[Improving quality of life in older adults with the decline syndrome: The role of occupational therapy in primary care]. / Mejorando la calidad de vida en personas mayores con el síndrome del declive: el rol de la terapia ocupacional en Atención Primaria.

OBJECTIVE: To evaluate the effect of an occupational therapy intervention in users recently diagnosed with the decline syndrome, who have experienced a decrease in the Barthel and/or Lawton index in the last month and susceptible to improvement based on medical opinion. DESIGN: Non-controlled, quasi-experimental longitudinal study. A pre-post intervention. LOCATION: Sant Hipòlit de Voltregà health centre. Osona, Barcelona. PARTICIPANTS: Patients referred by the centre's primary care nursing, social work or medical staff with a recent diagnosis of decline syndrome who may benefit from the intervention of an occupational therapy professional. INTERVENTION: Following the initial assessment visit, four training sessions were conducted to improve functional independence, mobility and adaptation of the home environment, providing training to primary caregivers. MAIN MEASUREMENTS: Patient autonomy was assessed using the Barthel and Lawton scales, quality of life using the EuroQol questionnaire (EQ-5D) and home suitability using the home suitability assessment questionnaire. RESULTS: Improvements were observed in autonomy in activities of daily living (p=0.003), mobility (p=0.001) and housing adaptation (p<0.001). The level of anxiety/depression was reduced (p=0.028), and the mean health status score increased markedly (p<0.001). CONCLUSIONS: This study highlights the improvement in the quality of life and autonomy in the basic activities of daily living for individuals receiving occupational therapy, emphasizing the need for home adaptation and family support.

Clinical characteristics and degree of cardiovascular risk factor control in patients with newly-diagnosed type 2 diabetes in Catalonia.

Introduction: Women with type 2 diabetes mellitus (T2DM) face a greater risk of cardiovascular disease (CVD) and encounter challenges in managing cardiovascular risk factors (CVRF); however, limited data are available in individuals with newlydiagnosed T2DM. Methods: This study aimed to examine differences between women and men at the onset of T2DM in terms of clinical characteristics, glycaemic status, and CVRF management. This was a retrospective cohort study including subjects with newly-diagnosed T2DM from the System for the Development of Research in Primary Care (SIDIAP) database in Catalonia (Spain). Sex differences (Dif) were assessed at baseline and 1-year post-diagnosis, by calculating the absolute difference of means or proportions. Results: A total of 13,629 subjects with newly-diagnosed T2DM were analyzed. Women were older and had a higher BMI than men. At baseline, women had higher total cholesterol [Dif (95%CI) 10 mg/dL (9.1/10.8)] and low-density lipoprotein cholesterol (LDL-c) [Dif (95%CI) 7 mg/dL (6.3/7.7)], while men had higher rates of smoking and alcohol intake. Lipid target achievement was lower in women, in both primary prevention (LDL-c < 100 mg/dL) [Dif (95%CI) -7.3 mg/dL (-10.5/-4.1)] and secondary prevention (LDL-c < 70 mg/dL) [Dif (95%CI) -8.3 mg/dL (-17.3/0.7)], along with lower statin and antiplatelet prescriptions, especially one year after diagnosis. Changes in clinical and laboratory data one year post-diagnosis revealed that, in the primary prevention group, men experienced greater improvements in total cholesterol, LDL-c and triglycerides, while women had less success in achieving CVRF control targets compared to men. Additionally, cardiovascular events, such as coronary artery disease and peripheral artery disease increased more in men than in women within the first year of diagnosis, especially in primary prevention subjects. Conclusion: Differences between men and women CVRF are already apparent at the onset of T2DM, particularly in primary prevention, with notable differences in lipid profile and target level attainment.

Contribution of Elevated Glucose and Oxidized LDL to Macrophage Inflammation: A Role for PRAS40/Akt-Dependent Shedding of Soluble CD14.

Atherosclerosis, a process in which macrophages play a key role, is accelerated in diabetes. Elevated concentrations of serum-oxidized low-density lipoproteins (oxLDL) represent a common feature of both conditions. The main goal of this study was to determine the contribution of oxLDL to the inflammatory response of macrophages exposed to diabetic-mimicking conditions. THP1 cells and peripheral blood monocytes purified from non-diabetic healthy donors were cultured under normal (5 mM) or high glucose (HG) (15 mM) with oxLDL. Then, foam cell formation, expression of CD80, HLADR, CD23, CD206, and CD163, as well as toll-like receptor 4 (TLR4) and co-receptors CD36 and CD14 (both at the cell surface and soluble (sCD14)), and inflammatory mediators' production were measured by flow cytometry, RT-qPCR, or ELISA. Additionally, serum sCD14 was determined in subjects with subclinical atherosclerosis with and without diabetes by ELISA. Our results showed that oxLDL-mediated intracellular lipid accumulation via CD36 increased under HG and that HG + oxLDL enhanced TNF, IL1B, and IL8, and decreased IL10. Moreover, TLR4 was upregulated in macrophages under HG and monocytes of subjects with diabetes and atherosclerosis. Interestingly, HG-oxLDL upregulated CD14 gene expression, although its total cellular protein abundance remained unaltered. sCD14 shedding via PRAS40/Akt-dependent mechanisms, with pro-inflammatory activity, was significantly increased in cultured macrophages and plasma from subjects with diabetes and subclinical atherosclerosis or hypercholesterolemia. Our data support an enhanced synergistic pro-inflammatory effect induced by HG and oxLDL in cultured human macrophages, possibly explained by increased sCD14 shedding.

Sustained seropositivity up to 20.5 months after COVID-19.

This study evaluated the persistence of IgM, IgA, and IgG to SARS-CoV-2 spike and nucleocapsid antigens up to 616 days since the onset of symptoms in a longitudinal cohort of 247 primary health care workers from Barcelona, Spain, followed up since the start of the pandemic. The study also assesses factors affecting antibody levels, including comorbidities and the responses to variants of concern as well as the frequency of reinfections. Despite a gradual and significant decline in antibody levels with time, seropositivity to five SARS-CoV-2 antigens combined was always higher than 90% over the whole study period. In a subset of 23 participants who had not yet been vaccinated by November 2021, seropositivity remained at 95.65% (47.83% IgM, 95.65% IgA, 95.65% IgG). IgG seropositivity against Alpha and Delta predominant variants was comparable to that against the Wuhan variant, while it was lower for Gamma and Beta (minority) variants and for IgA and IgM. Antibody levels at the time point closest to infection were associated with age, smoking, obesity, hospitalization, fever, anosmia/hypogeusia, chest pain, and hypertension in multivariable regression models. Up to 1 year later, just before the massive roll out of vaccination, antibody levels were associated with age, occupation, hospitalization, duration of symptoms, anosmia/hypogeusia, fever, and headache. In addition, tachycardia and cutaneous symptoms associated with slower antibody decay, and oxygen supply with faster antibody decay. Eight reinfections (3.23%) were detected in low responders, which is consistent with a sustained protective role for anti-spike naturally acquired antibodies. Stable persistence of IgG and IgA responses and cross-recognition of the predominant variants circulating in the 2020-2021 period indicate long-lasting and largely variant-transcending humoral immunity in the initial 20.5 months of the pandemic, in the absence of vaccination.

Eleven-month longitudinal study of antibodies in SARS-CoV-2 exposed and naïve primary health care workers upon COVID-19 vaccination.

We evaluated the kinetics of antibody responses to Two years into the COVID-19 pandemic and 1 year after the start of vaccination rollout, the world faced a peak of cases associated with the highly contagious Omicron variant of concern (VoC) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) and nucleocapsid (N) antigens over five cross-sectional visits (January-November 2021), and the determinants of pre-booster immunoglobulin levels, in a prospective cohort of vaccinated primary health care workers in Catalonia, Spain. Antibodies against S antigens after a full primary vaccination course, mostly with BNT162b2, decreased steadily over time and were higher in pre-exposed (n = 247) than naïve (n = 200) individuals, but seropositivity was maintained at 100% (100% IgG, 95.5% IgA, 30.6% IgM) up to 319 days after the first dose. Antibody binding to variants of concern was highly maintained for IgG compared to wild type but significantly reduced for IgA and IgM, particularly for Beta and Gamma. Factors significantly associated with longer-term antibodies included age, sex, occupation, smoking, adverse reaction to vaccination, levels of pre-vaccination SARS-CoV-2 antibodies, interval between disease onset and vaccination, hospitalization, oxygen supply, post COVID and symptomatology. Earlier morning vaccination hours were associated with higher IgG responses in pre-exposed participants. Symptomatic breakthroughs occurred in 9/447 (2.01%) individuals, all among naïve (9/200, 4.5%) and generally boosted antibody responses. Additionally, an increase in IgA and/or IgM seropositivity to variants, and N seroconversion at later time points (6.54%), indicated asymptomatic breakthrough infections, even among pre-exposed. Seropositivity remained highly stable over almost a year after vaccination. However, gradually waning of anti-S IgGs that correlate with neutralizing activity, coupled to evidence of an increase in breakthrough infections during the Delta and Omicron predominance, provides a rationale for booster immunization.

Correction: Ramírez-Morros et al. Sex Differences in Cardiovascular Prevention in Type 2: Diabetes in a Real-World Practice Database. J. Clin. Med. 2022, 11, 2196.

In the original publication [...].

Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients.

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when <20% of recruitment target was achieved. A Bayesian-adaptive individual patient data meta-analysis was implemented. Outpatients aged ≥50 years and symptomatic for ≤7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with ≤5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution. TRIAL REGISTRATION: Clinicaltrials.gov NCT04621123 and NCT04589949. REGISTRATION: NCT04621123 and NCT04589949 on https://www. CLINICALTRIALS: gov.

Motivation for Vaccination against COVID-19 in Persons Aged between 18 and 60 Years at a Population-Based Vaccination Site in Manresa (Spain).

Our purpose was to identify the reasons why members of the population, aged 18-60 years, are vaccinated against COVID-19 at the mass vaccination point in Bages, Spain. This is 1 of 42 provisional spaces outside of health centres which have been set up in Catalonia in the context of the COVID-19 pandemic, and where people from all over Catalonia could go to be vaccinated by appointment. METHODOLOGY: We performed a cross-sectional study of users attending mass vaccination points in Bages during the months of July, August, and September 2021. RESULTS: A total of 1361 questionnaires were statistically analysed. The most common reasons for vaccination were fear of infecting family (49.52%) and fear of self-infection (39.45%), followed by socialising (31.00%) and travel (30.56%). However, by applying a logistic regression model to each reason for vaccination, it was possible to estimate the associations regarding age, sex, marital status, educational level, production sector, mass vaccination point, previous COVID-19 infection, and COVID-19 infection of a family member. RELEVANCE: The data generated will inform decisions and formulations of appropriate campaigns that will promote vaccination in specific population groups.

Sex Differences in Cardiovascular Prevention in Type 2: Diabetes in a Real-World Practice Database.

Women with type 2 diabetes mellitus (T2DM) have a 40% excess risk of cardiovascular diseases (CVD) compared to men due to the interaction between sex and gender factors in the development, risk, and outcomes of the disease. Our aim was to assess differences between women and men with T2DM in the management and degree of control of cardiovascular risk factors (CVRF). This was a matched cross-sectional study including 140,906 T2DM subjects without previous CVD and 39,186 T2DM subjects with prior CVD obtained from the System for the Development of Research in Primary Care (SIDIAP) database. The absolute and relative differences between means or proportions were calculated to assess sex differences. T2DM women without previous CVD showed higher levels of total cholesterol (12.13 mg/dL (0.31 mmol/L); 95% CI = 11.9−12.4) and low-density lipoprotein cholesterol (LDL-c; 5.50 mg/dL (0.14 mmol/L); 95% CI = 5.3−5.7) than men. The recommended LDL-c target was less frequently achieved by women as it was the simultaneous control of different CVRF. In secondary prevention, women showed higher levels of total cholesterol (16.89 mg/dL (0.44 mmol/L); 95% CI = 16.5−17.3), higher levels of LDL-c (8.42 mg/dL (0.22 mmol/L); 95% CI = 8.1−8.8), and higher levels of triglycerides (11.34 mg/dL (0.13 mmol/L); 95% CI = 10.3−12.4) despite similar rates of statin prescription. Recommended targets were less often achieved by women, especially LDL-c < 100 mg/dL (2.59 mmol/L). The composite control was 22% less frequent in women than men. In conclusion, there were substantial sex differences in CVRF management of people with diabetes, with women less likely than men to be on LDL-c target, mainly those in secondary prevention. This could be related to the treatment gap between genders.

High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial.

BACKGROUND: Convalescent plasma has been proposed as an early treatment to interrupt the progression of early COVID-19 to severe disease, but there is little definitive evidence. We aimed to assess whether early treatment with convalescent plasma reduces the risk of hospitalisation and reduces SARS-CoV-2 viral load among outpatients with COVID-19. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled trial in four health-care centres in Catalonia, Spain. Adult outpatients aged 50 years or older with the onset of mild COVID-19 symptoms 7 days or less before randomisation were eligible for enrolment. Participants were randomly assigned (1:1) to receive one intravenous infusion of either 250-300 mL of ABO-compatible high anti-SARS-CoV-2 IgG titres (EUROIMMUN ratio ≥6) methylene blue-treated convalescent plasma (experimental group) or 250 mL of sterile 0·9% saline solution (control). Randomisation was done with the use of a central web-based system with concealment of the trial group assignment and no stratification. To preserve masking, we used opaque tubular bags that covered the investigational product and the infusion catheter. The coprimary endpoints were the incidence of hospitalisation within 28 days from baseline and the mean change in viral load (in log10 copies per mL) in nasopharyngeal swabs from baseline to day 7. The trial was stopped early following a data safety monitoring board recommendation because more than 85% of the target population had received a COVID-19 vaccine. Primary efficacy analyses were done in the intention-to-treat population, safety was assessed in all patients who received the investigational product. This study is registered with ClinicalTrials.gov, NCT04621123. FINDINGS: Between Nov 10, 2020, and July 28, 2021, we assessed 909 patients with confirmed COVID-19 for inclusion in the trial, 376 of whom were eligible and were randomly assigned to treatment (convalescent plasma n=188 [serum antibody-negative n=160]; placebo n=188 [serum antibody-negative n=166]). Median age was 56 years (IQR 52-62) and the mean symptom duration was 4·4 days (SD 1·4) before random assignment. In the intention-to-treat population, hospitalisation within 28 days from baseline occurred in 22 (12%) participants who received convalescent plasma versus 21 (11%) who received placebo (relative risk 1·05 [95% CI 0·78 to 1·41]). The mean change in viral load from baseline to day 7 was -2·41 log10 copies per mL (SD 1·32) with convalescent plasma and -2·32 log10 copies per mL (1·43) with placebo (crude difference -0·10 log10 copies per mL [95% CI -0·35 to 0·15]). One participant with mild COVID-19 developed a thromboembolic event 7 days after convalescent plasma infusion, which was reported as a serious adverse event possibly related to COVID-19 or to the experimental intervention. INTERPRETATION: Methylene blue-treated convalescent plasma did not prevent progression from mild to severe illness and did not reduce viral load in outpatients with COVID-19. Therefore, formal recommendations to support the use of convalescent plasma in outpatients with COVID-19 cannot be concluded. FUNDING: Grifols, Crowdfunding campaign YoMeCorono.

Study of the sensitivity and specificity of smell and taste disorders as a predictive factor of SARS-CoV-2 infection among primary care healthcare professionals: a retrospective observational study.

BACKGROUND: Among the manifestations of COVID-19 are taste and smell disorders (TSDs). AIM: To evaluate the sensitivity and specificity of TSDs and other associated symptoms to estimate predictive values for determining SARS-CoV-2 infection. DESIGN & SETTING: A retrospective observational study of healthcare professionals in Catalonia, Spain. METHOD: A study of the sensitivity and specificity of TSDs has been carried out using the polymerase chain reaction (PCR) test for the diagnosis of SARS-CoV-2 as the gold standard value. Logistic regressions adjusted for age and sex were performed to identify additional symptoms that might be associated with COVID-19. RESULTS: The results are based on 226 healthcare workers with clinical symptoms suggestive of COVID-19, 116 with positive PCR and 110 with negative PCR. TSDs had an odds ratio (OR) of 12.4 (95% confidence interval [CI] = 6.3 to 26.2), sensitivity 60.3% and specificity 89.1%. In the logistic regression model, the association of TSD, fever or low-grade fever, shivering, dyspnoea, arthralgia, and myalgia obtained an area under the curve (AUC) of 85.7% (95% CI = 80.7 % to 90.7 %), sensitivity 82.8 %, specificity 80.0%, and positive predictive values 81.4% and negative 81.5%. CONCLUSION: TSDs are a strong predictor of COVID-19. The association of TSD, fever, low-grade fever or shivering, dyspnoea, arthralgia, and myalgia correctly predicts 85.7% of the results of the COVID-19 test.

Spike-based COVID-19 immunization increases antibodies to nucleocapsid antigen.

Antibodies to the nucleocapsid (N) antigen are suggested to be used to monitor infections after COVID-19 vaccination, as first generation subunit vaccines are based on the spike (S) protein. We used multiplex immunoassays to simultaneously measure antibody responses to different fragments of the SARS-CoV-2 S and N antigens for evaluating the immunogenicity of the mRNA-1273 (Spykevax) and the BNT162b2 (Comirnaty) vaccines in 445 health care workers. We report a >4-fold increase post-vaccination of IgG levels to the full length (N FL) and C-terminus of N (N CT) in 5.2% and 18.0% of individuals, respectively, and of IgA in 3.6% (N FL) and 9.0% (N CT) of them. The increase in IgG levels and avidity was more pronounced after Spykevax than Comirnaty vaccination (36.2% vs 13.1% for N CT, and 10.6% vs 3.7% for N FL). Data suggest the induction of cross-reactive antibodies against the N CT region after administering these S-based vaccines, and this should be taken into account when using N seropositivity to detect breakthroughs.

Characterization and Identification of Variations in Types of Primary Care Visits Before and During the COVID-19 Pandemic in Catalonia: Big Data Analysis Study.

BACKGROUND: The COVID-19 pandemic has turned the care model of health systems around the world upside down, causing the abrupt cancellation of face-to-face visits and redirection of the model toward telemedicine. Digital transformation boosts information systems-the more robust they are, the easier it is to monitor the health care system in a highly complex state and allow for more agile and reliable analysis. OBJECTIVE: The purpose of this study was to analyze diagnoses from primary care visits and distinguish between those that had higher and lower variations, relative to the 2019 and 2020 periods (roughly before and during COVID-19), to identify clinical profiles that may have been most impaired from the least-used diagnostic codes for visits during the pandemic. METHODS: We used a database from the Primary Care Services Information Technologies Information System of Catalonia. We analyzed the register of visits (n=2,824,185) and their International Classification of Diseases (ICD-10) diagnostic codes (n=3,921,974; mean 1.38 per visit), as approximations of the reasons for consultations, at 3 different grouping levels. The data were represented by a term frequency matrix and analyzed recursively in different partitions aggregated according to date. RESULTS: The increase in non-face-to-face visits (+267%) did not counterbalance the decrease in face-to-face visits (-47%), with an overall reduction in the total number of visits of 1.36%, despite the notable increase in nursing visits (10.54%). The largest increases in 2020 were visits with diagnoses related to COVID-19 (ICD-10 codes Z20-Z29: 2.540%), along with codes related to economic and housing problems (ICD-10 codes Z55-Z65: 44.40%). Visits with most of the other diagnostic codes decreased in 2020 relative to those in 2019. The largest reductions were chronic pathologies such as arterial hypertension (ICD-10 codes I10-I16: -32.73%) or diabetes (ICD-10 codes E08-E13: -21.13%), but also obesity (E65-E68: -48.58%) and bodily injuries (ICD-10 code T14: -33.70%). Visits with mental health-related diagnostic codes decreased, but the decrease was less than the average decrease. There was a decrease in consultations-for children, adolescents, and adults-for respiratory infections (ICD-10 codes J00-J06: -40.96%). The results show large year-on-year variations (in absolute terms, an average of 12%), which is representative of the strong shock to the health system. CONCLUSIONS: The disruption in the primary care model in Catalonia has led to an explosive increase in the number of non-face-to-face visits. There has been a reduction in the number of visits for diagnoses related to chronic pathologies, respiratory infections, obesity, and bodily injuries. Instead, visits for diagnoses related to socioeconomic and housing problems have increased, which emphasizes the importance of social determinants of health in the context of this pandemic. Big data analytics with routine care data yield findings that are consistent with those derived from intuition in everyday clinical practice and can help inform decision making by health planners in order to use the next few years to focus on the least-treated diseases during the COVID-19 pandemic.

Physical activity, emotional state and socialization in the elderly: study protocol for a clinical multicentre randomized trial.

OBJECTIVE: To evaluate whether a 4-month physical activity (PA) group program and visits to sociocultural organizations improve emotional state, social support levels and health-related quality of life in elderly individuals with depression and/or anxiety and/or loneliness. METHODS: This will be a multicentre, randomized, two-group clinical trial with a 1-year follow-up. Participants will be 150 primary care patients aged >64 years allocated equally to a control group and an intervention group. Inclusion criteria are Beck Depression Inventory (BDI-II) score ≥14 and/or General Anxiety Disorder (GAD-7) scale score ≥10 and/or Duke-UNC-11 scale score ≥32. The intervention group will participate in a 4-month group PA program. The program will comprise two walks per week and a monthly visit to a sociocultural facility. RESULTS: Measured outcomes are clinical remission of depression (BDI-II score <14) and anxiety (GAD-7 scale score <10), improved social support (reduction in DUKE-UNC-11 score), improved quality of life and/or response to the intervention at 4 and 12 months post-intervention. Intervention satisfaction and adherence and post-intervention links with sociocultural organizations will also be assessed. CONCLUSION: The findings could encourage the provision of activity-based community interventions for older individuals.

Persistence and baseline determinants of seropositivity and reinfection rates in health care workers up to 12.5 months after COVID-19.

We assessed the duration and baseline determinants of antibody responses to SARS-CoV-2 spike antigens and the occurrence of reinfections in a prospective cohort of 173 Spanish primary health care worker patients followed initially for 9 months and subsequently up to 12.5 months after COVID-19 symptoms onset. Seropositivity to SARS-CoV-2 spike and receptor-binding domain antigens up to 149-270 days was 92.49% (90.17% IgG, 76.3% IgA, 60.69% IgM). In a subset of 64 health care workers who had not yet been vaccinated by April 2021, seropositivity was 96.88% (95.31% IgG, 82.81% IgA) up to 322-379 days post symptoms onset. Four suspected reinfections were detected by passive case detection, two among seronegative individuals (5 and 7 months after the first episode), and one low antibody responder. Antibody levels significantly correlated with fever, hospitalization, anosmia/hypogeusia, allergies, smoking, and occupation. Stable sustainment of IgG responses raises hope for long-lasting COVID-19 vaccine immunity.

Role of the Scavenger Receptor CD36 in Accelerated Diabetic Atherosclerosis.

Diabetes mellitus entails increased atherosclerotic burden and medial arterial calcification, but the precise mechanisms are not fully elucidated. We aimed to investigate the implication of CD36 in inflammation and calcification processes orchestrated by vascular smooth muscle cells (VSMCs) under hyperglycemic and atherogenic conditions. We examined the expression of CD36, pro-inflammatory cytokines, endoplasmic reticulum (ER) stress markers, and mineralization-regulating enzymes by RT-PCR in human VSMCs, cultured in a medium containing normal (5 mM) or high glucose (22 mM) for 72 h with or without oxidized low-density lipoprotein (oxLDL) (24 h). The uptake of 1,1'-dioctadecyl-3,3,3',3-tetramethylindocarbocyanine perchlorate-fluorescently (DiI) labeled oxLDL was quantified by flow cytometry and fluorimetry and calcification assays were performed in VSMC cultured in osteogenic medium and stained by alizarin red. We observed induction in the expression of CD36, cytokines, calcification markers, and ER stress markers under high glucose that was exacerbated by oxLDL. These results were confirmed in carotid plaques from subjects with diabetes versus non-diabetic subjects. Accordingly, the uptake of DiI-labeled oxLDL was increased after exposure to high glucose. The silencing of CD36 reduced the induction of CD36 and the expression of calcification enzymes and mineralization of VSMC. Our results indicate that CD36 signaling is partially involved in hyperglycemia and oxLDL-induced vascular calcification in diabetes.

Assessment of Inner Retinal Layers and Choroidal Thickness in Type 1 Diabetes Mellitus: A Cross-Sectional Study.

Recent studies have shown that retinal neurodegeneration may precede visible vascular changes in diabetic retinopathy (DR). In addition, the relationship of choroidal thickness (CT) with DR stage is not well defined. To assess the inner retinal and choroidal structural changes in type 1 diabetic subjects (T1D), a cross-sectional study was conducted in 242 T1D patients and in 69 age-matched, non-diabetic individuals. The nasal retinal nerve fibre layer (RNFL) thickness was lower in T1D patients without DR (p < 0.001), with mild DR (p < 0.001), and with advanced DR (p < 0.001) compared to control subjects. The ganglion cell layer (GCL) thickness was lower in T1D patients with advanced DR compared to those with mild DR (p = 0.003) and without DR (p < 0.001) and compared to the control subjects (p < 0.001). T1D subjects with no DR and mild DR had higher CT than the control subjects, but the CT in T1D patients with advanced DR was lower (p = 0.038) than that in T1D subjects with mild DR and was not significantly different from that of the control subjects. In conclusion, T1D subjects showed a significant thinning of the nasal RNFL in the early stages of the disease, even before any vascular changes in the retina. A decrease in the GCL thickness during advanced DR stages was observed. Choroidal thickness was higher in T1D subjects without DR and in early DR stages but decreased in advanced stages.

Development and Validation of a Simplified Magnetic Resonance Index of Activity for Crohn's Disease.

BACKGROUND & AIMS: The magnetic resonance index of activity (MARIA) for Crohn's disease (CD) is used to assess the activity of luminal CD. However, it has a number of practical limitations. We aimed to develop and validate a simplified MARIA to more easily and quickly assess CD activity and response to therapy. PATIENTS AND METHODS: We performed a retrospective analysis of magnetic resonance imaging data from 98 participants in 2 studies. We used logistic regression analysis to identify magnetic resonance imaging parameters independently associated with CD endoscopic index of severity (CDEIS) scores (the reference standard). We validated the responsiveness and reliability of the simplified MARIA in an independent cohort of 37 patients who underwent magnetic resonance imaging and endoscopy before and after a therapeutic intervention. RESULTS: Logistic regression analysis showed that dichotomous qualitative assessment of wall thickening (>3 mm), presence of mural edema, perienteric fat stranding, and ulcers were independently associated with CDEIS scores; we used these factors to create a simplified MARIA. Simplified MARIA scores greater than 1 identified segments with active CD with 90% sensitivity and 81% specificity (area under the curve 0.91; 95% confidence interval 0.88-0.94). Simplified MARIA scores of 2 or more detected severe lesions (ulcers) with 85% sensitivity and 92% specificity (area under the curve 0.94; 95% confidence interval 0.91-0.96). For each patient, there was a high level of correlation between simplified MARIA scores and CDEIS scores (r = 0.83) and simplified MARIA scores and original MARIA scores (and r = 0.93) (P < .001). The simplified MARIA score accurately detected changes in lesion severity in response to therapy and was as reliable as endoscopy for the assessment of mucosal healing. CONCLUSION: We developed and validated a simplified MARIA for easier and faster assessment of CD activity and severity. This index identifies patients with a response to therapy with a high level of accuracy. These findings require confirmation in independent, multireader studies.

Ultrasound Tissue Characterization of Carotid Plaques Differs Between Patients with Type 1 Diabetes and Subjects without Diabetes.

The aim of the study was to investigate ultrasound tissue characterization of carotid plaques in subjects with and without diabetes type 1 (T1D). B-mode carotid ultrasound was performed to assess the presence and type of plaque in a group of 340 subjects with and 304 without T1D, all of them without cardiovascular disease. One hundred and seven patients with T1D (49.5% women; age 54 ± 9.8 years) and 67 control subjects without diabetes who had at least one carotid plaque were included in the study. The proportion of subjects who had only echolucent plaques was reduced in the group of patients with T1D (48.6% vs. 73.1%). In contrast, the proportion with only echogenic (25.2% vs. 7.5%) and calcified plaques (9.4% vs. 1.5%) was increased compared with subjects without diabetes. Moreover, having at least one echogenic plaque was more frequent in T1D patients compared with subjects without diabetes (49.5% vs. 26.9% p = 0.005). In addition to diabetes (OR 2.28; p = 0.026), age (OR 1.06, p = 0.002) was the other variable associated with echogenic plaque existence in multiple regression analysis. Patients with T1D exhibit a differential pattern of carotid plaque type compared with subjects without diabetes, with an increased frequency of echogenic and extensively calcified plaques.