ABSTRACT
KEY MESSAGE: Estimating genetic gains and formulating a future salinity elite breeding panel for rice pave the way for developing better high-yielding salinity tolerant lines with enhanced genetic gains. Genetic gain is a crucial parameter to check the breeding program's success and help optimize future breeding strategies for enhanced genetic gains. To estimate the genetic gains in IRRI's salinity breeding program and identify the best genotypes based on high breeding values for grain yield (kg/ha), we analyzed the historical data from the trials conducted in the IRRI, Philippines and Bangladesh. A two-stage mixed-model approach accounting for experimental design factors and a relationship matrix was fitted to obtain the breeding values for grain yield and estimate genetic trends. A positive genetic trend of 0.1% per annum with a yield advantage of 1.52 kg/ha was observed in IRRI, Philippines. In Bangladesh, we observed a genetic gain of 0.31% per annum with a yield advantage of 14.02 kg/ha. In the released varieties, we observed a genetic gain of 0.12% per annum with a 2.2 kg/ha/year yield advantage in the IRRI, Philippines. For the Bangladesh dataset, a genetic gain of 0.14% per annum with a yield advantage of 5.9 kg/ha/year was observed in the released varieties. Based on breeding values for grain yield, a core set of the top 145 genotypes with higher breeding values of > 2400 kg/ha in the IRRI, Philippines, and > 3500 kg/ha in Bangladesh with a reliability of > 0.4 were selected to develop the elite breeding panel. Conclusively, a recurrent selection breeding strategy integrated with novel technologies like genomic selection and speed breeding is highly required to achieve higher genetic gains in IRRI's salinity breeding programs.
Subject(s)
Oryza , Oryza/genetics , Reproducibility of Results , Salinity , Plant Breeding , Bangladesh , Edible GrainABSTRACT
PURPOSE: This study investigates the potential of inflammatory parameters (IP), symptoms, and patient-related outcome measurements as biomarkers of severity and their ability to predict tuberculosis (TB) evolution. METHODS: People with TB were included prospectively in the Stage-TB study conducted at five clinical sites in Barcelona (Spain) between April 2018 and December 2021. Data on demographics, epidemiology, clinical features, microbiology, and Sanit George Respiratory Questionnaire (SGRQ) and Kessler-10 as Health-Related Quality of Life (HRQoL) were collected at three time points during treatment. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil/lymphocyte, and monocyte/lymphocyte ratios (NLR and MLR), complement factors C3, C4, and cH50, clinical and microbiological data, and HRQoL questionnaires were assessed at baseline, 2 months, and 6 months. Their ability to predict sputum culture conversion (SCC) and symptom presence after 2 months of treatment was also analysed. RESULTS: The study included 81 adults and 13 children with TB. The CRP, ESR, NLR, and MLR values, as well as the presence of symptoms, decreased significantly over time in both groups. Higher IP levels at baseline were associated with greater bacillary load and persistent symptoms. Clinical severity at baseline predicted a delayed SCC. Kessler-10 improved during follow-up, but self-reported lung impairment (SGRQ) persisted in all individuals after 6 months. CONCLUSIONS: IP levels may indicate disease severity, and sustained high levels are linked to lower treatment efficacy. Baseline clinical severity is the best predictor of SCC. Implementing health strategies to evaluate lung function and mental health throughout the disease process may be crucial for individuals with TB.
Subject(s)
Quality of Life , Tuberculosis , Adult , Child , Humans , Prospective Studies , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Tuberculosis/microbiology , Longitudinal Studies , C-Reactive ProteinABSTRACT
OBJECTIVE: To compare the incidences of early and late-onset neonatal sepsis, including group B streptococcus (GBS) and Escherichia coli (E. coli) before and after implementation of universal screening and intrapartum antibiotics prophylaxis (IAP). DESIGN: Retrospective cohort study. SETTING: Eight public hospitals and 31 Maternal and Child Health Centres (in Hong Kong. POPULATION: 460 552 women attending routine antenatal service from 2009 to 2020. METHODS: Universal culture-based GBS screening has been offered to eligible women since 2012. Total births, GBS screening tests, maternal GBS colonisation and neonatal sepsis with positive blood or cerebrospinal fluid were retrieved from clinical and laboratory database. MAIN OUTCOME MEASURES: Maternal GBS colonisation rate, early- and late-onset neonatal sepsis (including GBS and E. coli). RESULTS: Of 318 740 women with universal culture-based screening, 63 767 women (20.0%) screened positive. After implementation of GBS screening and IAP, the incidence of early-onset neonatal sepsis decreased (3.25 versus 2.26 per 1000 live births, p < 0.05), including those caused by GBS (1.03 versus 0.26 per 1000 live births, p < 0.05). Segmented regression showed that change in early-onse GBS sepsis incidence after screening was the only significant variable in the outcome trend. There was no significant evidence of increase in incidence of late-onset neonatal sepsis including those caused by GBS. CONCLUSIONS: Universal culture-based GBS screening and IAP were associated with reduction in early-onset neonatal sepsis including GBS disease. Although an increase in incidence of late-onset neonatal sepsis including those caused by GBS cannot be totally ruled out, we did not identify significant evidence that this occurred.
Subject(s)
Neonatal Sepsis , Pregnancy Complications, Infectious , Sepsis , Streptococcal Infections , Infant, Newborn , Child , Female , Pregnancy , Humans , Incidence , Anti-Bacterial Agents/therapeutic use , Neonatal Sepsis/diagnosis , Neonatal Sepsis/epidemiology , Neonatal Sepsis/prevention & control , Streptococcal Infections/diagnosis , Streptococcal Infections/drug therapy , Streptococcal Infections/epidemiology , Retrospective Studies , Escherichia coli , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/epidemiology , Streptococcus agalactiae , Antibiotic Prophylaxis , Sepsis/diagnosis , Sepsis/epidemiology , Sepsis/prevention & control , Infectious Disease Transmission, Vertical/prevention & controlABSTRACT
Berries comprise an economically important group of crops. Knowledge about their arthropod pests and biological control agents is important in the development of more efficient integrated pest management programs. Identification of potential biocontrol agents based solely on morphological attributes may be difficult and so molecular techniques should be incorporated. Here we studied the species diversity of predatory mites in the family Phytoseiidae, and how this diversity is affected by the berry species and crop management approaches, specifically pesticide application regimes. We sampled 15 orchards in the State of Michoacán, Mexico. Sites were selected based on berry species and pesticide regimes. Mite identification was achieved by combining morphological attributes and molecular techniques. Phytoseiidae diversity was compared amongst blackberry, raspberry and blueberry. Subsequently we studied the effect of berry species and pesticide regime on the abundance of the most prevalent phytoseiid species. We identified 11 species of phytoseiid mites. The greatest species diversity was found in raspberry, followed by blackberry and then blueberry. The most abundant species were Typhlodromalus peregrinus and Neoseiulus californicus. The abundance of T. peregrinus was significantly affected by pesticide application but not by berry species. In contrast, abundance of N. californicus was significantly affected by berry species but not by pesticide regime.
Subject(s)
Acari , Mites , Pesticides , Animals , Fruit , Pest Control , Predatory Behavior , Pest Control, Biological/methodsABSTRACT
Anthonomus eugenii Cano (Coleoptera: Curculionidae) is a key pest of cultivated peppers (Capsicum species) in tropical and subtropical America. Here we evaluated the effect of five pepper varieties on the susceptibility of A. eugenii to the parasitoids Bracon sp. (Hymenoptera: Braconidae), Eupelmus cushmani (Crawford) (Hymenoptera: Eupelmidae), and Jaliscoa hunteri Crawford (Hymenoptera: Pteromalidae). Potential parasitism was estimated by comparative analysis of parasitoid ovipositor size and the depth to which host larvae develop inside the fruit. Highest potential parasitism rates were achieved by Bracon sp. and E. cushmani on árbol and habanero peppers (84-99%) while the lowest rates were achieved by J. hunteri on serrano, bell, and jalapeño (7-18%). To validate potential parasitism rates, the actual parasitism rate by Bracon sp. and J. hunteri on three varieties of peppers was assessed. Actual parasitism rates of A. eugenii larvae in árbol were similar for Bracon sp. and J. hunteri (33%), while on bell and jalapeño Bracon sp. achieved 24% and 13% parasitism and J. hunteri achieved 14% and 8%, respectively. In most cases, actual parasitism was lower than estimated potential parasitism, although the latter had a notable predictive power (predicted R2 = 0.84). Results showed that the host was more vulnerable on small-fruited varieties because larvae were closer to the pericarp and could be reached by parasitoid ovipositors; likewise, in varieties with little placenta and seed, some larvae fed in the pericarp, where they were more vulnerable.
Subject(s)
Capsicum , Hymenoptera , Weevils , Animals , Capsicum/classification , Capsicum/parasitology , Hymenoptera/physiology , Larva/parasitology , Weevils/parasitology , Host-Parasite InteractionsABSTRACT
Aims: The aim of the present study was to evaluate the performance of 'high'-'low' yielding pyramided lines (PLs), having the same combinations of qDTYs in Samba Mahsuri, MR219 and IR64-Sub1 genetic backgrounds, and to understand the genetic interactions among QTL and/with genetic background affecting grain yield. Background: Epistasis regulates the expression of traits governed by several major/minor genes/QTL. Multiple pyramided lines (PLs) with the same grain yield QTL (qDTYs) combinations but possessing grain yield variability under different levels of reproductive stage drought stress were identified in different rice genetic backgrounds at International Rice Research Institute (IRRI). Objectives: The objectives of the present study were to evaluate the performance pyramided lines (PLs) with drought QTL in the backgrounds of Samba Mahsuri, MR219 and IR64-Sub1 under reproductive stage drought stress (RS) and NS (non-stress) conditions, to understand the effect of epistatic interactions among qDTYs and with genetic background on GY under the differential level of stress and to identify the promising drought-tolerant lines with high yield under drought and higher background recovery in different genetic backgrounds. Methods: The experiments were conducted in 2015 DS (dry season), 2015 WS (wet season) and 2017 DS at IRRI, Los Baños, Philippines, in a transplanted lowland ecosystem under lowland severe stress (LSS), lowland moderate stress (LMS) and lowland non-stress (LNS). The experiments were laid out in alpha lattice design with two replications. Results: Several digenic interactions were found in different genetic backgrounds, 13 interactions in Samba Mahsuri, 11 in MR219 and 20 in IR64-Sub1 backgrounds. Among all digenic interactions, one QTL × QTL interaction, 17 QTL × background and 26 background × background interactions resulted in GY reduction in low yielding PLs in different genetic backgrounds under LSS or LMS. Negative interaction of qDTY3.1 , qDTY4.1 and qDTY9.1 with background markers and background × background interactions caused up to 15% GY reduction compared to the high yielding PLs under LMS in the Samba Mahsuri PLs. In MR219 PLs, the negative interaction of qDTY2.2 , qDTY3.2 , qDTY4.1 and qDTY12.1 with the background marker interval RM314-RM539, RM273-RM349 and RM445-RM346, RM473D-RM16, respectively resulted 52% GY reduction compared to the high yielding PLs under LSS. In IR64-Sub1 PLs, qDTY6.1 interacted with background loci at RM16-RM135, RM228-RM333, RM202-RM287 and RM415-RM558A marker interval under LSS and at RM475-RM525 marker interval under LMS, causing GY reduction to 58% compared to the high yielding PLs. Conclusion: High yielding PLs in Samba Mahsuri (IR 99734:1-33-69-1-22-6), MR219 (IR 99784-156-87-2-4-1) and IR64-Sub1 (IR 102784:2-89-632-2-1-2) backgrounds without any negative interactions were identified. The identified selected promising PLs may be used as potential drought-tolerant donors or may be released as varieties for drought-prone ecosystems in different countries.
ABSTRACT
INTRODUCTION: Our study compared the prospective risks of intrauterine fetal death (IUFD), neonatal death (NND), perinatal death (PND), and neonatal morbidities in monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies. METHODS: This retrospective cohort study included twin pregnancies who had antenatal care and delivery in a public hospital from 2011 to 2018. Exclusion criteria included monoamnionicity, one/both twin miscarriage, twin-twin transfusion syndrome, or lethal congenital abnormalities. All twins were managed in multiple pregnancy clinic with standardized protocols. Gestational age-specific IUFD, NND, PND, and neonatal morbidity rates were compared according to chorionicity. RESULTS: Three hundred seventy-eight MCDA and 1282 DCDA twins were included. MCDA twins had higher risks of PND (1.9% vs. 0.7% in DCDA twins, p = 0.05), composite neonatal morbidity (p = 0.01), preterm delivery (p < 0.01), and low birth weight (p < 0.01). The prospective risk of IUFD was 0.6% and 0.4% for MCDA and DCDA twins, respectively after 34 weeks' gestation. No NND occurred among deliveries after 30 weeks. The risk of neonatal morbidity of MCDA twins fell from 22.7% at 34 weeks to 2.7% at 37 weeks (p < 0.01). For DCDA twins, the risk of morbidity fell insignificantly from 36 to 38 weeks (4.0% vs. 3.4%, p = 0.60). Logistic regression analysis suggested that the increased risk of perinatal morbidities was related to the higher rate of preterm delivery in MCDA twins rather than chorionicity. CONCLUSION: With close fetal monitoring, the risk of late IUFD in twin pregnancies without major complications is low. Perinatal morbidity can be minimized by avoiding late preterm deliveries in twin pregnancies.
Subject(s)
Pregnancy, Twin , Stillbirth , Female , Humans , Infant, Newborn , Pregnancy , Prospective Studies , Retrospective Studies , Stillbirth/epidemiology , Twins, Dizygotic , Twins, MonozygoticABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the cause of the coronavirus disease 2019 (COVID-19) pandemic, which has a high case fatality rate. Most severely ill patients develop a special type of coagulopathy that had not been described before and that is now considered the main cause of death. For this reason, anticoagulant treatment has become one of the cornerstones of the treatment of this infection. However, the rate at which the evidence regarding the use of anticoagulants is generated is quite fast, and sometimes it is difficult to interpret and conflicting. After having performed an extensive review of the published literature, this proposal for the use of anticoagulant treatment is made, taking into account available resources in Mexico.
La infección por coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) es la causante de la pandemia de enfermedad por coronavirus 2019 (COVID-19), con un índice de letalidad alto. La mayoría de los pacientes graves desarrollan un tipo especial de coagulopatía no descrito hasta ahora y la cual se considera ahora la principal causa de muerte. Por esta razón, el tratamiento anticoagulante se ha convertido en una de las piedras angulares del tratamiento de esta infección. Sin embargo, la velocidad con la que se genera la evidencia respecto al uso de anticoagulantes es muy rápida y, en ocasiones difícil de interpretar y contradictoria. Luego de hacer una revisión extensa de la literatura publicada, se hace esta propuesta para el uso del tratamiento anticoagulante tomando en cuenta los recursos disponibles en México.
Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/therapy , COVID-19/complications , Adult , Algorithms , Blood Coagulation Disorders/prevention & control , Guidelines as Topic , Humans , MexicoABSTRACT
INTRODUCTION: Vitamin K antagonists (VKA) are a therapeutic alternative in patients with venous thromboembolic disease; however, numerous factors affect their pharmacology. OBJECTIVE: To evaluate the quality of VKA anticoagulation at three different time periods in Mexico. METHODS: Prospective study, nested in patient cohorts at three different clinical scenarios between 2013 and 2019. Outpatients with indication for treatment with VKAs for at least 12 months were included. Patients were managed according to the criteria of the treating physician. RESULTS: Patient general characteristics were similar between groups, except for the VKA indication. The results of 4,148 patients and 38,548 INR assessments were analyzed. The times in therapeutic range during the three phases of the study and pooled data were significantly higher for the anticoagulation clinic. Only the number of patient visits was significantly associated with the results, unlike age, gender, and type of VKA. CONCLUSIONS: VKAs are widely used, but it is difficult for therapeutic goals to be achieved, especially in non-specialized clinical services. Creation of anticoagulation clinics is an urgent need for the Mexican health system.
INTRODUCCIÓN: Los antagonista de la vitamina K (AVK) son una alternativa terapéutica en los pacientes con enfermedad tromboembólica venosa; sin embargo, numerosos factores afectan su farmacología. OBJETIVO: Evaluar la calidad de la anticoagulación AVK durante tres diferentes periodos en México. MÉTODOS: Estudio prospectivo, anidado en cohortes de pacientes en tres escenarios clínicos entre los años 2013-2019. Se incluyeron pacientes no hospitalizados con indicación para recibir AVK por al menos 12 meses, quienes fueron manejados de acuerdo con el criterio del médico tratante. RESULTADOS: Las características generales de los pacientes fueron similares entre los grupos, excepto por la indicación para usar los AVK. Se analizaron los resultados de 4148 pacientes y 38 548 evaluaciones de INR. Los tiempos en rango terapéutico durante las tres fases del estudio y los datos acumulados fueron significativamente mayores en la clínica de anticoagulación. Solo el número de visitas de control de los pacientes se asoció significativamente con los resultados, a diferencia de la edad, el sexo y el tipo de AVK. CONCLUSIONES: Los AVK se utilizan ampliamente, pero es difícil alcanzar la meta terapéutica, sobre todo en servicios clínicos no especializados. La creación de clínicas de anticoagulación es una necesidad urgente en el sistema mexicano de salud.
Subject(s)
Anticoagulants , Vitamin K , Fibrinolytic Agents , Humans , Mexico , Prospective StudiesABSTRACT
The [Fe2S2]-RsrR gene transcription regulator senses the redox status in bacteria by modulating DNA binding, while its cluster cycles between +1 and +2 states-only the latter binds DNA. We have previously shown that RsrR can undergo remarkable conformational changes involving a 100° rotation of tryptophan 9 between exposed (Out) and buried (In) states. Here, we have used the chemical modification of Trp9, site-directed mutagenesis, and crystallographic and computational chemical studies to show that (i) the Out and In states correspond to oxidized and reduced RsrR, respectively, (ii) His33 is protonated in the In state due to a change in its pKa caused by cluster reduction, and (iii) Trp9 rotation is conditioned by the response of its dipole moment to environmental electrostatic changes. Our findings illustrate a novel function of protonation resulting from electron transfer.
Subject(s)
DNA-Binding Proteins/chemistry , DNA/chemistry , Electrons , Iron-Sulfur Proteins/chemistry , Protons , Transcription Factors/chemistry , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , DNA/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Histidine/chemistry , Histidine/genetics , Iron-Sulfur Proteins/genetics , Iron-Sulfur Proteins/metabolism , Molecular Dynamics Simulation , Mutation , Oxidation-Reduction , Protein Binding , Protein Conformation , Streptomyces/enzymology , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
The recently discovered Rrf2 family transcriptional regulator RsrR coordinates a [2Fe-2S] cluster. Remarkably, binding of the protein to RsrR-regulated promoter DNA sequences is switched on and off through the facile cycling of the [2Fe-2S] cluster between +2 and +1 states. Here, we report high resolution crystal structures of the RsrR dimer, revealing that the [2Fe-2S] cluster is asymmetrically coordinated across the RsrR monomer-monomer interface by two Cys residues from one subunit and His and Glu residues from the other. To our knowledge, this is the first example of a protein bound [Fe-S] cluster with three different amino acid side chains as ligands, and of Glu acting as ligand to a [2Fe-2S] cluster. Analyses of RsrR structures revealed a conformational change, centered on Trp9, which results in a significant shift in the DNA-binding helix-turn-helix region.
Subject(s)
Bacterial Proteins/chemistry , Transcription Factors/chemistry , Amino Acid Sequence , Bacterial Proteins/metabolism , Crystallography, X-Ray , DNA/metabolism , Models, Molecular , Protein Multimerization , Protein Structure, Quaternary , Transcription Factors/metabolismABSTRACT
AIM: No studies have investigated if national guidelines to manage diabetic foot disease differ from international guidelines. This study aimed to compare guidelines of Western Pacific nations with the International Working Group on the Diabetic Foot (IWGDF) guidance documents. METHODS: The 77 recommendations in five chapters of the 2015 IWGDF guidance documents were used as the international gold standard reference. The IWGDF national representative(s) from 12 Western Pacific nations were invited to submit their nation's diabetic foot guideline(s). Four investigators rated information in the national guidelines as "similar," "partially similar," "not similar," or "different" when compared with IWGDF recommendations. National representative(s) reviewed findings. Disagreements in ratings were discussed until consensus agreement achieved. RESULTS: Eight of 12 nations (67%) responded: Australia, China, New Zealand, Taiwan, and Thailand provided national guidelines; Singapore provided the Association of Southeast Asian Nations guidelines; and Hong Kong and the Philippines advised no formal national diabetic foot guidelines existed. The six national guidelines included were 39% similar/partially similar, 58% not similar, and 2% different compared with the IWGDF recommendations. Within individual IWGDF chapters, the six national guidelines were similar/partially similar with 53% of recommendations for the IWGDF prevention chapter, 42% for wound healing, 40% for infection, 40% for peripheral artery disease, and 20% for offloading. CONCLUSIONS: National diabetic foot disease guidelines from a large and diverse region of the world showed limited similarity to recommendations made by international guidelines. Differences between recommendations may contribute to differences in national diabetic foot disease outcomes and burdens.
Subject(s)
Diabetic Foot/prevention & control , Evidence-Based Medicine , International Agencies , National Health Programs/standards , Practice Guidelines as Topic/standards , Adult , Disease Management , Female , Humans , MaleABSTRACT
BACKGROUND: When cell-free DNA (cfDNA) testing is used as a secondary screening tool following combined first-trimester screening (cFTS), cFTS is used to estimate the prior risk for chromosome abnormalities. This study aimed to assess the factors that are associated with common and atypical abnormalities following cFTS, including cFTS risk, advanced maternal age, increased nuchal translucency (NT) ≥3.5 mm, and abnormal levels of serum markers. METHODS: We reviewed a historical cohort of 1855 Chinese women carrying singleton pregnancies with a positive cFTS [at a threshold of 1:250 for trisomy (T) 21 or 1:180 for T18] in one public hospital over a five-year period. All chromosome abnormalities were confirmed by invasive prenatal diagnosis (IPD) with karyotyping, with or without array comparative genomic hybridization. Using multivariable binary logistic regression analysis, we determined the parameters that were associated with common and atypical abnormalities. RESULTS: Overall, the prevalence of common and atypical abnormalities was 6.2 and 1.2%, respectively, and the prevalence increased with the risk of T21 by cFTS. In pregnancies with a risk of T21 > 1 in 100, a high risk of both T21 and T18, an increased NT, or a pregnancy-associated plasma A (PAPP-A) level < 0.2 multiple of medians (MoM), the prevalence of common abnormalities was 12.2, 64.7, 25.5 and 33.8%, respectively, while that of atypical abnormalities was 1.6, 3.9, 4.2, and 7.4%, respectively. In the multivariable binary logistic regression analysis, out of these four factors, only two (increased NT and PAPP_A < 0.2 MoM) were significant predictors of common and atypical abnormalities, respectively. Of all positive cFTS pregnancies, 50.4% did not have any of these four factors, and the prevalence of common and atypical abnormalities was 1.1 and 0.6%, respectively. There were three atypical abnormalities, all of which were mosaicism, and they were detected among women with IPD alone. The ages of these women were ≥ 35 years. All three pregnancies were continued after proper counseling. After giving birth, only one child had mild abnormalities, while the other two were phenotypically normal. CONCLUSIONS: Our study identified factors associated with common and atypical abnormalities after cFTS. These factors can be used to estimate the prior risk for these abnormalities to help with post-cFTS counseling in terms of choosing between cfDNA testing and IPD.
Subject(s)
Chromosome Aberrations/embryology , Chromosome Disorders/diagnosis , Genetic Testing/statistics & numerical data , Maternal Serum Screening Tests/statistics & numerical data , Pregnancy Trimester, First/blood , Adult , Asian People/genetics , Biomarkers/blood , Cell-Free Nucleic Acids/analysis , China/epidemiology , Chromosome Disorders/embryology , Chromosome Disorders/epidemiology , Comparative Genomic Hybridization , Female , Genetic Testing/methods , Humans , Karyotyping , Logistic Models , Maternal Age , Maternal Serum Screening Tests/methods , Nuchal Translucency Measurement , Pregnancy , Pregnancy-Associated Plasma Protein-A/analysis , Retrospective Studies , Risk Factors , Young AdultABSTRACT
It is difficult to prenatally identify 5p deletion (-) syndrome. Here, we report five cases of 5p- syndrome diagnosed by invasive prenatal diagnosis. Of them, three had a small cerebellum in the second trimester. In one case, a prominent renal pelvis and an absent nasal bone were also found in the first trimester. However, there were no abnormal ultrasound findings in the other two cases. Two cases had noninvasive prenatal testing and one showed a '5p- syndrome positive result' because of reduced amount of cell-free DNA in 5p. Two had combined first-trimester screening performed where one had a high-risk result for trisomy 18 and a low pregnancy-associated plasma protein-A level. Two cases of 5p- syndrome resulted from a parental balanced translocation. Prenatal diagnosis will only be made on invasive prenatal diagnosis for abnormal ultrasound findings with small cerebellum, abnormal prenatal screening or a parental reciprocal translocation involving 5p.
Subject(s)
Cri-du-Chat Syndrome/diagnostic imaging , Cri-du-Chat Syndrome/pathology , Ultrasonography, Prenatal , Adult , Female , Humans , PregnancyABSTRACT
The purpose of this investigation was to develop an exploratory two-step level A IVIVC for three telmisartan oral immediate release formulations, the reference product Micardis, and two generic formulations (X1 and X2). Correlation was validated with a third test formulation, Y1. Experimental solubility and permeability data were obtained to confirm that telmisartan is a class II compound under the Biopharmaceutic Classification System. Bioequivalence (BE) studies plasma profiles were combined using a previously published reference scaling procedure. X2 demonstrated in vivo BE, while X1 and Y1 failed to show BE due to the lower boundary of the 90% confidence interval for Cmax being outside the acceptance limits. Average plasma profiles were deconvoluted by the Loo-Riegelman method to obtain the oral fractions absorbed ( fa). Fractions dissolved ( fdiss) were obtained in several conditions in USP II and USP IV apparatus, and later, the results were compared in order to find the most biopredictive model, calculating the f2 similarity factor. The apparatus and conditions showing the same rank order than in vivo data were selected for further refinement of conditions. A Levy plot was constructed to estimate the time scaling factor and to make both processes, dissolution and absorption, superimposable. The in vitro dissolution experiment that reflected more accurately the in vivo behavior of the different formulations of telmisartan employed the USP IV dissolution apparatus and a dissolution environment with a flow rate of 8 mL/min and a three-step pH change, from 1.2 to 4.5 and 6.8, with a 0.05% of Tween 80. Thus, these conditions gave rise to a biopredictive dissolution test. This new model is able to predict the formulation differences in dissolution that were previously observed in vivo, which could be used as a risk-analysis tool for formulation selection in future bioequivalence trials.
Subject(s)
Drugs, Generic/pharmacokinetics , Telmisartan/pharmacokinetics , Administration, Oral , Biological Availability , Caco-2 Cells , Cross-Over Studies , Drug Liberation , Drugs, Generic/administration & dosage , Drugs, Generic/chemistry , Healthy Volunteers , Humans , Intestinal Absorption , Solubility , Telmisartan/administration & dosage , Telmisartan/chemistry , Therapeutic EquivalencyABSTRACT
Aim: Intra-atrial re-entrant tachycardia (IART) is a common complication in patients with congenital heart disease (CHD) and is related to increased morbidity and mortality. Few reports have been published about factors associated to IART severity. The aim of this study is to analyse factors associated to severe clinical presentation of IART. Methods and Results: Observational study of all consecutive CHD patients who underwent a first IART ablation from January 2009 to December 2015 (94 patients, 39.4% female, and age: 36.55 ± 14.9 years). Severe clinical presentation was defined as heart failure, syncope, shock, electromechanical dissociation (EMD), or aborted sudden death. The majority of patients had moderately or highly complex cardiac defect (90.4%). Types of IART included cavotricuspid isthmus(CTI) dependent in 51% (48), non-CTI-related in 22.3% (20), and both types in 27.7% (26). In 38 patients (40.4%), a severe event occurred and in 16 (17%), the symptoms included shock, syncope, sudden death, or EMD. In 21 (22.3%), severe symptoms were the first manifestation of IART. In multivariate analysis, transposition of the great arteries (TGA) with right systemic ventricle (OR 5.32, 95% C.I. 1.6-7.02, P = 0.0005) and severe dilation of the venous atrium (VsA) (OR 4.17; 95% CI 1.4-8.12, P = 0.0009) were factors independently associated with severity. Conclusion: In our series of 94 CHD patients with a high proportion of moderately to highly complex cardiac defects, severe consequences of IART were frequent. Transposition of the great arteries with systemic right ventricle and severe dilation of VsA were independently associated to severity. Early invasive procedures should be considered for these high-risk patients.
Subject(s)
Heart Defects, Congenital/complications , Tachycardia, Supraventricular/etiology , Action Potentials , Adult , Catheter Ablation , Echocardiography , Electrocardiography , Electrophysiologic Techniques, Cardiac , Female , Heart Defects, Congenital/diagnosis , Heart Rate , Humans , Male , Middle Aged , Risk Assessment , Risk Factors , Severity of Illness Index , Tachycardia, Supraventricular/diagnosis , Tachycardia, Supraventricular/physiopathology , Tachycardia, Supraventricular/surgery , Time Factors , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: To know the epidemiology (prevalence, incidence, progression and morbidity and mortality associated) of peripheral artery disease in general population and the factors associated with this progression is essential to know the evolution of atherosclerosis and develop preventive strategies. The aim of the study was to determine the incidence of PAD after 5 years of follow-up population-based cohort ARTPER, and the evolution of Ankle brachial Index (ABI) in this period. METHODS: Peripheral artery disease incidence analysis after 5 years of follow-up of 3786 subjects > 50 years old. Peripheral artery disease incident when the second cross section Ankle brachial Index was <0.9 in any of the lower limbs, with normal baseline (0.9 to 1.4). RESULTS: Between 2012 and 2013 2762 individuals (77% participation) were re-examined . Finally analyzed 2256 subjects (after excluding pathological Ankle brachial Index) followed for 4.9 years (range 3.8 to 5.8 years), totalling 11,106 person-years. Peripheral artery disease 95 new cases were detected, representing an incidence of 4.3% at 5 years and 8.6 per 1000 person-years (95% CI 6.9 to 10.5) being higher in men (10.2, 95% CI 7.4 to 13.5) than in women (7.5, 95% CI 5.5 to 9.9). Linear correlation between the baseline Ankle brachial Index and the second cross section was low (r = 0.23). CONCLUSIONS: The incidence of peripheral artery disease in ARTPER cohort was 8.6 cases per 1000 person-years, being higher in men, especially <65 years. The correlation between two measures Ankle brachial Index after 5 years of follow-up was low. One might consider whether Ankle brachial Index repeated measures could improve the correlation.