Treating depressive disorders with the unified protocol: A preliminary randomized evaluation.

OBJECTIVES: This study aims to examine the efficacy of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) for individuals diagnosed with a depressive disorder. METHOD: Participants included 44 adults who met criteria for major depressive disorder, persistent depressive disorder, or another specified depressive disorder according to the Anxiety Disorder Interview Schedule (ADIS). These individuals represent a subset of patients from a larger clinical trial comparing the UP to single-disorder protocols (SDPs) for discrete anxiety disorders and a waitlist control (WLC) condition (Barlow et al., 2017); inclusion criteria for the parent study required participants to have a principal anxiety disorder. RESULTS: Significant reductions in depressive symptoms were observed within the UP condition across clinician-rated and self-report measures of depression from baseline to post-treatment, as well as to the 12-month follow-up assessment. Compared to the WLC group, individuals in the UP condition demonstrated significantly lower levels on our continuous, clinician-rated measure of depressive symptoms at post-treatment. There were no differences between the UP and SDP conditions on depressive symptoms at post-treatment or at the 12-month follow-up timepoint. CONCLUSIONS: In this exploratory set of analyses, the UP evidenced efficacy for reduction of depressive symptoms, adding to the growing support for its utility in treating depression.R01 MH090053 - NIMH NIH HHSAccepted manuscrip

Health and Reproductive Performance of Lactating Dairy Cows with Mild Fatty Liver Receiving Exogenous Glucagon

The data demonstrate that mild fatty liver is associated with decreased general health and reproductive performance as evidenced by more days to first estrus and service, more days open, decreased conception, increased number of days with elevated body temperature at days 9 - 22 postpartum, and increased incidence of mastitis at days 32 – 150 postpartum. The latter two were decreased in dairy cows with mild fatty liver injected with 15 mg/d of glucagon during weeks 2 and 3 postpartum. Therefore, treatment of mild fatty liver with exogenous glucagon or better prevention of fatty liver might improve health and reproductive performance of lactating dairy cows, thereby preventing loss of income of dairy farmers

Influence of energy balance on the antimicrobial peptides S100A8 and S100A9 in the endometrium of the postpartum dairy cow

Uterine inflammation occurs after calving in association with extensive endometrial remodelling and bacterial contamination. If the inflammation persists, it leads to reduced fertility. Chronic endometritis is highly prevalent in high-yielding cows that experience negative energy balance (NEB) in early lactation. This study investigated the effect of NEB on the antimicrobial peptides S100A8 and S100A9 in involuting uteri collected 2 weeks post partum. Holstein-Friesian cows (six per treatment) were randomly allocated to two interventions designed to produce mild or severe NEB (MNEB and SNEB) status. Endometrial samples were examined histologically, and the presence of neutrophils, macrophages, lymphocytes and natural killer cells was confirmed using haematoxylin and eosin and immunostaining. SNEB cows had greater signs of uterine inflammation. Samples of previously gravid uterine horn were used to localise S100A8 and S100A9 by immunohistochemistry. Both S100 proteins were present in bovine endometrium with strong staining in epithelial and stromal cells and in infiltrated leucocytes. Immunostaining was significantly higher in SNEB cows along with increased numbers of segmented neutrophils. These results suggest that the metabolic changes of a post-partum cow suffering from NEB delay uterine involution and promote a chronic state of inflammation. We show that upregulation of S100A8 and S100A9 is clearly a key component of the early endometrial response to uterine infection. Further studies are warranted to link the extent of this response after calving to the likelihood of cows developing endometritis and to their subsequent fertility

Construct validity and factor structure of the Kessler-10 in South Africa

Background The Kessler Psychological Distress Scale (K-10) is a short screening tool developed to identify, with good sensitivity, non-specific psychological distress in the general population. Sensitivity and specificity of the K-10 have been examined in various clinical populations in South Africa; however, other psychometric properties, such as construct validity and factor structure, have not been evaluated. We present evidence of the prevalence and severity of psychological distress in an outpatient setting in South Africa and evaluate the internal reliability, construct validity, and factor structure of the K-10 in this population. Methods We explored prevalence estimates of psychological distress using previously established cutoffs and assessed the reliability (consistency) of the K-10 by calculating Cronbach’s alpha, item-total correlations and omega total and hierarchical coefficients. Construct validity and factor structure of the K-10 were examined through split-sample exploratory factor analysis (EFA) followed by confirmatory factor analysis (CFA), comparing several theoretical models and the EFA. Results Overall, there was low prevalence of psychological distress in our sample of 2591 adults, the majority of whom were between the ages of 18–44 (77.7%). The K-10 showed good construct validity and reliability, with a Cronbach’s alpha of 0.84 and omega total of 0.88. EFA yielded a four-factor solution with likely measurement artifacts. CFA showed that the four-factor model from EFA displayed the best comparative fit indices, but was likely overfitted. The unidimensional model with correlated errors was deemed the best fitting model based on fit indices, prior theory, and previous studies. Conclusion The K-10 displays adequate psychometric properties, good internal reliability, and good fit with a unidimensional-factor structure with correlated errors. Further work is required to determine appropriate cutoff values in different populations and clinical subgroups within South Africa to aid in determining the K-10’s clinical utility

Vitamin D Signaling in the Bovine Immune System: A Model for Understanding Human Vitamin D Requirements

The endocrine physiology of vitamin D in cattle has been rigorously investigated and has yielded information on vitamin D requirements, endocrine function in health and disease, general metabolism, and maintenance of calcium homeostasis in cattle. These results are relevant to human vitamin D endocrinology. The current debate regarding vitamin D requirements is centered on the requirements for proper intracrine and paracrine vitamin D signaling. Studies in adult and young cattle can provide valuable insight for understanding vitamin D requirements as they relate to innate and adaptive immune responses during infectious disease. In cattle, toll-like receptor recognition activates intracrine and paracrine vitamin D signaling mechanism in the immune system that regulates innate and adaptive immune responses in the presence of adequate 25-hydroxyvitamin D. Furthermore, experiments with mastitis in dairy cattle have provided in vivo evidence for the intracrine vitamin D signaling mechanism in macrophages as well as vitamin D mediated suppression of infection. Epidemiological evidence indicates that circulating concentrations above 32 ng/mL of 25-hydroxyvitamin D are necessary for optimal vitamin D signaling in the immune system, but experimental evidence is lacking for that value. Experiments in cattle can provide that evidence as circulating 25-hydroxyvitamin D concentrations can be experimentally manipulated within ranges that are normal for humans and cattle. Additionally, young and adult cattle can be experimentally infected with bacteria and viruses associated with significant diseases in both cattle and humans. Utilizing the bovine model to further delineate the immunomodulatory role of vitamin D will provide potentially valuable insights into the vitamin D requirements of both humans and cattle, especially as they relate to immune response capacity and infectious disease resistance

1,25-Dihydroxyvitamin D3 modulates the phenotype and function of Monocyte derived dendritic cells in cattle

Abstract Background The active form of the vitamin D3, 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to have major effects not only on physiological processes but also on the regulation of the immune system of vertebrates. Dendritic cells are specialised antigen presenting cells which are in charge of the initiation of T-cell dependant immune responses and as such are key regulators of responses towards pathogens. In this study we set out to evaluate the effects of 1,25-(OH)2D3 on the phenotype of cattle monocyte-derived dendritic cells (MoDCs) and how the conditioning with this vitamin affects the function of these myeloid cells. Results MoDCs were generated from CD14+ monocytes with bovine IL-4 and GM-CSF with or without 1,25-(OH)2D3 supplementation for 10 days. Vitamin D conditioned MoDCs showed a reduced expression of co-stimulatory and antigen presenting molecules, as well as a reduced capability of endocytose ovalbumin. Furthermore, the capacity of MoDCs to induce proliferation in an allogeneic mixed leukocyte reaction was abolished when MoDCs were generated in presence of 1,25-(OH)2D3. LPS induced maturation of 1,25-(OH)2D3conditioned MoDCs resulted in lower secretion of IL-12 and higher IL-10 than that observed in MoDCs. Conclusions The typical immunotolerant phenotype observed in cattle DCs after exposure to 1,25-(OH)2D3 has a significant effect on the functionality of these immune cells, inhibiting the T-cell stimulatory capacity of MoDCs. This could have profound implications on how the bovine immune system deals with pathogens, particularly in diseases such as tuberculosis or paratuberculosis

Serum acute phase proteins in cows with SARA (Subacute Ruminal Acidosis) suspect

The aim of this study was to evaluate the variations of Acute Phase Proteins (APPs) and other blood constituents during the onset of the sub-acute ruminal acidosis (SARA) pathological status. A total of 108 cows from 12 dairy herds were randomly selected and divided into three Groups of 36 animals each. All animals were subjected to a rumenocentesis. Group A was composed by subjects with a rumen pH>5.8, Group B was composed by subjects with a rumen pH ≤5.5≤5.8 and Group C was composed by subjects with a rumen pH<5.5. Blood samples were collected by jugular venipuncture and Haptoglobin (Hp), Serum Amyloid A (SAA), Total Proteins, Albumin and White Blood Cells (WBC) were determined. One-way ANOVA showed a statistical significance on Rumen pH, Hp, SAA. SARA seems not stimulate the APPs production from liver

Repeated oronasal exposure to lipopolysaccharide induced mucosal IgA responses in periparturient dairy cows.

This study investigated the effects of repeated oronasal treatment with lipopolysaccharide (LPS) on the humoral immune responses in saliva, vaginal mucus, and the plasma markers of the acute phase response in periparturient dairy cows. One hundred pregnant Holstein cows were administered either 3 increasing doses of LPS (n = 50) as follows: 1) 0.01 µg/kg body weight (BW) on d -28, 2) 0.05 µg/kg BW on d -25, and -21, and 3) 0.1 µg/kg BW on d -18, and -14, or sterile saline solution (controls; n = 50) oronasally for 3 consecutive wk starting at 28 d before parturition. Intensive sampling was conducted on thirty cows (n = 15/group). Multiple saliva, vaginal mucus and blood samples were collected around parturition and analyzed for total immunoglobulin-(Ig)A, plasma serum amyloid A (SAA), lipopolysaccharide-binding protein (LBP), anti-LPS IgA, IgG, IgM, tumour necrosis factor(TNF)-α, and interleukin(IL)-1. Results regarding total secretory IgA (sIgA) antibodies showed greater concentrations in the saliva and an overall tendency for higher total sIgA in the vaginal mucus of the LPS-treated cows. Treatment had no effect on plasma sIgA, IgG, IgM anti-LPS antibodies, haptoglobin, SAA, LBP, TNF-α, and IL-1. Treatments by time interactions were observed for SAA and IL-1 with lowered concentrations of both variables in the plasma of LPS-treated cows after parturition. Overall, repeated oronasal LPS treatment clearly enhanced total sIgA antibodies in the saliva, stimulated their production in vaginal mucus shortly before calving, and lowered plasma IL-1 around parturition, but showed limited effects on markers of the acute phase response in the plasma in dairy cows around parturition