High unrecognized SARS-CoV-2 exposure of newly admitted and hospitalized psychiatric patients.

BACKGROUND: Patients with pre-existing mental disorders are at higher risk for SARS-CoV-2 infection and adverse outcomes, and severe mental illness, including mood and psychosis spectrum disorders, is associated with increased mortality risk. Despite their increased risk profile, patients with severe mental illness have been understudied during the pandemic, with limited estimates of exposure in inpatient settings. OBJECTIVE: The aim of this study was to describe the SARS-CoV-2 seroprevalence and antibody titers, and pro-inflammatory cytokine concentrations of newly admitted or hospitalized psychiatric inpatients without known history of COVID-19 infection, using robust quantitative multi-antigen assessments, and compare patients' exposure to that of hospital staff. METHODS: This multi-centric, cross-sectional study compared SARS-CoV-2 seroprevalence and titers of 285 patients (University Psychiatric Centre Duffel [UPCD] N = 194; Assistance-Publique-Hopitaux de Paris [AP-HP] N = 91), and 192 hospital caregivers (UPCD N = 130; AP-HP N = 62) at two large psychiatric care facilities between January 1st and the May 30th 2021. Serum levels of SARS-CoV-2 antibodies against Spike proteins (full length), spike subunit 1 (S1), spike subunit 2 (S2), spike subunit 1 receptor binding domain (S1-RBD) and Nucleocapsid proteins were quantitatively determined using an advanced capillary Western Blot technique. To assess the robustness of the between-group seroprevalence differences, we performed sensitivity analyses with stringent cut-offs for seropositivity. We also assessed peripheral concentrations of IL-6, IL-8 and TNF-a using ELLA assays. Secondary analyses included comparisons of SARS-CoV-2 seroprevalence and titers between patient diagnostic subgroups, and between newly admitted (hospitalization ≤ 7 days) and hospitalized patients (hospitalization > 7 days) and correlations between serological and cytokines. RESULTS: Patients had a significantly higher SARS-CoV-2 seroprevalence (67.85 % [95% CI 62.20-73.02]) than hospital caregivers (27.08% [95% CI 21.29-33.77]), and had significantly higher global SARS-CoV-2 titers (F = 29.40, df = 2, p < 0.0001). Moreover, patients had a 2.51-fold (95% CI 1.95-3.20) higher SARS-CoV-2 exposure risk compared to hospital caregivers (Fisher's exact test, P < 0.0001). No difference was found in SARS-CoV-2 seroprevalence and titers between patient subgroups. Patients could be differentiated most accurately from hospital caregivers by their higher Spike protein titers (OR 136.54 [95% CI 43.08-481.98], P < 0.0001), lower S1 (OR 0.06 [95% CI 0.02-0.15], P < 0.0001) titers and higher IL-6 (OR 3.41 [95% CI 1.73-7.24], P < 0.0001) and TNF-α (OR 34.29 [95% CI 5.00-258.87], P < 0.0001) and lower titers of IL-8 (OR 0.13 [95% CI 0.05-0.30], P < 0.0001). Seropositive patients had significantly higher SARS-COV-2 antibody titers compared to seropositive hospital caregivers (F = 19.53, df = 2, P < 0.0001), while titers were not different in seronegative individuals. Pro-inflammatory cytokine concentrations were not associated with serological status. CONCLUSION: Our work demonstrated a very high unrecognized exposure to SARS-CoV-2 among newly admitted and hospitalized psychiatric inpatients, which is cause for concern in the context of highly robust evidence of adverse outcomes following COVID-19 in psychiatric patients. Attention should be directed toward monitoring and mitigating exposure to infectious agents within psychiatric hospitals.

[Acute geriatric treatment of older trauma patients : Influence on mobility, autonomy and postdischarge destination]. / Geriatrische Komplexbehandlung bei alterstraumatologischen Patienten : Einfluss auf Mobilität, Selbsthilfefähigkeit und Austrittsdestination.

BACKGROUND: Acute geriatric treatment is a type of early rehabilitation for hospitalized seniors to maintain personal autonomy and to avoid nursing home placement. OBJECTIVE: The aim of the study was to describe the changes of mobility and functional independence of older trauma patients during acute geriatric treatment. MATERIAL AND METHODS: This study analyzed admission and discharge assessment data from 164 patients in the geriatric department with fall-related injuries. Mobility and performance in activities of daily living were assessed using the short physical performance battery (SPPB), gait speed and Barthel index. We analyzed changes in mobility from admission to discharge (t-test) and examined differences in mobility between patients returning home and those admitted to long-term care (age-adjusted and gender-adjusted linear regression model). RESULTS: Patients improved their mobility measured by the SPPB by 1.8 points ±â€¯2.1 points, gait speed by 0.10 ±â€¯0.14 m/s and the Barthel index by 13 ±â€¯16 points, all p < 0.001). The number of patients not able to walk decreased from 43% to 14% (p = 0.003). Of the community-dwelling patients 73% were discharged either directly back home or after rehabilitation outside the hospital as a transitional solution. CONCLUSION: In the context of acute geriatric treatment older trauma patients significantly improved their mobility and performance. The majority of patients could return home.

Gain and loss of subcutaneous and abdominal adipose tissue depot mass of German Holstein dairy cows with different body conditions during the transition period.

Subcutaneous adipose tissue (SCAT) and abdominal adipose tissue (AAT) depots are mobilized during the fresh cow period (FCP) and early lactation period (ELP) to counteract the negative energy balance (NEB). Earlier studies suggested that fat depots contribute differently to lipomobilization and may vary in functionality. Differences between the adipose depots might influence the development of metabolic disorders. Thus, the gain and loss of subcutaneous and abdominal adipose depot masses in Holstein cows with lower and higher body condition (mean body condition scores: 3.48 and 3.87, respectively) were compared in the period from d -42 to d 70 relative to parturition in this study. Animals of the 2 experimental groups represented adequately conditioned and overconditioned cows. Estimated depot mass (eDM) of SCAT, AAT, retroperitoneal, omental, and mesenteric adipose depots of 31 pluriparous German Holstein cows were determined via ultrasonography at d -42, 7, 28, and 70 relative to parturition. The cows were grouped according to the eDM of SCAT on d -42 [low body condition (LBC) group: n = 16, mean eDM 8.6 kg; high body condition (HBC) group: n = 15, mean eDM 15.6 kg]. Average daily change (prepartum gain and postpartum loss) in depot masses during dry period (DP; from d -42 to d 7), FCP (d 7 to d 28), and ELP (d 28 to d 70) were calculated and daily dry matter intake and lactation performance recorded. Cows of this study stored about 2 to 3 times more fat in AAT than in SCAT depots. After parturition, on average more adipose tissue mass was lost from the AAT than the SCAT depot (0.23 kg/d vs. 0.14 kg/d). Cows with high compared with low body condition had similar gains in AAT (0.33 kg/d) and SCAT (0.14 kg/d) masses during the DP but mobilized significantly more adipose tissue mass from both depots after calving (AAT, HBC vs. LBC: 0.30 vs. 0.17 kg/d; SCAT, HBC vs. LBC: 0.19 vs. 0.10 kg/d). Correlation analysis indicated a functional disparity between AAT and SCAT. In the case of AAT (R2 = 0.36), the higher the gain in adipose mass during DP, the higher the loss in FCP, but this was not the case for SCAT. During FCP, a greater NEB resulted in greater loss of mass from SCAT (R2 = 0.18). In turn, greater mobilization of SCAT mass led to a higher calculated feed efficiency (R2 = 0.18). However, AAT showed no such correlations. On the other hand, during ELP, loss of both SCAT and AAT mass correlated positively with feed efficiency (R2 = 0.35 and 0.33, respectively). The results indicate that feed efficiency may not be an adequate criterion for performance evaluation in cows during NEB. Greater knowledge of functional disparities between AAT and SCAT depots may improve our understanding of excessive lipomobilization and its consequences for metabolic health and performance of dairy cows during the transition period.

Modeling reticular and ventral ruminal pH of lactating dairy cows using ingestion and rumination behavior.

The prevention and control of metabolic and digestive diseases is an enormous challenge in dairy farming. Subacute ruminal acidosis (SARA) is assumed to be the most severe feed-related disorder and it impairs both animal health and economic efficiency. Currently, ruminal pH as well as variables derived from the daily pH curve are the main indicators for SARA. The objective of this study was to explain the daily pH course in the ventral rumen and reticulum of dairy cows using ingestion pattern and rumination behavior data gathered by automated data recording systems. The data of 13 ruminally fistulated lactating cows were collected at the experimental station of the Friedrich-Loeffler-Institut (Brunswick, Germany). The data included continuous pH measurements, which were recorded simultaneously in the reticulum by pH-measuring boluses and in the ventral rumen by a separate data logger. In addition, rumination behavior was measured using jaw movement sensors, and feed and water intakes were recorded by transponder-assisted systems. Milk yield and body weight were determined during and after each milking, respectively. For statistical evaluation, the data were analyzed using time-series modeling with multiple linear mixed regressions. Before applying the developed mathematical statistical modeling, we performed a plausibility assessment to ensure data quality. The major part of the mathematical statistical modeling consisted of data preparation, where all variables were transformed into a uniform 1-min resolution. Signal transformations were used to model individual feed and water intakes as well as rumination behavior events over time. Our results indicated that diurnal pH curves of both the reticulum and ventral rumen could be predicted by the transformed feed and water intake rates. Rumination events were associated with a marginal temporal increase in pH. We observed that the pH of the ventral rumen was delayed by approximately 37 min compared with that of the reticulum, which was therefore considered in the modeling. With the models developed in this study, 67.0% of the variance of the reticular pH curves and 37.8% of the variance of the ruminal pH curves could be explained by fixed effects. We deduced that the diurnal pH course is, to a large extent, associated with the animal's individual feed intake and rumination behavior.

Physical performance among patients aged 70 + in acute care: a preliminar comparison between the Short Physical Performance Battery and the De Morton Mobility Index with regard to sensitivity to change and prediction of discharge destination.

BACKGROUND: The Short Physical Performance Battery (SPPB) and the De Morton Mobility Index (DEMMI) are two commonly used instruments to assess mobility in older patients. AIMS: To compare the two assessments in acute senior trauma patients with regard to sensitivity to change during an acute care, and prediction of discharge destination. METHODS: Medical records were extracted for consecutive trauma patients aged 70 + receiving acute care rehabilitation in the geriatric ward during 9 months. SPPB and DEMMI were obtained at admission and discharge. Sensitivity was analyzed using paired t tests and Cohen's d, and discharge destination with logistic regression predicting the probability of returning home. RESULTS: A total of 69 patients were included in the study [83.7 years (SD 6.3), 78% women, length of stay 10 (IQR 8-10) days]. Overall, SPPB improved from 2.0 (SD 2.5) to 3.8 (SD 2.7; p ≤ 0.001) and DEMMI from 41 (SD 19) to 53 (SD 14; p ≤ 0.001) (Cohen's d: 0.72 for SPPB, 0.62 for DEMMI). Among patients admitted from home each additional point in SPPB at admission and acquired during acute care rehabilitation increased the odds of returning home by 1.7 times (95% CI 1.1-2.8, p = 0.02) and 1.6 times (95% CI 1.1-2.5, p = 0.02). For DEMMI, every 10 points at admission, but not in change, increased the odds of returning home by 2.5 times (95% CI 1.3-5.0, p = 0.007). DISCUSSION AND CONCLUSION: SPPB and DEMMI are both valid mobility assessments for senior patients in acute care. However, SPPB is a better predictor than DEMMI for discharge destination.

Relationship between bone mineral content and bone turnover markers, sex hormones and calciotropic hormones in pre- and early pubertal children.

We investigated associations between bone mineral content (BMC) and bone-related biomarkers (BM) in pre-and early pubertal children of both sexes. In this population, we found that bone turnover markers explain a small part of BMC variance. INTRODUCTION: It is still debated whether BM including bone turnover markers (BTM), sex hormones and calciotropic (including cortisol) hormones provide information on BMC changes during growth. METHODS: Three hundred fifty-seven girls and boys aged 6 to 13 years were included in this study. BM was measured at baseline and BMC twice at 9 months and 4 years using DXA. Relationship between BMs was assessed using principal component analysis (PCA). BM was tested in its ability to explain BMC variation by using structural equation modelling (SEM) on cross-sectional data. Longitudinal data were used to further assess the association between BM and BMC variables. RESULTS: BMC and all BMs, except calciotropic hormones, increased with age. PCA in BM revealed a three-factor solution (BTM, sex hormones and calciotropic hormones). In the SEM, age accounted for 61% and BTM for 1.2% of variance in BMC (cross-sectional). Neither sex nor calciotropic hormones were BMC explanatory variables. In the longitudinal models (with single BM as explanatory variables), BMC, age and sex at baseline accounted for 79-81% and 70-75% in BMC variance at 9 months and 4 years later, respectively. P1NP was consistently associated with BMC. CONCLUSION: BMC strongly tracks in pre- and early pubertal children. In this study, only a small part of BMC variance was explained by single BTM at the beginning of pubertal growth.

Interrelations between the rumen microbiota and production, behavioral, rumen fermentation, metabolic, and immunological attributes of dairy cows.

Different studies have shown a strong correlation between the rumen microbiome and a range of production traits (e.g., feed efficiency, milk yield and components) in dairy cows. Underlying dynamics concerning cause and effect are, however, still widely unknown and warrant further investigation. The aim of the current study was to describe possible functional interrelations and pathways using a large set of variables describing the production, the metabolic and immunological state, as well as the rumen microbiome and fermentation characteristics of dairy cows in early lactation (n = 36, 56 ± 3 d in milk). It was further hypothesized that the feed intake-associated behavior may influence the ruminal fermentation pattern, and a set of variables describing these individual animal attributes was included. Principal component analysis as well as Spearman's rank correlations were conducted including a total of 265 variables. The attained plots describe several well-known associations between metabolic, immunological, and production traits. Main drivers of variance within the data set included milk production and efficiency as well as rumen fermentation and microbiome diversity attributes, whereas behavioral, metabolic, and immunological variables did not exhibit any strong interrelations with the other variables. The previously well-documented strong correlation of production traits with distinct prokaryote groups was confirmed. This mainly included a negative correlation of operational taxonomic units ascribed to the Prevotella genus with milk and fat yield and feed efficiency. A central role of the animals' feed intake behavior in this context could not be affirmed. Furthermore, different methodological and interpretability aspects concerning the microbiome analysis by 16S rRNA gene sequencing, such as the discrepancy between taxonomic classification and functional communality, as well as the comparability with other studies, are discussed. We concluded that, to further investigate the driving force that causes the difference between efficient and inefficient animals, studies including more sophisticated methods to describe phenotypical traits of the host (e.g., rumen physiology, metabolic and genetic aspects) as well as the rumen microbiome (e.g., metagenome, metatranscriptome, metaproteome, and metabolome analysis) are needed.

International practices in the dietary management of fructose 1-6 biphosphatase deficiency.

BACKGROUND: In fructose 1,6 bisphosphatase (FBPase) deficiency, management aims to prevent hypoglycaemia and lactic acidosis by avoiding prolonged fasting, particularly during febrile illness. Although the need for an emergency regimen to avoid metabolic decompensation is well established at times of illness, there is uncertainty about the need for other dietary management strategies such as sucrose or fructose restriction. We assessed international differences in the dietary management of FBPase deficiency. METHODS: A cross-sectional questionnaire (13 questions) was emailed to all members of the Society for the Study of Inborn Errors of Metabolism (SSIEM) and a wide database of inherited metabolic disorder dietitians. RESULTS: Thirty-six centres reported the dietary prescriptions of 126 patients with FBPase deficiency. Patients' age at questionnaire completion was: 1-10y, 46% (n = 58), 11-16y, 21% (n = 27), and >16y, 33% (n = 41). Diagnostic age was: <1y, 36% (n = 46); 1-10y, 59% (n = 74); 11-16y, 3% (n = 4); and >16y, 2% (n = 2). Seventy-five per cent of centres advocated dietary restrictions. This included restriction of: high sucrose foods only (n = 7 centres, 19%); fruit and sugary foods (n = 4, 11%); fruit, vegetables and sugary foods (n = 13, 36%). Twenty-five per cent of centres (n = 9), advised no dietary restrictions when patients were well. A higher percentage of patients aged >16y rather than ≤16y were prescribed dietary restrictions: patients aged 1-10y, 67% (n = 39/58), 11-16y, 63% (n = 17/27) and >16y, 85% (n = 35/41). Patients classified as having a normal fasting tolerance increased with age from 30% in 1-10y, to 36% in 11-16y, and 58% in >16y, but it was unclear if fasting tolerance was biochemically proven. Twenty centres (56%) routinely prescribed uncooked cornstarch (UCCS) to limit overnight fasting in 47 patients regardless of their actual fasting tolerance (37%). All centres advocated an emergency regimen mainly based on glucose polymer for illness management. CONCLUSIONS: Although all patients were prescribed an emergency regimen for illness, use of sucrose and fructose restricted diets with UCCS supplementation varied widely. Restrictions did not relax with age. International guidelines are necessary to help direct future dietary management of FBPase deficiency.

Effects of energy supply and nicotinic acid supplementation on phagocytosis and ROS production of blood immune cells of periparturient primi- and pluriparous dairy cows.

Effects of energy supply and nicotinic acid (NA) supplementation on the phagocytic activity of polymorphonuclear leukocytes (PMN) and peripheral blood mononuclear cells (PBMC), and on ROS production in PMN of periparturient cows differing in parity were examined. 29 pluriparous and 18 primiparous cows were allocated to four different feeding groups from 42days prepartum until 100days postpartum. They were fed either a ration with a low concentrate proportion of 30% (LC) or a high concentrate proportion of 60% (HC). After parturition all animals received 30% concentrate which was increased to 50% either within 16 (LC) or within 24days (HC). The different concentrate feeding strategies aimed at triggering differences in postpartum lipolysis. Half of the animals per group were supplemented with 24g per day of NA from 42days prepartum until 24days postpartum. All investigated parameters varied significantly over time compared to parturition (p<0.05). Numbers of phagocytosing PMN and PBMC increased in the course of the experiment, whereas the amount of engulfed bacteria per cell decreased between 42 and 11days prepartum. Percentage of basal ROS producing PMN decreased strongly before parturition and reached initial values only at 28days in milk again. Mean fluorescence intensity (MFI) in these ROS producing cells, however, increased before parturition. Oxidative burst stimulation in PMN was reduced around parturition but the amount of ROS produced in the stimulated cells was increased. Pluriparous cows exhibited higher numbers of basal ROS producing PMN and phagocytic PBMC. NA supplementation influenced phagocytosis in blood leukocytes.

Reconceptualization of translocator protein as a biomarker of neuroinflammation in psychiatry.

A great deal of interest in psychiatric research is currently centered upon the pathogenic role of inflammatory processes. Positron emission tomography (PET) using radiolabeled ligands selective for the 18 kDa translocator protein (TSPO) has become the most widely used technique to assess putative neuroimmune abnormalities in vivo. Originally used to detect discrete neurotoxic damages, TSPO has generally turned into a biomarker of 'neuroinflammation' or 'microglial activation'. Psychiatric research has mostly accepted these denotations of TSPO, even if they may be inadequate and misleading under many pathological conditions. A reliable and neurobiologically meaningful diagnosis of 'neuroinflammation' or 'microglial activation' is unlikely to be achieved by the sole use of TSPO PET imaging. It is also very likely that the pathological meanings of altered TSPO binding or expression are disease-specific, and therefore, not easily generalizable across different neuropathologies or inflammatory conditions. This difficulty is intricately linked to the varying (and still ill-defined) physiological functions and cellular expression patterns of TSPO in health and disease. While altered TSPO binding or expression may indeed mirror ongoing neuroinflammatory processes in some cases, it may reflect other pathophysiological processes such as abnormalities in cell metabolism, energy production and oxidative stress in others. Hence, the increasing popularity of TSPO PET imaging has paradoxically introduced substantial uncertainty regarding the nature and meaning of neuroinflammatory processes and microglial activation in psychiatry, and likely in other neuropathological conditions as well. The ambiguity of conceiving TSPO simply as a biomarker of 'neuroinflammation' or 'microglial activation' calls for alternative interpretations and complimentary approaches. Without the latter, the ongoing scientific efforts and excitement surrounding the role of the neuroimmune system in psychiatry may not turn into therapeutic hope for affected individuals.

Influence of conjugated linoleic acids and vitamin E on biochemical, hematological, and immunological variables of dairy cows during the transition period.

The objective of this experiment was to determine the effects of conjugated linoleic acid (CLA) and vitamin E as well as their interaction on biochemical and hematological variables and on leukocyte populations and their functionality. We assigned 59 German Holstein cows between the 2nd and 9th lactation to 4 dietary groups in a 2 × 2 factorial design with the factors CLA and vitamin E. Six weeks before calving the cows had a BCS of 3.7 to provoke a higher risk of developing ketosis, which might impair their immune function. Blood samples for analyses were taken on d -42, -14, -7, -3, 1, 3, 7, 10, 14, 21, 28, 35, 42, 56, and 70 relative to parturition. Furthermore, peripheral blood mononuclear cells were cultured on d -42, -7, 1, 7, 14, 28, and 70 relative to calving. Most variables were characterized by a high variation between d 7 antepartum and d 7 postpartum. Treatments did not elicit any effect, with the exception of vitamin E, which increased serum urea concentrations and decreased monocyte percentages. Haptoglobin, aspartate-aminotransferase, red blood cell count, leukocyte percentage and populations, as well as peripheral blood mononuclear cells were influenced by parity. In conclusion, the impairment of immune function caused by calving was more severe in cows in ≥3rd parity than in younger cows. However, neither vitamin E nor CLA supplementation was successful to stabilize parity or parturition related variance in hematological and immunological traits.

Influence of conjugated linoleic acids and vitamin E on milk fatty acid composition and concentrations of vitamin A and α-tocopherol in blood and milk of dairy cows.

The objective of this trial was to investigate the influences of conjugated linoleic acid (CLA) and vitamin E (Vit. E) and their interactions on fatty acid composition and vitamins in milk (α-tocopherol, retinol and ß-carotene) as well as on α-tocopherol in blood of pluriparous cows from week 6 ante partum until week 10 post-partum (p.p.). We assigned 59 pluriparous German Holstein cows to four treatment groups with the treatment factors CLA and Vit. E at two levels in a 2 × 2 factorial design. Milk fatty acid composition and milk vitamins were analysed on lactation days 7 and 28. α-tocopherol in blood serum was analysed on days -42, -7, 1, 7, 14, 28 and 70 relative to parturition. Milk concentration of α-tocopherol was influenced by Vit. E (p < .001) and CLA (p = .034). Percentage of cis-9, trans-11 CLA in total milk fat was influenced by treatment with CLA (p < .001), while for percentage of trans-10, cis-12 CLA an interaction between treatment and day (p = .019), driven by an increase in both CLA groups from day 7 to day 28, was found. Serum ratios of α-tocopherol to cholesterol were influenced by Vit. E (p < .001). Results suggest that treatment with CLA during late pregnancy and early lactation is suitable to enhance the proportion of trans-10, cis-12 CLA in milk and thereby influencing nutritional properties. As treatment with Vit. E did not have an impact on milk fatty acid composition, it might be possible to increase the antioxidative capacity of the dairy cow without affecting milk properties. Consequently, combined treatment with CLA and Vit. E might elicit synergistic effects on the cow and milk quality by increasing the proportion of CLA in milk fat as well as the excretion of Vit. E and the Vit. E levels in serum.

Translational evaluation of translocator protein as a marker of neuroinflammation in schizophrenia.

Positron emission tomography (PET) imaging with radiotracers that target translocator protein 18 kDa (TSPO) has become a popular approach to assess putative neuroinflammatory processes and associated microglia activation in psychotic illnesses. It remains unclear, however, whether TSPO imaging can accurately capture low-grade inflammatory processes such as those present in schizophrenia and related disorders. Therefore, we evaluated the validity of TSPO as a disease-relevant marker of inflammation using a translational approach, which combined neurodevelopmental and neurodegenerative mouse models with PET imaging in patients with recent-onset schizophrenia and matched controls. Using an infection-mediated neurodevelopmental mouse model, we show that schizophrenia-relevant behavioral abnormalities and increased inflammatory cytokine expression are associated with reduced prefrontal TSPO levels. On the other hand, TSPO was markedly upregulated in a mouse model of acute neurodegeneration and reactive gliosis, which was induced by intrahippocampal injection of kainic acid. In both models, the changes in TSPO levels were not restricted to microglia but emerged in various cell types, including microglia, astrocytes and vascular endothelial cells. Human PET imaging using the second-generation TSPO radiotracer [11C]DPA-713 revealed a strong trend towards reduced TSPO binding in the middle frontal gyrus of patients with recent-onset schizophrenia, who were previously shown to display increased levels of inflammatory cytokines in peripheral and central tissues. Together, our findings challenge the common assumption that central low-grade inflammation in schizophrenia is mirrored by increased TSPO expression or ligand binding. Our study further underscores the need to interpret altered TSPO binding in schizophrenia with caution, especially when measures of TSPO are not complemented with other markers of inflammation. Unless more selective microglial markers are available for PET imaging, quantification of cytokines and other inflammatory biomarkers, along with their molecular signaling pathways, may be more accurate in attempts to characterize inflammatory profiles in schizophrenia and other mental disorders that lack robust reactive gliosis.

Effects of energy supply and nicotinic acid supplementation on serum anti-oxidative capacity and on expression of oxidative stress-related genes in blood leucocytes of periparturient primi- and pluriparous dairy cows.

The periparturient period is accompanied by metabolic and oxidative stress. Niacin is known to decrease lipolysis but is also reported to have anti-oxidative effects. Therefore, we examined the effects of energy supply and a nicotinic acid (NA) supplementation on anti-oxidative serum parameters and on the expression of oxidative stress-related genes in blood leucocytes of periparturient dairy cows, differing in parity. Twenty-nine pluriparous and 18 primiparous cows were allocated to four different feeding groups 42 days before expected parturition until 100 days postpartum and fed a ration with either a low concentrate proportion of 30% (LC) or a high concentrate proportion of 60% (HC). After parturition, all animals received 30% concentrate which was increased to 50% either within 16 (LC group) or 24 days (HC group). Half of the animals per group were supplemented with 24 g NA per day from 42 days prepartum until 24 days postpartum. All investigated parameters varied significantly over time compared to parturition (p < .05). Ferric reducing ability (FRA) exhibited a nadir before parturition, and the antioxidant enzymes glutathione peroxidase (GPX) and superoxide dismutase (SOD) showed peak activities around parturition. Expression levels of GPX1, SOD2, xanthine dehydrogenase (XDH) and nuclear factor (erythroid-derived 2)-like 2 (NRF2) peaked before calving. The concentrate level influenced GPX activity and mRNA abundance of SOD2, XDH and poly (ADP-ribose) polymerase 1 (PARP1). Pluriparous animals exhibited higher serum GPX activities, a more distinct nadir for FRA and higher expression levels for GPX1, SOD2 and XDH. Primiparous cows displayed higher serum SOD activities. NA supplementation increased serum SOD activity antepartum in LC animals. Parturition was characterised by an increased need for antioxidants and an increased expression of oxidative stress-related genes that clearly differed with parity and was influenced by energy supply while NA exerted only minor effects on the investigated parameters.

Impact of diet composition and temperature-humidity index on water and dry matter intake of high-yielding dairy cows.

The temperature-humidity index (THI) is widely used to characterize heat stress in dairy cattle. Diet composition is known to induce variation in metabolic-associated heat production. However, the relationships between THI and diet are poorly characterized with regard to performance and intake behaviour. Therefore, the objectives were to evaluate the impact of THI on water intake (WI), dry matter intake (DMI) and the frequency of drinking and feeding bouts in lactating dairy cows offered four dietary treatments: each contained 20% grass silage and additionally (i) 20% maize silage, 60% concentrate (M-HC); (ii) 60% maize silage, 20% concentrate (M-LC); (iii) 20% pressed beet pulp silage, 60% concentrate (BPS-HC); or (iv) 60% pressed beet pulp silage, 20% concentrate (BPS-LC) (DM basis). Individual WI and DMI were recorded from April to July 2013. Furthermore, dietary effects on milk production and reticular pH were estimated. Milk yield was lowest for M-LC, while energy-corrected milk was similar for all diets. Milk fat percentage was higher and milk protein amount lower for cows offered both LC diets. Reticular pH below 6.3, 6.0 and 5.8 lasted longest for BPS-LC. WI was higher for HC diets. However, the frequency of drinking bouts was not influenced by the ration. Lower DMI occurred for BPS-LC compared to M-LC. Frequency of feeding bouts was significantly higher for LC diets. THI was significantly related to WI, DMI as well as drinking and feeding bouts. Per increasing THI, WI increased slightly more for LC diets and DMI decreased more for HC diets. Frequency of drinking bouts increased slightly higher for BPS rations per rising THI, while the decrease in feeding bouts was highest for M-HC. In conclusion, TMR composition and moderate heat stress impacted WI and DMI of dairy cows, while both dietary energy density and ruminal filling might intensify the THI impact.

Dietary practices in propionic acidemia: A European survey.

BACKGROUND: The definitive dietary management of propionic acidaemia (PA) is unknown although natural protein restriction with adequate energy provision is of key importance. AIM: To describe European dietary practices in the management of patients with PA prior to the publication of the European PA guidelines. METHODS: This was a cross-sectional survey consisting of 27 questions about the dietary practices in PA patients circulated to European IMD dietitians and health professionals in 2014. RESULTS: Information on protein restricted diets of 186 PA patients from 47 centres, representing 14 European countries was collected. Total protein intake [PA precursor-free L-amino acid supplements (PFAA) and natural protein] met WHO/FAO/UNU (2007) safe protein requirements for age in 36 centres (77%). PFAA were used to supplement natural protein intake in 81% (n = 38) of centres, providing a median of 44% (14-83%) of total protein requirement. Seventy-four per cent of patients were prescribed natural protein intakes below WHO/FAO/UNU (2007) safe levels in one or more of the following age groups: 0-6 m, 7-12 m, 1-10 y, 11-16 y and > 16 y. Sixty-three per cent (n = 117) of patients were tube fed (74% gastrostomy), but only 22% received nocturnal feeds. CONCLUSIONS: There was high use of PFAA with intakes of natural protein commonly below WHO/FAO/UNU (2007) safe levels. Optimal dietary management can only be determined by longitudinal, multi-centre, prospective case controlled studies. The metabolic instability of PA and small patient cohorts in each centre ensure that this is a challenging undertaking.

Influence of fumaric acid on ruminal parameters and organ weights of growing bulls fed with grass or maize silage.

The influence of the potential methane reducer, fumaric acid (FA), on ruminal parameters, the rumen wall and organ weights was investigated in a long-term study with growing bulls. In all, 20 bulls were fed with maize or grass silage as roughage, and with concentrate with or without 300 g FA per animal and day during the whole fattening period. After slaughtering, the organs were weighed and blood serum was analysed for glucose, ß-hydroxybutyric acid (BHB) and non-esterified fatty acid concentration. The ruminal fluid was analysed for short-chain fatty acids, ammonia-N and the microbial community via single strand conformation polymorphism analysis. The rumen wall was examined histopathologically and results were graded as 'no visible lesions', 'few inflammatory infiltrates', 'some inflammatory infiltrates' or 'several inflammatory infiltrates'. In addition, the dimensions of the rumen villi were measured. The FA supplementation decreased the serum BHB concentration and the butyric acid concentration in the ruminal fluid. The microbial community in the ruminal fluid was not influenced by FA. An interaction between FA and silage type was observed for the inflammation centres counted in the villous area of rumen papillae. This interaction was also observed in the length and surface of the rumen villi. Rumen villi results show that the influence of FA depends on the roughage used in the diet.

Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia.

Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or environmental risks relevant to diverse etiological aspects of these disorders show PVI deficits to be all accompanied by oxidative stress in the anterior cingulate cortex. Specifically, oxidative stress is negatively correlated with the integrity of PVIs and the extracellular perineuronal net enwrapping these interneurons. Oxidative stress may result from dysregulation of systems typically affected in schizophrenia, including glutamatergic, dopaminergic, immune and antioxidant signaling. As convergent end point, redox dysregulation has successfully been targeted to protect PVIs with antioxidants/redox regulators across several animal models. This opens up new perspectives for the use of antioxidant treatments to be applied to at-risk individuals, in close temporal proximity to environmental impacts known to induce oxidative stress.

Effect of increasing body condition on oxidative stress and mitochondrial biogenesis in subcutaneous adipose tissue depot of nonlactating dairy cows.

With the onset of lactation, dairy cows with a body condition score >3.5 are sensitive to oxidative stress and metabolic disorders. Adipose tissue (AT) can adapt to varying metabolic demands and energy requirements by the plasticity of its size during lactation. In AT, angiogenesis is necessary to guarantee sufficient oxygen and nutrient supply for adipocytes. Cellular energy metabolism is reflected mainly by mitochondria, which can be quantified by the mitochondrial DNA copy number per cell. In the present study, we aimed to investigate the effect of overconditioning on angiogenesis and mitochondrial biogenesis in AT of nonlactating cows, irrespective of the physiological influences of lactation and pregnancy. Eight nonpregnant, nonlactating cows received a ration of increasing energy density for 15 wk, during which body weight and body condition increased substantially. Subcutaneous AT was biopsied every 8 wk, and blood was sampled monthly. The blood concentrations of indicators of oxidative stress increased continuously throughout the experimental period, possibly damaging mitochondrial DNA. Concomitantly, HIF-1α, a major marker for hypoxia, increased until wk 8, indicating insufficient angiogenesis in the rapidly expanding AT. Based on the observation that the number of apoptotic cells decreased with increasing hypoxia, the increasing mitochondrial DNA copy numbers might compensate for the hypoxia, reinforcing the production of oxidative stressors. Key transcription factors of mitochondrial biogenesis were largely unaffected. Thus, increased oxidative stress does not impair mitochondrial DNA.