A novel needle-free method of lidocaine administration during standing castration of Holstein bulls.

The American Veterinary Medical Association recognizes castration to be important for both human and animal safety. Lidocaine delivered through-the-needle has been shown to be effective at reducing cortisol response to castration, but this method has drawbacks for both animals and caretakers. As such, a study was conducted to examine the potential benefits of lidocaine delivery using a pneumatic needle-free device immediately before standing bovine castration. Twelve Holstein bulls weighing 400.7 ± 39.5 kg (mean ± standard deviation) were enrolled. Bulls were allocated to receive a local anesthetic block of 2% lidocaine for surgical castration by traditional needle injection or by needle-free injection. Outcomes were collected out to 48 h postcastration. Outcome variables included plasma cortisol concentrations, visual analog scale scores for pain, medial canthus temperatures as measured using infrared thermography, pressure mat changes, and chute defense scores. A time effect was observed for cortisol, visual analog scale scores, infrared thermography temperatures, and some pressure mat outcomes. No statistically significant differences between lidocaine delivery methods were observed, but further research is needed to build upon this small dataset.

Low-temperature 3D printing of transparent silica glass microstructures.

Transparent silica glass is one of the most essential materials used in society and industry, owing to its exceptional optical, thermal, and chemical properties. However, glass is extremely difficult to shape, especially into complex and miniaturized structures. Recent advances in three-dimensional (3D) printing have allowed for the creation of glass structures, but these methods involve time-consuming and high-temperature processes. Here, we report a photochemistry-based strategy for making glass structures of micrometer size under mild conditions. Our technique uses a photocurable polydimethylsiloxane resin that is 3D printed into complex structures and converted to silica glass via deep ultraviolet (DUV) irradiation in an ozone environment. The unique DUV-ozone conversion process for silica microstructures is low temperature (~220°C) and fast (<5 hours). The printed silica glass is highly transparent with smooth surface, comparable to commercial fused silica glass. This work enables the creation of arbitrary structures in silica glass through photochemistry and opens opportunities in unexplored territories for glass processing techniques.

Cold-programmed shape-morphing structures based on grayscale digital light processing 4D printing.

Shape-morphing structures that can reconfigure their shape to adapt to diverse tasks are highly desirable for intelligent machines in many interdisciplinary fields. Shape memory polymers are one of the most widely used stimuli-responsive materials, especially in 3D/4D printing, for fabricating shape-morphing systems. They typically go through a hot-programming step to obtain the shape-morphing capability, which possesses limited freedom of reconfigurability. Cold-programming, which directly deforms the structure into a temporary shape without increasing the temperature, is simple and more versatile but has stringent requirements on material properties. Here, we introduce grayscale digital light processing (g-DLP) based 3D printing as a simple and effective platform for fabricating shape-morphing structures with cold-programming capabilities. With the multimaterial-like printing capability of g-DLP, we develop heterogeneous hinge modules that can be cold-programmed by simply stretching at room temperature. Different configurations can be encoded during 3D printing with the variable distribution and direction of the modular-designed hinges. The hinge module allows controllable independent morphing enabled by cold programming. By leveraging the multimaterial-like printing capability, multi-shape morphing structures are presented. The g-DLP printing with cold-programming morphing strategy demonstrates enormous potential in the design and fabrication of shape-morphing structures.

One-Pot Synthesis of Depolymerizable δ-Lactone Based Vitrimers.

A depolymerizable vitrimer that allows both reprocessability and monomer recovery by a simple and scalable one-pot two-step synthesis of vitrimers from cyclic lactones is reported. Biobased δ-valerolactone with alkyl substituents (δ-lactone) has low ceiling temperature; thus, their ring-opening-polymerized aliphatic polyesters are capable of depolymerizing back to monomers. In this work, the amorphous poly(δ-lactone) is solidified into an elastomer (i.e., δ-lactone vitrimer) by a vinyl ether cross-linker with dynamic acetal linkages, giving the merits of reprocessing and healing. Thermolysis of the bulk δ-lactone vitrimer at 200 °C can recover 85-90 wt% of the material, allowing reuse without losing value and achieving a successful closed-loop life cycle. It further demonstrates that the new vitrimer has excellent properties, with the potential to serve as a biobased and sustainable replacement of conventional soft elastomers for various applications such as lenses, mold materials, soft robots, and microfluidic devices.

Single-vat single-cure grayscale digital light processing 3D printing of materials with large property difference and high stretchability.

Multimaterial additive manufacturing has important applications in various emerging fields. However, it is very challenging due to material and printing technology limitations. Here, we present a resin design strategy that can be used for single-vat single-cure grayscale digital light processing (g-DLP) 3D printing where light intensity can locally control the conversion of monomers to form from a highly stretchable soft organogel to a stiff thermoset within in a single layer of printing. The high modulus contrast and high stretchability can be realized simultaneously in a monolithic structure at a high printing speed (z-direction height 1 mm/min). We further demonstrate that the capability can enable previously unachievable or hard-to-achieve 3D printed structures for biomimetic designs, inflatable soft robots and actuators, and soft stretchable electronics. This resin design strategy thus provides a material solution in multimaterial additive manufacture for a variety of emerging applications.

Turing pattern-based design and fabrication of inflatable shape-morphing structures.

Turing patterns are self-organizing stripes or spots widely found in biological systems and nature. Although inspiring, their applications are limited. Inflatable shape-morphing structures have attracted substantial research attention. Traditional inflatable structures use isotropic materials with geometrical features to achieve shape morphing. Recently, gradient-based optimization methods have been used to design these structures. These methods assume anisotropic materials whose orientation can vary freely. However, this assumption makes fabrication a considerable challenge by methods such as additive manufacturing, which print isotropic materials. Here, we present a methodology of using Turing patterns to bridge this gap. Specifically, we use Turing patterns to convert a design with distributed anisotropic materials to a distribution with two materials, which can be fabricated by grayscale digital light processing 3D printing. This work suggests that it is possible to apply patterns in biological systems and nature to engineering composites and offers new concepts for future material design.

Determination of milk concentrations and pharmacokinetics of salicylic acid following acetylsalicylic acid (aspirin) administration in postpartum dairy cows.

The objectives of this descriptive study were to (1) describe the pharmacokinetics of salicylic acid (SA) in the milk and plasma of postpartum dairy cattle following oral administration of acetylsalicylic acid (ASA; aspirin), (2) to estimate a recommended milk withdrawal period for dairy cattle treated with ASA, and (3) to determine the effect of ASA administration on plasma prostaglandin E2 metabolite (PGEM) concentrations. Primiparous (n = 3) and multiparous (n = 7) postpartum Holstein dairy cows received 2 oral treatments with ASA at 200 mg/kg of body weight, 24 h apart. Concentrations of SA in plasma and milk from 0 h through 120 h after ASA administration were analyzed using ultra performance liquid chromatography triple quadrupole mass spectrometry and a milk withdrawal period was estimated using the United States Food and Drug Administration Milk Discard App in R. Two withdrawal periods were estimated: (1) a whole-herd treatment scenario with no dilution factor and (2) an individual animal treatment scenario with a bulk tank factor included in analysis. Plasma PGEM concentrations in samples from 0 h to 24 h after ASA administration were determined using a commercially available competitive ELISA. Milk SA concentrations were undetected in all cows by 48 h after the last ASA treatment. Secondary peaks were observed in plasma at 58 and 82 h after the last treatment and in milk at 87 h after the last treatment. In the absence of a tolerance for SA in milk, the estimated milk withdrawal periods were (1) 156 h for the whole-herd treatment scenario and (2) 120 h for the individual animal treatment scenario. Plasma PGEM concentrations were reduced compared with baseline for up to 12 h after ASA administration, with the greatest reduction observed at 2 h. Results from this study suggest that the current milk withhold recommendation for dairy cattle administered ASA may need revision to 120 h (5 d) and that ASA administration may mitigate postpartum inflammation through reduction in prostaglandin production for up to 12 h after treatment. Pharmacokinetic and milk withdrawal data from this study will inform future recommendations for extra-label use of aspirin in postpartum dairy cows. Further research is required to determine the basis for the secondary SA peaks and to elucidate the long-term effects of ASA administration on dairy cow health.

4D Printing of Freestanding Liquid Crystal Elastomers via Hybrid Additive Manufacturing.

Liquid crystal elastomers (LCE) are appealing candidates among active materials for 4D printing, due to their reversible, programmable and rapid actuation capabilities. Recent progress has been made on direct ink writing (DIW) or Digital Light Processing (DLP) to print LCEs with certain actuation. However, it remains a challenge to achieve complicated structures, such as spatial lattices with large actuation, due to the limitation of printing LCEs on the build platform or the previous layer. Herein, a novel method to 4D print freestanding LCEs on-the-fly by using laser-assisted DIW with an actuation strain up to -40% is proposed. This process is further hybridized with the DLP method for optional structural or removable supports to create active 3D architectures in a one-step additive process. Various objects, including hybrid active lattices, active tensegrity, an actuator with tunable stability, and 3D spatial LCE lattices, can be additively fabricated. The combination of DIW-printed functionally freestanding LCEs with the DLP-printed supporting structures thus provides new design freedom and fabrication capability for applications including soft robotics, smart structures, active metamaterials, and smart wearable devices.

Stick or twist? Cost-effectiveness of siponimod compared with continuing existing disease-modifying therapies in the treatment of active secondary progressive multiple sclerosis in the UK.

OBJECTIVE: Identification of the phenotypic transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) is often delayed due to disease complexity and an unwillingness to withdraw RRMS disease-modifying therapies (DMTs), driven by limited SPMS treatment options. Despite the paucity of clinical evidence for efficacy in patients with SPMS, DMTs licensed for RRMS are frequently continued into the early stages of SPMS. The cost-effectiveness of oral siponimod, an active SPMS DMT, versus continued oral or infused RRMS DMTs for patients with active SPMS, was evaluated. METHODS: A cohort Markov model based on disease progression through Expanded Disability Status Scale health states, with annual cycles and lifetime horizon, was employed to determine the cost-effectiveness of siponimod from a UK National Health Service (NHS) perspective for patients with active SPMS. Baseline characteristics, health state utility values, hazard ratios for time to 6-month confirmed disability progression, annualized relapse rate ratios and adverse events for siponimod were obtained from the phase 3 EXPAND clinical trial, supplemented by published literature. Published costs, resource use data and comparator efficacy data were obtained from the literature and, in the absence of data, reasonable assumptions were made. RESULTS: Quality-adjusted life years (QALYs) were greater for siponimod versus all comparators (3.45 versus 2.69-2.83). Incremental cost-effectiveness ratios (ICERs), calculated as cost per QALY, for siponimod versus natalizumab (dominant), ocrelizumab (£4,760), fingolimod (£10,033) and dimethyl fumarate (£15,837) indicated that siponimod was cost-effective at the commonly accepted willingness-to-pay threshold of £30,000/QALY. CONCLUSIONS: Recognition of active SPMS and treatment of this phenotype with siponimod offers a cost-effective and clinically beneficial treatment approach compared with the continuation of oral or infused RRMS DMTs.

Magnetic Dynamic Polymers for Modular Assembling and Reconfigurable Morphing Architectures.

Shape-morphing magnetic soft materials, composed of magnetic particles in a soft polymer matrix, can transform shape reversibly, remotely, and rapidly, finding diverse applications in actuators, soft robotics, and biomedical devices. To achieve on-demand and sophisticated shape morphing, the manufacture of structures with complex geometry and magnetization distribution is highly desired. Here, a magnetic dynamic polymer (MDP) composite composed of hard-magnetic microparticles in a dynamic polymer network with thermally responsive reversible linkages, which permits functionalities including targeted welding for magnetic-assisted assembly, magnetization reprogramming, and permanent structural reconfiguration, is reported. These functions not only provide highly desirable structural and material programmability and reprogrammability but also enable the manufacturing of functional soft architected materials such as 3D kirigami with complex magnetization distribution. The welding of magnetic-assisted modular assembly can be further combined with magnetization reprogramming and permanent reshaping capabilities for programmable and reconfigurable architectures and morphing structures. The reported MDP are anticipated to provide a new paradigm for the design and manufacture of future multifunctional assemblies and reconfigurable morphing architectures and devices.

Effects of milk feeding strategies on short- and long-term productivity of Holstein heifers.

Research investigating the effects of feeding raw or pasteurized nonsaleable milk (NSM) on heifers' performance beyond the period of supplementation is limited. This study aimed to examine the effects of type of milk [NSM or milk replacer (MR)] and pasteurization of NSM on preweaning and first-lactation performance of heifers born with low (<36.3 kg) or normal birth weight (≥36.3 kg). Holstein heifers (n = 154) were sequentially assigned to 1 of 3 treatments: MR, pasteurized NSM, or raw NSM. Heifers assigned to raw NSM were fed raw colostrum, whereas heifers assigned to MR and pasteurized NSM were fed pasteurized colostrum. The low birth weight heifers were fed 1.4 L at each feeding until they reached 36.3 kg body weight, whereas normal birth weight heifers were fed 1.9 L at each feeding. A grain mix starter was offered throughout the study. Heifers were weaned ≥42 d old if consuming at least 0.9 kg/d of starter for 3 consecutive days. Data were analyzed with the MIXED procedure of SAS (SAS Institute Inc., Cary, NC), and the basic model included milk treatments, birth weight group, and treatment × birth weight group. The low birth weight heifers fed raw colostrum and NSM versus pasteurized colostrum and NSM had lower serum protein concentrations. Heifers fed MR versus NSM had or tended to have greater concentrations of hematocrit, red blood cells, and eosinophils but lesser concentrations of platelets, although some of those responses were temporary. Pasteurization tended to increase blood lymphocyte concentrations. Heifers with normal birth weight had greater concentrations of blood neutrophils, lymphocytes, and monocytes, compared with low birth weight heifers. For the first 42 d of life, low birth weight heifers fed pasteurized versus raw NSM had greater weight gain, grain intake, and feed efficiency and were weaned earlier (hazard ratio for weaning by 56 d: 2.90). These pasteurization effects for low birth weight heifers tended to be sustained through 24 wk of age, indicated by greater weight gain and hip height growth. In their first lactation, low birth weight heifers produced less mature-equivalent (MEq) protein and tended to produce less MEq milk and fat than normal birth weight heifers. However, the negative effects of low birth weight on MEq milk and fat yield was only evident in heifers fed raw NSM, whereas the performance of low birth weight heifers was similar to that of normal birth weight when fed MR or pasteurized NSM. These findings confirm that calf management practices influence future performance; in this case, failing to pasteurize milk and colostrum for low birth weight heifers had effects that remained apparent for more than 2 years.

Mind and body exercises (MBE), prescribed antidepressant medication, physical exercise and depressive symptoms - a longitudinal study.

AIMS: Earlier studies show that participation in mind and body exercises (MBE) is cross-sectionally associated with high levels of depressive symptoms and antidepressants. This study investigates the longitudinal interrelationship between depressive symptoms, MBE and antidepressants. METHODS: 3269 men and 4318 women aged 24-74 years participated in the Swedish Longitudinal Occupational Survey of Health (SLOSH). Measures of MBE practice and depressive symptoms were drawn from the SLOSH questionnaire, data on prescription drugs were obtained from the Swedish Prescribed Drug Register. Structural Equation Modeling (SEM) was used to analyze temporal relationships. RESULTS: Both MBE practice and antidepressants in 2012 was associated with higher levels of depressive symptoms two years later. Depressive symptoms in turn were associated with higher levels of later MBE practice and antidepressants. These relationships seemed to be explained by confounding by indication and were of higher magnitude for antidepressants than for MBE. CONCLUSION: Overall, SEM analysis shows that MBE and antidepressant treatment were both bi-directionally associated with depressive symptoms over time. Part of the explanation is likely to be confounding by indication: those with symptoms of depression more likely to undertake treatment, and MBE alone may be more common among those with less severe depression. The results clarify some of our findings from earlier studies and give some important, new information on what people are doing to manage depressive symptoms on a societal level, regarding self-care, medication, and the combination of both.

Magnetic Shape Memory Polymers with Integrated Multifunctional Shape Manipulation.

Shape-programmable soft materials that exhibit integrated multifunctional shape manipulations, including reprogrammable, untethered, fast, and reversible shape transformation and locking, are highly desirable for a plethora of applications, including soft robotics, morphing structures, and biomedical devices. Despite recent progress, it remains challenging to achieve multiple shape manipulations in one material system. Here, a novel magnetic shape memory polymer composite is reported to achieve this. The composite consists of two types of magnetic particles in an amorphous shape memory polymer matrix. The matrix softens via magnetic inductive heating of low-coercivity particles, and high-remanence particles with reprogrammable magnetization profiles drive the rapid and reversible shape change under actuation magnetic fields. Once cooled, the actuated shape can be locked. Additionally, varying the particle loadings for heating enables sequential actuation. The integrated multifunctional shape manipulations are further exploited for applications including soft magnetic grippers with large grabbing force, reconfigurable antennas, and sequential logic for computing.

Proteomic analysis reveals greater abundance of complement and inflammatory proteins in subcutaneous adipose tissue from postpartum cows treated with sodium salicylate.

This study aimed to investigate sodium salicylate (SS) treatment effects on the proteome of adipose tissue (AT) in postpartum cows. Twenty Holstein cows were assigned to control (CON, n = 10) or SS (n = 10) provided via drinking water (2.3 g/L) during the first 7 d of lactation. Subcutaneous AT was collected on d 7 of treatment and label-free quantitative shotgun proteomics and immunoblotting were analyzed in a subset of 5 AT per group. Eighty out of 1422 proteins (5.6%) were differentially abundant between CON and SS [fold change ±1.5, P < 0.05]. Top canonical pathways differing between CON and SS (Ingenuity) were complement system, interleukin-10 signaling, and acute phase response signaling. The abundances of complement C1r, C1qC, C1qB and C6 were greater in SS than CON. Regarding IL-10 signaling, the abundances of BLVRB, STAT3, and lipopolysaccharide binding protein (LBP) were greater in SS AT compared to CON. Immunoblots revealed increased abundance of paraoxanase-1 and tumor necrosis factor-alpha, as well as a tendency for greater abundance of cluster differentiation 172a in SS AT, which may indicate of increased macrophage infiltration. SS treatment postpartum likely promotes inflammatory signaling in AT of dairy cows, perhaps due to immune cell recruitment. SIGNIFICANCE: This work demonstrates that treating early lactating cows with sodium salicylate, an anti-inflammatory agent that has been shown to have metabolic effects and increase milk production in dairy cows, affects the proteome of subcutaneous adipose tissue in early lactating dairy cows. Unexpectedly, sodium salicylate treatment enriched inflammatory pathways of the complement system, cytokine signaling, and acute phase response, as revealed by proteomic analysis of subcutaneous adipose tissues from cows at 7 d postpartum. These findings imply that SS treatment during the first 7 d of lactation likely promotes inflammatory signaling in AT of the dairy cow, perhaps due to immune cell recruitment. Tissue-specific impacts of systemic sodium salicylate requires further scrutiny.

Clinical factors predicting treatment resistant depression: affirmative results from the European multicenter study.

OBJECTIVES: Clinical variables were investigated in the 'treatment resistant depression (TRD)- III' sample to replicate earlier findings by the European research consortium 'Group for the Study of Resistant Depression' (GSRD) and enable cross-sample prediction of treatment outcome in TRD. EXPERIMENTAL PROCEDURES: TRD was defined by a Montgomery and Åsberg Depression Rating Scale (MADRS) score ≥22 after at least two antidepressive trials. Response was defined by a decline in MADRS score by ≥50% and below a threshold of 22. Logistic regression was applied to replicate predictors for TRD among 16 clinical variables in 916 patients. Elastic net regression was applied for prediction of treatment outcome. RESULTS: Symptom severity (odds ratio (OR) = 3.31), psychotic symptoms (OR = 2.52), suicidal risk (OR = 1.74), generalized anxiety disorder (OR = 1.68), inpatient status (OR = 1.65), higher number of antidepressants administered previously (OR = 1.23), and lifetime depressive episodes (OR = 1.15) as well as longer duration of the current episode (OR = 1.022) increased the risk of TRD. Prediction of TRD reached an accuracy of 0.86 in the independent validation set, TRD-I. CONCLUSION: Symptom severity, suicidal risk, higher number of lifetime depressive episodes, and comorbid anxiety disorder were replicated as the most prominent risk factors for TRD. Significant predictors in TRD-III enabled robust prediction of treatment outcome in TRD-I.

Atopic dermatitis, educational attainment and psychological functioning: a national cohort study.

BACKGROUND: Atopic dermatitis (AD) might adversely affect academic performance, possibly through influences on psychological functioning such as stress resilience. OBJECTIVES: To investigate the association of atopic dermatitis with stress resilience, cognitive function and educational attainment. METHODS: We used data from a national cohort of men who underwent a military conscription examination at ages 17-20 years in Sweden between 1969 and 1976. All potential conscripts met a physician who assessed current or previous history of AD. Stress resilience was measured by a psychologist using a semistructured interview. The conscription assessment included a written cognitive function test. The highest level of education achieved was identified through record linkage. RESULTS: The study population included 234 715 men, 1673 (0·7%) of whom had a diagnosis of AD. AD was associated with a greater risk of low stress resilience [adjusted relative risk ratio (RRR) 1·60, 95% confidence interval (CI) 1·38-1·86]. AD was associated with higher cognitive function (ß-coefficient 0·15, 95% CI 0·05-0·24) and higher educational level (RRR 1·29, 95% CI 1·13-1·47). However, adjustment for socioeconomic characteristics of the family of origin attenuated the magnitude of the associations and eliminated the statistical significance (ß-coefficient 0·06, 95% CI -0·03 to 0·15; RRR 1·16, 95% CI 1·00-1·35). CONCLUSIONS: Swedish men with AD had lower stress resilience in late adolescence but did not have lower cognitive function or poorer educational attainment. The lower stress resilience associated with AD is consistent with an increased risk of possible long-term adverse health outcomes.

Association of major California freight railyards with asthma-related pediatric emergency department hospital visits.

Asthma is a major health threat and leading cause of chronic morbidity among children. Air pollutants have been linked to exacerbations and promotion of initial development of asthma. Extensive research already conducted assessing adverse health impacts associated with exposure to pollutants from vehicular traffic. However, little research conducted assessing exposure to pollutants stemming from goods movement industry, such as freight railyards. This study's purpose to assess potential association between residential proximity to major freight railyards and asthma-related emergency room (ER) visits in children. This study included children ≤14 yrs. old, living within 30-mile radius of one of 18 freight railyards in California, and having utilized emergency room services between 2007 and 2009, identified through California Office of Statewide Health Planning and Development (OSHPD) database. Logistic regression modeling with all 18 railyards, and models with top 5 polluting railyards, conducted to assess for potential association between asthma related ER visit (asthma vs. non-asthma visit) and railyard residential proximity. A total 109,645 asthma related ER visits identified, majority among low income, minority populations. Within 18 railyard model, children closest to railyard (0-5 miles) were at significant increased odds (OR = 1.15, 95%CI: 1.10-1.20) for asthma related ER visit and stronger odds observed for 5 top emitting railyards (OR = 1.40, 95%CI: 1.29-1.52). Our findings indicate a strong link between asthma ER visits for children and residential proximity to railyards, especially among low-income and minority communities. There's a critical need to better understand complex health risks for individuals residing in these communities and mitigation efforts for this vulnerable population.

Effects of sodium salicylate on glucose kinetics and insulin signaling in postpartum dairy cows.

Low-grade inflammation has been implicated as a contributor to metabolic disease during the transition to lactation. In previous work, administration of sodium salicylate (SS) for 7 d led to hypoglycemia in mature dairy cows in early lactation. The purpose of this study was to identify the mode of action underlying this response to SS. Twenty mature (parity 3) cows were assigned alternately at time of calving to either control or SS treatments; the control received a molasses placebo in drinking water, whereas SS received 2.3 g/L of SS with the molasses carrier in drinking water for 7 d after parturition. Blood samples were collected daily. A glucose turnover assay was performed on d 7, followed by liver, muscle, and adipose tissue biopsies. There were no treatment effects on intake of dry matter or water. Tumor necrosis factor α mRNA abundance tended to be decreased by SS in adipose tissue but not in muscle or liver, and plasma haptoglobin and adiponectin concentrations were not altered by treatment. Treatment did not significantly alter plasma glucose or insulin concentrations, but plasma glucagon concentration tended to be increased by SS and the insulin:glucagon molar ratio was significantly decreased. Cows on SS had a tendency for a 25% decrease in glucose turnover rate compared with control cows. However, there were no differences in transcript abundance of pyruvate carboxylase (PC) or glucose-6-phosphatase (G6PC) in liver or of glucose transporter 4 (GLUT4) in any of the tissues. Finally, SS did not alter insulin receptor substrate-1 phosphorylation in muscle or adipose, but tended to increase phosphorylation of AMP-activated protein kinase and decrease protein kinase B phosphorylation in adipose tissue. These findings may be explained by enhanced hepatic insulin sensitivity leading to posttranscriptional suppression of gluconeogenesis and adaptive responses to decreased glucose supply in the pancreas and adipose tissue.

Dietary Patterns and Retinal Vessel Caliber in the Irish Nun Eye Study.

BACKGROUND: Retinal vessel abnormalities are associated with cardiovascular disease risk. Widening of retinal venules is associated with increased risk of stroke while narrowing of retinal arterioles independently predicts incident hypertension, coronary heart disease and diabetes. Dietary factors are known to play an important role in cardiovascular health. However, few studies have examined the association between dietary patterns (DPs) and retinal microvascular health. OBJECTIVE: To examine the association between 'a posteriori'-derived DPs and retinal vascular caliber (RVC) in older women with a restricted lifestyle. METHODS: This was a cross-sectional study of 1233 participants (mean age: 76.3 years) from the Irish Nun Eye Study (INES). Computer-assisted software was used to measure RVC from digital eye images using standardized protocols. Dietary intake was assessed using a food frequency questionnaire (FFQ). DP analysis was performed using principal component analysis from completed FFQs. Regression models were used to assess associations between DPs and retinal vessel diameters, adjusting for age, body mass index, refraction, hypertension, diabetes mellitus, ischemic heart disease, cerebrovascular accident and fellow eye RVC. RESULTS: Two DPs were identified: a 'healthy' pattern with high factor loadings for fruit, vegetables, wholegrains and oily fish and an 'unhealthy' pattern with high factor loadings for sugar and sweets, chips, high fat dairy products and French fries. Adjusted linear regression analysis revealed that those who adhered most closely to the unhealthy DP had wider central retinal venular equivalent (CRVE) (p=0.03) and narrower central retinal arteriolar equivalent (CRAE) (p=0.01) compared to the least unhealthy DP. No independent relationship was observed between the healthy DP and RVC. CONCLUSION: In this cohort of older women with a restricted lifestyle, an unhealthy DP was independently associated with an unfavorable retinal profile, namely a widening of retinal venules and narrowing of retinal arterioles.

Clinical correlates of augmentation/combination treatment strategies in major depressive disorder.

OBJECTIVE: This multicenter, multinational, cross-sectional study aimed to investigate clinical characteristics and treatment outcomes associated with augmentation/combination treatment strategies in major depressive disorder (MDD). METHOD: Sociodemographic, clinical, and treatment features of 1410 adult MDD patients were compared between MDD patients treated with monotherapy and augmentation/combination medication using descriptive statistics, analyses of covariance (ancova), and Spearman's correlation analyses. RESULTS: 60.64% of all participants received augmentation and/or combination strategies with a mean number of 2.18 ± 1.22 simultaneously prescribed psychiatric drugs. We found male gender, older age, Caucasian descent, higher weight, low educational status, absence of occupation, psychotic symptoms, melancholic and atypical features, suicide risk, in-patient treatment, longer duration of hospitalization, some psychiatric comorbidities (panic disorder, agoraphobia, obsessive-compulsive disorder, and bulimia nervosa), comorbid somatic comorbidity in general and concurrent hypertension, thyroid dysfunction, diabetes, and heart disease in particular, higher current and retrospective Montgomery and Åsberg Depression Rating Scale total scores, treatment resistance, and higher antidepressant dosing to be significantly associated with augmentation/combination treatment. These findings were corroborated when examining the number of concurrently administered psychiatric drugs in the statistical analyses. CONCLUSION: Our findings suggest a clear association between augmentation/combination strategies and treatment-resistant/difficult-to-treat MDD conditions characterized by severe symptomatology and high amount of psychiatric and somatic comorbidities.