Development and validation of a model to predict ceiling of care in COVID-19 hospitalized patients.

BACKGROUND: Therapeutic ceiling of care is the maximum level of care deemed appropiate to offer to a patient based on their clinical profile and therefore their potential to derive benefit, within the context of the availability of resources. To our knowledge, there are no models to predict ceiling of care decisions in COVID-19 patients or other acute illnesses. We aimed to develop and validate a clinical prediction model to predict ceiling of care decisions using information readily available at the point of hospital admission. METHODS: We studied a cohort of adult COVID-19 patients who were hospitalized in 5 centres of Catalonia between 2020 and 2021. All patients had microbiologically proven SARS-CoV-2 infection at the time of hospitalization. Their therapeutic ceiling of care was assessed at hospital admission. Comorbidities collected at hospital admission, age and sex were considered as potential factors for predicting ceiling of care. A logistic regression model was used to predict the ceiling of care. The final model was validated internally and externally using a cohort obtained from the Leeds Teaching Hospitals NHS Trust. The TRIPOD Checklist for Prediction Model Development and Validation from the EQUATOR Network has been followed to report the model. RESULTS: A total of 5813 patients were included in the development cohort, of whom 31.5% were assigned a ceiling of care at the point of hospital admission. A model including age, COVID-19 wave, chronic kidney disease, dementia, dyslipidaemia, heart failure, metastasis, peripheral vascular disease, chronic obstructive pulmonary disease, and stroke or transient ischaemic attack had excellent discrimination and calibration. Subgroup analysis by sex, age group, and relevant comorbidities showed excellent figures for calibration and discrimination. External validation on the Leeds Teaching Hospitals cohort also showed good performance. CONCLUSIONS: Ceiling of care can be predicted with great accuracy from a patient's clinical information available at the point of hospital admission. Cohorts without information on ceiling of care could use our model to estimate the probability of ceiling of care. In future pandemics, during emergency situations or when dealing with frail patients, where time-sensitive decisions about the use of life-prolonging treatments are required, this model, combined with clinical expertise, could be valuable. However, future work is needed to evaluate the use of this prediction tool outside COVID-19.

Stability mapping of bipartite tight-binding graphs with losses and gain: PTPT-symmetry and beyond.

We consider bipartite tight-binding graphs composed by N nodes split into two sets of equal size: one set containing nodes with on-site loss, the other set having nodes with on-site gain. The nodes are connected randomly with probability p. Specifically, we measure the connectivity between the two sets with the parameter α, which is the ratio of current adjacent pairs over the total number of possible adjacent pairs between the sets. For general undirected-graph setups, the non-Hermitian Hamiltonian H(γ,α,N) of this model presents pseudo-Hermiticity, where γ is the loss/gain strength. However, we show that for a given graph setup H(γ,α,N) becomes PT-symmetric. In both scenarios (pseudo-Hermiticity and PT-symmetric), depending on the parameter combination, the spectra of H(γ,α,N) can be real even when it is non-Hermitian. Then we demonstrate, for both setups, that there is a well-defined sector of the γα-plane (which grows with N) where the spectrum of H(γ,α,N) is predominantly real.

Achievements and challenges in the health of Mexican women, 1990 and 2019: ecological analysis based on the global burden of disease data.

OBJECTIVES: To describe the burden and causes of disease in Mexican women in 1990 and 2019, based on the data disaggregation by age groups and states. Also, to evaluate the relationship of years of healthy life lost with the Socio-demographic Index (SDI) and with the Healthcare Access and Quality (HAQ) Index. STUDY DESIGN: This was an ecological descriptive study. METHODS: Based on the Global Burden of Disease, Injuries, and Risk Factors Study study, the age-standardized and age-specific rates for mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) were reported. RESULTS: At the national level, the all-cause age-standardized rates for Mexican women decreased in mortality -28.8%; YLLs -39.8%; YLDs -1.3%; and DALYs -26.2%. For 2019, the indicators analyzed had the worst performances in Chiapas and Chihuahua, while women in Sinaloa had the lowest age-standardized rates. In 1990, it is worth noting that there was a remarkable presence of CDs, mainly in YLLs. In all age groups, diabetes mellitus was the leading cause of DALYs in Mexico's 32 states, followed by CKD (in 24 states), and ischemic heart disease (in 18 states). In both 1990 and 2019, a negative and statistically significant correlation between DALYs and the HAQ Index was evident. The correlation between DALYs and the SDI was only significant in 1990. CONCLUSION: In the last 30 years, the burden of disease on Mexican women has undergone substantial changes that reflect progress in the improvement of their health conditions. However, the current scenario is complex because the convergence of communicable diseases, non-communicable diseases, and injuries is evident, which implies important challenges that must be addressed as soon as possible.

Plant-parasitic Nematodes Associated with Grasses Grown for Seed in the Willamette Valley of Oregon.

Plant-parasitic nematodes (PPN) are an understudied pathogen group in the Oregon cool-season grass seed cropping system. In this survey, the PPN associated with annual ryegrass, bentgrass, fine fescue, orchardgrass, perennial ryegrass, and tall fescue were determined. Thirty-seven fields were sampled in the 2022 or 2023 growing season by collecting 10 soil cores in each of six 100-m transects for nematode extraction and visual identification. PerMANOVA testing indicated significant differences in PPN community composition across grass host and sampling time. Pratylenchus and Meloidogyne were the most commonly encountered nematodes, with maximum population densities of 1,984 and 2,496 nematodes/100 g soil, respectively. Sequencing of the COX1 gene region indicated the presence of P. crenatus, P. fallax, P. neglectus, P. penetrans, and P. thornei, with some of these species being detected for the first time on these grass hosts. The only Meloidogyne sp. found in these grasses was M. nassi, based upon sequencing of the ITS gene region. This first-of-its-kind survey indicates the need for further assessment of the impact of these PPNs on yield and stand longevity in cool-season grass seed fields in Oregon.

Nuclear Charge Radius of

Collinear laser spectroscopy was performed on the isomer of the aluminium isotope ^{26m}Al. The measured isotope shift to ^{27}Al in the 3s^{2}3p ^{2}P_{3/2}^{○}→3s^{2}4s ^{2}S_{1/2} atomic transition enabled the first experimental determination of the nuclear charge radius of ^{26m}Al, resulting in R_{c}=3.130(15) fm. This differs by 4.5 standard deviations from the extrapolated value used to calculate the isospin-symmetry breaking corrections in the superallowed ß decay of ^{26m}Al. Its corrected Ft value, important for the estimation of V_{ud} in the Cabibbo-Kobayashi-Maskawa matrix, is thus shifted by 1 standard deviation to 3071.4(1.0) s.

Carriage of multidrug-resistant Gram-negative bacilli: duration and risk factors.

Identification of risk factors influencing the duration of carriage of multidrug-resistant Gram-negative bacilli (MDR-GNB) may be useful for infection control. The aim of this study is to estimate the impact of several factors collected for routine hospital surveillance on the duration of carriage of selected MDR-GNB. From January 2015 to July 2021, patients with at least two clinical/surveillance samples positive for MDR-GNB different from ESBL-producing E. coli or AmpC - exclusively producing Enterobacterales were assessed. Microorganisms, age, number of admissions, clinical or rectal sample, sex, and admission service were evaluated as risk factors. Multivariate analysis was performed by a Cox proportional hazard model. A total of 1981 episodes of colonization were included. Involved microorganisms were ESBL-Klebsiella pneumoniae (KP) in 1057 cases (53.4%), other ESBL-non-E. coli Enterobacterales in 91 (4.6%), OXA-48-KP in 263 (13.3%), KPC-KP in 90 (4.5%), VIM-KP in 29 (1.5%), carbapenemase-producing non-KP Enterobacterales (CP-non-KP) in 124 (6.3%), and MDR Pseudomonas aeruginosa (MDR-PAER) in 327 (16.5%). No differences in duration of colonization were observed among ESBL-KP (median colonization time 320 days), ESBL-non-E. coli Enterobacterales (226 days), OXA48-KP (305 days), and MDR-PAER (321 days). For each group, duration of colonization was significantly longer than that of KPC-KP (median colonization time 60 days), VIM-KP (138 days), and CP-non-KP (71 days). Male sex (HR = 0.88; 95% CI 0.78-0.99), detection in Hepatology-Gastroenterology (HR = 0.71; 95% CI 0.54-0.93), clinical sample (HR = 0.61; 95% CI 0.53-0.69), and > 2 admissions after first detection (HR = 0.47; 95% CI 0.42-0.52) were independent predictors of longer carriage, whereas VIM-KP (HR = 1.61; 95% CI 1.04-2.48), KPC-KP (HR = 1.85; 95% CI 1.49-2.3), and CP-non-KP (HR = 1.92; 95% CI 1.49-2.47) were associated with shorter colonization time. Duration of colonization was significantly longer for ESBL-KP, other ESBL-non-E. coli Enterobacterales, OXA-48-KP, and MDR-PAER. For these microorganisms, prolonging surveillance up to 2.5-3 years should be considered. Male sex, clinical sample, multiple readmissions, admission service, and type of microorganism are independent predictors of the duration of carriage.

Lower uterine segment thickness assessed by transvaginal ultrasound before labor induction: reproducibility analysis and relationship with delivery outcome.

OBJECTIVES: To evaluate the reproducibility of lower uterine segment (LUS) thickness measurement before induction of labor (IOL), and to assess the relationship between LUS thickness and IOL outcomes. METHODS: This was a prospective cohort study of pregnant women undergoing IOL at term, conducted in a single tertiary hospital between July 2014 and February 2017. Women with a singleton pregnancy at ≥ 37 weeks' gestation, with a live fetus in cephalic presentation and a Bishop score of ≤ 6, were eligible for inclusion. Both nulliparous and parous women, and those with a previous Cesarean section (CS), were eligible. All women underwent transvaginal ultrasound assessment before IOL admission, and cervical length and LUS thickness were measured offline after delivery. Maternal and obstetric characteristics and Bishop score were recorded. The main outcome was the overall rate of CS after IOL, and secondary outcomes were CS for either failure to progress in the active phase of labor or failed IOL, and CS for failed IOL only. Interobserver agreement for measurement of LUS thickness between two operators was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis with the ANOVA test to evaluate systematic bias. Univariable and multivariable analysis were employed to evaluate the relationship between clinical and sonographic characteristics and IOL outcomes. RESULTS: Of 265 women included in the analysis, 195 (73.6%) had a vaginal delivery and 70 (26.4%) required a CS after IOL. Reproducibility analysis showed excellent interobserver agreement for the measurement of LUS thickness (ICC, 0.96 (95% CI, 0.93-0.98)). On Bland-Altman analysis, the mean difference in LUS thickness between the two operators was 0.15 mm (95% limits of agreement, -1.84 to 2.14 mm), and there was no evidence of systematic bias (ANOVA test, P = 0.46). Univariable analysis showed that LUS thickness was associated significantly with overall CS (P = 0.002), CS for failure to progress in the active phase of labor or failed IOL (P = 0.03) and CS for failed IOL (P = 0.037). On multivariable logistic regression analysis, LUS thickness was an independent predictive factor for overall CS (odds ratio (OR), 1.149 (95% CI, 1.031-1.281)) and CS for failure to progress in the active phase of labor or failed IOL (OR, 1.226 (95% CI, 1.039-1.445)). CONCLUSIONS: In women undergoing IOL at term, measurement of LUS thickness is feasible and reproducible, and is associated significantly with IOL outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Effects of bisphenol F, bisphenol S, and bisphenol AF on cultured human osteoblasts.

Bisphenol A (BPA) analogs, like BPA, could have adverse effects on human health including bone health. The aim was to determine the effect of BPF, BPS and BPAF on the growth and differentiation of cultured human osteoblasts. Osteoblasts primary culture from bone chips harvested during routine dental work and treated with BPF, BPS, or BPAF for 24 h at doses of 10-5, 10-6, and 10-7 M. Next, cell proliferation was studied, apoptosis induction, and alkaline phosphatase (ALP) activity. In addition, mineralization was evaluated at 7, 14, and 21 days of cell culture in an osteogenic medium supplemented with BP analog at the studied doses. BPS treatment inhibited proliferation in a dose-dependent manner at all three doses by inducing apoptosis; BPF exerted a significant inhibitory effect on cell proliferation at the highest dose alone by an increase of apoptosis; while BPAF had no effect on proliferation or cell viability. Cell differentiation was adversely affected by treatment with BPA analogs in a dose-dependent, observing a reduction in calcium nodule formation at 21 days. According to the results obtained, these BPA analogs could potentially pose a threat to bone health, depending on their concentration in the organism.

Physical and physiological effects of dobutamine stress echocardiography in low-gradient aortic stenosis.

Dobutamine stress echocardiography (DSE) is a useful tool for assessing low-gradient significant aortic stenosis (AS) and contractile reserve (CR), but its prognostic utility has become controversial in recent studies. We evaluated the impact of DSE on aortic valve physiological, structural, and left ventricular parameters in low-gradient AS. Consecutive patients undergoing DSE for low-gradient AS evaluation from September 2010 to July 2016 were retrospectively studied, and DSE findings were divided into four groups: with and without severe AS and/or CR. Relationships between left ventricular chamber quantification, CR, aortic valve Doppler during DSE, and calcium score [by computerized tomography (CT)] were analyzed. There were 258 DSE studies performed on 243 patients, mean age 77.6 ± 10.8 yr and 183 (70.1%) were males. With increasing dobutamine dose, apart from systolic blood pressure, left ventricular ejection fraction, flow, cardiac power output, and longitudinal strain magnitude, along with aortic valve area and mean aortic gradient were all significantly increased (P < 0.05). Flow and mean gradient increased in both the presence and absence of CR, whereas stroke volume and aortic valve area increased mainly in those with CR only. The aortic valve area increased in both patients with low and high calcium scores; however, the baseline area was lower in those with a higher calcium score. During DSE, aortic valve area increases with increase in aortic valve gradient. Higher calcium score is associated with lower baseline aortic valve area, but the aortic valve area still increases with dobutamine even in presence of a high calcium score.NEW & NOTEWORTHY We show that even in most severe aortic stenosis, there is some residual valve pliability. This suggests that a complete loss of pliability is not compatible with survival.

Nuclear Charge Radii of the Nickel Isotopes

Collinear laser spectroscopy is performed on the nickel isotopes ^{58-68,70}Ni, using a time-resolved photon counting system. From the measured isotope shifts, nuclear charge radii R_{c} are extracted and compared to theoretical results. Three ab initio approaches all employ, among others, the chiral interaction NNLO_{sat}, which allows an assessment of their accuracy. We find agreement with experiment in differential radii δ⟨r_{c}^{2}⟩ for all employed ab initio methods and interactions, while the absolute radii are consistent with data only for NNLO_{sat}. Within nuclear density functional theory, the Skyrme functional SV-min matches experiment more closely than the Fayans functional Fy(Δr,HFB).

Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015-04 (PANGEA-Breast) study.

BACKGROUND: We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. METHODS: HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. RESULTS: Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon's design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5-32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. CONCLUSION: Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit. TRIAL REGISTRATION: ClinicalTrials.gov and EudraCT (NCT03025880 and 2016-001,779-54, respectively). Registration dates: 20/01/2017 and 18/11/2016, respectively.

Detection of nonpregnant cows and potential embryo losses by color Doppler ultrasound and interferon-stimulated gene expression in grazing dairy cows.

Many studies have been conducted to estimate pregnancy losses between 19 and 34 d after artificial insemination (AI) in dairy cows managed under confinement-based systems, but few studies have examined embryo mortality during this interval in dairy cows managed under gazing systems. The objectives of this prospective cohort study were (1) to assess the diagnostic value of the corpus luteum (CL) blood perfusion (BP) evaluation by Doppler ultrasound (US) to detect nonpregnant cows at 19 to 20 d post-AI, and (2) to assess the rate of potential embryo mortality between 19 to 34 d post-AI. The CL-BP of all cows included in the study (n = 131) was examined on farm by power and color mode of Doppler US and later using an image processing software by a second evaluator. The endometrium thickness and echotexture were evaluated by B-mode US at the same visit to assess if the nonpregnancy diagnosis could be improved at 19 to 20 d post-AI by this additional diagnostic tool. Blood samples were obtained at 19 to 20 d post-AI for progesterone (P4) measurement by chemiluminescence and to determine the mRNA expression of ISG by real-time PCR. Pregnancy diagnosis based on embryo visualization was performed at 33 to 34 d post-AI by US B-mode. In parallel interpretation, ISG15 and MX2 mRNA expression in leukocytes [sensitivity (Se), 100%] were regarded as suitable biomarkers for early pregnancy and were selected for molecular characterization of pregnancy at 19 to 20 d post-AI. At 19 to 20 d post-AI, 61.1% of the cows had positive CL-BP by Doppler US (Se, 98.0%), 62.7% had ISG mRNA expression in leukocytes over the cutoff point (Se, 95.7%), and 50.8% were positive, based on the combination of ISG mRNA expression, CL-BP by Doppler US, and P4 concentration (Se, 100%), and were considered as possible pregnant. At 33 to 34 d, the pregnancy rate was 37.4% diagnosed by the B-mode US. Based on the expression of the selected biomarkers in cows with active CL, we found that 28.1% of the cows could have potentially lost their pregnancy between 19 and 34 d post-AI. The Doppler US color mode showed similar accuracy and a higher negative predictive value than the genes selected as biomarkers. The additional B-mode ultrasound evaluation of the uterine stratum vasculare and the endometrium thickness improved the diagnostic accuracy. Therefore, assessing the CL-BP by Doppler US allowed early detection of nonpregnant cows at 19 to 20 d post-AI. The combination of early CL-BP by Doppler US (d 19 to 20) with early embryo detection by B-mode US (d 33-34) could be used to facilitate earlier rebreeding of dairy cows.

First-generation BNT162b2 and AZD1222 vaccines protect from COVID-19 pneumonia during the Omicron variant emergence.

OBJECTIVE: This study aimed to identify factors predicting pneumonia in adults with coronavirus disease 2019 (COVID-19) during the Omicron variant (B.1.1.529) emergence. We also evaluated, in fully vaccinated (BNT162b2 or AZD1222) individuals, if the time (<6 or ≥6 months) elapsed since the last shot was received was associated with the risk of severe illness. STUDY DESIGN: A retrospective cohort study was conducted in Mexico. METHODS: Data from 409,493 were analyzed, and risk ratios (RRs) and 95% confidence intervals (CIs) were computed through generalized linear models. RESULTS: We documented a total of 3513 COVID-19 pneumonia cases (69.5 per 100,000 person-days). In multiple analyses, a protective effect was observed in vaccinated adults (RR = 0.996, 95% CI 0.995-0.997). Male gender, increasing age, and smoking were associated with a greater risk of pneumonia. Individuals with chronic comorbidities (pulmonary obstructive disease, type 2 diabetes mellitus, arterial hypertension, kidney disease, and immunosuppression) were also at higher risk. Among fully vaccinated subjects (n = 166,869), those who had received the last shot at 6 more months were at increased risk for developing pneumonia (RR = 1.002, 95% CI 1.001-1.003). CONCLUSIONS: Our results suggest that the first-generation BNT162b2 and AZD1222 vaccines reduce the risk of COVID-19 pneumonia during the Omicron emergence. We also found that adults with longer interval from the administration of the second shot to illness onset were at increased risk of severe manifestations.

Decreased risk of COVID-19 pneumonia in children and adolescents during the Delta variant emergence.

OBJECTIVES: This study aimed to evaluate factors associated with the risk of COVID-19 pneumonia in children (aged <10 years) and adolescents (aged 10-19 years) before (March 2020-April 2021) and during (May-July 2021) the Delta (B.1.617.2) variant emergence. STUDY DESIGN: A retrospective and nationwide cohort study was conducted in Mexico. METHODS: Data from 26,961 laboratory-confirmed cases of COVID-19 were analyzed. Risk ratios (RRs) and 95% confidence intervals (CIs) were used to evaluate the association of the evaluated exposures with the risk of COVID-19 pneumonia. RESULTS: The overall incidence rate of pneumonia was 23.0 per 10,000 person-days, and it was lower during the Delta variant emergence (30.3 vs. 9.4 person-days, p < 0.001). In multiple analysis, a decreased risk of pneumonia was observed among those cases occurring in May 2021 or later (vs. March 2020-April 2021, RR = 0.98, 95% CI 0.97-0.99) and among older patients (RRper year = 0.998, 95% CI 0.996-0.998). Other comorbidities (namely, obesity, chronic kidney disease, diabetes mellitus, immunosuppression, or malignant tumors) were associated with an increased risk of severe COVID-19 manifestations. CONCLUSIONS: Our findings suggest that during the Delta variant emergence, children and adolescent patients were at reduced risk of COVID-19 pneumonia in Mexico. Further research is needed to identify factors determining the observed scenario.

Prevalence of three Mycoplasma sp. by multiplex PCR in cattle with and without respiratory disease in central Mexico.

This study aimed to identify Mycoplasma bovis, Myc. dispar, and Myc. bovirhinis, which are involved in bovine respiratory disease through a multiplex PCR as an alternative to culture's features that hamper Mycoplasma isolation. Nasal swabs were taken from 335 cattle with and without respiratory disease background (RDB) from dairy herds in the central region of Mexico. Each sample was divided in two; the first part was processed for the direct DNA extraction of the nasal swab and the second for Mycoplasma isolation, culture, and then the multiplex PCR was performed. In the nasal swabs, Myc. bovis was identified in 21.1%; Myc. dispar, in 11.8%; and Myc. bovirhinis, in 10.8% in cattle with RDB. Isolates were identified as Myc. bovis, 20.1%; Myc. dispar, 11.8%; and Myc. bovirhinis, 6.1%. There is a strong correlation between the presence of Mycoplasma identified by PCR and the clinical history of the disease (ρ < 0.0000). In animals without RDB, Myc. bovirhinis was the only species detected in 6.1% of the samples processed directly for multiplex PCR, and in 2% of the isolates. There is an excellent correlation (kappa 0.803) between the isolation and the 16S PCR and a high correlation (kappa 0.75) between the isolation and the multiplex PCR. Therefore, we conclude that the PCR multiplex test is highly sensitive and may be used for the diagnosis and surveillance of the three species in biological samples and mycoplasma isolates.

Moderate to Severe Psoriasis in Pediatric and Young Patients: The BIOBADADERM Registry Experience. / Psoriasis moderada-grave en pacientes pediátricos y jóvenes: experiencia en el registro BIOBADADERM.

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. They had mean age of 16.1 years on starting treatment. When the registry was started, they had a Psoriasis Area and Severity Index of 9.4 and 67% were being treated with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs.

Examining if the relationship between BMI and incident type 2 diabetes among middle-older aged adults varies by race/ethnicity: evidence from the Multi-Ethnic Study of Atherosclerosis (MESA).

AIMS: Disparities persist on the prevalence of undiagnosed type 2 diabetes in racial/ethnic minorities in the USA. This study evaluated the association between BMI and incident type 2 diabetes risk by racial/ethnic group, to determine whether BMI and presence of type 2 diabetes risk factors may help clinicians better target type 2 diabetes screening. METHODS: This prospective cohort analysis included 5659 adults free of type 2 diabetes at baseline from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort (2000-2011). BMI was measured at baseline and time-updated at subsequent visits. Incident type 2 diabetes was defined as fasting glucose ≥ 7.0 mmol/l, or use of any diabetes medications. RESULTS: The mean (sd) age was 62 (10) years and 42% of participants were white, 26% African American, 20% Hispanic and 12% Chinese American. During follow-up, 696 (12%) new type 2 diabetes cases were observed. In age- and sex-adjusted models, in the presence of one or more type 2 diabetes risk factors (the most common scenario), a 10% risk of incident type 2 diabetes was observed at a BMI of 21.7 kg/m2 [95% confidence interval (CI) 20.1 to 22.8] in Chinese Americans, 23.8 kg/m2 (22.7 to 24.9) in Hispanics, 24.7 kg/m2 (23.7 to 25.6) in African Americans and 26.2 kg/m2 (25.1 to 26.9) in white participants. CONCLUSIONS: This study supports including BMI and presence of type 2 diabetes risk factors as action points for clinicians to prioritize which adults aged ≥ 45 years should be screened. The application of race/ethnicity-specific BMI thresholds may reduce the disparity of undiagnosed type 2 diabetes observed in minority groups.

Stimulation of brown adipose tissue by polyphenols in extra virgin olive oil.

Obesity is one of the main public health problems of the 21st century resulting from an imbalance between calorie intake and energy expenditure. Currently, the search for new treatments against this pathology has become a priority. One of the therapeutic strategies against obesity could be the activation of brown adipose tissue through different molecules such as the phenolic compounds of extra virgin olive oil (EVOO). The objective of this review was to provide an update of scientific knowledge on the relationship between EVOO phenolic compounds and brown adipose tissue.According to this review, it has been demonstrated that extra virgin olive oil phenolic compounds can have beneficial effects on obesity by activating brown adipose tissue and enhance thermogenesis through different signaling pathways mediated by molecules such as AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α) or sirtuin 1 (Sirt1).

Improvement in dyspareunia after vaginal mesh removal measured by a validated questionnaire.

INTRODUCTION AND HYPOTHESIS: The objective was to examine the effect of the surgical removal of vaginally placed prolapse and incontinence mesh on sexual function. We hypothesize that patients with painful complications of mesh will experience improvement in dyspareunia and sexual function after mesh removal. METHODS: The eligible cohort consisted of 133 women who presented with a new onset of pain attributed to mesh-augmented incontinence or prolapse surgery and who elected to undergo mesh removal between 1 August 2012 and 1 July 2013. Sexual function symptoms were assessed before and after mesh removal surgery using the Pelvic Organ Prolapse and Urinary Incontinence Sexual Function Questionnaire short form (PISQ-12). Multivariate analysis was performed to identify predictors of improvement in dyspareunia. RESULTS: Ninety-four patients undergoing mesh removal completed a pre-operative questionnaire, 63 of whom also completed a post-operative questionnaire. After mesh removal, there was a nearly 50% reduction in the proportion of women reporting always experiencing post-operative pain with intercourse among those experiencing pre-operative pain. There was a statistically significant quantitative improvement in pain with intercourse after mesh removal based on mean change score of PISQ-12 question 5 "How often do you experience pain with intercourse?". In multivariate analysis, only history of vaginal delivery was associated with symptom improvement. CONCLUSION: Removal of transvaginal prolapse mesh is associated with improvement in self-reported dyspareunia based on a standardized question on a validated instrument in a small cohort of women. Although larger studies are needed to confirm the relationship between mesh-augmented surgeries and post-procedural dyspareunia, these data suggest that consideration of mesh removal is a reasonable step for patients with painful intercourse attributed to mesh-augmented prolapse and incontinence surgeries.

An adventitious agent-free clonal cell line that is highly susceptible to foot -and-mouth disease virus.

Porcine LFBKαVß6 cells have been successfully used for diagnostics and propagation of all FMDV serotypes/subtypes. Unfortunately, after initial characterization, these cells showed contamination with bovine viral diarrhea virus (BVDV), a non-cytopathic adventitious agent. Persistent infection with BVDV could interfere with diagnostic tests and, also prevent consideration for other uses, i.e., vaccine production. In this study, we developed a three-prong methodology to completely remove BVDV from LFBKαVß6 cells. Combined treatment with siRNA against BVDV NS5A, porcine interferon alpha and ribavirin resulted in the elimination of BVDV, as determined by immunohistochemistry analysis, quantitative RT-PCR and RNA sequencing. Importantly, elimination of BVDV from LFBKαVß6 did not affect FMDV growth and plaque phenotype from different serotypes isolated and propagated in the clean cell line, newly named MGPK αVß6-C5. Additionally, isolation of FMDV from field oro-pharyngeal samples, was successful at the same sensitivity as in BVDV-contaminated LFBKαVß6 cells. Our results identified a direct method to efficiently eliminate BVDV from porcine cells without altering FMDV permissiveness, diagnostic value, or potential for use in vaccine production. Furthermore, these cells may provide an improved platform for diagnostics and propagation of other viruses of interest in the veterinary field and the virology community at large.