Analysis of fecal microbiome and metabolome changes in goats with pregnant toxemia.

BACKGROUND: Pregnancy toxemia is a common disease, which occurs in older does that are pregnant with multiple lambs in the third trimester. Most of the sick goats die within a few days, which can seriously impact the economic benefits of goat breeding enterprises. The disease is believed to be caused by malnutrition, stress, and other factors, that lead to the disorder of lipid metabolism, resulting in increased ketone content, ketosis, ketonuria, and neurological symptoms. However, the changes in gut microbes and their metabolism in this disease are still unclear. The objective of this experiment was to evaluate the effect of toxemia of pregnancy on the fecal microbiome and metabolomics of does. RESULTS: Eight pregnant does suspected of having toxemia of pregnancy (PT group) and eight healthy does during the same pregnancy (NC group) were selected. Clinical symptoms and pathological changes at necropsy were observed, and liver tissue samples were collected for pathological sections. Jugular venous blood was collected before morning feeding to detect biochemical indexes. Autopsy revealed that the liver of the pregnancy toxemia goat was enlarged and earthy yellow, and the biochemical results showed that the serum levels of aspartate aminotransferase (AST) and ß-hydroxybutyric acid (B-HB) in the PT group were significantly increased, while calcium (Ca) levels were significantly reduced. Sections showed extensive vacuoles in liver tissue sections. The microbiome analysis found that the richness and diversity of the PT microbiota were significantly reduced. Metabolomic analysis showed that 125 differential metabolites were screened in positive ion mode and enriched in 12 metabolic pathways. In negative ion mode, 100 differential metabolites were screened and enriched in 7 metabolic pathways. CONCLUSIONS: Evidence has shown that the occurrence of pregnancy toxemia is related to gut microbiota, and further studies are needed to investigate its pathogenesis and provide research basis for future preventive measures of this disease.

Association of vitamin D status with redox balance and insulin resistance and its predicting ability for subclinical pregnancy toxemia in pregnant sheep.

The study aimed to evaluate the role of vitamin D on redox balance, insulin resistance and its predicting value for subclinical pregnancy toxemia (SPT) in pregnant ewes. At four weeks pre-lambing, fifteen healthy pregnant ewes were divided into two groups, ewes with sufficient vitamin D (25-hydroxy-vitamin D (25VitD) (SVD, n = 9) and ewes with insufficient 25VitD (ISVD, n = 6). Blood samples were collected at 4 weeks pre-lambing using modified frequently sampled intravenous glucose tolerance test for the estimation of various metabolites. The baseline glucose, insulin, non-esterified fatty acid (NEFA), fructosamine, beta-hydroxy butyric acid (ß-BHA), calcium, phosphorus concentration and total oxidant status (TOS) did not differ significantly between the two groups, however, total antioxidant capacity (TAC) was significantly (p = 0.031) low in ISVD ewes. Area under the curve for glucose, insulin, elimination rate of glucose and peak insulin also did not differ significantly between the two groups. Correlation analysis revealed, positive association of 25VitD with fructosamine, calcium and TAC, and negative correlation with NEFA and TOS. Subsequent blood sampling at 2 weeks pre-lambing and at lambing showed significant difference in NEFA (p = 0.001), ß-HBA (p = 0.001), and fructosamine(p = 0.012) between the two groups. A significant time x group interaction was observed in NEFA (p = 0.019), ß-HBA (p = 0.031), and fructosamine (p = 0.026) concentration. The NEFA concentrations were increased and fructosamine decreased at 2 weeks pre-lambing and at lambing along with significantly increased ß-HBA at 2 weeks pre-lambing in ISVD compared to SVD. Taking 0.8 mmol/L ß-HBA as the cut off limit for SPT, ISVD ewes had higher odds of developing SPT two weeks prior to lambing (OD 16.00; p = 0.042) and at lambing (OD 10; p = 0.077). This study concludes that 25VitD significantly influence redox balance and energy profile and serves as a valuable predictor for SPT in pregnant sheep.

Changes in free amino acid profile in goats with pregnancy toxemia.

Pregnancy toxemia is a metabolic disorder that afflicts goats when the heightened energy requirements preceding parturition are not sufficiently satisfied. At present, the potential association between pregnancy toxemia and the free amino acid composition in hair goats remains uncharted territory. The purpose of this study is to investigate the free amino acid profile in goats during the pivotal three weeks preceding delivery, distinguishing among those with subclinical pregnancy toxemia (SPT), clinical pregnancy toxemia (CPT), and those in the control group (CG). Additionally, the study aims to investigate any potential relationship between the amino acid profile and beta hydroxy butyric acid (BHBA) levels. The researchers analyzed a total of 50 goats, comprising 20 goats with SPT, 20 with CPT, and 10 in the CG. The serum free amino acid profile was determined using a gas chromatography flame ionization detector (GC-FID) device. BHBA concentration in goats with CPT and SPT was significantly higher than KG (p < 0.001). Furthermore, in goats with CPT, the glucose concentration was significantly lower than in CG (p < 0.012). In goats with CPT and SPT, the concentration of valine, one of the gluconeogenic amino acids, was significantly higher than in control group (p < 0.001), while histidine concentration was significantly lower (p < 0.020) than in control group. Specifically in goats with CPT, the concentrations of alanine (p < 0.002), serine (p < 0.001), and threonine (p < 0.043) were significantly lower than in control group. Moreover, the concentration of phenylalanine, which is both a glycogenic and ketogenic amino acid, was significantly lower (p < 0.028) in goats with SPT compared to the control group. The Fisher ratio (p < 0.010) and Glycine/Alanine ratio (p < 0.001) were significantly higher in pregnancy toxemia goats with than in control group goats, indicating a poor nutritional and energy status of the goats during the prepartum period. In summation, the findings of this study underscore that amino acids exhibiting marked concentration variations hold considerable promise in the diagnosis, prognosis, and therapeutic management of pregnancy toxemia.

Clinical and Biochemical Study of Pregnancy Toxemia in Iraqi Ewes.

Pregnancy toxemia (PT), also known as ketosis or twin lamb disease, is a group of in-sequence metabolic disorders usually observed in the last pregnancy period of ewes. Blood samples from 60 Awassi ewes were collected, including 50 ewes suffering from PT and 10 healthy ewes (2-8 years old) as a control group. All of them were in their final month of pregnancy from different regions of Salah Aldin Governorate, Iraq. The samples were collected between October 2021 and February 2022. Biochemical analysis of serum concentrations of all parameters was performed using the atomic absorption spectrophotometer, except for the beta-hydroxybutyrate and non-esterified fatty acids that were analyzed by enzyme-linked immunosorbent assay method. The results of the clinical criteria tests for temperature, respiration, and pulse showed nonsignificant differences (P<0.05) in the infected animals, compared to the healthy group. Clinical signs included depression, loss of appetite, weight loss, lying down, odor of ketogenic bodies through breathing, inability to walk, neurological signs, dental grinding, jaundice, blindness, bloat, dystocia, animal death, and fetal death. Based on the results of the biochemical parameters tests of the blood, a significant increase (P<0. 05) was observed in the parameters of the results of beta-hydroxybutyrate, non-esterified fatty acids, triglycerides, total bilirubin, and liver enzymes (ALT, AST, ALP, and GGT) in the animals affected by PT, compared to the control group. However, a significant decrease (P<0.05) was observed in the parameters of glucose, cholesterol, total protein, albumin, and globulin in the affected animals, compared to the healthy group. Concerning the association between disease and oxidative stress criteria, the infected animals showed a substantial (P<0.05) increase in malondialdehyde concentration and a significant (P<0.05) drop in glutathione and superoxide dismutase levels.

Pulse wave Doppler ultrasound of umbilical cord in experimentally induced pregnancy toxemia in sheep.

Contrary to its widespread use in human cases, the use of Doppler ultrasonography is only recently becoming prevalent in farm animals. This study aimed to determine the effects of maternal metabolic and clinical changes on fetal hemodynamics during pregnancy toxemia with the doppler examination of umbilical cord. In the study twenty ewes with a single healthy fetus were included in the study. At the end of the 120th day of pregnancy, 20 single-bearing pregnant ewes were randomly categorized into two groups. Ewes in the control group were fed to meet all nutritional requirements. On the other contrary, the experimental ewes were fed to meet equivalent to 50 % of the daily needs and then fasted for 96 h. Doppler ultrasonographic examinations of umbilical cord were performed once every two days and once a day during fasting. Beta hydroxybutyric acid (BHBA) concentration was measured by taking blood from sheep on examination days. Pulse systolic velocity (PSV), end diastolic velocity (EDV), PSV/EDV, pulsatility index (PI), resistance index (RI), and fetal heart rate (FHR) as well as BHBA values and how those parameters has changed over time (time by treatment effect) due to energy deprivation during pregnancy were evaluated using repeated measure analysis of variance. No clinical signs were observed in both toxemia and control groups during restricted feeding. BHBA concentration increased and there was a significant time, time by treatment and main effect of treatment effect between groups. No significant main effect of treatment and time by treatment interaction was observed in the changes of PI, RI, FHR, and systolic/diastolic velocity values over time in both groups. FHR was reduced over time, and there was a significant time effect in FHR in both groups. Although doppler indices didn't increase, both PSV and EDV values increased significantly in the pregnancy toxemia group compared with the controls (Time P = 0.03, time by treatment interaction P < 0.05) and the main effect of treatment P < 0.05). The marked increase in blood velocities (PSV and EDV) in the umbilical cord is probably due to the compensatory functioning for excessive energy deprivation of the fetus. Therefore, PSV and EDV might be a valuable indicator for evaluating the fetus's health status during the management of the PT.

Pregnancy Toxemia Therapeutic Options.

This review covers the treatment options for pregnancy toxemia in small ruminants. Clinical assessment and detection of underlying metabolic and electrolyte derangements direct resuscitation efforts and provide prognostic indications. Treatment programs are dependent on producer goals and case specifics. Options include oral glucogenic precursors (eg, propylene glycol, glycerol), intravenous glucose solutions, insulin, and other supportive care measures. Induction of parturition or C-section is often carried out to minimize ongoing energy deficits, with variable survival rates. Prolonging gestation to maximize fetal viability often requires intensive care in a hospital setting and carries significant risk to both dam and offspring.

Pregnancy Toxemia in Sheep and Goats.

Pregnancy toxemia is a common metabolic disease of late pregnant ewes and does, which potentially has devastating impacts on health and performance. This metabolic syndrome is not only one of over conditioned animals but is more typically associated with inadequate energy intake to support pregnancy requirements leading to body protein and fat mobilization. Blood chemistries provide insight into diagnosis and possibly may predict responsiveness to treatment and outcome. Early recognition of the disease with appropriate intervention is the best approach to minimizing the impact of this disease in the sheep flock or goat herd.

Evaluation of Freestyle Optium Neo H and TaiDoc-TD4235 point-of-care meters for measuring blood ß-hydroxybutyrate concentration in sheep.

BACKGROUND: Accurate and rapid measurement of blood ß-hydroxybutyrate (ß-OHB) concentrations is critical to identify hyperketonemia in sheep. OBJECTIVE: The objective of this study was to test the performance of Freestyle Optium Neo H and TaiDoc-TD4235 point-of-care (POC) devices for measuring blood ß-OHB concentrations in sheep. METHODS: Venous blood samples from 105 sheep were evaluated with Freestyle Optium Neo H and TaiDoc-TD4235 meters. A reference approach was the laboratory measurement of serum BHB concentrations using the Randox D-3 Hydroxybutyrate reagent kit. Data were analyzed using Passing- Bablok regression and Bland-Altman analysis. The diagnostic accuracy was assessed using serum ß-OHB concentration at a cut-off value of 0.8 mmol/L. RESULTS: Passing-Bablok regression analysis revealed an intercept of 0.066 (CI95 : 0.018-0.125) and slope of 1.242 (CI95 : 1.136-1.342) for Freestyle Optium Neo H. Intercept and slope values for the TaiDoc-TD4235 meter were 0.625 (CI95 : 0.539-0.724) and 1.265 (CI95 : 1.044-1.497), respectively. The Bland-Altman plot revealed a bias of 0.224 mmol/L and 0.737 mmol/L for Freestyle Optium Neo H and TaiDoc-TD4235 meters, respectively, compared with the reference method. Observed Total Error (TEobs ) was 56.7% for the Freestyle Optium Neo H and 168.7% for the Taidoc-TD4235. The sensitivity and specificity for the Freestyle Optium Neo H were 100% and 80.9%, respectively, at the threshold of 0.8 mmol/L. The Taidoc-TD4235 demonstrated a sensitivity of 93.3% and specificity of 8.9% at the threshold of 0.8 mmol/L. CONCLUSIONS: Because of the large TEobs , the Freestyle Optium Neo H and TaiDoc-TD4235 meters should not be used to quantify blood ß-OHB concentrations in sheep.

Pregnancy Toxemia in Ewes: A Review of Molecular Metabolic Mechanisms and Management Strategies.

Pregnancy toxemia is a nutritional metabolic disease during late gestation in small ruminants. The condition is characterized by disorders in carbohydrate and fat metabolism. Obese and multiparous ewes are particularly susceptible to pregnancy toxemia, which may lead to maternal death, abortion, or premature birth. Highly productive multiparous meat ewes are major breeding animals, which has led to an increased incidence of the disease. However, the pathogenesis of pregnancy toxemia remains unclear and adequate disease prevention and treatment strategies are absent. Investigating the pathogenesis of pregnancy toxemia, especially the metabolic pathways of hepatic lipids, is key to an improved understanding of the condition. This review provides a snapshot of the genes that are associated with lipid metabolism in the ovine liver, including genes involved in fatty acid oxidation, acetyl coenzyme metabolism, and triglyceride synthesis; describes the interrelationships between these genes; and summarizes the diagnosis, prevention, and treatment of pregnancy toxemia.

Serum concentrations of folic acid and cobalamin and energy metabolism of ewes as a function of the energy density of the diet, peripartum period, and pregnancy toxemia.

The aim of this study was to determine the serum levels of folic acid, cobalamin, and indicators of energy metabolism during the peripartum period of ewes submitted to different diets and with or without pregnancy toxemia. Forty Santa Inês ewes were divided into three groups, a group of 20 animals fed only roughage-diet with low energy density (G1), a group of 10 ewes submitted to diet containing roughage and concentrate-diet with high energy density (G2), and a group of 10 ewes with diagnosis of pregnancy toxemia (PT) (G3). In the ewes of groups G1 and G2, blood samples were collected -30, -15, -7 days pre-partum, on the day of partum, and 7, 15, and 30 days postpartum; blood samples from G3 animals were collected during the veterinary clinic care. Significant variations were observed in the plasma concentration of glucose and serum folic acid, cobalamin, fructosamine, NEFA, and ß-hydroxybutyrate in the groups fed diets with different energy levels, with and without PT (P < 0.05). A positive correlation of folic acid and cobalamin was observed with plasma glucose and serum NEFA concentrations, in addition to negative correlation of glucose with NEFA and ß-hydroxybutyrate and positive correlation between the latter biomarkers of energy metabolism. The ewes diagnosed with PT showed higher levels of folic acid, NEFA, and ß-hydroxybutyrate (P < 0.05). Ewes fed diet containing roughage and concentrate present higher serum levels of folic acid, cobalamin, and glucose, in the pre-partum period and in the lactation period. The results obtained contribute to better understanding of the application of blood concentration tests for folic acid and cobalamin in the energy metabolism and in PT in ewes.

Evaluation of metabolic and oxidative profile in ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of disease.

This study was conducted on ewes with pregnancy toxemia (PT) with an attempt to evaluate metabolic and oxidative profile in subclinical and clinical ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of the disease. A total of 20 ewes having beta-hydroxy butyric acid (ß-HBA) > 2.5 mmol/L and proven clinical sings of PT, categorized as clinical PT (CPT); 12 ewes having ß-HBA 0.8-2.5 mmol/L and no clinical signs of PT, categorized at subclinical PT (SPT); and 10 ewes having ß-HBA ≤ 0.8 mmol/L, categorized as healthy control (CON) were enrolled. Among 20 CPT ewes, 11 had negative outcomes (non-survivors), six ewes had positive outcomes (survivors), and three were lost during follow-up. A significant increase in non-esterified fatty acid, ß-HBA, triglycerides, gamma-glutamyl transferase, lactate dehydrogenase, and malondialdehyde levels and a significant decrease in fructosamine were observed in CPT and SPT compared to CON. A significant increase in cholesterol, aspartate amino transferase, and creatinine kinase and a significant decrease in albumin, potassium, calcium, superoxide dismutase, and catalase were observed in CPT only. Glucose was significantly decreased in SPT only. The highest area under the curve (AUC) was observed for fructosamine (89.7% and 87.5% for CPT and SPT, respectively) with the optimum cutoff point calculated on the basis of maximum sensitivity (SE) and specificity (SP) being 0.607 mmol/L (SE: 89.3% and SP: 72.2%) and 1.005 mmol/L (SE: 90.0% and SP: 75.3%) for CPT and SPT, respectively. At the cutoff limit of 0.607 mmol/L and 1.005 mmol/L, the odds ratio was 10.8 and 8.0 for CPT and SPT, respectively. A significant decrease in fructosamine and potassium and a significant increase in creatinine, lactate dehydrogenase, and malondialdehyde were observed in non-survivors compared to survivors. It was thus concluded that fructosamine was the best diagnostic indicator of both CPT and SPT followed by non-esterified fatty acid. Fructosamine, creatinine, potassium, lactate dehydrogenase, and malondialdehyde were the best prognostic indicators of PT.

Preeclampsia and eclampsia: the conceptual evolution of a syndrome.

Preeclampsia, one of the most enigmatic complications of pregnancy, is considered a pregnancy-specific disorder caused by the placenta and cured only by delivery. This article traces the condition from its origins-once thought to be a disease of the central nervous system, recognized by the occurrence of seizures (ie, eclampsia)-to the present time when preeclampsia is conceptualized primarily as a vascular disorder. We review the epidemiologic data that led to the recommendation to use diastolic hypertension and proteinuria as diagnostic criteria, as their combined presence was associated with an increased risk of fetal death and the birth of small-for-gestational-age neonates. However, preeclampsia is a multisystemic disorder with protean manifestations, and the condition can be present even in the absence of hypertension and proteinuria. Toxins gaining access to the maternal circulation have been proposed to mediate the clinical manifestations-hence, the term "toxemia of pregnancy," which was used for several decades. The search for putative toxins has challenged investigators for more than a century, and a growing body of evidence suggests that products of an ischemic or a stressed placenta are responsible for the vascular changes that characterize this syndrome. The discovery that the placenta can produce antiangiogenic factors, which regulate endothelial cell function and induce intravascular inflammation, has been a major step forward in the understanding of preeclampsia. We view the release of antiangiogenic factors by the placenta as an adaptive response to improve uterine perfusion by modulating endothelial function and maternal cardiovascular performance. However, this homeostatic response can become maladaptive and lead to damage of target organs during pregnancy or the postpartum period. Early-onset preeclampsia has many features in common with atherosclerosis, whereas late-onset preeclampsia seems to result from a mismatch of fetal demands and maternal supply, that is, a metabolic crisis. Preeclampsia, as it is understood today, is essentially vascular dysfunction unmasked or caused by pregnancy. A subset of patients diagnosed with preeclampsia are at greater risk of the subsequent development of hypertension, ischemic heart disease, heart failure, vascular dementia, and end-stage renal disease. However, these adverse events may be the result of a preexisting vascular pathologic process; it is not known if the occurrence of preeclampsia increases the baseline risk. Therefore, the understanding, prediction, prevention, and treatment of preeclampsia are healthcare priorities.

Prediction of preeclampsia throughout gestation with maternal characteristics and biophysical and biochemical markers: a longitudinal study.

BACKGROUND: The current approach to predict preeclampsia combines maternal risk factors and evidence from biophysical markers (mean arterial pressure, Doppler velocimetry of the uterine arteries) and maternal blood proteins (placental growth factor, soluble vascular endothelial growth factor receptor-1, pregnancy-associated plasma protein A). Such models require the transformation of biomarker data into multiples of the mean values by using population- and site-specific models. Previous studies have focused on a narrow window in gestation and have not included the maternal blood concentration of soluble endoglin, an important antiangiogenic factor up-regulated in preeclampsia. OBJECTIVE: This study aimed (1) to develop models for the calculation of multiples of the mean values for mean arterial pressure and biochemical markers; (2) to build and assess the predictive models for preeclampsia based on maternal risk factors, the biophysical (mean arterial pressure) and biochemical (placental growth factor, soluble vascular endothelial growth factor receptor-1, and soluble endoglin) markers collected throughout pregnancy; and (3) to evaluate how prediction accuracy is affected by the presence of chronic hypertension and gestational age. STUDY DESIGN: This longitudinal case-cohort study included 1150 pregnant women: women without preeclampsia with (n=49) and without chronic hypertension (n=871) and those who developed preeclampsia (n=166) or superimposed preeclampsia (n=64). Mean arterial pressure and immunoassay-based maternal plasma placental growth factor, soluble vascular endothelial growth factor receptor-1, and soluble endoglin concentrations were available throughout pregnancy (median of 5 observations per patient). A prior-risk model for preeclampsia was established by using Poisson regression based on maternal characteristics and obstetrical history. Next, multiple regression was used to fit biophysical and biochemical marker data as a function of maternal characteristics by using data collected at 8 to 15+6, 16 to 19+6, 20 to 23+6, 24 to 27+6, 28 to 31+6, and 32 to 36+6 week intervals, and observed values were converted into multiples of the mean values. Then, multivariable prediction models for preeclampsia were fit based on the biomarker multiples of the mean data and prior-risk estimates. Separate models were derived for overall, preterm, and term preeclampsia, which were evaluated by receiver operating characteristic curves and sensitivity at fixed false-positive rates. RESULTS: (1) The inclusion of soluble endoglin in prediction models for all preeclampsia, together with the prior-risk estimates, mean arterial pressure, placental growth factor, and soluble vascular endothelial growth factor receptor-1, increased the sensitivity (at a fixed false-positive rate of 10%) for early prediction of superimposed preeclampsia, with the largest increase (from 44% to 54%) noted at 20 to 23+6 weeks (McNemar test, P<.05); (2) combined evidence from prior-risk estimates and biomarkers predicted preterm preeclampsia with a sensitivity (false-positive rate, 10%) of 55%, 48%, 62%, 72%, and 84% at 8 to 15+6, 16 to 19+6, 20 to 23+6, 24 to 27+6, and 28 to 31+6 week intervals, respectively; (3) the sensitivity for term preeclampsia (false-positive rate, 10%) was 36%, 36%, 41%, 43%, 39%, and 51% at 8 to 15+6, 16 to 19+6, 20 to 23+6, 24 to 27+6, 28 to 31+6, and 32 to 36+6 week intervals, respectively; (4) the detection rate for superimposed preeclampsia among women with chronic hypertension was similar to that in women without chronic hypertension, especially earlier in pregnancy, reaching at most 54% at 20 to 23+6 weeks (false-positive rate, 10%); and (5) prediction models performed comparably to the Fetal Medicine Foundation calculators when the same maternal risk factors and biomarkers (mean arterial pressure, placental growth factor, and soluble vascular endothelial growth factor receptor-1 multiples of the mean values) were used as input. CONCLUSION: We introduced prediction models for preeclampsia throughout pregnancy. These models can be useful to identify women at risk during the first trimester who could benefit from aspirin treatment or later in pregnancy to inform patient management. Relative to prediction performance at 8 to 15+6 weeks, there was a substantial improvement in the detection rate for preterm and term preeclampsia by using data collected after 20 and 32 weeks' gestation, respectively. The inclusion of plasma soluble endoglin improves the early prediction of superimposed preeclampsia, which may be valuable when Doppler velocimetry of the uterine arteries is not available.

High Serum Levels of Toxin A Correlate with Disease Severity in Patients with Clostridioides difficile Infection.

Cloistridioides difficile (CD) represents a major public healthcare-associated infection causing significant morbidity and mortality. The pathogenic effects of CD are mainly caused by the release of two exotoxins into the intestine: toxin A (TcdA) and toxin B (TcdB). CD infection (CDI) can also cause toxemia, explaining the systemic complications of life-threatening cases. Currently, there is a lack of sensitive assays to detect exotoxins circulating in the blood. Here, we report a new semi-quantitative diagnostic method to measure CD toxins serum levels. The dot-blot assay was modified to separately detect TcdA and TcdB in human serum with a limit of detection at the pg/mL levels. TcdA and TcdB concentrations in the plasma of 35 CDI patients were measured at the time of CDI diagnosis and at the fourth and tenth day after CDI diagnosis and initiation of anti-CDI treatment. TcdA and TcdB levels were compared to those determined in nine healthy blood donors. Toxemia was detected in the plasma of 33 out of the 35 CDI cases. We also assessed the relationship between TcdA serum levels and CDI severity, reporting that at the time of CDI diagnosis the proportion of severe CDI cases with a TcdA serum level > 60 pg/µL was higher than in mild CDI cases (29.4% versus 66.6%, p = 0.04). In conclusion, data reported here demonstrate for the first time that toxemia is much more frequent than expected in CDI patients, and specifically that high serum levels of TcdA correlate with disease severity in patients with CDI.

BHBA regulates the expressions of lipid synthesis and oxidation genes in sheep hepatocytes through the AMPK pathway.

Pregnancy toxemia (PT) is the most frequent metabolic disease of sheep during late pregnancy, which can lead to enormous economic losses in sheep farm industry. However, the underlying mechanism of PT in sheep has not been fully elucidated. High levels of ß-hydroxy butyric acid (BHBA) exist in PT sheep. The AMP-activated protein kinase (AMPK) pathway plays a major role in regulating liver function. The aim of this study was to explore the effects of gradient concentrations of BHBA on lipid metabolism of sheep hepatocytes and the underlying molecular mechanism in vitro. The results showed that 0.6, 1.2 mmol/L BHBA could activate AMPKα, promoted the expressions of peroxisome proliferator-activated receptor alpha (PPARα) and its target genes, and inhibited the expressions of sterol regulatory element binding protein-1c (SREBP-1c) as well as its downstream genes. When the concentration of BHBA was beyond 1.2 mmol/L, the expressions of the above-mentioned proteins and genes were just the opposite. However, the expressions of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) did not change significantly. The levels of very low density lipoprotein (VLDL), triglyceride (TG) and cholesterol (T-CHOL) showed a gradually increasing trend with the increase of BHBA concentration. According to the results above, it demonstrates that high levels of BHBA can inhibit the expression of the AMPK pathway and cause lipid metabolism disorders in sheep hepatocytes, which may lead to the occurrence of PT.

Hepatic Perisinusoidal Myofibroblast Proliferation and Systemic Inflammatory Response Precedes Sep/Tox Hepatitis in Broilers.

Septicemia-toxemia (sep/tox) falls under U.S. Department of Agriculture (USDA) food safety Category 1 and is the most common and economically significant cause of broiler carcass condemnations. Hepatic lesions are considered a possible consequence of septicemia and associated bacterial contamination of the carcass. Thus, these lesions are considered an indicator of sep/tox (sep/tox hepatitis). This study was undertaken to analyze the histologic lesions preceding grossly visible liver lesions leading to condemnation because of sep/tox at the processing plant. Livers from carcasses of broilers condemned by USDA inspectors for sep/tox were used to establish microscopic and gross criteria of end-stage sep/tox hepatitis. Following the characterization of sep/tox hepatitis, broilers from a farm with a history of sep/tox condemnations were submitted for postmortem examination and bacteriologic investigation at four intervals during the final 20 days of production. Five healthy and five clinically ill chickens were submitted from four houses at 18, 25, 32, and 38 days of production (160 total). Microscopic lesions representing hepatic perisinusoidal myofibroblast proliferation (HPMP), periportal extramedullary granulopoiesis (PEMG), splenic follicular histiocytosis, and bone marrow cellularity (BMC) were graded subjectively for each bird, and subjective grading was evaluated with digital quantitative techniques. Perisinusoidal hepatic stellate cell morphology and progressive transformation of these cells into myofibroblasts was confirmed by immunohistochemistry for smooth muscle actin and desmin. Aerobic cultures of livers and gall bladders from sep/tox birds yielded no growth of bacteria associated with septicemia. Mild to severe HPMP was observed in all age groups, representing 28% of examined birds. Increases in inflammatory cells observed by PEMG and BMC were positively correlated with progressive HPMP and end-stage sep/tox hepatitis in broiler chickens.

Artículo regular­Proliferación de miofibroblastos perisinusoidales hepáticos y respuesta inflamatoria sistémica que precede a la hepatitis por septicemia y toxemia (sep/tox) en pollos de engorde. La septicemia-toxemia (sep/tox) se incluye en la Categoría 1 de seguridad alimentaria del Departamento de Agricultura de los Estados Unidos. (USDA) y es la causa más común y económicamente significativa de decomisos de canales de pollos de engorde. Las lesiones hepáticas se consideran una posible consecuencia de la septicemia y de la contaminación bacteriana asociada con la canal. Por lo tanto, estas lesiones se consideran un indicador de septicemia/toxemia (hepatitis sep/tox). Este estudio se llevó a cabo para analizar las lesiones histológicas que preceden a las lesiones hepáticas muy visibles que conducen a los decomisos debido a septicemia/toxemia en la planta de procesamiento. Se utilizaron hígados de canales de pollos de engorde decomisados por los inspectores del USDA por septicemia/toxemia para establecer criterios microscópicos y generales de hepatitis en etapa terminal de la septicemia/toxemia. Después de la caracterización de la hepatitis por septicemia/toxemia, los pollos de engorde de una granja con un historial de decomisos por septicemia/toxemia se sometieron a examen post mortem e investigación bacteriológica en cuatro intervalos durante los últimos 20 días de producción. Se enviaron cinco pollos sanos y cinco clínicamente enfermos de cuatro casetas a los 18, 25, 32 y 38 días de producción (160 en total). Las lesiones microscópicas que representan la proliferación de miofibroblastos perisinusoidales hepáticos (HPMP), la granulopoyesis extramedular periportal (PEMG), la histocitosis folicular esplénica y la celularidad de la médula ósea (BMC) se clasificaron subjetivamente para cada ave, y la clasificación subjetiva se evaluó con técnicas cuantitativas digitales. La morfología de las células estrelladas hepáticas perisinusoidales y la transformación progresiva de estas células en miofibroblastos se confirmó mediante inmunohistoquímica para actina y desmina del músculo liso. Los cultivos aeróbicos de hígados y vesícula biliar de aves con septicemia/toxemia no produjeron crecimiento de bacterias asociadas con la septicemia. Se observó proliferación de miofibroblastos perisinusoidales hepáticos de leve a severa en todos los grupos de edad, lo que representa el 28% de las aves examinadas. Los aumentos en las células inflamatorias observados por granulopoyesis extramedular periportal y celularidad de la médula ósea se correlacionaron positivamente con proliferación progresiva de miofibroblastos perisinusoidales hepáticos y con hepatitis por septicemia/toxemia en etapa terminal en pollos de engorde.

Evaluación del rendimiento diagnóstico de un nomograma de predicción de preeclampsia / Evaluation of the diagnostic performance of a preeclampsia prediction nomogram

OBJETIVO: Determinar el rendimiento diagnóstico de un nomograma de predicción de preeclampsia en gestantes atendidas en el Hospital Nacional Dos de Mayo en Lima, Perú de enero de 2016 a julio de 2019. MÉTODO: Estudio de tipo pruebas diagnósticas. Se contó con una muestra de 513 pacientes; de ellas, 225 con diagnóstico de preeclampsia y 288 sin dicho diagnóstico. El análisis de los datos obtenidos se realizó en STATA v.14 y se determinaron la sensibilidad, la especificidad, el valor predictivo positivo y el valor predictivo negativo. RESULTADOS: Se analizó la curva ROC y se encontró un área bajo la curva de 0,91 (intervalo de confianza del 95%: 0,89-0,93), obteniendo 187 puntos como valor de corte de mejor rendimiento diagnóstico, con una sensibilidad del 81,33% y una especificidad del 85,76%. CONCLUSIONES: El nomograma de predicción de preeclampsia tiene un buen rendimiento diagnóstico para las gestantes atendidas en el servicio de ginecología y obstetricia del Hospital Nacional Dos de Mayo.

OBJECTIVE: Determine the diagnostic performance of a preeclampsia prediction nomogram in pregnant women attended at the Dos de Mayo National Hospital during the period from January 2016 to July 2019. METHOD: Study of diagnostic tests. There was a sample of 513 patients, 225 patients with a diagnosis of pre-eclampsia and 288 patients without such diagnosis were selected. The analysis of the data obtained was carried out in STATA v.14, obtaining the values of sensitivity, specificity, PPV and NPV. RESULTS: The ROC curve was analyzed obtaining an AUC of 0.91 (95% CI: 0.89 - 0.93), obtaining 187 points as the cut-off point for the best diagnostic performance, with a sensitivity of 81.33% and a specificity of 85.76%. CONCLUSIONS: The preeclampsia prediction nomogram has a good diagnostic performance for pregnant women attended at the Gynecology and Obstetrics service of the Dos de Mayo National Hospital.

The effects of desert dust storms, air pollution, and temperature on morbidity due to spontaneous abortions and toxemia of pregnancy: 5-year analysis.

Epidemiological studies have suggested an association between particulate air pollution, increased temperatures, and morbidity related to pregnancy outcomes. However, the roles of desert dust storms and climatological factors have not been fully addressed. The objectives of the present study were to investigate the association between desert dust storms, particulate matter with a diameter ≤10 µm (PM10), daily temperatures, and toxemia of pregnancy and spontaneous abortion in Gaziantep, South East Turkey. The study was conducted retrospectively at emergency department of two hospitals in Gaziantep city. Data from January 1, 2009, to March 31, 2014, were collected. Patients, who were diagnosed with toxemia of pregnancy and spontaneous abortion by radiological imaging modalities, were included in the study. Daily temperature ranges, mean temperature values, humidity, pressure, wind speed, daily PM10 levels, and records of dust storms were collected. A generalized additive regression model was designed to assess variable effects on toxemia of pregnancy and spontaneous abortion, while adjusting for possible confounding factors. Our findings demonstrated that presence of dust storms was positively associated with the toxemia of pregnancy both in outpatient admissions (OR=1.543 95% CI=1.186-2.009) and inpatient hospitalizations (OR=1.534; 95% CI=1.162-2.027). However, neither PM10 nor maximum temperature showed a marked association with spontaneous abortion or toxemia of pregnancy in our study population. Our findings suggest that desert dust storms may have an impact on the risk for adverse pregnancy outcomes such as toxemia of pregnancy. Health authorities should take necessary measures to protect pregnant women against detrimental effects of these storms.

Acid-base disorders in sick goats and their association with mortality: A simplified strong ion difference approach.

OBJECTIVES: To investigate the acid-base status of sick goats using the simplified strong ion difference (sSID) approach, to establish the quantitative contribution of sSID variables to changes in blood pH and HCO3 - and to determine whether clinical, acid-base, and biochemical variables on admission are associated with the mortality of sick goats. ANIMALS: One hundred forty-three sick goats. METHODS: Retrospective study. Calculated sSID variables included SID using 6 electrolytes unmeasured strong ions (USI) and the total nonvolatile buffer ion concentration in plasma (Atot ). The relationship between measured blood pH and HCO3 - , and the sSID variables was examined using forward stepwise linear regression. Cox proportional hazard models were constructed to assess associations between potential predictor variables and mortality of goats during hospitalization. RESULTS: Hypocapnia, hypokalemia, hyperchloremia, hyperlactatemia, and hyperproteinemia were common abnormalities identified in sick goats. Respiratory alkalosis, strong ion acidosis, and Atot acidosis were acid-base disorders frequently encountered in sick goats. In sick goats, the sSID variables explained 97% and 100% of the changes in blood pH and HCO3 - , respectively. The results indicated that changes in the respiratory rate (<16 respirations per minute), USI, and pH at admission were associated with increased hazard of hospital mortality in sick goats. CONCLUSIONS AND CLINICAL IMPORTANCE: The sSID approach is a useful methodology to quantify acid-base disorders in goats and to determine the mechanisms of their development. Clinicians should consider calculation of USI in sick goats as part of the battery of information required to establish prognosis.

Toxemia in Human Naturally Acquired Botulism.

Human botulism is a severe disease characterized by flaccid paralysis and inhibition of certain gland secretions, notably salivary secretions, caused by inhibition of neurotransmitter release. Naturally acquired botulism occurs in three main forms: food-borne botulism by ingestion of preformed botulinum neurotoxin (BoNT) in food, botulism by intestinal colonization (infant botulism and intestinal toxemia botulism in infants above one year and adults), and wound botulism. A rapid laboratory confirmation of botulism is required for the appropriate management of patients. Detection of BoNT in the patient's sera is the most direct way to address the diagnosis of botulism. Based on previous published reports, botulinum toxemia was identified in about 70% of food-borne and wound botulism cases, and only in about 28% of infant botulism cases, in which the diagnosis is mainly confirmed from stool sample investigation. The presence of BoNT in serum depends on the BoNT amount ingested with contaminated food or produced locally in the intestine or wound, and the timeframe between serum sampling and disease onset. BoNT levels in patient's sera are most frequently low, requiring a highly sensitive method of detection. Mouse bioassay is still the most used method of botulism identification from serum samples. However, in vitro methods based on BoNT endopeptidase activity with detection by mass spectrometry or immunoassay have been developed and depending on BoNT type, are more sensitive than the mouse bioassay. These new assays show high specificity for individual BoNT types and allow more accurate differentiation between positive toxin sera from botulism and autoimmune neuropathy patients.