Effects of Major Families of Modulators on Performances and Gastrointestinal Microbiota of Poultry, Pigs and Ruminants: A Systematic Approach.

Considering the ban on the use of antibiotics as growth stimulators in the livestock industry, the use of microbiota modulators appears to be an alternative solution to improve animal performance. This review aims to describe the effect of different families of modulators on the gastrointestinal microbiota of poultry, pigs and ruminants and their consequences on host physiology. To this end, 65, 32 and 4 controlled trials or systematic reviews were selected from PubMed for poultry, pigs and ruminants, respectively. Microorganisms and their derivatives were the most studied modulator family in poultry, while in pigs, the micronutrient family was the most investigated. With only four controlled trials selected for ruminants, it was difficult to conclude on the modulators of interest for this species. For some modulators, most studies showed a beneficial effect on both the phenotype and the microbiota. This was the case for probiotics and plants in poultry and minerals and probiotics in pigs. These modulators seem to be a good way for improving animal performance.

PMIDigest: Interactive Review of Large Collections of PubMed Entries to Distill Relevant Information.

Scientific knowledge is being accumulated in the biomedical literature at an unprecedented pace. The most widely used database with biomedicine-related article abstracts, PubMed, currently contains more than 36 million entries. Users performing searches in this database for a subject of interest face thousands of entries (articles) that are difficult to process manually. In this work, we present an interactive tool for automatically digesting large sets of PubMed articles: PMIDigest (PubMed IDs digester). The system allows for classification/sorting of articles according to different criteria, including the type of article and different citation-related figures. It also calculates the distribution of MeSH (medical subject headings) terms for categories of interest, providing in a picture of the themes addressed in the set. These MeSH terms are highlighted in the article abstracts in different colors depending on the category. An interactive representation of the interarticle citation network is also presented in order to easily locate article "clusters" related to particular subjects, as well as their corresponding "hub" articles. In addition to PubMed articles, the system can also process a set of Scopus or Web of Science entries. In summary, with this system, the user can have a "bird's eye view" of a large set of articles and their main thematic tendencies and obtain additional information not evident in a plain list of abstracts.

Mechanical Ventilation in Pregnancy Due to COVID-19: A Cohort of Three Cases.

We describe our experience with three pregnant women with novel coronavirus disease 2019 (COVID-19) who required mechanical ventilation. Recent data suggest a mortality of 88% in nonpregnant patients with COVID-19 who require intubation and mechanical ventilation. The three women we report were intubated and mechanically ventilated during pregnancy due to respiratory failure and pneumonia resulting from COVID-19. After several days of ventilation, all three were successfully weaned off mechanical ventilation and extubated, and are continuing their pregnancies with no demonstrable adverse effects. Our experience suggests that the mortality in pregnant women with COVID-19 requiring mechanical ventilation is not necessarily as high as in nonpregnant patients with COVID-19. KEY POINTS: · Coronavirus disease 2019 (COVID-19) is now a pandemic.. · COVID-19 may cause pneumonia or respiratory failure in pregnant women.. · Approximately 5% of women with COVID-19 will develop severe or critical disease.. · Mechanical ventilation in pregnant women may not necessarily result in high mortality rates..

Wine markers in archeological potteries: detection by GC-MS at ultratrace levels.

The detection of organic residues that remain absorbed into the pores of ceramic artifacts constitutes a source of information regarding their management. Taking into account the poor conservation state of the potteries and the low amount of the organic tracers together with the main drawbacks to get the relevant information concerning different aspects of past societies, the detection of organic biomarkers is still an analytical challenge. In this work, an improved analytical methodology to maximize the recovery of organic markers related to wine in archeological ceramics is presented. The developed method consists on the extraction of wine-related organic compounds including tartaric acid, malic acid, fumaric acid, succinic acid, citric acid, and syringic acid by means of ultrasonic probe-assisted extraction (UPAE) followed by a preconcentration step by mixed-mode strong anion exchange and reversed-phase solid-phase extraction (SPE) and a derivatization step prior to analysis by means of gas chromatography-mass spectrometry (GC-MS). Finally, the method was applied to real archeological ceramic fragments (two dolia), suspected to have been used to store wine, together with organic residues found inside two amphorae from Zaragoza (Spain). Graphical abstract.

Are Women With Threatened Preterm Labor More Dehydrated Than Women Without It?

OBJECTIVE: To determine if women who present to the labor and delivery unit at 23 0/7 to 36 6/7 weeks gestation with threatened preterm labor (TPTL) are more likely to be dehydrated than women who present at the same gestational age for other reasons. DESIGN: Retrospective cohort study. SETTING: An academic medical center in the northeastern United States. PARTICIPANTS: All women at preterm gestational ages 23 0/7 to 36 6/7 weeks who presented to the labor and delivery unit for care in 2014. METHODS: We compared hydration status by urine specific gravity of women with TPTL to that of women with other chief complaints. Women for whom data were missing and those with hypertension, diabetes, renal disease, vaginal bleeding, ruptured membranes, advanced dilation (>3 cm), multiple gestation, or fetal demise were excluded. Chi-square statistic and a receiver operating characteristic (ROC) curve were used for data analysis. RESULTS: A total of 840 women at 23 0/7 to 36 6/7 weeks gestation presented during the study period; 188 of these had TPTL, 261 had other chief complaints, and 391 were excluded. The proportion of women diagnosed with dehydration was similar between those with TPTL (39%) and those with other complaints (46%, p = .12). An ROC curve showed no association between TPTL and hydration status (area under the curve = 0.57, 95% confidence interval [0.46, 0.67]). CONCLUSION: At 23 0/7 to 36 6/7 weeks gestation, the hydration status of women with TPTL was not different from those without TPTL. Because there is no relationship, it is unlikely that hydration is a worthwhile therapy for women with TPTL, although additional prospective study is warranted.

Vasa Previa: Prenatal Diagnosis and Outcomes: Thirty-five Cases From a Single Maternal-Fetal Medicine Practice.

OBJECTIVES: To assess the accuracy and effectiveness of routine screening for vasa previa, to describe our experience, and to assess factors that contribute to missed cases of vasa previa. METHODS: A retrospective descriptive study of all cases of vasa previa from a single maternal-fetal medicine service between 2009 and 2017 was performed. Ultrasound findings and obstetric and neonatal outcomes were reviewed and analyzed. RESULTS: Thirty-five cases of vasa previa were identified. Most cases (33 of 35 [94.3%]) were diagnosed antenatally. All 33 cases that followed our screening protocol were diagnosed antenatally and had favorable outcomes. Two cases that did not follow our protocol were not diagnosed antenatally and were delivered emergently. The mean gestational age ± SD at delivery of antenatally diagnosed cases was 34.9 ± 1.69 weeks. All neonates survived. CONCLUSIONS: Routine ultrasound screening for vasa previa using American Institute of Ultrasound in Medicine criteria will almost universally lead to good outcomes and prevent perinatal mortality.

Cave acoustics in prehistory: Exploring the association of Palaeolithic visual motifs and acoustic response.

During the 1980 s, acoustic studies of Upper Palaeolithic imagery in French caves-using the technology then available-suggested a relationship between acoustic response and the location of visual motifs. This paper presents an investigation, using modern acoustic measurement techniques, into such relationships within the caves of La Garma, Las Chimeneas, La Pasiega, El Castillo, and Tito Bustillo in Northern Spain. It addresses methodological issues concerning acoustic measurement at enclosed archaeological sites and outlines a general framework for extraction of acoustic features that may be used to support archaeological hypotheses. The analysis explores possible associations between the position of visual motifs (which may be up to 40 000 yrs old) and localized acoustic responses. Results suggest that motifs, in general, and lines and dots, in particular, are statistically more likely to be found in places where reverberation is moderate and where the low frequency acoustic response has evidence of resonant behavior. The work presented suggests that an association of the location of Palaeolithic motifs with acoustic features is a statistically weak but tenable hypothesis, and that an appreciation of sound could have influenced behavior among Palaeolithic societies of this region.

Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays: outcomes, benefits, and challenges.

PURPOSE: Chromosomal microarray analysis (CMA) is currently considered first-tier testing in pediatric care and prenatal diagnosis owing to its high diagnostic sensitivity for chromosomal imbalances. The aim of this study was to determine the efficacy and diagnostic power of CMA in both fresh and formalin-fixed paraffin-embedded (FFPE) samples of products of conception (POCs). METHODS: Over a 44-month period, 8,118 consecutive samples were received by our laboratory for CMA analysis. This included both fresh (76.4%) and FFPE samples (22.4%), most of which were ascertained for recurrent pregnancy loss and/or spontaneous abortion (83%). The majority of samples were evaluated by a whole-genome single-nucleotide polymorphism (SNP)-based array (81.6%); the remaining samples were evaluated by array-comparative genomic hybridization (CGH). RESULTS: A successful result was obtained in 7,396 of 8,118 (91.1%), with 92.4% of fresh tissue samples and 86.4% of FFPE samples successfully analyzed. Clinically significant abnormalities were identified in 53.7% of specimens (3,975 of 7,396), 94% of which were considered causative. CONCLUSION: Analysis of POC specimens by karyotyping fails in 20-40% of cases. SNP-based CMA is a robust platform, with successful results obtained in >90% of cases. SNP-based CMA can identify aneuploidy, polyploidy, whole-genome homozygosity, segmental genomic imbalances, and maternal cell contamination, thus maximizing sensitivity and decreasing false-negative results. Understanding the etiology of fetal loss enables clarification of recurrence risk and assists in determining appropriate management for future family planning.Genet Med 19 1, 83-89.

Is there an association between assisted reproductive technologies and time and complications of the third stage of labor?

PURPOSE: To determine if vaginal deliveries exposed to assisted reproductive technologies (ART) are associated with an increased time between delivery of the neonate and placenta and select complications. METHODS: A retrospective cohort of patients enrolled in an infertility practice who had term, singleton, vaginal deliveries at two academic hospitals from 2008 to 2013 was analyzed. Controls were patients with spontaneous conceptions after infertility consultations. The exposure groups were patients with controlled ovarian hyper-stimulation (COH) with in vivo fertilization, COH with in vitro fertilization and fresh embryo transfer (COH/IVF), and frozen embryo transfer or oocyte donation recipients without COH (non-COH ET). Multiple gestations and stillbirths were excluded. Median time of third stage was compared using the Mann-Whitney U test. Secondary outcomes of retained placenta, manual placental extraction, and post-partum hemorrhage (PPH) were compared using Chi-square or Fisher's exact analyses. RESULTS: A total of 769 patients met criteria and were analyzed. While there were no differences in time of third stage of labor, retained placenta, or PPH, manual extraction was significantly more common among non-COH ET [age-adjusted OR 5.6 (95 % CI 2.2-13.8); p < 0.001]. CONCLUSIONS: Patients who conceived after non-COH ET were at increased risk for manual placental extraction. This association was not influenced by age differences between groups. Further research must be done to determine which elements of the ART process are responsible for these differences.

A prenatal presentation of severe microcephaly and brain anomalies in a patient with novel compound heterozygous mutations in the STIL gene found postnatally with exome analysis.

OBJECTIVE: This report outlines how current fetal neuroimaging and genomic technologies can aid in determining the causes of prenatal microcephaly. BACKGROUND: The differential diagnosis and prognosis of fetal microcephaly is a challenging and common presenting problem to the child neurologist and perinatologist. There was a time that the prospective parents could only be told that the child would be microcephalic. Not much could be determined in regard to exact diagnosis or prognosis. METHODS: At 20 weeks' gestation the fetus was observed to have isolated microcephaly on fetal ultrasound. Karyotyping and a nontargeted genomic microarray were performed at 21&4/7 weeks gestation on amniocytes and the results were normal. At this time, toxoplasmosis, rubella, syphilis, cytomegalovirus and herpes studies were also negative. Fetal magnetic resonance imaging at 31 weeks' gestation revealed severe microcephaly with an anomaly consistent with holoprosencephaly. Whole-exome sequence analysis was performed. RESULTS: Postnatal whole-exome sequence analysis revealed two novel compound heterozygous mutations in the STIL gene (c.2354_2355dupGA and c.3835C>T), which is consistent with microcephaly and migrational anomalies. The postnatal magnetic resonance imaging reveals agenesis of the corpus callosum, agyria of the frontal and temporal lobes, and a large cyst along the interhemispheral fissure extending to the parietal and occipital regions in addition to pontine and cerebellar dysgenesis. CONCLUSION: This case demonstrates the state-of-the-art approach to the clinical challenge of prenatal microcephaly and defines unique findings associated with compound heterozygous STIL gene mutations c.2354_2355dupGA and c.3835C>T.

1H MR spectroscopy in the assessment of gliomatosis cerebri.

OBJECTIVE: Gliomatosis cerebri is a rare brain tumor with a short survival time; for this reason, it is difficult to establish the degree of aggressivity in vivo. The MR spectroscopic findings on this tumor often do not agree with choline level. The purpose of this study was to evaluate whether MR spectroscopy can be used to measure tumor choline levels and whether the findings give useful information about tumor growth rate and patient survival time. SUBJECTS AND METHODS: We performed MRI and 1H MR spectroscopic studies on seven treatment-naive patients with gliomatosis cerebri and on 16 healthy volunteers. We then analyzed the association between survival time and levels of choline (Cho) and N-acetyl aspartate (NAA) normalized to creatine (Cr). RESULTS: The results showed a statistically significant (p = 0.05) inverse relation between Cho/Cr ratio and survival time. In addition, NAA/Cr ratio was significantly lower in the patient group than in the control group (p = 0.001). CONCLUSION: Cho/Cr ratio measured with MR spectroscopy seems to be related to survival time, possibly explaining the inconsistent findings previously reported for this parameter.

Dorsolateral prefrontal and superior temporal volume deficits in first-episode psychoses that evolve into schizophrenia.

Regions with a likely involvement in schizophrenia may differ between patients with first-episodes of psychosis respectively with and without evolution into schizophrenia following the initial episode. We have used magnetic resonance imaging (MRI) to assess the volumes of dorsolateral prefrontal (DLPF) and superior temporal gyrus (STG) in a group of 37 first-episode psychotic patients. After an initial MRI study performed by the time of the first episode, the subjects were followed for two years. After this period 22 cases were diagnosed with schizophrenia, while the other 15 did not show clinical evidence for this illness. A Talairach-based tool was used for segmentation and volumetry of the MRI scans. A group of 44 healthy controls was used for comparison and, using lineal regression, to control for the normal effects of age and intracranial volume on the regional parameters of the patients. By the time of their first episode, patients with schizophrenia had significantly less grey matter in the right DLPF and STG regions as compared to both controls and FE without schizophrenia. Nevertheless, these parameters could not predict final diagnosis in a discriminant analysis model. Our findings indicate that subtle structural defects are already found by the time of the first psychotic break in schizophrenia, although clinical implications for these differences seem unclear.

No association between dorsolateral prefrontal gray matter deficit and N-acetyl aspartate ratios in schizophrenia.

The cellular substrates of cortical volume deficit in schizophrenia are unclear. We may hypothesize that, if that deficit was related to a decrease in the amount in neuronal tissue, it should correlate with N-acetyl aspartate levels. We studied a group of 34 schizophrenia patients (of them, 17 first episodes) with both structural and spectroscopic magnetic resonance (MR). Using the data of 50 controls, we were able to calculate for each case residuals of gray matter and cortical cerebrospinal fluid (CSF) in the dorsolateral prefrontal (DLPF) region, representing the deviation from the expected values in normals, given individual intracranial volume and age. Although our patients showed a significant deficit in gray matter and excess in cortical CSF in the DLPF region, that deficit was unrelated to N-acetyl aspartate levels. This was also true for the chronic and first episode groups analyzed separately. These results do not support a neuronal tissue deficit as contributing to the cortical volume deficit in schizophrenia, at least in the DLPF region.

Increase in gray matter and decrease in white matter volumes in the cortex during treatment with atypical neuroleptics in schizophrenia.

The effects of atypical antipsychotic treatment on the brain volume deficits associated with schizophrenia are poorly understood. We assessed the brain volumes of eleven healthy controls and 29 patients with schizophrenia, using magnetic resonance imaging at baseline and at follow-up after two years of treatment with atypical neuroleptics. Two groups of patients were analyzed: treatment-naïve patients (n = 17) and chronic treatment-resistant patients (n = 12). Treatment-naïve patients received risperidone during the follow-up period, whereas chronic patients received clozapine. Gray matter (GM) and white matter (WM) volumes in the frontal, parietal, occipital, and temporal lobes were measured. Contrary to the controls, both groups of patients presented GM increases and WM decreases in the parietal and occipital lobes (p < .005). Frontal GM also increased in the chronic group with clozapine. There was a significant (p < .001) inverse relationship between the baseline volumes (GM deficit/WM excess) and the longitudinal change. These GM and WM changes were not related to changes in weight. Thus, treatment with risperidone and clozapine in schizophrenia may have an effect on gray and white matter volume and needs further exploration.

Association between excessive frontal cerebrospinal fluid and illness duration in males but not in females with schizophrenia.

OBJECTIVE: Excessive cortical cerebrospinal fluid (CSF) has been acknowledged as a possible marker of a gray matter loss. This excess in schizophrenia is found predominantly in the prefrontal and temporal regions. We hypothesized that the poorer global outcome and treatment response in males with schizophrenia are related to a greater cortical volume loss as compared to females. SUBJECTS AND METHODS: In order to test this hypothesis we have used magnetic resonance imaging (MRI) to study the cortical (prefrontal, temporal, and hemispheric) CSF values in a group of 85 patients with schizophrenia, of whom 56 were males and 29, females. We calculated the residual values of CSF in the patients based on the data pertaining to 45 control subjects and linear regression, from which the normal effects of age and intracranial volume were discounted. These residual scores constitute a quantitative measurement of the excess of CSF due to the disease. RESULTS: Males, but not females, presented a trend-level significant excess of left prefrontal CSF. The prefrontal and temporal residual values were significantly associated with illness duration in males, but not in females. DISCUSSION: These results conform to the worse outcome and the higher severity of structural abnormalities generally found in schizophrenia in male subjects. CONCLUSION: Our data support the hypothesis of accelerated prefrontal cortical loss in males, but not in females with schizophrenia.

Elevated factor VII as a risk factor for recurrent fetal loss. Relationship to factor VII gene polymorphisms.

Haemostatic abnormalities can be detected in a portion of the women who have recurrent fetal loss. We measured factor VII coagulant activity (FVII:C) in 65 women with 3 or more fetal losses (recurrent cases), 31 women with one 2nd or 3rd trimester loss (late loss cases), and 81 women with only live births (controls). FVII:C was greater than 2 standard deviations above the mean for controls in 9 recurrent cases (13.8%) and 2 controls (2.5%) for an odds ratio of 6.35 (95% CI 1.32-30.52, p=0.012). In recurrent cases, mean levels were significantly higher than controls for FVII:C (p=0.003), FVII antigen (p=0.024), and FVIIa (p=0.001). Late loss cases had an odds ratio of 4.23 (95% CI 0.67-26.67, p=0.098) with FVII:C, FVII antigen, and FVIIa not significantly different from the controls. DNA was examined for the presence of mutations or polymorphisms in the promoter region of the FVII gene, using denaturing HPLC. Abnormal patterns were confirmed with direct sequencing. A previously reported polymorphism, -402 G>A, was found to be present in 11/14 subjects with elevated FVII:C (79%) and 43% of those with normal levels (p=0.029). FVII:C, FVII antigen and FVIIa varied significantly with genotype; however, genotype frequencies did not differ between controls and either case group. No other promoter polymorphisms were identified. This is the first report of a significant elevation of FVII in a population with recurrent fetal loss. These data suggest the need for further investigation of this potential risk factor.

N-acetyl-aspartate levels in the dorsolateral prefrontal cortex in the early years of schizophrenia are inversely related to disease duration.

Magnetic resonance spectroscopy studies in schizophrenia have revealed consistently reduced N-acetyl aspartate (NAA) levels in chronic patients, but not in recent-onset patients. Studies on the relationship between this marker and disease duration have commonly been negative, although it is also true that they have been conducted in patients with long-standing disease. We compared NAA levels in the dorsolateral prefrontal cortex in 16 recent-onset patients (duration: 1.8+/-0.6 years), 19 chronic patients (duration: 9.7+/-6.1 years), and 20 healthy controls. We studied the NAA/creatine and choline/creatine ratios in the dorsolateral prefrontal cortex in both hemispheres, controlling for the effect of age. Chronic patients had significantly lower NAA/Cr ratios in the left hemisphere compared to recent-onset patients and healthy controls, with no difference in Cho/Cr ratio. There were no differences between controls and recent-onset patients. There was a significant inverse relationship between left-side NAA/Cr and disease duration, suggesting that prefrontal NAA levels may progressively decrease in schizophrenia. Taken within the context of the existing literature, these results indicate that this process may be limited to the early years following the onset of the disease. Therefore, reduced prefrontal levels of NAA may be limited to chronic schizophrenia patients.

Prefrontal atrophy in first episodes of schizophrenia associated with limbic metabolic hyperactivity.

Reduced volume and activity of the prefrontal (PF) cortical gray matter (GM) and hippocampal hypermetabolism are repeated findings in schizophrenia. There is still an information deficit about the significance of reduction of PF GM in schizophrenia, and a simultaneous study of PF anatomy and activity and limbic metabolism can contribute to fill that deficit. In order to do so, we used positron emission tomography (PET) with 18-fluoro-deoxy-glucose (FDG) during an attention task and magnetic resonance imaging (MRI) to study a sample of first episodes of psychosis. We included 21 first episodes (FE) of psychosis and 16 healthy controls. A diagnosis of schizophrenia was confirmed in the follow-up in eleven of these patients and ruled out in the remaining 10 cases. Volumes of PF GM were determined and also activity in the same region and in the hippocampus. Residual GM was estimated in the PF region as a quantitative measurement of the degree of atrophy in each individual, using age and intracranial volume data from a set of 45 healthy controls and linear regression. Patients with schizophrenia had lower PF metabolic activation and greater hippocampal activity than controls. FE patients without schizophrenia were no different in any parameter as compared to controls. Patients with schizophrenia presented an inverse and significant association between GM deficit and hippocampal activity that was not observed in controls or in patients without schizophrenia. The same association was previously described by our group using PET in the resting state in recent-onset and chronic patients with schizophrenia. These findings support a loss in PF inhibitory capacity as a possible link between anatomical and functional alterations in schizophrenia.

Lower prefrontal gray matter volume in schizophrenia in chronic but not in first episode schizophrenia patients.

Although a lower volume of prefrontal (PF) gray matter (GM) in patients with schizophrenia than in normal control subjects is a replicated finding, it is not yet clear whether this finding is present at the onset of illness. Clinical and imaging data suggest that the reduction in PF GM becomes apparent only some years following the onset of illness. To test this hypothesis, we used magnetic resonance imaging to study PF GM and sulcal cerebrospinal fluid (CSF) volumes in 81 schizophrenic patients. A Talairach-based tool was used for segmentation. Subjects included 44 healthy controls, 22 first-episode (FE), treatment-naïve patients with duration of illness of less than 1 year; 29 short-term chronic (SC) patients with durations of illness between 1.5 and 6 years; and 30 long-term chronic (LC) patients with duration of illness of more than 6 years. The data from healthy controls were used to calculate volume residuals in the patients, defined as deviations from the expected values given individual age and intracranial volume. The FE group did not show significant differences in GM or in CSF volumes compared with controls. However, both the SC and the LC patients showed the expected pattern of lower values for PF GM and an excess of PF sulcal CSF compared with controls. There were no significant differences between SC and LC patients in any of these measurements. There was a significant and inverse association between duration of illness and GM residuals. That association fit a nonlinear rather than a linear model, which was consistent with a decrease of GM volume during the first years following illness onset. No significant differences were found between those receiving atypical and typical antipsychotic drugs during the previous year.