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We reported that a Mediterranean Diet (MedDiet), supplemented with extra-virgin olive oil (EVOO) and pistachios, reduces GDM incidence and several other adverse outcomes. In order to assess its translational effects in the real world we evaluated the effect of MedDiet from 1st gestational visit in GDM rate compared with control (CG) and intervention (IG) groups from the previously referred trial. As secondary objective we also compared adverse perinatal outcomes between normoglycemic and diabetic women. This trial is a prospective, clinic-based, interventional study with a single group. 1066 eligible normoglycaemic women before 12 gestational weeks were assessed. 932 women (32.4 ± 5.2 years old, pre-gestational BMI 22.5 ± 3.5 kg/m 2 ) received a motivational lifestyle interview with emphasis on daily consumption of EVOO and nuts, were followed-up and analysed. Binary regression analyses were used to examine the risk for each pregnancy outcome, pregnancy-induced hypertension, preeclampsia, gestational weight gain (GWG), caesarean-section, perineal trauma, preterm delivery, small (SGA) and large for gestational age (LGA), and Neonatal Intensive Care Unit admissions. GDM was diagnosed in 13.9%. This rate was significantly lower than the CG: RR 0.81 (0.73-0.93), p < 0.001 and no different from the IG: RR 0.96 (0.85-1.07), p = 0.468. GWG was lower in diabetic women (10.88 ± 6.46 vs. 12.30 ± 5.42 Kg; p = 0.013). Excessive weight gain (EWG) was also lower in GDM [RR 0.91 (0.86-0.96); p < 0.001] without a significant increase of insufficient weight gain. LGA were also lower (1 (0.8%) vs. 31 (3.9%); p < 0.05)), and SGA were similar (5 (3.8%) vs. 30 (3.7%)). LGA were associated to EWG (RR 1.61 (1.35-1.91), p < 0.001). Differences in other maternal-foetal outcomes were not found. In conclusions an early MedDiet nutritional intervention reduces GDM incidence and maternal-foetal adverse outcomes and should be universally applied as 1st line therapy. GDM might not be consider as a high risk pregnancy any longer.

Aims: The aim of the study was to evaluate the effect of a Mediterranean diet (MedDiet), enhanced with extra virgin olive oil (EVOO) and nuts, on a composite of adverse maternofoetal outcomes of women with normoglycemia during pregnancy., Methods: This was a sub-analysis of the St Carlos gestational diabetes mellitus Prevention Study. Only normoglycemic women were analysed (697). They were randomized (at 8-12th gestational weeks) to: standard-care control group (337), where fat consumption was limited to 30% of total caloric intake; or intervention group (360), where a MedDiet, enhanced with EVOO and pistachios (40-42% fats of total caloric intake) was recommended. The primary outcome was a composite of maternofoetal outcomes (CMFOs): at least having 1 event of emergency C-section, perineal trauma, pregnancy-induced hypertension and preeclampsia, prematurity, large-for-gestational-age and small-for gestational-age., Results: Crude relative risk showed that the intervention was associated with a significant reduction in the risk of CMFOs (0.48 [0.37-0.63]; p = 0.0001), with a number-needed-to-treat = 5. Risk of urinary tract infections, emergency C-sections, perineal trauma, large-for-gestational-age and small-for gestational age new-borns were also significantly reduced., Conclusion: A MedDiet, enhanced with EVOO and nuts, was associated with a risk reduction of CMFOs in over 50% in normoglycemic pregnant women. Therefore, it might be a potentially adequate diet for pregnant women., Trial Registration: Identifier ISRCTN84389045. The study was registered on September 27, 2013. Last edited on September 26, 2018., (The Author(s). Published by S. Karger AG, Basel.)

A prenatal diet affects materno-foetal outcomes. This is a post hoc analysis of the St. Carlos gestational diabetes mellitus (GDM) Prevention Study. It aims to evaluate the effect of a late first-trimester (>12 gestational weeks) degree of adherence to a MedDiet pattern-based on six food targets-on a composite of materno-foetal outcomes (CMFCs). The CMFCs were defined as having emergency C-section, perineal trauma, pregnancy-induced hypertension and preeclampsia, prematurity, large-for-gestational-age, and/or small-for-gestational-age. A total of 874 women were stratified into three groups according to late first-trimester compliance with six food targets: >12 servings/week of vegetables, >12 servings/week of fruits, <2 servings/week of juice, >3 servings/week of nuts, >6 days/week consumption of extra virgin olive oil (EVOO), and ≥40 mL/day of EVOO. High adherence was defined as complying with 5⁻6 targets; moderate adherence 2⁻4 targets; low adherence 0⁻1 targets. There was a linear association between high, moderate, and low adherence, and a lower risk of GDM, CMFCs, urinary tract infections (UTI), prematurity, and small-for-gestational-age (SGA) newborns (all p < 0.05). The odds ratios (95% CI) for GDM and CMFCs in women with a high adherence were 0.35((0.18⁻0.67), p = 0.002) and 0.23((0.11⁻0.48), p < 0.001), respectively. Late first-trimester high adherence to the predefined six food targets is associated with a reduction in the risk of GDM, CMFCs, UTI, prematurity, and SGA new-borns.

Correction for 'Controlled p-type substitutional doping in large-area monolayer WSe2 crystals grown by chemical vapor deposition' by Stephen A. Campbell et al., Nanoscale, 2018, 10, 21374-21385.

Tungsten diselenide (WSe 2 ) is a particularly interesting 2D material due to its p-type conductivity. Here we report a systematic single-step process to optimize crystal size by variation of multiple growth parameters resulting in hexagonal single crystals up to 165 μm wide. We then show that these large single crystals can be controllably in situ doped with the acceptor Niobium (Nb). First principles calculations suggest that substitutional Nb doping of W would yield p-doping with no gap trap states. When used as the active layer of a field effect transistor (FET), doped crystals exhibit conventional p-type behavior, rather than the ambipolar behaviour seen in undoped WSe 2 FETs. Nb-doped WSe 2 FETs yield a maximum field effect mobility of 116 cm 2 V -1 s -1 , slightly higher than its undoped counterpart, with an on/off ratio of 10 6 . Doping reduces the contact resistance of WSe 2 , reaching a minimum value of 0.55 kΩμm in WSe 2 FETs. The areal density of holes in Nb-doped WSe 2 is approximately double that of undoped WSe 2 , indicating that Nb doping is working as an effective acceptor. Doping concentration can be controlled over several orders of magnitudes, allowing it to be used to control: FET threshold voltage, FET off-state leakage, and contact resistance.

Objectives: To assess whether Mediterranean Diet (MedDiet)-based medical nutrition therapy facilitates near-normoglycemia in women with gestational diabetes mellitus (GDMw) and observe the effects on adverse pregnancy outcomes., Research Design and Methods: This is a secondary analysis of the St Carlos GDM Prevention Study, conducted between January and December 2015 in Hospital Clínico San Carlos (Madrid, Spain). One thousand consecutive women with normoglycemia were included before 12 gestational weeks (GWs), with 874 included in the final analysis. Of these, 177 women were diagnosed with gestational diabetes mellitus (GDM) and 697 had normal glucose tolerance. All GDMw received MedDiet-based medical nutrition therapy with a recommended daily extra virgin olive oil intake ≥40 mL and a daily handful of nuts. The primary goal was comparison of hemoglobin A1c (HbA 1c ) levels at 36-38 GWs in GDMw and women with normal glucose tolerance (NGTw)., Results: GDMw as compared with NGTw had higher HbA 1c levels at 24-28 GWs (5.1%±0.3% (32±0.9 mmol/mol) vs 4.9%±0.3% (30±0.9 mmol/mol), p=0.001). At 36-38 GWs values were similar between the groups. Similarly, fasting serum insulin and homeostatic model assessment insulin resitance (HOMA-IR) were higher in GDMw at 24-28 GWs (p=0.001) but became similar at 36-38 GWs. 26.6% of GDMw required insulin for glycemic control. GDMw compared with NGTw had higher rates of insufficient weight gain (39.5% vs 22.0%, p=0.001), small for gestational age (6.8% vs 2.6%, p=0.009), and neonatal intensive care unit admission (5.6% vs 1.7%, p=0.006). The rates of macrosomia, large for gestational age, pregnancy-induced hypertensive disorders, prematurity and cesarean sections were comparable with NGTw., Conclusions: Using a MedDiet-based medical nutrition therapy as part of GDM management is associated with achievement of near-normoglycemia, subsequently making most pregnancy outcomes similar to those of NGTw., Competing Interests: Competing interests: None declared.

Introduction and Objectives: Cerebrovascular disease (CVD), especially in its asymptomatic forms, is relatively common in patients with serious mental illness (SMI). Nevertheless, the literature on this topic is scarce and sometimes contradictory. Antipsychotic medications, especially atypical agents, play an important role in the overall cardiovascular health of these patients. The goal of this study was to analyze the frequency of CVD in patients with and without SMI., Patients and Methods: This retrospective cohort study compared the frequency of CVD, including silent forms, in a group of patients without mental illness and without a history of taking antipsychotic medication, with another group of patients diagnosed with SMI who had received antipsychotic treatment. The 2 groups were matched for age and sex, and the mean age of the subjects in the 2 groups was 63 years., Results: The frequency of CVD was the same in both groups and it was not modified by the use of antipsychotic medications. A nonsignificant trend toward an association between CVD and prolonged use of antipsychotic polypharmacy was found., Conclusions: In this study, in contrast to previous reports, use of antipsychotic medications and the presence of SMI were not associated with an increased risk of CVD.

In 2015, Legionnaires' disease was diagnosed in a street cleaning worker. We found Legionella pneumophila serogroup 1 in the water and internal foam from the tanks of 2 trucks used by the worker during the incubation period. The internal foam was removed, and a Legionella prevention program was implemented.

Background: Gestational diabetes mellitus (GDM) prevalence is increasing and becoming a major public health concern. Whether a Mediterranean diet can help prevent GDM in unselected pregnant women has yet to be studied., Methods: We conducted a prospective, randomized controlled trial to evaluate the incidence of GDM with two different dietary models. All consecutive normoglycemic (<92 mg/dL) pregnant women at 8-12 gestational weeks (GW) were assigned to Intervention Group (IG, n = 500): MedDiet supplemented with extra virgin olive oil (EVOO) and pistachios; or Control Group (CG, n = 500): standard diet with limited fat intake. Primary outcome was to assess the effect of the intervention on GDM incidence at 24-28 GW. Gestational weight gain (GWG), pregnancy-induced hypertension, caesarean section (CS), preterm delivery, perineal trauma, small and large for gestational age (SGA and LGA) and admissions to neonatal intensive care unit were also assessed. Analysis was by intention-to-treat., Results: A total of 874 women completed the study (440/434, CG/IG). According to nutritional questionnaires and biomarker analysis, women in the IG had a good adherence to the intervention. 177/874 women were diagnosed with GDM, 103/440 (23.4%) in CG and 74/434(17.1%) in IG, p = 0.012. The crude relative risk (RR) for GDM was 0.73 (95% CI: 0.56-0.95; p = 0.020) IG vs CG and persisted after adjusted multivariable analysis, 0.75(95% CI: 0.57-0.98; p = 0.039). IG had also significantly reduced rates of insulin-treated GDM, prematurity, GWG at 24-28 and 36-38 GW, emergency CS, perineal trauma, and SGA and LGA newborns (all p<0.05)., Conclusions: An early nutritional intervention with a supplemented MedDiet reduces the incidence of GDM and improves several maternal and neonatal outcomes.

Non-Hodgkin lymphoma comprises a variety of neoplasms, many of which arise from germinal center (GC)-experienced B cells. microRNA-28 (miR-28) is a GC-specific miRNA whose expression is lost in numerous mature B-cell neoplasms. Here we show that miR-28 regulates the GC reaction in primary B cells by impairing class switch recombination and memory B and plasma cell differentiation. Deep quantitative proteomics combined with transcriptome analysis identified miR-28 targets involved in cell-cycle and B-cell receptor signaling. Accordingly, we found that miR-28 expression diminished proliferation in primary and lymphoma cells in vitro. Importantly, miR-28 reexpression in human Burkitt (BL) and diffuse large B-cell lymphoma (DLBCL) xenografts blocked tumor growth, both when delivered in viral vectors or as synthetic, clinically amenable, molecules. Further, the antitumoral effect of miR-28 is conserved in a primary murine in vivo model of BL. Thus, miR-28 replacement is uncovered as a novel therapeutic strategy for DLBCL and BL treatment., (© 2017 by The American Society of Hematology.)

Patients with chronic schizophrenia-related disorders are at a heightened risk of developing cardiovascular disease. The presence and interpretation of cerebral vascular lesions in neuroimaging tests in these patients represents a common clinical challenge. Nevertheless, the literature on cerebrovascular disease in this population is scarce and contradictory. The aim of this study was to analyse the relationship between schizophrenia-related disorders and cerebrovascular morbidity. A case-control study compared cerebrovascular morbidity in a group of patients with schizophrenia-related disorder versus a group of patients with another severe mental illness. The risk of presenting cerebrovascular morbidity was four times higher and statistically significant in patients with schizophrenia-related disorders compared with controls, paired by age and sex. However, both groups were homogeneous in terms of cardiovascular risk factors. There were significant differences between the two groups only in the time using first-generation antipsychotic drugs and taking two or more antipsychotic medications simultaneously. The relationship between chronic schizophrenia-related disorders and cerebrovascular disease may be beyond the classic cardiovascular risk factors and related to certain medications. This is one of the first studies to focus on the relation among cerebrovascular morbidity, antipsychotic drugs and disorders related to schizophrenia in middle-aged and elderly adults.

Background: Obesity and gestational diabetes mellitus (GDM) increase the morbidity of the mother and newborn, which could increase further should they coexist. We aimed to determine the risk of adverse pregnancy and neonatal outcomes associated with excess weight (EW), and within this group identify potential differences between those with and without GDM., Methods: We carried out a post-hoc analysis of the St. Carlos Gestational Study which included 3312 pregnant women, arranged in 3 groups: normal-weight women (NWw) (2398/72.4%), overweight women (OWw) (649/19.6%) and obese women (OBw) (265/8%). OWw and OBw were grouped as EW women (EWw). We analyzed variables related to adverse pregnancy and neonatal outcomes., Results: The relative risk (95% CI) for GDM was 1.82 (1.47 to 2.25; p<0.0001) for OWw, and 3.26 (2.45 to 4.35; p<0.0001) in OBw. Univariate analysis showed associations of EW to higher rates of prematurity, birth weight >90th centile, newborns admitted to neonatal intensive care unit (NICU), instrumental delivery and cesarean delivery (all p<0.005). Multivariate analysis, adjusted for parity and ethnicity, showed that EW increased the risk of prematurity, admission to NICU, cesarean and instrumental delivery, especially in EWw without GDM. NWw with GDM had a significantly lower risk of admission to NICU and cesarean delivery, compared with NWw without GDM., Conclusions: EW is detrimental for pregnancy and neonatal outcomes, and treatment of GDM contributes to lowering the risk in EWw and NWw. Applying the same lifestyle changes to all pregnant women, independent of their weight or GDM condition, could improve these outcomes., Competing Interests: Conflicts of Interest: None declared.

Aims: To compare rates of FPG-HbA1C-based postpartum-glucose disorder (PGD) of women with prior gestational diabetes mellitus (GDM) by Carpenter-Coustan criteria (CCc) versus International Association of Diabetes and Pregnancy Study Groups criteria (IADPSGc)., Methods: 1620 women with GDM were divided into CCc group (2007-March 2012, n=915), and IADPSGc group (April 2012-2013, n=705). Pregravid (PG) body weight (BW) and body mass index (BMI) and postdelivery (PD) BW, BMI, waist circumference (WC), HOMA-insulin resistance (HOMA-IR), HbA1c, glucose and lipid profile were analysed. PGD definition: HbA1c ≥5.7% and/or FPG ≥5.6mmol/l., Results: Postpartum screening attendance rates (PSAr) were similar in both groups, CCc: 791 (86.5%) and IADPSGc: 570 (81%) as in PGD rates (PGDr), CCc: 233 (29.5%) and IADPSGc: 184 (32.3%). Both cohorts had similar PG-BMI, WC and PD-BMI. Both CCc and IADPSGc women had a significantly higher probability of having PGD when PG-BMI ≥25Kg/m(2) (CCc: OR: 1.55; IC 95% 1.06-2.26; p=0.016), (IADPSGc: OR: 1.42; IC 95% 1.03-2.38; p=0.046) as well as when WC ≥89.5cm, and age ≥34years, and in CCc women when PD-WG >0Kg, all adjusted by ethnicity and parity., Conclusions: Changing GDM diagnostic methodology did not affect PSAr and PGDr, in spite of screening more women. Thus, using IADPSGc allowed the identification of a larger number of women with PGD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Intimate partner violence (IPV) is a complex and global phenomenon that requires a multi-perspective analysis. Nevertheless, the number of neuroscientific studies conducted on this issue is scarce as compared with studies of other types of violence, and no neuroimaging studies comparing batterers to other criminals have been conducted. Thus, the main aim of this study was to compare the brain functioning of batterers to that of other criminals when they are exposed to IPV or general violence pictures. An fMRI study was conducted in 21 batterers and 20 other criminals while they observed IPV images (IPVI), general violence images (GVI) and neutral images (NI). Results demonstrated that batterers, compared with other criminals, exhibited a higher activation in the anterior and posterior cingulate cortex and in the middle prefrontal cortex and a decreased activation in the superior prefrontal cortex to IPVI compared to NI. The paired t-test comparison between IPVI and GVI for each group showed engagement of the medial prefrontal cortex, the posterior cingulate and the left angular cortices to IPVI in the batterer group only. These results could have important implications for a better understanding of the IPV phenomenon., (© The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

Objective: The use of the new International Association of the Diabetes and Pregnancy Study Groups criteria (IADPSGC) for the diagnosis of gestational diabetes mellitus (GDM) results in an increased prevalence of GDM. Whether their introduction improves pregnancy outcomes has yet to be established. We sought to evaluate the cost-effectiveness of one-step IADPSGC for screening and diagnosis of GDM compared with traditional two-step Carpenter-Coustan (CC) criteria., Research Design and Methods: GDM risk factors and pregnancy and newborn outcomes were prospectively assessed in 1,750 pregnant women from April 2011 to March 2012 using CC and in 1,526 pregnant women from April 2012 to March 2013 using IADPSGC between 24 and 28 weeks of gestation. Both groups received the same treatment and follow-up regimes., Results: The use of IADPSGC resulted in an important increase in GDM rate (35.5% vs. 10.6%) and an improvement in pregnancy outcomes, with a decrease in the rate of gestational hypertension (4.1 to 3.5%: -14.6%, P < 0.021), prematurity (6.4 to 5.7%: -10.9%, P < 0.039), cesarean section (25.4 to 19.7%: -23.9%, P < 0.002), small for gestational age (7.7 to 7.1%: -6.5%, P < 0.042), large for gestational age (4.6 to 3.7%: -20%, P < 0.004), Apgar 1-min score <7 (3.8 to 3.5%: -9%, P < 0.015), and admission to neonatal intensive care unit (8.2 to 6.2%: -24.4%, P < 0.001). Estimated cost savings was of €14,358.06 per 100 women evaluated using IADPSGC versus the group diagnosed using CC., Conclusions: The application of the new IADPSGC was associated with a 3.5-fold increase in GDM prevalence in our study population, as well as significant improvements in pregnancy outcomes, and was cost-effective. Our results support their adoption., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

microRNAs are a class of regulators of gene expression that have been shown critical for a great number of biological processes; however, little is known of their role in germinal center (GC) B cells. Although the GC reaction is crucial to ensure a competent immune response, GC B cells are also the origin of most human lymphomas, presumably due to bystander effects of the immunoglobulin gene remodeling that takes place at these sites. Here we report that miR-217 is specifically upregulated in GC B cells. Gain- and loss-of-function mouse models reveal that miR-217 is a positive modulator of the GC response that increases the generation of class-switched antibodies and the frequency of somatic hypermutation. We find that miR-217 down-regulates the expression of a DNA damage response and repair gene network and in turn stabilizes Bcl-6 expression in GC B cells. Importantly, miR-217 overexpression also promotes mature B-cell lymphomagenesis; this is physiologically relevant as we find that miR-217 is overexpressed in aggressive human B-cell lymphomas. Therefore, miR-217 provides a novel molecular link between the normal GC response and B-cell transformation., (© 2014 by The American Society of Hematology.)

Solvothermal synthesis was used to create a low-dimensional iron(II) chloride formate compound, NH4FeCl2(HCOO), that exhibits interesting magnetic properties. NH4FeCl2(HCOO) crystallizes in the monoclinic space group C2/c (No. 15) with a = 7.888(1) Å, b = 11.156(2) Å, c = 6.920(2) Å, and β = 108.066(2)°. The crystal structure consists of infinite zigzag chains of distorted Fe(2+)-centered octahedra linked by μ2-Cl and syn-syn formate bridges, with interchain hydrogen bonding through NH4(+) cations holding the chains together. The unique Fe(2+) site is coordinated by four equatorial chlorides at a distance of 2.50 Å and two axial oxygens at a distance of 2.08 Å. Magnetic measurements performed on powder and oriented single-crystal samples show complex anisotropic magnetic behavior dominated by antiferromagnetic interactions (TN = 6 K) with a small ferromagnetic component in the direction of chain propagation. An anisotropic metamagnetic transition was observed in the ordered state at 2 K in an applied magnetic field of 0.85-3 T. (57)Fe Mössbauer spectroscopy reveals mixed hyperfine interactions below the ordering temperature, with strong electric field gradients and complex noncollinear arrangement of the magnetic moments.

Introduction: The state of health of patients with schizophrenia is a field of growing interest that has probably not received sufficient attention in the past. It is currently held that physical health should form a part of the overall therapeutic strategy in these patients since reference is made to certain treatable conditions that may affect the final prognosis. One example is cardiovascular disease and its associated reduction in life expectancy., Development: We carried out a retrospective study in which we described the consultations held between the psychiatric acute care service and the neurology service during a one-year period. We have analyzed the frequency of cerebrovascular complications in our sample and have included a summary of the most relevant published data regarding cerebrovascular disease (CVD) in patients with schizophrenia., Conclusions: We have described the high frequency of CVD in both our series of patients with severe mental illness receiving attention as well as in those from the neurology service (25.7%), and in the subgroup presenting psychotic disorders (25%). There are several studies focusing on the possible causes of increased cardiovascular morbidity and mortality, especially in schizophrenia. However, in regards to CVD specifically, little has been found in the literature and that found shows contradictory results. Given the direct relation between cardiovascular disease and CVD, a consistent relation between CVD and schizophrenia is to be expected.

MicroRNAs (miRNAs) have emerged as a new class of gene expression regulators whose functions influence a myriad of biological processes, from developmental decisions through immune responses and numerous pathologies, including cancer and autoimmunity. miRNAs are small RNA molecules that drive post-transcriptional negative regulation of gene expression by promoting the degradation or translational block of their target mRNAs. Here, we review some of the data relating to the role of miRNAs in the regulation of the B-cell lineage, with a special focus on results obtained in vivo. We start by giving a general overview of miRNA activity, including the issue of target specificity and the experimental approaches more widely used to analyze the function of these molecules. We then go on to discuss the function of miRNAs during B-cell differentiation in the bone marrow and in the periphery as well as during the humoral immune response. Finally, we describe a few examples of the contribution of miRNAs, both as oncogenes and tumor suppressors, to the development of B-cell neoplasias., (© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Introduction and Development: The non-motor symptoms of Parkinson's disease have a great impact in terms of quality of life. They are frequently underdiagnosed and clinical experience suggests that not only is dopamine therapy ineffective but that in many cases it is also responsible for the appearance of some of these symptoms. Different studies have drawn attention to the involvement of the dopaminergic pathways in the pathogenesis of some non-motor symptoms. It has been observed that they can undergo fluctuations in relation to dopaminergic stimulation, generally in wearing off states, while displaying a significant correlation with motor fluctuations and a clinical response with continuous dopaminergic therapy., Conclusions: Although recent reviews offer insufficient evidence for treatment of non-motor symptoms with dopaminergic therapy, involvement of the dopaminergic pathways in the aetiopathogenesis of some of these disorders and the clinical observation that such symptoms undergo fluctuations in relation to pulsatile dopaminergic stimulation may lead us to reconsider the possible role of dopaminergic therapy in the treatment of these symptoms.

AM3 (Inmunoferon) is an orally effective immunomodulator that influences the regulatory and effector functions of the immune system whose molecular mechanisms of action are mostly unknown. We hypothesized that the polysaccharide moiety of AM3 (IF-S) might affect immune responses by modulating the lectin-dependent pathogen recognition abilities of human dendritic cells. IF-S inhibited binding of viral, fungal, and parasite pathogens by human monocyte-derived dendritic cells in a dose-dependent manner. IF-S specifically impaired the pathogen recognition capabilities of DC-SIGN, as it reduced the attachment of Candida, Aspergillus, and Leishmania to DC-SIGN transfectants. IF-S also inhibited the interaction of DC-SIGN with both its cellular counterreceptor (intercellular adhesion molecule 3) and the human immunodeficiency virus (HIV) type 1 gp120 protein and blocked the DC-SIGN-dependent capture of HIV virions and the HIV trans-infection capability of DC-SIGN transfectants. IF-S promoted DC-SIGN internalization in DCs without affecting mannose receptor expression, and (1)D saturation transfer difference nuclear magnetic resonance demonstrated that IF-S directly interacts with DC-SIGN on the cell surface. Therefore, the polysaccharide moiety of AM3 directly influences pathogen recognition by dendritic cells by interacting with DC-SIGN. Our results indicate that DC-SIGN is the target for an immunomodulator and imply that the adjuvant and immunomodulatory actions of AM3 are mediated, at least in part, by alteration of the DC-SIGN functional activities.

Human immunodeficiency virus type 1 (HIV-1) genotyping assays have come to be widely used for monitoring antiretroviral drug resistance. We report a case in which primer-template mismatches during nested PCR-based amplification biased the composition of the original viral population in the sample, magnifying a distinct minority HIV-1 population. This observation might help to explain some unexpected HIV-1 genotypes.

Objectives: To describe the phenotype of Leber congenital amaurosis (LCA) in 26 probands with mutations in aryl hydrocarbon receptor interacting protein-like 1 protein (AIPL1) and compare it with phenotypes of other LCA-related genes. To describe the electroretinogram (ERG) in heterozygote carriers., Methods: Patients with AIPL1-related LCA were identified in a cohort of 303 patients with LCA by polymerase chain reaction single-strand confirmational polymorphism mutation screening and/or direct sequencing. Phenotypic characterization included clinical and ERG evaluation. Seven heterozygous carrier parents also underwent ERG testing., Results: Seventeen homozygotes and 9 compound heterozygotes were identified. The W278X mutation was most frequent (48% of alleles). Visual acuities ranged from light perception to 20/400. Variable retinal appearances, ranging from near normal to varying degrees of chorioretinal atrophy and intraretinal pigment migration, were noted. Atrophic and/or pigmentary macular changes were present in 16 (80%) of 20 probands. Keratoconus and cataracts were identified in 5 (26%) of 19 patients, all of whom were homozygotes. The ERG of a parent heterozygote carrier revealed significantly reduced rod function, while ERGs for 6 other carrier parents were normal., Conclusions: The phenotype of LCA in patients with AIPL1 mutations is relatively severe, with a maculopathy in most patients and keratoconus and cataract in a large subset. Rod ERG abnormalities may be present in heterozygous carriers of AIPL1 mutations., Clinical Relevance: Understanding and recognizing the phenotype of LCA may help in defining the course and severity of the disease. Identifying the gene defect is the first step in preparation for therapy since molecular diagnosis in LCA will mandate the choice of treatment.

We analyzed the evolution of the human immunodeficiency virus type 1 (HIV-1) env gene in 12 chronically infected individuals who underwent structured treatment interruptions (STIs). Analyses of length variation and of clonal sequences demonstrated highly unpredictable evolution, which may limit the strengthening of HIV-specific immune responses by STIs because of the variability in exposure to viral antigens.

We undertook a non-concurrent prospective study of 191 Puerto Rican patients from August 1993 to April 1994. All patients had open angle glaucoma (OAG) (age ranged from 50 to 80 yrs; mean = 65 yrs). Patient's symptomatology associated to side effects of their glaucoma medicadons was reviewed. Incidence percent of ocular and/or systemic side effects per medication were: levobunolol 45.0%; betaxolol 42.0%; timolol 27.3%; pilocarpine 100%; dipivefrin 14.0%; and acetazolamide 250 mg 64.1%. Incidence percent of ocular and/or systemic side effects of topical beta-blockers used with concomittant medications were determined. Ocular side effects were more frequent in patients using levobunolol 44.2% than in those patients using betaxolol 42.0%, 8.5% of patients using levobunolol did report systemic side effects. No systemic side effects were reported by patients using betaxolol. Ocular side effects in patients using pilocarpine were frequent (100%); whereas the frequency of systemic side effects was low (6.1%). Systemic side effects were common in patients using carbonic anhydrase inhibitors. These results suggest that non-selective and cardio-selective topical Beta-blockers, differ in their ocular or systemic side effects.

Objectives: The aim of this study was to analyze the prediction of mortality in patients with severe acute pancreatitis., Patients and Methods: In a retrospective study 43 patients with severe acute pancreatitis were included. All patients required ICU admittance and surgical treatment. We evaluated severity according to Ranson's criteria, APACHE II score, CT scan classification (Hill), intraoperative findings (Vankemmel's classification) and number of organs failure. We performed a univariant and multivariant statistic study with lineal discriminant analysis., Results: The overall mortality was 46.5%. Ranson's score and APACHE II did not correlate with mortality. Hill's classification did not reach significance either. However, only the Vankemmel's classification and the number of organs failure had statistic value (p < 0.01). After lineal discriminant analysis, the association of more than 4 Ranson's criteria, APACHE II up to 9 points, grades IV and V in Hill's classification and 4 organs failure had a predictive value for mortality., Conclusions: In our limited experience the Vankemmel's classification and the number of organs failure had a predictive value for mortality in patients with acute pancreatitis. The association of more than 4 Ranson's criteria. APACHE II up to 8 points, grades IV-V in Hill's classification and 4 organs failure disclosed poor prognosis.

Background: The Hermansky-Pudlak syndrome (HPS) is defined by the autosomal recessively inherited triad of tyrosinase-positive oculocutaneous albinism, bleeding diathesis and accumulation of ceroid in tissues. Late complications include: interstitial pulmonary fibrosis; inflammatory bowel disease; and renal failure., Patients and Methods: We undertook a non-concurrent prospective study of 55 Puerto Rican patients with HPS (age range 1 to 54 yrs; mean = 19.7 yrs). These patients had a comprehensive ocular examination and a systemic evaluation for HPS., Results: Visual acuities ranged from 20/50 to 5/200. All patients had nystagmus. Forty-three patients had strabismus; esotropia was found in 24 patients; exotropia in 18 patients; and one patient had hypertropia. Posterior embryotoxon occurred in 15 patients and Axenfeld anomaly in 4 patients. Iris pigmentation varied from minimal to almost completely normal. Three patients had cataract formation. The retina was typically albinotic with macular hypoplasia. All patients had cutaneous albinism, bleeding diathesis and various systemic manifestations as part of HPS., Conclusion: Ocular findings in HPS include reduced visual acuity; congenital nystagmus, strabismus and cataract. Diagnosis of the syndrome ought to be made preoperatively to help minimize the potential complications associated with bleeding diathesis at the time of extraocular muscle and intraocular surgery in patients with HPS.

We studied 573 patients with the Marfan syndrome for the presence of ocular misalignment, refractive errors, and amblyopia. A total of 110 patients (19.2%) had strabismus. Of 573 patients, exotropia occurred in 67 (11.7%), esotropia in 12 (2.1%), vertical deviations in eight (1.4%), and primary inferior oblique muscle overaction in three (0.5%). Of 67 patients with exotropia, 18 had anisometropia and 39 had amblyopia. Of the 12 patients with esotropia, four had amblyopia and none had anisometropia. Exotropia and esotropia are more common in patients with the Marfan syndrome than in the general population of the United States (P < .001 for exotropia and .05 < P < .10 for esotropia). Abnormal afferent visual inputs to cortical centers caused by ectopia lentis, craniofacial abnormalities, and mechanical and genetic factors may all contribute to the higher prevalence of strabismus in this disease.

The authors examined two patients with deletions of the terminal end of the long arm of chromosome 18. The ocular findings in one patient with 46, XX, del 18 (q21) consisted of hypertelorism, epicanthus, strabismus, myopia, microphthalmia, microcornea, corneal opacities, iris hypoplasia with full thickness defects, corectopia and large peripapillary staphylomata. The second patient with 46, XX, del (18) (pter --> q21.2 :: q22 --> qter), inv (21) (q21 --> p12 :: q21 --> qter) only had epicanthus, strabismus, myopia and peripapillary crescents. Based on the findings in these two patients and on a review of previously reported patients with del 18 qter it appears that the loss of band 18q23 may be responsible for malformations of the anterior segment in the 18q-syndrome.

Five out of six albino persons in Puerto Rico suffer from the Hermansky-Pudlak syndrome. This syndrome has been reported also in other countries such as Great Britain, the Netherlands, Belgium, and Mexico, among others. Due to the geographical isolation of the island it is likely that these patients share a common ancestor. In explaining how the gene may have arrived to Puerto Rico the following possibilities are considered: (1) British soldiers attacking the island since 1595. (2) Dutch attackers in 1625. (3) aboriginal tribes. (4) slave traders.

The prevalence of microbioogic flora was determined in a convenience sample of contact lens wearers at the Puerto Rico Medical Center, ophthalmology clinics obtaining cultures from the conjunctival fornices. Gram positive bacterial prevalence was 100% in the control group, as well as in rigid gas permeable lens wearers. In the soft contact lens group, gram positive bacterial prevalence was 94.7%. On the other hand prevalence of Gram negative bacteria is null in the soft contact lens wearer population, being only 2.5% in control group, and 45.5% for Rigid Gas Permeable wearers. These contact lens wearers were using different disinfection systems.

In a total of 112 slaughtered sterile cows of the Zebu cattle, originating from the Camaguey region, Cuba, 25 tumors were found in 22 animals (in three of the cows the tumors were bilateral). Histologically, the tumors were differentiated as follows: 1 papillary adenoma, 6 papillary cystadenomas, 1 adenocarcinoma, 1 papillary adenocarcinoma, 8 granulosocellular tumors, 1 thecoma, 2 luteomas, 4 hemangiomas, and 1 angiocarcinoma. In two of the cases, beside tumors there were in the ovaries parovarian cysts. The differentiation of the tumors were made on the basis of the international histologic classification of tumors of the World Health Organization. Most frequently, the tumors turned out to be granulosocellular ones as well as papillary cystadenomas and hemangiomas.

Gross and histologic studies were carried out with a total of 118 Fallopian tubes of 59 slaughtered sterile cows of the Zebu breed originating from the Gamagüey region in Cuba. Morphologically, there were changes in 53 of the animals (89.8 per cent); of these in 29 cases both oviducts were affected, and in 24 of them only one was with lesions. In 6 of the cases (5 per cent) there were signs of acute salpingitis--hyperaemia, serous exudate, infiltration with lymphocytes and neutrophile granulocytes, and desquamation of the epithelium paving the folds. In 15 cases (13 per cent) there was subacute salpingitis--desquamation of the fold epithelium, negligible hyperaemia with oedema of the mucous membrane, and numerous plasmatic cells, fibroblasts, lymphocytes, and neutrophile granulocytes. In 61 cases (51 per cent) there were chronic salpingitis with varying fibrosis, atrophy of the folds, and cysts in the base of the folds. There were also sporadic cases of perisalpingitis.