely and on an individual basis where to administer the neuromodulator deep or superficial or when the injection location is at risk to cause eyebrow ptosis.

Pharmacodynamic monitoring by residual gene expression of the nuclear factor of activated T cell-regulated genes in lung transplant recipients and its correlation with tacrolimus blood levels.

Introduction: Trough blood levels (C0) of tacrolimus are used to adjust drug dosage, but they do not consistently correlate with clinical outcomes. Measurement of residual gene expression of nuclear factor of activated T cell (NFAT)-regulated genes (NFAT-RGE) has been proposed as a pharmacodynamic biomarker to assess the degree of immunosuppression in certain solid organ transplantations, but little is known regarding lung transplant recipients (LTR). Our primary objective is to correlate tacrolimus blood levels with NFAT-RGE. Methods: NFAT-RGE and tacrolimus C0 and peak (C1.5) levels were determined in 42 patients at three, six and 12 months post-transplantation. Results: Tacrolimus C0 did not exhibit a correlation with NFAT-RGE, whereas C1.5 did. Besides, over 20% of measurements indicated high levels of immunosuppression based on the below 30% NFAT-RGE threshold observed in many studies. Among those measurements within the therapeutic range, 19% had an NFAT-RGE<30%. Conclusion: Consequently, a subset of patients within the tacrolimus therapeutic range may be more susceptible to infection or cancer, potentially benefiting from NFAT-RGE and tacrolimus peak level monitoring to tailor their dosage. Further quantitative risk assessment studies are needed to elucidate the relationship between NFAT-RGE and the risk of infection, cancer, or rejection.

Circadian rhythm of salivary and serum urea concentration in alpacas and sheep receiving diets with different levels of protein.

All vertebrates possess a daily rhythm, encompassing a comprehensive set of physiological, cognitive, and behavioral patterns that manifest throughout a 24-hour period. The aim of this study was to compare the effect of crude protein (CP) levels in the diet on the daily rhythm of urea in serum (US) and saliva in alpacas and sheep. Ten alpacas and ten sheep, adult, clinically healthy males, were used; they were maintained in natural light conditions and fed ad libitum with two levels of CP (16 and 7%). Blood and saliva samples were taken every 4 h for 48 h. A two-way ANOVA was conducted to analyze the parameters, including adjusted mean rhythm (MESOR), amplitude, and acrophase. It was found that both US and saliva urea exhibited circadian rhythms with a peak during the midday (10:59 - 12:16 h). The MESOR with low CP diets was higher (P < 0.05) in alpacas. The MESOR of urea levels in saliva was greater (P < 0.05) at the highest level of CP in the diet, with no differences between alpacas and sheep (P > 0.05). The amplitude was greater (P < 0.05) in alpacas and at the high level of CP compared to the low level of CP in the diet. Our findings reveal that both serum and saliva urea levels in alpacas and sheep follow a daily rhythm and the MESOR of US was higher in alpacas when they consume food with low CP content, and this difference disappears when CP levels are increased in the diet.

The "Central Tendency Bias" in the assessment of facial attractiveness in group-based and individual ratings-A survey-based study in 727 volunteers.

BACKGROUND: The increasing number of esthetic procedures emphasizes the need for effective evaluation methods of outcomes. Current practices include the individual practitioners' judgment in conjunction with standardized scales, often relying on the comparison of before and after photographs. This study investigates whether comparative evaluations influence the perception of beauty and aims to enhance the accuracy of esthetic assessments in clinical and research settings. OBJECTIVE: To compare the evaluation of attractiveness and gender characteristics of faces in group-based versus individual ratings. METHODS: A sample of 727 volunteers (average age of 29.5 years) assessed 40 facial photographs (20 male, 20 female) for attractiveness, masculinity, and femininity using a 5-point Likert scale. Each face was digitally edited to display varying ratios in four lip-related proportions: vertical lip position, lip width, upper lip esthetics, and lower lip esthetics. Participants rated these images both in an image series (group-based) and individually. RESULTS: Differences in the perception of the most attractive/masculine/feminine ratios for each lip proportion were found in both the group-based and individual ratings. Group ratings exhibited a significant central tendency bias, with a preference for more average outcomes compared with individual ratings, with an average difference of 0.50 versus 1.00. (p = 0.033) CONCLUSION: A central tendency bias was noted in evaluations of attractiveness, masculinity, and femininity in group-based image presentation, indicating a bias toward more "average" features. Conversely, individual assessments displayed a preference for more pronounced, "non-average" appearances, thereby possibly pointing toward a malleable "intrinsic esthetic blueprint" shaped by comparative context.

Dietary and Smoking Acrylamide and Prostate Cancer Risk: CAPLIFE Study.

Acrylamide is a probable carcinogen. Its main sources are the diet and tobacco. The association between acrylamide intake from the diet and tobacco and prostate cancer (PCa) has not been previously evaluated. We aimed to evaluate the relationship between dietary acrylamide intake and exposure to acrylamide through cigarettes and PCa risk. A population-based case-control (CAPLIFE) study was conducted, including 428 incident PCa cases and 393 controls. Smoking and dietary information, with a validated food frequency questionnaire, was collected. We calculated the amount of acrylamide from both sources, and tertiles (Ts) were created. Multivariable logistic regression and restricted cubic spline models were applied to assess the association between exposure to acrylamide and PCa risk. The median was similar for acrylamide in both dietary and smoking acrylamide among PCa cases and controls. No association was observed between dietary acrylamide intake and overall PCa risk (adjusted ORT3vsT1 = 0.90 (95% CI 0.59, 1.37)). A risk trend was observed for acrylamide exposure from cigarette smoking (p-trend = 0.032), with the highest odds in those subjects with the high exposure to acrylamide through cigarettes (adjusted ORT3vsT1 = 1.67 (95% CI 0.92, 3.04)). The restricted cubic splines suggested a linear relationship. In conclusion, acrylamide from smoking could be positively associated with PCa risk, but no association was observed for dietary acrylamide.

Blood selenium and zinc concentration of female alpacas (Vicugna pacos) and their offspring during different physiological conditions.

Background: Minerals are important for animals in many biological functions. There is scarce information, however, about micromineral content in the blood of South American camelids under their prevalent production system. Aim: This study aims to determine whole blood selenium (Se) and serum zinc (Zn) concentrations of grazing alpacas at three different physiological states in the Peruvian Andean Highland. Methods: Blood samples were collected for measurement of whole blood Se and serum Zn concentrations from 15 female alpacas at late gestation, peripartum, and late lactation, as well as their respective offspring, for them only two times were taken it account (10 days after birth and late lactation). The female alpacas at the beginning had a body weight of 47.5 ± 8 kg and an estimated age of 4.03 ± 0.93 years. Se and Zn content of pastures consumed by alpacas also were determined. The samples were taken during three different months according to the productive calendar of the alpacas. Results: The content of Se and Zn of the diet selected by alpacas met the requirements for the physiological states they go through in comparison with literature references. Serum Zn concentration of female alpacas was higher in peripartum (0.26 µg/ml), compared to late gestation and late lactation (p < 0.05). A similar result was found in the case of their offspring at 10 days after birth (0.23 µg/ml) Zn concentration was higher than for late lactation (p < 0.05). Unlike Zn, in the case of Se, no differences were found between the physiological states studied for alpacas or their offspring. Conclusion: Serum Zn concentration changes through late gestation, peripartum, and late lactation in the female alpacas and their offspring 10 days after birth and late lactation. Further investigation is needed to define the alpaca adequacy of Zn and Se in relation to the blood content of both minerals.

SWOT Analysis and Recommendations for Community Health Workers and Stakeholders Responding to COVID-19 Health Inequities.

Background. By 2023, 1,080,000 cases of COVID-19 have been reported in Harris County. Systemic inequity and vaccine hesitancy have contributed to COVID-19 disparities. Community Health Workers provide health education and instrumental support to alleviate health disparities among vulnerable communities. We conducted an analysis of Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis in June 2022 among a broad coalition of Community Health Work stakeholders to better understand the local landscape in the context of the COVID-19 pandemic. Methods. We recruited 33 community health workers and industry stakeholders in Harris County, Texas, to participate in the SWOT analysis. Participants were asked to describe their opinions on the SWOT facing the Community Health Work landscape and then rank the outcomes of the analysis to prioritize action. Results. A total of 19 themes were identified. Weaknesses included lack of respect and resources for Community Health Workers and poor coordination and capacity among the workforce infrastructure. Limited funding and lack of appreciation for Community Health Workers were deemed important threats. Diversity and community connection were critical strengths, and strong education, training, and raising awareness for community health work were considered opportunities to overcome identified weaknesses and threats. Discussion. Increased funding, greater coordination, greater respect, and amplified training can improve capacity for Community Health Workers and, therefore, improve public health outcomes for respiratory illness and viral infections such as COVID-19. This analysis helps fill an important research gap on the topic Community Health Workers responding to public health crises with racially disparate outcomes.

Dietary Iron, Anemia Markers, Cognition, and Quality of Life in Older Community-Dwelling Subjects at High Cardiovascular Risk.

Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55-75 years (men) and 60-75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoroughly tested through methodologically rigorous studies that minimize the risk of reverse causality.

Association between serum copper levels and risk of cardiovascular disease: A nested case-control study in the PREDIMED trial.

BACKGROUND AND AIM: Certain trace elements have been associated with increased cardiovascular risk. The aim of this study was to evaluate the association between serum copper (S-Cu) levels and the risk of a first event of cardiovascular disease (CVD) in a population of older adults with high cardiovascular risk. METHODS AND RESULTS: We conducted a case-control study nested within the PREDIMED trial. During a median follow-up of 4.8 years, a total of 207 incident cases diagnosed with CVD were matched for sex, age, and intervention group with 436 controls. Personal interviews, reviews of medical records, and validated questionnaires were used to assess known CVD risk factors. Biological serum samples were collected annually. Inductively coupled plasma mass spectrometry analysis was used to determine S-Cu levels. Adjusted odds ratios were calculated using multivariate conditional logistic regression models. All participants had S-Cu levels within the reference values, 750 µg/L to 1450 µg/L. Among men, but not among women, the mean S-Cu concentration was higher in cases 1014.1 µg/L than in controls 959.3 µg/L; (p = 0.004). In men, the multivariable-adjusted odds ratio for CVD was 2.36 (95% CI 1.07-5.20 for the comparison of the highest vs. the lowest quartile; p for trend = 0.02), in women, it was 0.43 (95% CI 0.11-1.70; p for trend = 0.165). CONCLUSION: In older Spanish men with high cardiovascular risk, a significant association was observed between high S-Cu levels, but still within the reference values, and an increased risk of a first event of CVD. Our findings suggest a sex difference in CVD risk and S-Cu levels. To confirm this relationship and to analyze the differences observed between men and women, further studies are needed.

Serum copper levels and risk of major adverse cardiovascular events: a systematic review and meta-analysis.

Background: Despite the fact that several studies have investigated the association between serum copper levels (S-Cu) and the risk of cardiovascular diseases, this relationship remains unclear. The aims of this study were to investigate the association between S-Cu and risk of major adverse cardiovascular events (MACE), including total stroke, ischemic stroke, hemorrhagic stroke, myocardial infarction and cardiovascular mortality, and identify potential sources of results heterogeneity. Methods: We carried out a systematic review and meta-analysis. The selection criteria were: (1) Observational studies (cohort studies, case-control studies and hybrid studies); (2) Studies containing quantitative data about the relationship between S-Cu and risk of MACE; (3) Estimating association measures; and (4) Studies written in English, French or Spanish. Overall pooled Odds ratio (pOR) and 95% confidence intervals (95% CI) of MACE for the highest vs. lowest S-Cu category were calculated using random-effects models. Results: Sixteen studies with a total of 41,322 participants were included in the meta-analysis: 10 prospective cohort studies, 5 nested case-control studies and 1 case-control study. Comparing highest vs. lowest category, high S-Cu levels were associated with total stroke (pOR: 1.49, 95% CI 1.22-1.82; I2 = 0%, p = 0.54), myocardial infarction (pOR: 1.31, 95% CI 1.17-1.46; I2 = 0.0%, p = 0.92) and cardiovascular mortality (pOR: 1.60, 95% CI 1.39-1.86; I2 = 0.0%, p = 0.54). Subgroup analysis showed that studies with a hybrid design had higher risks for cardiovascular mortality (pOR: 3.42, 95% CI 1.98-5.92) and ischemic stroke (pOR: 1.54, 95% CI 1.30-1.83). Conclusion: High S-Cu levels were associated with an increased risk of total stroke, myocardial infarction and cardiovascular mortality. Hybrid studies seems to modify the strength of the association between S-Cu and the risk of cardiovascular mortality and ischemic stroke. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022370782], identifier [CRD42022370782].

Systematic measuring cortical thickness in tibiae for bio-mechanical analysis.

BACKGROUND AND OBJECTIVE: Measuring the thickness of cortical bone tissue helps diagnose bone diseases or monitor the progress of different treatments. This type of measurement can be performed visually from CAT images by a radiologist or by semi-automatic algorithms from Hounsfield values. This article proposes a mechanism capable of measuring thickness over the entire bone surface, aligning and orienting all the images in the same direction to have comparable references and reduce human intervention to a minimum. The objective is to batch process large numbers of patients' CAT images obtaining thicknesses profiles of their cortical tissue to be used in many applications. METHODS: Classical morphological and Deep Learning segmentation is used to extract the area of interest, filtering and interpolation to clean the bones and contour detection and Signed Distance Functions to measure the cortical Thickness. The alignment of the set of bones is achieved by detecting their longitudinal direction, and the orientation is performed by computing their principal component of the center of mass slice. RESULTS: The method processed in an unattended manner 67% of the patients in the first run and 100% in the second run. The difference in the thickness values between the values provided by the algorithm and the measures done by a radiologist was, on average, 0.25 millimetres with a standard deviation of 0.2. CONCLUSION: Measuring the cortical thickness of a bone would allow us to prepare accurate traumatological surgeries or study their structural properties. Obtaining thickness profiles of an extensive set of patients opens the way for numerous studies to be carried out to find patterns between bone thickness and the patients' medical, social or demographic variables.

Comparative effects of glucagon-like peptide-1 receptors agonists, 4-dipeptidyl peptidase inhibitors, and metformin on metabolic syndrome.

AIMS: To assess the comparative effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), 4-dipeptidyl peptidase inhibitors (DPP-4I), and metformin treatment during one year on metabolic syndrome (MetS) components and severity in MetS patients. METHODS: Prospective study (n = 6165 adults) within the frame of PREDIMED-Plus trial. The major end-point was changes on MetS components and severity after one- year treatment of GLP-1RA, DPP-4I, and metformin. Anthropometric measurements (weight, height and waist circumference), body mass index (BM), and blood pressure were registered. Blood samples were collected after overnight fasting. Plasma glucose, glycosylated hemoglobin (HbA1c), plasma triglycerides and cholesterol were measured. Dietary intakes as well as physical activity were assessed through validated questionnaires. RESULTS: MetS parameters improved through time. The treated groups improved glycaemia compared with untreated (glycaemia ∆ untreated: -1.7 mg/dL(± 13.5); ∆ metformin: - 2.5(± 23.9) mg/dL; ∆ DPP-4I: - 4.5(± 42.6); mg/dL ∆ GLP-1RA: - 4.3(± 50.9) mg/dL; and HbA1c: ∆ untreated: 0.0(± 0.3) %; ∆ metformin: - 0.1(± 0.7) %; ∆ DPP-4I: - 0.1(± 1.0) %; ∆ GLP-1RA: - 0.2(± 1.2) %. Participants decreased BMI and waist circumference. GLP-1RA and DPP-4I participants registered the lowest decrease in BMI (∆ untreated: -0.8(± 1.6) kg/m2; ∆ metformin: - 0.8(± 1.5) kg/m2; ∆ DPP-4I: - 0.6(± 1.3) kg/m2; ∆ GLP-1RA: - 0.5(± 1.2) kg/m2. and their waist circumference (∆ untreated: -2.8(± 5.2) cm; ∆ metformin: - 2.6(± 15.2) cm; ∆ DPP-4I: - 2.1(± 4.8) cm; ∆ GLP-1RA: - 2.4(± 4.1) cm. CONCLUSION: In patients with MetS and healthy lifestyle intervention, those treated with GLP-1RA and DPP-4I obtained better glycemic profile. Anthropometric improvements were modest.

Mediterranean diet and risk of breast cancer: An umbrella review.

BACKGROUND: The Mediterranean Diet (MedDiet) is a healthy dietary pattern which has been related to a lower risk of certain chronic diseases, such as some cancers. However, its role in breast cancer development remains unclear. This umbrella review aims to summarize the highest available evidence on MedDiet and breast cancer risk. METHODS: Pubmed, Web of Science, and Scopus electronic platforms were searched for relevant systematic reviews and meta-analyses. The selection criteria included systematic reviews with or without meta-analysis including women aged 18 years or older which evaluated the adherence to a MedDiet as the exposure and incidence of breast cancer as the outcome variable. Overlapping and quality of the reviews using AMSTAR-2 tool were independently assessed by two authors. RESULTS: Five systematic reviews and six systematic reviews with meta-analysis were included. Overall, 4 systematic reviews - two with and two without meta-analysis - were rated as of high quality. An inverse association was found in 5 of the 9 reviews which evaluated the role of MedDiet on the risk of total breast cancer. The meta-analyses showed moderate-high heterogeneity. The risk reduction seemed to be more consistent among postmenopausal women. No association was found for MedDiet among premenopausal women. CONCLUSIONS: The results of this umbrella review suggest that adherence to a MedDiet pattern had a protective effect on the risk of breast cancer, especially for postmenopausal breast cancer. The stratification of breast cancer cases and conducting high-quality reviews are aspects needed to overcome the current results' heterogeneity and to improve knowledge in this field.

Lymphangioleiomyomatosis: Searching for potential biomarkers.

Background: Vascular endothelial growth factor-D (VEGF-D) is the most commonly used biomarker for diagnosing lymphangioleiomyomatosis (LAM). However, lung biopsy is often necessary as well; therefore, defining new biomarkers for LAM is crucial. The aim of this study was to describe the diagnostic accuracy of a variety of biomarkers. Methods: We assessed 13 analytes in serum related to extracellular matrix remodeling, lymphatic involvement and angiogenesis in a cohort of patients with LAM, comparing them with patients with other cystic lung diseases (OCLD) and healthy women. A scoring method based on the cut-point of each VEGF-D and metalloproteinase-2 (MMP-2) was used to evaluate the diagnostic performance of the marker combination. Results: A total of 97 subjects were recruited: 59 (61%) LAM patients, 18 (19%) OCLD patients, and 20 (20%) healthy female controls. MMP-2 was the only extracellular matrix remodeling biomarker able to differentiate LAM patients from OCLD and healthy patients. Serum MMP-2 was higher in LAM patients [median 578 (465-832) ng/ml] than in patients with OCLD and healthy controls [medians 360 (314-546) and 427 (365-513) ng/ml, respectively (p < 0.0001)]. The area under ROC curve (AUC) of MMP-2 was 0.785 and that of VEGF-D 0.815 (p = 0.6214). The sensitivity/specificity profiles of each biomarker (54/92% for MMP-2, 59/95% for VEGF-D) yielded a composite score (-6.36 + 0.0059 × VEGF-D + 0.0069 × MMP-2) with higher accuracy than each component alone (AUC 0.88 and sensitivity/specificity 79/87%). Conclusion: Combining MMP-2 and VEGF-D may increase diagnostic accuracy for LAM.

Allometric growth and larval development in Pacific red snapper Lutjanus peru under culture conditions.

Allometric growth is a common feature during fish larval development. It has been proposed as a growth strategy to prioritize the development of body segments related to primordial functions like feeding and swimming to increase the probability of survival during this critical period. In the present study we evaluated the allometric growth patterns of body segments associated to swimming and feeding during the larval stages of Pacific red snapper Lutjanus peru. The larvae were kept under intensive culture conditions and sampled every day from hatching until day 33 after hatching. Each larva was classified according to its developmental stage into yolk-sac larva, preflexion larva, flexion larva or postflexion larva, measured and the allometric growth coefficient of different body segments was evaluated using the potential model. Based on the results we can infer the presence of different ontogenetic priorities during the first developmental stages associated with vital functions like swimming during the yolk-sac stage [total length (TL) interval = 2.27-3.005 mm] and feeding during the preflexion stage (TL interval = 3.007-5.60 mm) by promoting the accelerated growth of tail (post anal) and head, respectively. In the flexion stage (TL interval = 5.61-7.62 mm) a change in growth coefficients of most body segments compared to the previous stage was detected, suggesting a shift in growth priorities. Finally, in the postflexion stage (TL interval = 7.60-15.48 mm) a clear tendency to isometry in most body segments was observed, suggesting that growth priorities have been fulfilled and the larvae will initiate with the transformation into a juvenile. These results provide a framework of the larval growth of L. peru in culture conditions which can be useful for comparative studies with other species or in aquaculture to evaluate the changes in larval growth due to new conditions or feeding protocols.

Serum Selenium and Incident Cardiovascular Disease in the PREvención con DIeta MEDiterránea (PREDIMED) Trial: Nested Case-Control Study.

Background: Selenium is an essential trace mineral with potential interest for cardiovascular disease (CVD) prevention owing to its antioxidant properties. Epidemiological data on selenium status and CVD remain inconsistent. The objective of this study was to ascertain whether low serum selenium (SSe) concentrations are related to an increased risk of a first CVD event in a population at high cardiovascular risk. Methods: We undertook a case-control study nested within the "PREvención con DIeta MEDiterránea" (PREDIMED) trial. A total of 207 participants diagnosed with CVD (myocardial infarction, stroke, or cardiovascular death) during the follow-up period (2003−2010) were matched by sex, age, and intervention group to 436 controls by incidence density sampling. Median time between serum sample collection and subsequent CVD event occurrence was 0.94 years. SSe levels were determined using inductively coupled plasma mass spectrometry analysis. Covariates were assessed through validated questionnaires, in-person interviews, and medical record reviews. Conditional logistic regression was used to calculate multivariable-adjusted odds ratios (ORs). Results: Among women, the mean SSe concentration was lower in cases than in controls (98.5 µg/L vs. 103.8 µg/L; p = 0.016). In controls, SSe levels were directly associated with percentage of total energy intake from proteins and fish intake (p for linear trend < 0.001 and 0.049, respectively), whereas SSe concentrations were inversely associated with age, body mass index, and percentage of total energy intake from carbohydrates (p for linear trend < 0.001, 0.008 and 0.016 respectively). In the total group, we observed an inverse dose−response gradient between SSe levels and risk of CVD in the fully-adjusted model (highest vs. lowest quartile: OR = 0.47, 95% CI: 0.27−0.81; ptrend = 0.003). Conclusions: Among elderly individuals at high cardiovascular risk, high SSe concentrations within population reference values are associated with lower first CVD incidence.

Long-Term Follow-Up on Bilateral Posterior Hypothalamic Deep Brain Stimulation for Treating Refractory Aggressive Behavior in a Patient with Cri du Chat Syndrome: Analysis of Clinical Data, Intraoperative Microdialysis, and Imaging Connectomics.

Posterior hypothalamic-deep brain stimulation (pHyp-DBS) has been reported as a successful treatment for reducing refractory aggressive behaviors in patients with distinct primary diagnoses. Here, we report on a patient with cri du chat syndrome presenting severe self-injury and aggressive behaviors toward others, who was treated with pHyp-DBS. Positive results were observed at long-term follow-up in aggressive behavior and quality of life. Intraoperative microdialysis and imaging connectomics analysis were performed to investigate possible mechanisms of action. Our results suggest the involvement of limbic and motor areas and alterations in main neurotransmitter levels in the targeted area that are associated with positive results following treatment.

Morbid liver manifestations are intrinsically bound to metabolic syndrome and nutrient intake based on a machine-learning cluster analysis.

Metabolic syndrome (MetS) is one of the most important medical problems around the world. Identification of patient´s singular characteristic could help to reduce the clinical impact and facilitate individualized management. This study aimed to categorize MetS patients using phenotypical and clinical variables habitually collected during health check-ups of individuals considered to have high cardiovascular risk. The selected markers to categorize MetS participants included anthropometric variables as well as clinical data, biochemical parameters and prescribed pharmacological treatment. An exploratory factor analysis was carried out with a subsequent hierarchical cluster analysis using the z-scores from factor analysis. The first step identified three different factors. The first was determined by hypercholesterolemia and associated treatments, the second factor exhibited glycemic disorders and accompanying treatments and the third factor was characterized by hepatic enzymes. Subsequently four clusters of patients were identified, where cluster 1 was characterized by glucose disorders and treatments, cluster 2 presented mild MetS, cluster 3 presented exacerbated levels of hepatic enzymes and cluster 4 highlighted cholesterol and its associated treatments Interestingly, the liver status related cluster was characterized by higher protein consumption and cluster 4 with low polyunsaturated fatty acid intake. This research emphasized the potential clinical relevance of hepatic impairments in addition to MetS traditional characterization for precision and personalized management of MetS patients.