Comorbidity, poverty and social vulnerability as risk factors for mortality in pregnant women with confirmed SARS-CoV-2 infection: analysis of 13 062 positive pregnancies including 176 maternal deaths in Mexico.

OBJECTIVE: Mortality in pregnancy due to coronavirus disease 2019 (COVID-19) is a current health priority in developing countries. Identification of clinical and sociodemographic risk factors related to mortality in pregnant women with COVID-19 could guide public policy and encourage such women to accept vaccination. We aimed to evaluate the association of comorbidities and socioeconomic determinants with COVID-19-related mortality and severe disease in pregnant women in Mexico. METHODS: This is an ongoing nationwide prospective cohort study that includes all pregnant women with a positive reverse-transcription quantitative polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Mexican National Registry of Coronavirus. The primary outcome was maternal death due to COVID-19. The association of comorbidities and socioeconomic characteristics with maternal death was explored using a log-binomial regression model adjusted for possible confounders. RESULTS: There were 176 (1.35%) maternal deaths due to COVID-19 among 13 062 consecutive SARS-CoV-2-positive pregnant women. Maternal age, as a continuous (adjusted relative risk (aRR), 1.08 (95% CI, 1.05-1.10)) or categorical variable, was associated with maternal death due to COVID-19; women aged 35-39 years (aRR, 3.16 (95% CI, 2.34-4.26)) or 40 years or older (aRR, 4.07 (95% CI, 2.65-6.25)) had a higher risk for mortality, as compared with those aged < 35 years. Other clinical risk factors associated with maternal mortality were pre-existing diabetes (aRR, 2.66 (95% CI, 1.65-4.27)), chronic hypertension (aRR, 1.75 (95% CI, 1.02-3.00)) and obesity (aRR, 2.15 (95% CI, 1.46-3.17)). Very high social vulnerability (aRR, 1.88 (95% CI, 1.26-2.80)) and high social vulnerability (aRR, 1.49 (95% CI, 1.04-2.13)) were associated with an increased risk of maternal mortality, while very low social vulnerability was associated with a reduced risk (aRR, 0.47 (95% CI, 0.30-0.73)). Being poor or extremely poor were also risk factors for maternal mortality (aRR, 1.53 (95% CI, 1.09-2.15) and aRR, 1.83 (95% CI, 1.32-2.53), respectively). CONCLUSION: This study, which comprises the largest prospective consecutive cohort of pregnant women with COVID-19 to date, has confirmed that advanced maternal age, pre-existing diabetes, chronic hypertension, obesity, high social vulnerability and low socioeconomic status are risk factors for COVID-19-related maternal mortality. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

In cardiac fibroblasts, interferon-beta attenuates differentiation, collagen synthesis, and TGF-ß1-induced collagen gel contraction.

Cardiac fibroblasts (CF) play a key role in the homeostasis of the extracellular matrix in cardiac tissue and are newly recognized as inflammatory supporter cells. Besides, CF-to-Cardiac myofibroblast differentiation is commanded by TGF-b, through SMAD signaling pathways, and these last cells are strongly implicated in cardiac fibrosis. In the heart IFN-ß is produced by CF; however, the role of IFN-ß, STAT proteins, and STAT-homo or heterodimers in the regulation of CF function with or without a fibrotic environment is unknown. CF were isolated from hearts of adult rats, and by western blot analysis we studied STAT1, STAT2, and STAT3 phosphorylation and through specific siRNA against these proteins we analyzed their role in CF functions such as differentiation (α-SMA expression); and pro-collagen type-I synthesis and secretion expression levels; collagen gels contraction and CF migration. In cultured adult rats CF, IFN-ß increases phosphorylation of STAT1, STAT2, and STAT3. Both STAT1 and STAT2 were involved in decreasing α-SMA and CF migration induced by TGF-ß1. Also, IFN-ß through STAT1 regulated pro-collagen type-I protein expression levels, and collagen gels contraction induced by TGF-ß1. STAT3 was not involved in any effects of IFN-ß studied. In conclusion, IFN-ß through STAT1 and STAT2 shows antifibrotic effects on CF TGF-ß1-treated, whereas STAT3 did not participate in such effect.

Pregnant women with SARS-CoV-2 infection are at higher risk of death and pneumonia: propensity score matched analysis of a nationwide prospective cohort (COV19Mx).

OBJECTIVE: There are limited, unmatched data reporting low complication rates in pregnant women with coronavirus disease 2019 (COVID-19). The aim of this study was to compare COVID-19-related outcomes between pregnant and non-pregnant women after adjusting for potential risk factors for severe outcomes. METHODS: Data were obtained from the COVID-19 National Data Registry of Mexico, which is an ongoing prospective cohort of people of any age with clinically suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and admitted to 475 monitoring hospitals. This study included pregnant and non-pregnant women of reproductive age (15-45 years) with COVID-19 confirmed by reverse transcription polymerase chain reaction. To adjust for underlying risk factors, propensity score matching was conducted for chronic obstructive pulmonary disease, asthma, smoking, hypertension, cardiovascular disease, obesity, diabetes, chronic renal disease, immunosuppression, age, language, nationality and level of health insurance. The primary outcome was death. Secondary outcomes were pneumonia, intubation and intensive care unit (ICU) admission. RESULTS: The cohort comprised 5183 pregnant and 175 905 non-pregnant women with COVID-19. The crude (unmatched) rates of death, pneumonia, intubation and ICU admission in pregnant compared with non-pregnant women were 1.5% vs 1.5%, 9.9% vs 6.5%, 8.1% vs 9.9% and 13.0% vs 6.9%, respectively. After propensity score matching (5183 pregnant and 5183 non-pregnant matched women), pregnant women had a higher odds of death (odds ratio (OR), 1.84; 95% CI, 1.26-2.69), pneumonia (OR, 1.86; 95% CI, 1.60-2.16) and ICU admission (OR, 1.86; 95% CI, 1.41-2.45) than non-pregnant women, but similar odds of intubation (OR, 0.93; 95% CI, 0.70-1.25). CONCLUSION: After adjusting for background demographic and medical factors, pregnancy is a risk factor for death, pneumonia and ICU admission in SARS-CoV-2-infected women of reproductive age. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: preliminary translational findings across rats, monkeys and humans.

Aldosterone regulates electrolyte and fluid homeostasis through binding to the mineralocorticoid receptors (MRs). Previous work provides evidence for a role of aldosterone in alcohol use disorders (AUDs). We tested the hypothesis that high functional activity of the mineralocorticoid endocrine pathway contributes to vulnerability for AUDs. In Study 1, we investigated the relationship between plasma aldosterone levels, ethanol self-administration and the expression of CYP11B2 and MR (NR3C2) genes in the prefrontal cortex area (PFC) and central nucleus of the amygdala (CeA) in monkeys. Aldosterone significantly increased after 6- and 12-month ethanol self-administration. NR3C2 expression in the CeA was negatively correlated to average ethanol intake during the 12 months. In Study 2, we measured Nr3c2 mRNA levels in the PFC and CeA of dependent and nondependent rats and the correlates with ethanol drinking during acute withdrawal. Low Nr3c2 expression levels in the CeA were significantly associated with increased anxiety-like behavior and compulsive-like drinking in dependent rats. In Study 3, the relationship between plasma aldosterone levels, alcohol drinking and craving was investigated in alcohol-dependent patients. Non-abstinent patients had significantly higher aldosterone levels than abstinent patients. Aldosterone levels positively correlated with the number of drinks consumed, craving and anxiety scores. These findings support a relationship between ethanol drinking and the aldosterone/MR pathway in three different species.

Association of sedentary time and physical activity with pain, fatigue, and impact of fibromyalgia: the al-Ándalus study.

We examined the association of objectively measured sedentary time (ST) and physical activity (PA) levels with pain, fatigue, and the impact of the disease in women with fibromyalgia. Four hundred and nineteen (mean age ± SD = 51.7 ± 7.6 years old) women with fibromyalgia participated. ST and PA levels (light, moderate, and moderate-to-vigorous [MVPA]) were measured with triaxial accelerometry. We assessed experimental pain with algometry and clinical pain, fatigue, and impact of fibromyalgia with a number of questionnaires. The association of ST and light PA with most of the pain- and fatigue-related outcomes and impact of fibromyalgia (all, P ≤ 0.019) was independent of moderate and vigorous PA. Furthermore, the association of vigorous PA with general and physical fatigue was independent of ST and light and moderate PA (all, P < 0.001). In conclusion, lower levels of ST or higher levels of light PA are associated with lower pain, fatigue, and the overall impact of the disease independent of moderate and vigorous PA in women with fibromyalgia. Interestingly, higher vigorous PA is independently associated with lower general and physical fatigue. These results are significant for future ST and PA intervention studies in this population.

Physical fitness reference standards in fibromyalgia: The al-Ándalus project.

We aimed (1) to report age-specific physical fitness levels in people with fibromyalgia of a representative sample from Andalusia; and (2) to compare the fitness levels of people with fibromyalgia with non-fibromyalgia controls. This cross-sectional study included 468 (21 men) patients with fibromyalgia and 360 (55 men) controls. The fibromyalgia sample was geographically representative from southern Spain. Physical fitness was assessed with the Senior Fitness Test battery plus the handgrip test. We applied the Generalized Additive Model for Location, Scale and Shape to calculate percentile curves for women and fitted mean curves using a linear regression for men. Our results show that people with fibromyalgia reached worse performance in all fitness tests than controls (P < 0.001) in all age ranges (P < 0.001). This study provides a comprehensive description of age-specific physical fitness levels among patients with fibromyalgia and controls in a large sample of patients with fibromyalgia from southern of Spain. Physical fitness levels of people with fibromyalgia from Andalusia are very low in comparison with age-matched healthy controls. This information could be useful to correctly interpret physical fitness assessments and helping health care providers to identify individuals at risk for losing physical independence.

Physical fitness is associated with anxiety levels in women with fibromyalgia: the al-Ándalus project.

PURPOSE: To assess the independent associations of individual physical fitness components with anxiety in women with fibromyalgia and to test which physical fitness component shows the greatest association. METHODS: This population-based cross-sectional study included 439 women with fibromyalgia (age 52.2 ± 8.0 years). Anxiety symptoms were measured with the State Trait Anxiety Inventory (STAI) and the anxiety item of the Revised Fibromyalgia Impact Questionnaire (FIQR). Physical fitness was assessed through the Senior Fitness Test battery and handgrip strength test. RESULTS: Overall, lower physical fitness was associated with higher anxiety levels (all, p < 0.05). The coefficients of the optimal regression model (stepwise selection method) between anxiety symptoms and physical fitness components adjusted for age, body fat percentage and anxiolytics intake showed that the back scratch test (b = -0.18), the chair sit-and-reach test (b = -0.12; p = 0.027) and the 6-min walk test (b = -0.02; p = 0.024) were independently and inversely associated with STAI. The back scratch test and the arm- curl test were associated with FIQR-anxiety (b = -0.05; p < 0.001 and b = -0.07; p = 0.021, respectively). CONCLUSION: Physical fitness was inversely and consistently associated with anxiety in women with fibromyalgia, regardless of the fitness component evaluated. In particular, upper-body flexibility was an independent indicator of anxiety levels, followed by cardiorespiratory fitness and muscular strength.

Physical fitness as a mediator between objectively measured physical activity and clustered metabolic syndrome in children and adolescents: The UP&DOWN study.

BACKGROUND AND AIMS: The extent to which physical fitness (PF) attenuates or modifies the association between physical activity (PA) and clustered metabolic syndrome risk factors (CMetSRF) is controversial. We aimed: i) To examine the independent and combined association of objectively measured PA and PF with CMetSRF in children and adolescents; ii) To test the mediating effect of PF in the association of PA with CMetSRF. METHODS AND RESULTS: A total of 226 children and 256 adolescents participated. Levels of PA (light, moderate, vigorous and moderate-to-vigorous [MVPA]) and PF were measured by accelerometry and ALPHA battery, respectively. Cardiorespiratory and muscular fitness values were combined in a global PF variable. A CMetSRF was computed by assessing the following variables: waist circumference, systolic blood pressure, high-density lipoprotein cholesterol, triglycerides and glucose. In children, the highest vigorous PA (ß = -0.193; P = 0.003) and MVPA (ß = -0.149; P = 0.025) were individually associated with lower CMetSRF, but these associations were not independent of global PF. In adolescents, the association of moderate (ß = -0.123; P = 0.046) and MVPA (ß = -0.147; P = 0.024) with CMetSRF was independent of PF. Among unfit adolescents, the higher time they spent in MVPA the lower CMetSRF levels were found (P = 0.032). CONCLUSIONS: The results are suggestive of a full mediation of global PF in the association of MVPA and vigorous PA with CMetSRF in children. In adolescents, the association of higher moderate and MVPA with lower CMetSRF was independent of levels of PF, and mediation analyses suggest only a partial mediation of global PF in the association of MVPA with CMetSRF.

Reliability and feasibility of physical fitness tests in female fibromyalgia patients.

The aim of the present study was to determine the reliability and feasibility of physical fitness tests in female fibromyalgia patients. 100 female fibromyalgia patients (aged 50.6±8.6 years) performed the following tests twice (7 days interval test-retest): chair sit and reach, back scratch, handgrip strength, arm curl, chair stand, 8 feet up and go, and 6-min walk. Significant differences between test and retest were found in the arm curl (mean difference: 1.25±2.16 repetitions, Cohen d=0.251), chair stand (0.99±1.7 repetitions, Cohen d=0.254) and 8 feet up and go (-0.38±1.09 s, Cohen d=0.111) tests. Intraclass correlation coefficients (ICC) range from 0.92 in the arm curl test to 0.96 in the back scratch test. The feasibility of the tests (patients able to complete the test) ranged from 89% in the arm curl test to 100% in the handgrip strength test. Therefore, the reliability and feasibility of the physical fitness tests examined is acceptable for female fibromyalgia patients.

Are there differences in quality of life, symptomatology and functional capacity among different obesity classes in women with fibromyalgia? The al-Ándalus project.

Obesity may influence fibromyalgia severity. The present study aimed to examine fibromyalgia (FM) symptomatology, quality of life (QoL), and functional capacity across obesity class categories. A total sample of 208 obese FM patients and 108 obese control women were included in the study. The sample was further categorized following the international criteria for obesity classes: obesity I (BMI 30.0-34.99 kg/m(2)), obesity II (BMI 35.0-39.99 kg/m(2)), and obesity III (BMI ≥40.0 kg/m(2)). QoL was assessed by means of the Short-Form-36 Health Survey (SF-36) and FM symptomatology with the Fibromyalgia Impact Questionnaire (FIQ). Standardized field-based fitness tests were used to assess cardiorespiratory fitness, muscular strength, flexibility, agility, and balance. All the dimensions of QoL, as measured by SF-36, were worse in obese FM patients compared to the obese control group (all p < 0.001). Obese FM patients also scored worse in the entire functional capacity tests studied (all p < 0.001). Except for the higher FIQ-depression across obesity status categories (p < 0.05), no differences between obesity status groups were found in QoL and FM impact. However, upper-body muscular strength and cardiorespiratory fitness were worse across obesity class categories and pairwise comparisons showed differences mainly between obesity I and II (p < 0.05, and p < 0.01, respectively). The absence of clear differences in QoL and FM symptomatology among obesity classes suggests that just avoiding any obese status may be a useful advice for a better management of the disease. Nevertheless, upper-body muscular strength and cardiorespiratory fitness, which are important health indicators highly related to the mortality risk, were worse across obesity categories.

Effectiveness of Tai-Chi for decreasing acute pain in fibromyalgia patients.

Tai-Chi has shown benefits in physical and psychological outcomes in diverse populations. We aimed to determine the changes elicited by a Tai-Chi program (12 and 24 weeks) in acute pain (before vs. after session) in fibromyalgia patients. We also assessed the cumulative changes in pain brought about by a Tai-Chi program. Thirty-six patients (29 women) with fibromyalgia participated in a low-moderate intensity Tai-Chi program for 12 weeks (3 sessions/week). Twenty-eight patients (27 women) continued the program for an additional 12 weeks (i. e., 24 weeks). We assessed pain by means of a Visual Analogue Scale (VAS) before and after each single session (i. e., 72 sessions). We observed significant immediate changes (P-values from 0.037 to 0.0001) with an approximately 12% mean decrease of acute pain in the comparison of VAS-values before and after each session (72 sessions in total), with the exception of 4 sessions. We observed significant changes in cumulative pain pre-session (95% CI=-0.019; -0.014; P<0.001) and cumulative pain post-session (95% CI=-0.021; -0.015; P<0.001) along the 24-week intervention only. In conclusion, a low-moderate intensity Tai-Chi program for 12 weeks (3 times/week) decreased levels of acute pain in fibromyalgia patients. A longer period is necessary (e. g. 24 weeks) for observing cumulative changes in pain.

Structure of the vortex wake in hovering Anna's hummingbirds (Calypte anna).

Hummingbirds are specialized hoverers for which the vortex wake has been described as a series of single vortex rings shed primarily during the downstroke. Recent findings in bats and birds, as well as in a recent study on Anna's hummingbirds, suggest that each wing may shed a discrete vortex ring, yielding a bilaterally paired wake. Here, we describe the presence of two discrete rings in the wake of hovering Anna's hummingbirds, and also infer force production through a wingbeat with contributions to weight support. Using flow visualization, we found separate vortices at the tip and root of each wing, with 15% stronger circulation at the wingtip than at the root during the downstroke. The upstroke wake is more complex, with near-continuous shedding of vorticity, and circulation of approximately equal magnitude at tip and root. Force estimates suggest that the downstroke contributes 66% of required weight support, whereas the upstroke generates 35%. We also identified a secondary vortex structure yielding 8-26% of weight support. Lift production in Anna's hummingbirds is more evenly distributed between the stroke phases than previously estimated for Rufous hummingbirds, in accordance with the generally symmetric down- and upstrokes that characterize hovering in these birds.

A warm water pool-based exercise program decreases immediate pain in female fibromyalgia patients: uncontrolled clinical trial.

Fibromyalgia is characterized by chronic and extended musculoskeletal pain. The combination of exercise therapy with the warm water may be an appropriate treatment. However, studies focusing on the analysis of immediate pain during and after an exercise session are rare. This study aimed to determine the immediate changes of a warm water pool-based exercise program (12 weeks) on pain (before vs. after session) in female fibromyalgia patients. 33 Spanish women with fibromyalgia were selected to participate in a 12 weeks (2 sessions/week) low-moderate intensity warm water pool-based program. We assessed pain by means of a Visual Analogue Scale before and after each single session (i. e., 24 sessions). We observed immediate benefits on pain with a mean decrease ~15% in all sessions, except in the fourth one. There was an association of pain difference (pre-post) session with pain pre session (p=0.005; ß=0.097±0.034) and with age (p<0.001; ß=0.032±0.008). There were no significant accumulative differences on pain, pre session, post session, and pre-post changes (all p>0.05). Therefore this study showed that a warm water pool-based exercise program for 12 weeks (2 times/week) led to a positive immediate decrease in level of pain in female patients with fibromyalgia. Improvements were higher in older women and in those with more intense pain.

SU-101: a Bi(III)-based metal-organic framework as an efficient heterogeneous catalyst for the CO2 cycloaddition reaction.

A non-porous version of SU-101 (herein n-SU-101) was evaluated for the CO2 cycloaddition reaction. The findings revealed that open metal sites (Bi3+) are necessary for the reaction. n-SU-101 displays a high styrene oxide conversion of 96.6% under mild conditions (3 bar and 80 °C). The catalytic activity of n-SU-101 demonstrated its potential application for the cycloaddition of CO2 using styrene oxide.

Evaluation of the catalytic activity of Zn-MOF-74 for the alcoholysis of cyclohexene oxide.

In the present work, nanocrystalline Zn-MOF-74 is shown to be a heterogeneous catalyst for the acid-catalyzed ring-opening alcoholysis of cyclohexene oxide. The results corroborated that accessible open metal sites within the material are critical conditions (Zn(ii) Lewis acid sites) for this reaction. Zn-MOF-74 was tested at three different temperatures (30, 40, and 50 °C) for the alcoholysis reaction. Furthermore, the cyclohexene oxide conversion was 94% in less than two days. A comparison of the catalytic activity with different crystal sizes of Zn-MOF-74 and the homogenous phase, zinc acetate, was conducted. Zn-MOF-74 exhibited excellent catalytic cyclability for three cycles without losing its activity. The material showed chemical stability by retaining its crystalline structure after the reaction and cyclability process.

Absence of clinical symptoms upon introduction of egg into the diet of milk-allergic infants not previously sensitised to egg.

BACKGROUND: It is unclear how many children suffering from IgE mediated cow's milk allergy are sensitised to egg in early life and what the clinical implication of this sensitisation is. It is also unclear if those not sensitised to egg in early life, do later on develop sensitisation and clinical allergy to egg. METHODS: This study examines the prevalence of egg sensitisation among infants with allergy to cow's milk, prior to and following the introduction of egg and what this sensitisation clinically means. RESULTS: The percentage of egg-sensitised children seen among the group of children with cow's milk allergy was 43.2%, and predictive factors for egg sensitisation are discussed. 81.8% of the sensitised patients presented with symptoms when exposed to egg in at least one of its forms, although up to 54.5% of patients tolerated boiled egg and egg-based products. Of the non-sensitised patients, the vast majority (92.5%) did not present with symptoms after the introduction of egg in their diet. CONCLUSIONS: Coexistence of allergy to egg and milk allergy is common, and it is recommended that these patients be monitored, since children who are sensitised to egg despite having never been exposed to it in their diet, may present with symptoms immediately following first ingestion. Most children who are initially non-sensitised to egg do not require special care, and it is not generally recommended to delay or monitor these children, although a small number may have subsequently reacted to egg.

An study on the influence of collagen fiber directions in TAVs performance using FEM.

Transcatheter Aortic Valve Implantation (TAVI) or Replacement (TAVR) is a promising treatment for aortic valve stenosis, consisting of a procedure to replace a damaged native aortic valve by a bioprosthetic one. This replacement valve control the flow of blood using leaflets that are similar to the ones of a native aortic valve. Commonly manufactured using bovine or porcine pericardium, it is a tissue histologically composed of collagen fibers embedded into a nearly-isotropic matrix, where their distribution makes the pericardium behave as an anisotropic hyperelastic material. Because of such complicated behavior, bioprosthetic pericardium valves are, as expected, sensitive to the distribution and orientation of these fibers in such device. Therefore, the objective of this work is a thorough systematic study on the influence of these fibers' distribution. First, a Finite Element model of a bioprosthetic valve is generated; then, a material routine to accurately describe the behavior of pericardium is implemented in a commercial software package; in addition, a dedicated algorithm to specify the direction of fibers is developed. Finally, a systematic study on the influence that fiber orientations have on the overall behavior of the TAV is performed. As a result of this study, two extreme behaviors are highlighted depending on the preferential orientation of collagen fibers; namely, one with fibers in circumferential direction and the opposite with fibers in an axial orientation. Then, it is concluded that the behavior of fibers in circumferential direction is very sensitive to small variations of the orientation angle, whereas such orientation is not as determining when the aim is to achieve a behavior near to the one corresponding with axial orientation.

In vivo genetic engineering of murine pancreatic beta cells mediated by single-stranded adeno-associated viral vectors of serotypes 6, 8 and 9.

AIMS/HYPOTHESIS: The genetic engineering of pancreatic beta cells could be a powerful tool for examining the role of key genes in the cause and treatment of diabetes. Here we performed a comparative study of the ability of single-stranded (ss) adeno-associated viral vectors (AAV) of serotypes 6, 8 and 9 to transduce the pancreas in vivo. METHODS: AAV6, AAV8 and AAV9 vectors encoding marker genes were delivered to the pancreas via intraductal or systemic administration. Transduced cells were analysed by immunostaining. AAV9 vectors encoding hepatocyte growth factor (HGF) were delivered intraductally to a transgenic mouse model of type 1 diabetes and glycaemia was monitored. RESULTS: AAV6, AAV8 and AAV9 mediated efficient and long-term transduction of beta cells, with AAV6 and AAV8 showing the highest efficiency. However, alpha cells were poorly transduced. Acinar cells were transduced by the three serotypes tested and ductal cells only by AAV6. In addition, intraductal delivery resulted in higher AAV-mediated transduction of the pancreas than did systemic administration. As proof of concept, intraductal delivery of AAV9 vectors encoding for the beta cell anti-apoptotic and mitogenic HGF preserved beta cell mass, diminished lymphocytic infiltration of the islets and protected mice from autoimmune diabetes. CONCLUSIONS/INTERPRETATION: Intraductal administration of AAV6, AAV8 and AAV9 is an efficient way to genetically manipulate the pancreas in vivo. This technology may prove useful in the study of islet physiopathology and in assessment of new gene therapy approaches designed to regenerate beta cell mass during diabetes.

Expression and function of Cbl-b in T cells from patients with systemic lupus erythematosus, and detection of the 2126 A/G Cblb gene polymorphism in the Mexican mestizo population.

Systemic lupus erythematosus (SLE) is characterized by abnormalities in the function of T and B lymphocytes and in the signaling pathways induced through their receptors. Cbl-b is an intracellular adaptor protein that plays a key role in the negative regulation of lymphocyte activity. We explored the expression and function of Cbl-b in T lymphocytes from SLE patients. In addition, the possible association of SLE and a single nucleotide polymorphism (SNP) of the Cblb gene was determined. We studied 150 SLE patients, 163 healthy individuals, and 14 patients with rheumatoid arthritis (RA). The expression of Cbl-b was analyzed in the peripheral blood mononuclear cells, and the negative regulatory function of Cbl-b was assessed by analyzing actin polymerization and the phosphorylation of JNK and c-Jun induced through CD3. Furthermore, the 2126(A/G) SNP of the Cblb gene was detected by real-time polymerase chain reaction. We found a significant small reduction in the expression of Cbl-b as well as increased levels of activation of c-Jun and actin polymerization in T lymphocytes from patients with SLE compared with healthy controls or RA patients. In addition, a significant association between the 2126(A/G) SNP and SLE was detected. Our data suggest that Cbl-b may contribute to the deregulated activation of T lymphocytes observed in SLE.

First trimester fetal head and trunk volume predict growth disturbance in twin pregnancy.

OBJECTIVE: To evaluate the usefulness of first trimester fetal head and trunk volume (FHTV) in predicting growth disturbance in twin pregnancy. METHODS: We studied 46 twin pairs from 11 and 14 weeks to delivery. There were 35 dichorionic (76%) and 11 monochorionic (24%) pregnancies. FHTV was assessed by VOCALTM. An inter-twin discrepancy in FHTV, crown-rump length (CRL) and birthweight (BW) were defined by an inter-twin difference greater than 15%. Growth retardation was defined as BW of at least one twin below the 10th percentile. RESULTS: There were 17 cases (37%) of FHTV discrepancy. BW discrepancy and growth retardation were more significantly frequent in cases with FHTV discrepancy than without [11/17 (64.7%) vs 4/29 (13.8%), P = 0.0004 and 7/17 (41.2%) vs 3/29 (10.3%), P = 0.02, respectively]. The detection of BW discordance and growth retardation were significantly higher when using FHTV discordance than CRL discrepancy in the first trimester [11/15 (73%) vs 2/15 (13.3%), P = 0.00001 and 7/10 (70%) vs 1/10 (10%), P = 0.0001, respectively]. CONCLUSION: FHTV discrepancy is a predictor for growth disturbance in twins.