Hyperketonemia during lipopolysaccharide-induced mastitis affects systemic and local intramammary metabolism in dairy cows

Hyperketonemia interferes with the metabolic regulation in dairy cows. It is assumed that metabolic and endocrine changes during hyperketonemia also affect metabolic adaptations during inflammatory processes. We therefore studied systemic and local intramammary effects of elevated plasma β-hydroxybutyrate (BHBA) before and during the response to an intramammary lipopolysaccharide (LPS) challenge. Thirteen dairy cows received intravenously either a Na-DL-β-OH-butyrate infusion (n = 5) to achieve a constant plasma BHBA concentration (1.7 ± 0.1 mmol/L), with adjustments of the infusion rates made based on immediate measurements of plasma BHBA every 15 min, or an infusion with a 0.9% NaCl solution (control; n = 8) for 56 h. Infusions started at 0900 h on d 1 and continued until 1700 h 2 d later. Two udder quarters were challenged with 200 μg of Escherichia coli LPS and 2 udder quarters were treated with 0.9% saline solution as control quarters at 48 h after the start of infusion. Blood samples were taken at 1 wk and 2h before the start of infusions as reference samples and hourly during the infusion. Mammary gland biopsies were taken 1 wk before, and 48 and 56 h (8h after LPS challenge) after the start of infusions. The mRNA abundance of key factors related to BHBA and fatty acid metabolism, and glucose transporters was determined in mammary tissue biopsies. Blood samples were analyzed for plasma glucose, BHBA, nonesterified fatty acid, urea, insulin, glucagon, and cortisol concentrations. Differences were not different for effects of BHBA infusion on the mRNA abundance of any of the measured target genes in the mammary gland before LPS challenge. Intramammary LPS challenge increased plasma glucose, cortisol, glucagon, and insulin concentrations in both groups but increases in plasma glucose and glucagon concentration were less pronounced in the Na-DL-β-OH-butyrate infusion group than in controls. In response to LPS challenge, plasma BHBA concentration decreased in controls and decreased also slightly in the BHBA-infused animals because the BHBA concentration could not be fully maintained despite a rapid increase in BHBA infusion rate. The change in mRNA abundance of citrate synthase in LPS quarters was significant between the 2 treatment groups. The results indicate that elevated circulating BHBA concentration inhibits gluconeogenesis before and during immune response to LPS challenge, likely because BHBA can replace glucose as an energy source.

Cholesterol metabolism, transport, and hepatic regulation in dairy cows during transition and early lactation

The transition from the nonlactating to the lactating state represents a critical period for dairy cow lipid metabolism because body reserves have to be mobilized to meet the increasing energy requirements for the initiation of milk production. The purpose of this study was to provide a comprehensive overview on cholesterol homeostasis in transition dairy cows by assessing in parallel plasma, milk, and hepatic tissue for key factors of cholesterol metabolism, transport, and regulation. Blood samples and liver biopsies were taken from 50 multiparous Holstein dairy cows in wk 3 antepartum (a.p.), wk 1 postpartum (p.p.), wk 4 p.p., and wk 14 p.p. Milk sampling was performed in wk 1, 4, and 14 p.p. Blood and milk lipid concentrations [triglycerides (TG), cholesterol, and lipoproteins], enzyme activities (phospholipid transfer protein and lecithin:cholesterol acyltransferase) were analyzed using enzymatic assays. Hepatic gene expression patterns of 3-hydroxy-3-methylglutaryl-coenzyme A (HMGC) synthase 1 (HMGCS1) and HMGC reductase (HMGCR), sterol regulatory element-binding factor (SREBF)-1 and -2, microsomal triglyceride transfer protein (MTTP), ATP-binding cassette transporter (ABC) A1 and ABCG1, liver X receptor (LXR) α and peroxisome proliferator activated receptor (PPAR) α and γ were measured using quantitative RT-PCR. Plasma TG, cholesterol, and lipoprotein concentrations decreased from wk 3 a.p. to a minimum in wk 1 p.p., and then gradually increased until wk 14 p.p. Compared with wk 4 p.p., phospholipid transfer protein activity was increased in wk 1 p.p., whereas lecithin:cholesterol acyltransferase activity was lowest at this period. Total cholesterol concentration and mass, and cholesterol concentration in the milk fat fraction decreased from wk 1 p.p. to wk 4 p.p. Both total and milk fat cholesterol concentration were decreased in wk 4 p.p. compared with wk 1 and 14 p.p. The mRNA abundance of genes involved in cholesterol synthesis (SREBF-2, HMGCS1, and HMGCR) markedly increased from wk 3 a.p. to wk 1 p.p., whereas SREBF-1 was downregulated. The expression of ABCA1 increased from wk 3 a.p. to wk 1 p.p., whereas ABCG1 was increased in wk 14 p.p. compared with other time points. In conclusion, hepatic expression of genes involved in the biosynthesis of cholesterol as well as the ABCA1 transporter were upregulated at the onset of lactation, whereas plasma concentrations of total cholesterol, phospholipids, lipoprotein-cholesterol, and TG were at a minimum. Thus, at the gene expression level, the liver seems to react to the increased demand for cholesterol after parturition. Whether the low plasma cholesterol and TG levels are due to impaired hepatic export mechanisms or reflect an enhanced transfer of these compounds into the milk to provide essential nutrients for the newborn remains to be elucidated.

New perioperative fluid and pharmacologic management protocol results in reduced blood loss, faster return of bowel function, and overall recovery.

Cystectomy and urinary diversion have high morbidity, and strategies to reduce complications are of utmost importance. Epidural analgesia and optimized fluid management are considered key factors contributing to successful enhanced recovery after surgery. In colorectal surgery, there is strong evidence that an intraoperative fluid management aiming for a postoperative zero fluid balance results in lower morbidity including a faster return of bowel function. Recently, a randomized clinical trial focusing on radical cystectomy demonstrated that a restrictive intraoperative hydration combined with a concomitant administration of norepinephrine reduced intraoperative blood loss, the need for blood transfusion and morbidity. The purpose of this review is to highlight specific anesthesiological aspects which have been shown to improve outcome after RC with urinary diversion.

High-flow venous pouch aneurysm in the rabbit carotid artery: A model for large aneurysms.

BACKGROUND AND PURPOSE Currently one of the most widely used models for the development of endovascular techniques and coiling devices for treatment of aneurysm is the elastase-induced aneurysm model in the rabbit carotid artery. Microsurgical techniques for creating an aneurysm with a venous pouch have also been established, although both techniques usually result in aneurysms less than 1 cm in diameter. We investigated whether an increase in blood flow toward the neck would produce larger aneurysms in a microsurgical venous pouch model. MATERIALS AND METHODS Microsurgical operations were performed on 11 New Zealand white rabbits. Both carotid arteries and the right jugular vein were dissected, and the right carotid artery was temporarily clipped followed by an arteriotomy. The left carotid artery was also clipped proximally, ligated distally, and sutured onto the proximal half of the arteriotomy in the right carotid artery. The venous graft was sutured onto the distal half of the arteriotomy. Digital subtraction angiography was also performed. RESULTS Angiography showed patent anastomosed vessels and aneurysms in the seven surviving rabbits. Mean aneurysm measurements among surviving rabbits with patent vessels were: 13.9 mm length, 9.3 mm width, and neck diameter 4.7 mm. The resulting mean aspect ratio was 3.35 and the mean bottleneck ratio was 3.05. CONCLUSION A large venous graft and increased blood flow toward the base of the aneurysm seem to be key factors in the creation of large venous pouch aneurysms. These large aneurysms allow testing of endovascular devices designed for large and giant aneurysms.

Labour Migration, Trade and Investment: From Fragmentation to Coherence

Trade, investment and migration are strongly intertwined, being three key factors in international production. Yet, law and regulation of the three has remained highly fragmented. Trade is regulated by the WTO on the multilateral level, and through preferential trade agreements on the regional and bilateral levels – it is fragmented and complex in its own right. Investment, on the other hand, is mainly regulated through bilateral investment treaties with no strong links to the regulation of trade or migration. And, finally, migration is regulated by a web of different international, regional and bilateral agreements which focus on a variety of different aspects of migration ranging from humanitarian to economic. The problems of institutional fragmentation in international law are well known. There is no organizational forum for coherent strategy-making on the multilateral level covering all three areas. Normative regulations may thus contradict each other. Trade regulation may bring about liberalization of access for service providers, but eventually faces problems in recruiting the best people from abroad. Investors may withdraw investment without being held liable for disruptions to labour and to the livelihood and infrastructure of towns and communities affected by disinvestment. Finally, migration policies do not seem to have a significant impact as long as trade policies and investment policies are not working in a way that is conducive to reducing migration pressure, as trade and investment are simply more powerful on the regulatory level than migration. This chapter addresses the question as to how fragmentation of the three fields could be reme-died and greater coherence between these three areas of factor allocation in international economic relations and law could be achieved. It shows that migration regulation on the international level is lagging behind that on trade and investment. Stronger coordination and consideration of migration in trade and investment policy, and stronger international cooperation in migration, will provide the foundations for a coherent international architecture in the field.

A Nicotiana attenuata cell wall invertase inhibitor (NaCWII) reduces growth and increases secondary metabolite biosynthesis in herbivore-attacked plants

Plant invertases are sucrolytic enzymes that are essential for the regulation of carbohydrate metabolism and source–sink relationships. While their activity has been well documented during abiotic and biotic stresses, the role of proteinaceous invertase inhibitors in regulating these changes is unknown. Here, we identify a putative Nicotiana attenuata cell wall invertase inhibitor (NaCWII) which is strongly up-regulated in a jasmonate (JA)-dependent manner following simulated attack by the specialist herbivore Manduca sexta. To understand the role of NaCWII in planta, we silenced its expression by RNA interference and measured changes in primary and secondary metabolism and plant growth following simulated herbivory. NaCWII-silenced plants displayed a stronger depletion of carbohydrates and a reduced capacity to increase secondary metabolite pools relative to their empty vector control counterparts. This coincided with the attenuation of herbivore-induced CWI inhibition and growth suppression characteristic of wild-type plants. Together our findings suggest that NaCWII may act as a regulatory switch located downstream of JA accumulation which fine-tunes the plant's balance between growth and defense metabolism under herbivore attack. Although carbohydrates are not typically viewed as key factors in plant growth and defense, our study shows that interfering with their catabolism strongly influences plant responses to herbivory.

The unruptured intracranial aneurysm treatment score: a multidisciplinary consensus.

OBJECTIVE We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. METHODS An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* = 0 indicating excellent agreement and vr* = 1 indicating poor agreement). RESULTS The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019-0.033). CONCLUSIONS This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.

The Honey Bee Pathosphere of Mongolia: European Viruses in Central Asia

Parasites and pathogens are apparent key factors for the detrimental health of managed European honey bee subspecies, Apis mellifera. Apicultural trade is arguably the main factor for the almost global distribution of most honey bee diseases, thereby increasing chances for multiple infestations/infections of regions, apiaries, colonies and even individual bees. This imposes difficulties to evaluate the effects of pathogens in isolation, thereby creating demand to survey remote areas. Here, we conducted the first comprehensive survey for 14 honey bee pathogens in Mongolia (N = 3 regions, N = 9 locations, N = 151 colonies), where honey bee colonies depend on humans to overwinter. In Mongolia, honey bees, Apis spp., are not native and colonies of European A. mellifera subspecies have been introduced ~60 years ago. Despite the high detection power and large sample size across Mongolian regions with beekeeping, the mite Acarapis woodi, the bacteria Melissococcus plutonius and Paenibacillus larvae, the microsporidian Nosema apis, Acute bee paralysis virus, Kashmir bee virus, Israeli acute paralysis virus and Lake Sinai virus strain 2 were not detected, suggesting that they are either very rare or absent. The mite Varroa destructor, Nosema ceranae and four viruses (Sacbrood virus, Black queen cell virus, Deformed wing virus (DWV) and Chronic bee paralysis virus) were found with different prevalence. Despite the positive correlation between the prevalence of V. destructor mites and DWV, some areas had only mites, but not DWV, which is most likely due to the exceptional isolation of apiaries (up to 600 km). Phylogenetic analyses of the detected viruses reveal their clustering and European origin, thereby supporting the role of trade for pathogen spread and the isolation of Mongolia from South-Asian countries. In conclusion, this survey reveals the distinctive honey bee pathosphere of Mongolia, which offers opportunities for exciting future research.

The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites

Sequestration of red blood cells infected with the human malaria parasite Plasmodium falciparum in organs such as the brain is considered important for pathogenicity. A similar phenomenon has been observed in mouse models of malaria, using the rodent parasite Plasmodium berghei, but it is unclear whether the P. falciparum proteins known to be involved in this process are conserved in the rodent parasite. Here we identify the P. berghei orthologues of two such key factors of P. falciparum, SBP1 and MAHRP1. Red blood cells infected with P. berghei parasites lacking SBP1 or MAHRP1a fail to bind the endothelial receptor CD36 and show reduced sequestration and virulence in mice. Complementation of the mutant P. berghei parasites with the respective P. falciparum SBP1 and MAHRP1 orthologues restores sequestration and virulence. These findings reveal evolutionary conservation of the machinery underlying sequestration of divergent malaria parasites and support the notion that the P. berghei rodent model is an adequate tool for research on malaria virulence.

Lessons for emerging state Children's Health Insurance Premium Assistance programs: Case study of the Massachusetts Masshealth Family Assistance Program (MHFAP)

Providing health insurance coverage for vulnerable populations such as low-income high-risk children with limited access to health care is a challenge for many states. Over the past decade, higher private insurance premiums and unpredictable labor markets have increased the number of uninsured and underinsured children nationwide. Due to recent economic downfalls, many states such as Texas, have expressed interest in using premium assistance programs to increase enrollment of low income children and families in private coverage through employer sponsored health insurance. Massachusetts has been especially successful in reducing the number of uninsured children through the implementation of MassHealth Family Assistance Program (MHFAP), an employer based premium assistance program. The purpose of this study is to identify key implementation factors of a fully established premium assistance program which may provide lessons and facilitate implementation of emerging premium assistance programs. ^ The case study of the fully established MassHealth Family Assistance Program (MHFAP) has illustrated the ability of states to expand their Medicaid and SCHIP programs in order to provide affordable health coverage to uninsured and underinsured low income children and their families. As demonstrated by MHFAP, the success of a premium assistance program depends on four key factors: (1) determination of participant and employer eligibility; (2) determination of employer benefits meeting benchmark equivalency (Medicaid or State Children's Health Insurance Program); (3) the use of appropriate marketing and outreach strategies; and (4) establishment of adequate monitoring and reporting techniques. Successful implementation strategies, revealed by the case study of the Massachusetts MassHealth Family Assistance Program, may be used by emerging premium assistance programs, such as Texas Children's Health Insurance Premium Assistance Program (CHIP-PA) toward establishment of an effective, efficient, and equitable employer sponsored health program.^

A systematic review of the animal and human literature on the use of vaccines to prevent dental caries

Streptococcus mutans has been identified as the primary etiological agent of human dental caries. Since its identification, there has been research focused on the development of a vaccine to prevent this disease. Preliminary research has been conducted to test both active and passive vaccines for Streptococcus mutans in animals and humans. Although a vaccine for dental caries caused by Streptococcus mutans would most likely be administered to children, no testing of any type of dental caries vaccines has been conducted on children as of yet. The public health imperative for the development of a vaccine is great. Not only will a vaccine reduce the various consequences, but it would also improve quality of life for many individuals. Among the many possible vaccine antigen candidates, researchers have also been focusing on protein antigens, GTFs, and Gbps as possible candidates for a vaccine. There are also many routes of administration under research, with topical, oral, and intranasal showing a lot of promise. This review will provide an overview on the current state of research, present key factors influencing prevalence of caries, and summarize and discuss the results of animal and human studies on caries vaccines against Streptococcus mutans. The progress and obstacles facing the development of a vaccine to fight dental caries will also be discussed. ^

Integrating diabetes self-management with the health goals of older adults: A qualitative exploration

Objective. This study investigates the life and health goals of older adults with diabetes, and explores the factors that influence their diabetes self-management. Methods: Qualitative in-depth interviews were conducted with 24 older adults with diabetes and other morbid conditions and/or their caregivers, when appropriate. ^ Results. Participants’ provided a consistent set of responses when describing life and health goals. Participants described goals for longevity, better physical functioning, spending time with family, or maintaining independence. Diabetes discordant conditions, but not diabetes, were seen as barriers to life goals for participants with functional impairments. Functionally independent participants described additional health goals that related to diabetes self-management as diabetes was seen often a barrier to life goals. Caregivers, co-morbid conditions, denial and retirement were among the factors that influenced initiation of diabetes self-management. ^ Conclusion. Participants endorsed health goals and diabetes self-management practices that they believed would help them accomplish their life goals. Functional capabilities and social support were key factors in the relationship between diabetes self-management and their broader goals. ^ Practice implications. When planning diabetes treatments, clinicians, patients and caregivers should discuss the relationship between diabetes self-management and health and life goals as well as the affects of functional limitations and caregiver support.^

Goals, plans, and behavior changes: A relevant part of the post-treatment cancer experience

Background. Colorectal cancer (CRC) survivors have to manage treatment side effects, psychosocial issues, and co-morbidities, as well as modify their lifestyles to decrease risk of recurrence and prolong life. Identifying survivors’ goals and key factors that influence their goals will highlight the issues cancer survivors face post-treatment and the resources needed to help them engage in health-promoting behaviors.^ Objectives and methods. This dissertation examines the health-related goals of post-treatment CRC survivors using two studies: (1) a qualitative study to identify and describe the health goals of CRC survivors during the transition from active treatment to post-treatment survivorship and follow-up care; and (2) a cross-sectional survey to identify CRC survivors’ goals, and key factors that influence their goals.^ Results. (1) The 41 qualitative interviews indicated participants’ health-related goals were to be healthy, get back to normal, and not have a cancer recurrence. Most of the CRC survivors reported they maintained healthy behaviors, made healthy behavior changes, or had goals to change their behavior. Respondents were empowered to improve their health by maintaining follow-up care and regular health screenings, and many were managing treatment side effects in an effort to improve functional abilities. (2) The cross-sectional study found that CRC survivors’ most prevalent goals were related to healthy behaviors (i.e., eat a healthy diet and engage in physical activity), and cancer care or disease management (i.e., keep up with health screenings and monitor symptoms). Goals that survivors identified as important were similar to goals they perceived were important to their providers (i.e., goals related to cancer care, disease management). Certain goals were statistically associated with age, barriers to achieving goals, social support and health-related quality of life.^ Conclusions. CRC survivors have health-promoting goals post-treatment and are interested in making health behavior changes. Goals ranged from cancer care/surveillance and disease management to healthy lifestyle modifications. Patients may need help resolving or managing treatment side effects or co-morbidities prior to implementing health promoting behaviors. Healthcare providers’ recommendations may be a powerful resource to encourage survivors to engage in health-promoting behaviors. Self-management and goal setting support could be an appropriate strategy to assist patients with achieving their post-treatment health goals.^

THE RELATIONSHIP BETWEEN ATTITUDE ASSESSMENT/ROLE PERCEPTION AND THE FINANCIAL PERFORMANCE OF HOSPITAL DEPARTMENT MANAGERS

Much of the current healthcare financial literature addresses the concern of government officials, the public, and healthcare providers regarding the need for control of health care costs. The literature suggests that attitudes of hospital department managers toward their role in financial management affects their ability to effect favorable financial results.^ There were several objectives of the dissertation: (1) To identify whether or not there exists a relationship between the attitude/role perception of hospital managers and the financial performance of their departments. (2) To compile a descriptive survey data base of key factors identified in the financial literature from individual hospitals. (3) To compile a brief descriptive survey of hospital managers' financial management background and training (both formal and informal). (4) To conduct an attitude assessment/role perception survey regarding the importance or relevance of a suggested financial management role set (i.e., issues discussed in the current literature) as viewed by the selected hospital managers and their matched administrators. (5) To propose plausible theoretical models and statistical tests of seven proposed hypotheses.^ The statistical results of a variety of methods generally suggested, for the sample population, that the null hypothesis should not be rejected concerning the relationships between a department manager's financial attitudes and role perceptions and the resultant financial performance.^ The fact that the results of this study did not suggest that there was a significant relationship which existed between role perception and financial performance does not necessarily indicate that the theories supporting such a relationship in literature are false, not that such a relationship does not exist. Several alternative theories were postulated to explain the apparent lack of statistical relationship, and suggestions for refinement and/or improvement of further research were discussed. ^

Using spatial linear models with SAR and CAR structure to examine Texas lung cancer incidence rates

Scholars have found that socioeconomic status was one of the key factors that influenced early-stage lung cancer incidence rates in a variety of regions. This thesis examined the association between median household income and lung cancer incidence rates in Texas counties. A total of 254 individual counties in Texas with corresponding lung cancer incidence rates from 2004 to 2008 and median household incomes in 2006 were collected from the National Cancer Institute Surveillance System. A simple linear model and spatial linear models with two structures, Simultaneous Autoregressive Structure (SAR) and Conditional Autoregressive Structure (CAR), were used to link median household income and lung cancer incidence rates in Texas. The residuals of the spatial linear models were analyzed with Moran's I and Geary's C statistics, and the statistical results were used to detect similar lung cancer incidence rate clusters and disease patterns in Texas.^