Trend analysis and prediction of seasonal changes in milk composition from a pasture-based dairy research herd.

The composition of seasonal pasture-produced milk is influenced by stage of lactation, animal genetics, and nutrition, which affects milk nutritional profile and processing characteristics. The objective was to study the effect of lactation stage (early, mid, and late lactation) and diet on milk composition in an Irish spring calving dairy research herd from 2012 to 2020 using principal component and predictive analytics. Crude protein, casein, fat, and solids increased from 2012 to 2020, whereas lactose concentration peaked in 2017, then decreased. Based on seasonal data from 2013 to 2016, forecasting models were successfully created to predict milk composition for 2017 to 2020. The diet of cows in this study is dependent upon grass growth rates across the milk production season, which in turn, are influenced by weather patterns, whereby extreme weather conditions (rainfall and temperature) were correlated with decreasing grass growth and increasing nonprotein nitrogen levels in milk. The study demonstrates a significant change in milk composition since 2012 and highlights the effect that seasonal changes such as weather and grass growth have on milk composition of pasture-based systems. The potential to forecast milk composition at different stages of lactation benefits processers by facilitating the optimization of in-process and supply logistics of dairy products.

Assessing the impacts of citizen-led policies on emissions, air quality and health.

Air pollution is a global challenge, and especially urban areas are particularly affected by acute episodes. Traditional approaches used to mitigate air pollution primarily consider the technical aspects of the problem but not the role of citizen behaviour and day-to-day practices. ClairCity, a Horizon 2020 funded project, created an impact assessment framework considering the role of citizen behaviour to create future scenarios, aiming to improve urban environments and the wellbeing and health of its inhabitants. This framework was applied to six pilot cases: Bristol, Amsterdam, Ljubljana, Sosnowiec, Aveiro Region and Liguria Region, considering three-time horizons: 2025, 2035 and 2050. The scenarios approach includes the Business As Usual (BAU) scenario and a Final Unified Policy Scenarios (FUPS) established by citizens, decision-makers, local planners and stakeholders based on data collected through a citizen and stakeholder co-creation process. Therefore, this paper aims to present the ClairCity outcomes, analysing the quantified impacts of selected measures in terms of emissions, air quality, population exposure, and health. Each case study has established a particular set of measures with different levels of ambition, therefore different levels of success were achieved towards the control and mitigation of their specific air pollution problems. The transport sector was the most addressed by the measures showing substantial improvements for NO2, already with the BAU scenarios, and overall, even better results when applying the citizen-led FUPS scenarios. In some cases, due to a lack of ambition for the residential and commercial sector, the results were not sufficient to fulfil the WHO guidelines. Overall, it was found in all cities that the co-created scenarios would lead to environmental improvements in terms of air quality and citizens' health compared to the baseline year of 2015. However, in some cases, the health impacts were lower than air quality due to the implementation of the measures not affecting the most densely populated areas. Benefits from the FUPS comparing to the BAU scenario were found to be highest in Amsterdam and Bristol, with further NO2 and PM10 emission reductions around 10%-16% by 2025 and 19%-28% by 2050, compared to BAU.

The Efficacy and Tolerability of Levetiracetam as a First Line Monotherapy in Childhood Epilepsy.

Introduction To examine efficacy and tolerability of Levetiracetam monotherapy as a first line agent in a national cohort of children with epilepsy, naïve to anti-epileptic medication. Methods A retrospective analysis of children with epilepsy who attended 4 Irish tertiary Paediatric Neurology Clinics (2009-2015) started on Levetiracetam as a first line monotherapy. Results 182 children were identified aged one month to 16 years (mean 6.2 years (SD=5.1) Retention at 6 and 12 months was 88% (n=161) and 83% (n=145) respectively. 75% (n=104) achieved seizure freedom or > 50% improvement in seizure control at 12 months. 30% (n=55) experienced ≥1 adverse effect with aggression (12%; n=21) the most frequent. Treatment was discontinued in 16% (n=29) because of intolerance. Underlying conditions and epilepsy type were not found to influence efficacy or tolerability. Conclusion Levetiracetam monotherapy was observed as effective and safe for children with epilepsy although side effects limit tolerance in a sizeable minority.

Air pollution, deprivation and health: understanding relationships to add value to local air quality management policy and practice in Wales, UK.

Background: Air pollution exposure reduces life expectancy. Air pollution, deprivation and poor-health status combinations can create increased and disproportionate disease burdens. Problems and solutions are rarely considered in a broad public health context, but doing so can add value to air quality management efforts by reducing air pollution risks, impacts and inequalities. Methods: An ecological study assessed small-area associations between air pollution (nitrogen dioxide and particulate matter), deprivation status and health outcomes in Wales, UK. Results: Air pollution concentrations were highest in 'most' deprived areas. When considered separately, deprivation-health associations were stronger than air pollution-health associations. Considered simultaneously, air pollution added to deprivation-health associations; interactions between air pollution and deprivation modified and strengthened associations with all-cause and respiratory disease mortality, especially in 'most' deprived areas where most-vulnerable people lived and where health needs were greatest. Conclusion: There is a need to reduce air pollution-related risks for all. However, it is also the case that greater health gains can result from considering local air pollution problems and solutions in the context of wider health-determinants and acting on a better understanding of relationships. Informed and co-ordinated air pollution mitigation and public health action in high deprivation and pollution areas can reduce risks and inequalities. To achieve this, greater public health integration and collaboration in local air quality management policy and practice is needed.

Ventricular arrhythmia incidence in the rat is reduced by naloxone.

This study characterized the antiarrhythmic effects of the opioid receptor antagonist naloxone in rats subject to electrically induced and ischemic arrhythmias. Naloxone (2, 8 and 32 µmol/kg/min) was examined on heart rate, blood pressure, and the electrocardiogram (EKG) as well as for effectiveness against arrhythmias produced by occlusion of the left anterior descending coronary artery or electrical stimulation of the left ventricle. Naloxone reduced blood pressure at the highest dose tested while heart rate was dose-dependently reduced. Naloxone dose-dependently prolonged the P-R and QRS intervals and increased the RSh amplitude indicative of effects on cardiac sodium (Na) channels. Naloxone prolonged the Q-T interval suggesting a delay in repolarization. Naloxone effects were comparable to the comparator quinidine. Naloxone (32 µmol/kg/min) reduced ventricular fibrillation (VF) incidence to 38% (from 100% in controls). This same dose significantly increased the threshold for induction of ventricular fibrillation (VFt), prolonged the effective refractory period (ERP) and reduced the maximal following frequency (MFF). The patterns of ECG changes, reduction in ischemic arrhythmia (VF) incidence and changes in electrically induced arrhythmia parameters at high doses of naloxone suggest that it directly blocks cardiac Na and potassium (K) ion channels.

An Irish breast cancer survivorship study: are we meeting our patients' needs?

UNLABELLED: Irish breast cancer survivor's needs have not been studied. Physical, psychological, social and spiritual concerns were investigated. Patient satisfaction with hospital discharge, GP follow-up, and the benefit of a discharge pack was investigated. A cohort of patients from the South East Cancer Centre was identified. INCLUSION CRITERIA: localized breast cancer, completion of adjuvant therapy, GP-led follow-up in the last 5 years. An anonymous questionnaire was developed, and ethical approval obtained. Subgroup analyses for age and time since diagnosis and discharge were completed. 80 patients were identified. 44 patients (55%) completed the questionnaire, 5 (6%) were excluded. Commonest concerns included: fatigue (51%), fear of recurrence (69%) and second cancers concerns (69%) 23 (59%) and 25 patients (64%) were satisfied with discharge and GP follow-up respectively. 27 patients (67%) reported benefit from a discharge pack. Irish breast cancer survivors had concerns, and were satisfied with GP follow-up.

Skeletal muscle plasticity with marathon training in novice runners.

The purpose of this study was to investigate leg muscle adaptation in runners preparing for their first marathon. Soleus and vastus lateralis (VL) biopsies were obtained from six recreational runners (23 ± 1 years, 61 ± 3 kg) before (T1), after 13 weeks of run training (T2), and after 3 weeks of taper and marathon (T3). Single muscle fiber size, contractile function (strength, speed, and power) and oxidative enzyme activity [citrate synthase (CS)] were measured at all three time points, and fiber type distribution was determined before and after the 16-week intervention. Training increased VO(2max) ∼9% (P<0.05). All soleus parameters were unchanged. VL MHC I fiber diameter increased (+8%; P<0.05) from T1 to T2. VL MHC I V(o) (-12%), MHC I power (-22%) and MHC IIa power (-29%) were reduced from T1 to T2 (P<0.05). No changes in VL single fiber contractile properties were observed from T2 to T3. No change was observed in soleus CS activity, whereas VL CS activity increased 66% (P<0.05). Our observations indicate that modest marathon training elicits very specific skeletal muscle adaptations that likely support the ability to perform 42.2 km of continuous running - further strengthening the existing body of evidence for skeletal muscle specificity.

A review of the pharmacobiotic regulation of gastrointestinal inflammation by probiotics, commensal bacteria and prebiotics.

The idea that microbes induce disease has steered medical research toward the discovery of antibacterial products for the prevention and treatment of microbial infections. The twentieth century saw increasing dependency on antimicrobials as mainline therapy accentuating the notion that bacterial interactions with humans were to be avoided or desirably controlled. The last two decades, though, have seen a refocusing of thinking and research effort directed towards elucidating the critical inter-relationships between the gut microbiome and its host that control health/wellness or disease. This research has redefined the interactions between gut microbes and vertebrates, now recognizing that the microbial active cohort and its mammalian host have shared co-evolutionary metabolic interactions that span millennia. Microbial interactions in the gastrointestinal tract provide the necessary cues for the development of regulated pro- and anti-inflammatory signals that promotes immunological tolerance, metabolic regulation and other factors which may then control local and extra-intestinal inflammation. Pharmacobiotics, using nutritional and functional food additives to regulate the gut microbiome, will be an exciting growth area of therapeutics, developing alongside an increased scientific understanding of gut-microbiome symbiosis in health and disease.

Assessing air pollution in European cities to support a citizen centered approach to air quality management.

European cities have made significant progress over the last decades towards clean air. Despite this progress, several cities are still facing acute air pollution episodes, with various urban areas frequently exceeding air quality levels allowed by the European legal standards and WHO guidelines. In this paper, six European cities/ regions (Bristol, UK; Amsterdam, NL; Sosnowiec, PL; Ljubljana, SI; Aveiro, PT; Liguria, IT) are studied in terms of air quality, namely particulate matter, nitrogen dioxide and ozone. The concentrations trends from 2008 to 2017 in the different typology of monitoring stations are addressed, together with the knowledge of daily, weekly and seasonal pollution patterns to better understand the city specific profiles and to characterize pollutant dynamics and variations in multiple locations. Additionally, an analysis of the duration and severity of air pollution episodes is also discussed, followed by an analysis of the fulfillment of the legislated limit values. Each of our 6 case study locations face different air pollution problems, but all these case studies have made some progress in reducing ambient concentrations. In Bristol, there have been strong downward trends in many air pollutants, but the levels of NO2 remain persistently high and of concern. In recent years, decreasing concentration levels point to some success of Amsterdam air quality policies. PM10 exceedances are a seasonal pollution problem in Ljubljana, Sosnowiec and Aveiro region (even if with different levels of severity). While, exceedances of NO2 and O3 concentrations are still problematic in Liguria region. The main findings of this paper are particular relevant to define and compare future citizen-led strategies and policy initiatives that may be implemented to improve and fulfill the EU legislation and the WHO guidelines.

Molecular characterization of receptor binding proteins and immunogens of virulent Treponema pallidum.

Receptor binding proteins of Treponema pallidum were identified by incubation of [35S]methionine-labeled, soluble T. pallidum preparations with formaldehyde-fixed HEp-2 cells. Three major treponemal proteins (bands 1--3) that avidly bound to the eucaryotic cell surface were detected by sodium dodecylsulfate-polyacrylamide gel electrophoresis and fluorography. Brief trypsin treatment of HEp-2 cells before formaldehyde fixation reduced the extent of the interaction of these treponemal macromolecules, which implicated receptor-mediated attachment mechanisms. The presence of unlabeled T. pallidum preparations directly competed with radiolabeled T. pallidum samples for the available HEp-2 cells, which suggested a limiting number of membrane binding sites. Samples of unlabeled avirulent Reiter treponeme did not compete. T. Pallidum immunogens were examined by radioimmunoprecipitation with human and rabbit syphilitic sera. Of interest were the similarities and extent of the humoral response represented by the detection of antigen-antibody complexes against numberous treponemal proteins, including bands 1--3. T. pallidum portein band 1 appeared to be the major antigenic stimulus. Formation of antigen-antibody complexes between 35S-labeled T. pallidum proteins and human syphilitic sera was prevented by unlabeled T. pallidum but not by T. phagedenis preparations, which demonstrated specificity of the reaction. Gel profiles of radioimmunoprecipitation assays using radiolabeled T. pallidum antigens and human syphilitic and yaws sera delineated both the similarities and differences in the humoral response to these two spirochetes. The latter suggested both overlapping and distinguishing antigenic properties between T. pallidum and T. pertenue. Detection in yaws sera of specific antibody against T. pallidum protein bands 1--3 further incriminates the role of these three treponemal proteins as virulence determinants.

Cyclooxygenase blockade elevates leukotriene E4 production during acute anaphylaxis in sheep.

We examined changes in the levels of eicosanoids in blood and pulmonary lymph of anesthetized sheep undergoing acute anaphylaxis. Within 1-3 min of intravenous antigenic challenge of previously sensitized sheep, there were approximately 7-30-fold elevations in mean arterial plasma levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha, respectively, as measured by RIA. Negligible changes in levels of these cyclooxygenase products were found in both nonsensitized sheep and in sensitized sheep treated with indomethacin before antigenic challenge. In contrast, no changes in levels of sulfidopeptide leukotrienes (SPLT) in pulmonary lymph were detectable by RIA during anaphylaxis in sensitized or nonsensitized sheep, but levels of SPLT in indomethacin-treated sensitized sheep increased more than fivefold above levels in lymph from both other groups of animals. The immunoreactive SPLT in lymph from indomethacin-treated sheep was accounted for as LTE4, as demonstrated by mobility on HPLC and absorbance at 280 nm. These results support the possibility that certain undesirable effects of nonsteroidal antiinflammatory drugs, such as cardiopulmonary reactions in aspirin-sensitive individuals, and impaired renal and cardiac function during therapy with these drugs, may be related in part to augmented synthesis of the 5-lipoxygenase pathway products, especially those of the sulfidopeptide class. Increased LT production could also limit the antiinflammatory effectiveness of these drugs in many disease states.

Blockade of T lymphocyte costimulation with cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells.

Efficient T cell activation is dependent on the intimate contact between antigen-presenting cells (APCs) and T cells. The engagement of the B7 family of molecules on APCs with CD28 and CD152 (cytotoxic T lymphocyte-associated antigen 4 [CTLA-4]) receptors on T cells delivers costimulatory signal(s) important in T cell activation. We investigated the dependence of pathologic cellular activation in psoriatic plaques on B7-mediated T cell costimulation. Patients with psoriasis vulgaris received four intravenous infusions of the soluble chimeric protein CTLA4Ig (BMS-188667) in a 26-wk, phase I, open label dose escalation study. Clinical improvement was associated with reduced cellular activation of lesional T cells, keratinocytes, dendritic cells (DCs), and vascular endothelium. Expression of CD40, CD54, and major histocompatibility complex (MHC) class II HLA-DR antigens by lesional keratinocytes was markedly reduced in serial biopsy specimens. Concurrent reductions in B7-1 (CD80), B7-2 (CD86), CD40, MHC class II, CD83, DC-lysosomal-associated membrane glycoprotein (DC-LAMP), and CD11c expression were detected on lesional DCs, which also decreased in number within lesional biopsies. Skin explant experiments suggested that these alterations in activated or mature DCs were not the result of direct toxicity of CTLA4Ig for DCs. Decreased lesional vascular ectasia and tortuosity were also observed and were accompanied by reduced presence of E-selectin, P-selectin, and CD54 on vascular endothelium. This study highlights the critical and proximal role of T cell activation through the B7-CD28/CD152 costimulatory pathway in maintaining the pathology of psoriasis, including the newly recognized accumulation of mature DCs in the epidermis.

In vitro developmental potential of macaque oocytes, derived from unstimulated ovaries, following maturation in the presence of glutathione ethyl ester.

BACKGROUND: The inadequacies of oocyte in vitro maturation (IVM) systems for both non-human primates and humans are evidenced by reduced fertilization and poor embryonic development, and may be partly explained by significantly lower glutathione (GSH) contents compared with in vivo matured (IVO) oocytes. As this influence has not been fully explored, this study investigated the effect of the GSH donor, glutathione ethyl ester (GSH-OEt), on the IVM and development of macaque oocytes as a model of human oocyte IVM. METHODS: Macaque oocytes derived from unstimulated ovaries were cultured in mCMRL-1066 alone or supplemented with 3 or 5 mM GSH-OEt. In vitro matured oocytes were subjected to the GSH assay, fixed for the assessment of spindle morphology or prepared ICSI. Embryo development of zygotes cultured in mHECM-9 was assessed up to Day 9 post-ICSI. RESULTS Supplementation of the maturation medium with GSH-OEt significantly increased oocyte maturation and normal fertilization rates compared with control oocytes, but only 5 mM GSH-OEt significantly increased the oocyte and cumulus cell GSH content. Confocal microscopy revealed significant differences in the spindle morphology between IVO and control in vitro matured metaphase II oocytes. Oocytes matured with 5 mM GSH-OEt exhibited spindle area and spindle pole width similar to that seen in the IVO oocyte. While no significant differences were observed in blastocyst rates, addition of 3 mM GSH-OEt during IVM significantly increased the proportion of embryos developing to the 5-8 cell stage while 5 mM GSH-OEt significantly increased the proportion of morula-stage embryos compared with controls. CONCLUSIONS: Supplementation of the IVM medium with GSH-OEt promotes better maturation and normal fertilization of macaque oocytes compared with non-supplemented medium. However, further improvement of the primate oocyte IVM culture system is required to support better blastocyst development of oocytes derived from unstimulated ovaries.

Oocyte glutathione and fertilisation outcome of Macaca nemestrina and Macaca fascicularis in in vivo- and in vitro-matured oocytes.

Fertilisation and development of IVM non-human primate oocytes is limited compared with that of in vivo-matured (IVO) oocytes. The present study describes the IVM of macaque oocytes with reference to oocyte glutathione (GSH). Timing of maturation, comparison of IVM media and cysteamine (CYS) supplementation as a modulator of GSH were investigated. A significantly greater proportion of oocytes reached MII after 30 h compared with 24 h of IVM. Following insemination, IVM oocytes had a significantly lower incidence of normal fertilisation (i.e. 2PN = two pronuclei and at least one polar body) and a higher rate of abnormal fertilisation (1PN = one pronucleus and at least one polar body) compared with IVO oocytes. Immunofluorescence of 1PN zygotes identified incomplete sperm head decondensation and failure of male pronucleus formation as the principal cause of abnormal fertilisation in IVM oocytes. The IVO oocytes had significantly higher GSH content than IVM oocytes. Cumulus-denuded oocytes had significantly lower GSH following IVM compared with immature oocytes at collection. Cysteamine supplementation of the IVM medium significantly increased the GSH level of cumulus-intact oocytes and reduced the incidence of 1PN formation, but did not improve GSH levels of the denuded oocyte. Suboptimal GSH levels in macaque IVM oocytes may be related to reduced fertilisation outcomes.

Developmental potential of bovine oocytes following IVM in the presence of glutathione ethyl ester.

Glutathione (GSH) is synthesised during oocyte maturation and represents the oocyte's main non-enzymatic defence against oxidative stress. Inadequate defence against oxidative stress may be related to poor embryo quality and viability. In the present study, bovine oocytes were matured in vitro in the presence of GSH ethyl ester (GSH-OEt), a cell permeable GSH donor, and its effects on subsequent fertilisation and embryo development were assessed. GSH-OEt significantly increased the GSH content of IVM oocytes without affecting fertilisation or Day 3 cleavage rates. Maturation in the presence of GSH-OEt did not significantly increase the blastocyst rate compared with control oocytes. However, 5 mM GSH-OEt treatment resulted in significantly higher blastocyst total cell number. The GSH level of IVM oocytes was significantly decreased in the absence of cumulus cells and when cumulus-oocyte complexes were cultured in the presence of buthionine sulfoximine (BSO), an inhibitor of GSH synthesis. The addition of GSH-OEt to cumulus-denuded or BSO-treated oocytes increased the GSH content of bovine oocytes and restored the rate of normal fertilisation, but not embryo development, to levels seen in control oocytes. Thus, GSH-OEt represents a novel approach for effective in vitro elevation of bovine oocyte GSH and improvement in blastocyst cell number.

Energy resources available to the United States, 1985 to 2000.

Energy and the gross national product have grown hand in hand at 3 to 3(1/2) percent a year for almost 40 years. Our energy growth is slowing down and will sentially level off in the 1990's. Our production of oil and gas passed a peak in the early 1970's, and there is no resource base to justify predictions of increased yields. Coal is the only fossil fuel capable of increased production. There are serious doubts that our uranium resources can support a large light-water reactor program. Finding rates for petroleum, natural gas, and uranium are less than half of what they were 20 years ago.

Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry.

Nonpeptide agonists of each of the five somatostatin receptors were identified in combinatorial libraries constructed on the basis of molecular modeling of known peptide agonists. In vitro experiments using these selective compounds demonstrated the role of the somatostatin subtype-2 receptor in inhibition of glucagon release from mouse pancreatic alpha cells and the somatostatin subtype-5 receptor as a mediator of insulin secretion from pancreatic beta cells. Both receptors regulated growth hormone release from the rat anterior pituitary gland. The availability of high-affinity, subtype-selective agonists for each of the somatostatin receptors provides a direct approach to defining their physiological functions.

Midwife-led assessment of non-catastrophic obstetric emergencies; work activity and patient attitudes.

SUMMARY: A high proportion of pregnant women attending for urgent assessment do not need emergency care and they have lower clinical priority compared with women who have serious complications in labour. We are aware that this results in a high number of complaints about waiting times. We set up a midwife-led service founded on the introduction of integrated care pathways for the six commonest conditions, based on national recommendations. A review of the case notes of 100 consecutive women who attended the maternity assessment centre was undertaken, of which 99 were suitable for analysis. On average, eight new patients were seen each day. The study found that 60% of the sample were cared for by a midwife alone and just one in three underwent direct medical assessment. The proportion cared for by midwives alone varied widely according to the presenting condition; more than 90% of those with reduced fetal movement but just one in three of those attending with antepartum haemorrhage. On average, women waited for a total of 80 min (range 35-290 min). More than 80% were in the unit for less than 120 min. On average, the wait times appeared to be longer for those women presenting with hypertension, probably because of the greater need for laboratory testing. Of a subset of 20 women surveyed by telephone questionnaire, only one (5%) was surprised to have been seen by a midwife; 17 (85%) said the counselling was excellent or good; 18 (90%) said they would be content to see a midwife for any future visit but two women said they would prefer to see a doctor at a future visit.

Estimating Aspergillus fumigatus exposure from outdoor composting activities in England between 2005 and 14.

Bioaerosols, ubiquitous in ambient air, are released in elevated concentrations from composting facilities with open-air processing areas. However, spatial and temporal variability of bioaerosols, particularly in relation to meteorology, is not well understood. Here we model relative concentrations of Aspergillus fumigatus at each postcode-weighted centroid within 4 km of 217 composting facilities in England between 2005 and 2014. Facilities were geocoded with the aid of satellite imagery. Data from existing bioaerosol modelling literature were used to build emission profiles in ADMS. Variation in input parameters between each modelled facility was reduced to a minimum. Meteorological data for each composting facility was derived from the nearest SCAIL-Agriculture validated meteorological station. According to our results, modelled exposure risk was driven primarily by wind speed, direction and time-varying emissions factors incorporating seasonal fluctuations in compostable waste. Modelled A.fumigatus concentrations decreased rapidly from the facility boundary and plateaued beyond 1.5-2.0 km. Where multiple composting facilities were within 4 km of each other, complex exposure risk patterns were evident. More long-term bioaerosol monitoring near facilities is needed to help improve exposure estimation and therefore assessment of any health risks to local populations.