Is there a special mechanism behind the changes in somatic cell and polymorphonuclear leukocyte counts, and composition of milk after a single prolonged milking interval in cows?

<p>Abstract</p> <p>Background</p> <p>A single prolonged milking interval (PMI) e.g. after a technical stop in an automated milking system is of concern for the producer since it is associated with a short-lasting increase in milk somatic cell count (SCC), which is a major quality criterion used at the dairy plants. The content of polymorphonuclear leukocytes (PMN) and how the milk quality is influenced has not been much investigated. The SCC peak occurs without any obvious antigen challenge, possibly indicating a different leukocyte attraction mechanism after a PMI than we see during mastitis.</p> <p>Methods</p> <p>Composite cow milk samples were taken at the milkings twice daily during 7 days before and 5 days after a PMI of 24 h. Milk was analyzed for SCC, PMN, fat, protein and lactose, and at some occasions also casein and free fatty acids (FFA).</p> <p>Results</p> <p>During the PMI the proportion of milk PMN increased sharply in spite of marginally increased SCC. The peak SCC was not observed until the second milking after the PMI, in the afternoon day 1. However, the peak SCC value in <it>morning </it>milk did not occur until one day later, concomitantly with a <it>decrease </it>in the proportion of PMN. After declining, SCC still remained elevated while PMN proportion was decreased throughout the study as was also the milk yield, after the first accumulation of milk during the PMI. Milk composition was changed the day after the PMI, (increased fat and protein content; decreased lactose, whey protein and FFA content) but the changes in the following days were not consistent except for lactose that remained decreased the rest of the study.</p> <p>Conclusion</p> <p>The PMI resulted in increased SCC and proportion of PMN. Additionally, it gave rise to minor alterations in the milk composition in the following milkings but no adverse effect on milk quality was observed. The recruitment of PMN, which was further enhanced the first day <it>after </it>the PMI, appeared to be independent of milk volume or accumulation of milk per se. Hence, we suggest that there is a special immunophysiological/chemoattractant background to the increased migration of leukocytes into the milk compartment observed during and after the PMI.</p

The peroxisome: still a mysterious organelle

More than half a century of research on peroxisomes has revealed unique features of this ubiquitous subcellular organelle, which have often been in disagreement with existing dogmas in cell biology. About 50 peroxisomal enzymes have so far been identified, which contribute to several crucial metabolic processes such as β-oxidation of fatty acids, biosynthesis of ether phospholipids and metabolism of reactive oxygen species, and render peroxisomes indispensable for human health and development. It became obvious that peroxisomes are highly dynamic organelles that rapidly assemble, multiply and degrade in response to metabolic needs. However, many aspects of peroxisome biology are still mysterious. This review addresses recent exciting discoveries on the biogenesis, formation and degradation of peroxisomes, on peroxisomal dynamics and division, as well as on the interaction and cross talk of peroxisomes with other subcellular compartments. Furthermore, recent advances on the role of peroxisomes in medicine and in the identification of novel peroxisomal proteins are discussed

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Childhood trauma, life-time self-harm, and suicidal behaviour and ideation are associated with polygenic scores for autism

Abstract: Autistic individuals experience significantly elevated rates of childhood trauma, self-harm and suicidal behaviour and ideation (SSBI). Is this purely the result of negative environmental experiences, or does this interact with genetic predisposition? In this study we investigated if a genetic predisposition for autism is associated with childhood trauma using polygenic scores (PGS) and genetic correlations in the UK Biobank (105,222 < N < 105,638), and tested potential mediators and moderators of the association between autism, childhood trauma and SSBI. Autism PGS were significantly associated with childhood trauma (max R2 = 0.096%, P < 2 × 10−16), self-harm ideation (max R2 = 0.108%, P < 2 × 10−16), and self-harm (max R2 = 0.13%, P < 2 × 10−16). Supporting this, we identified significant genetic correlations between autism and childhood trauma (rg = 0.36 ± 0.05, P = 8.13 × 10−11), self-harm ideation (rg = 0.49 ± 0.05, P = 4.17 × 10−21) and self-harm (rg = 0.48 ± 0.05, P = 4.58 × 10−21), and an over-transmission of PGS for the two SSBI phenotypes from parents to autistic probands. Male sex negatively moderated the effect of autism PGS on childhood trauma (β = −0.023 ± 0.005, P = 6.74 × 10−5). Further, childhood trauma positively moderated the effect of autism PGS on self-harm score (β = 8.37 × 10−3 ± 2.76 × 10−3, P = 2.42 × 10−3) and self-harm ideation (β = 7.47 × 10−3 ± 2.76 × 10−3, P = 6.71 × 10−3). Finally, depressive symptoms, quality and frequency of social interactions, and educational attainment were significant mediators of the effect of autism PGS on SSBI, with the proportion of effect mediated ranging from 0.23 (95% CI: 0.09–0.32) for depression to 0.008 (95% CI: 0.004–0.01) for educational attainment. Our findings identify that a genetic predisposition for autism is associated with adverse life-time outcomes, which represent complex gene-environment interactions, and prioritizes potential mediators and moderators of this shared biology. It is important to identify sources of trauma for autistic individuals in order to reduce their occurrence and impact

Increased Sensory Processing Atypicalities in Parents of Multiplex ASD Families Versus Typically Developing and Simplex ASD Families

Recent studies have suggested that sensory processing atypicalities may share genetic influences with autism spectrum disorder (ASD). To further investigate this, the adolescent/adult sensory profile (AASP) questionnaire was distributed to 85 parents of typically developing children (P-TD), 121 parents from simplex ASD families (SPX), and 54 parents from multiplex ASD families (MPX). After controlling for gender and presence of mental disorders, results showed that MPX parents significantly differed from P-TD parents in all four subscales of the AASP. Differences between SPX and MPX parents reached significance in the Sensory Sensitivity subscale and also in subsequent modality-specific analyses in the auditory and visual domains. Our finding that parents with high genetic liability for ASD (i.e., MPX) had more sensory processing atypicalities than parents with low (i.e., SPX) or no (i.e., P-TD) ASD genetic liability suggests that sensory processing atypicalities may contribute to the genetic susceptibility for ASD

Systematic reviews and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: mortality, morbidity, and organ failure.

BACKGROUND: Mortality, morbidity, and organ failure are important and common serious harms after surgery. However, there are many candidate measures to describe these outcome domains. Definitions of these measures are highly variable, and validity is often unclear. As part of the International Standardised Endpoints in Perioperative Medicine (StEP) initiative, this study aimed to derive a set of standardised and valid measures of mortality, morbidity, and organ failure for use in perioperative clinical trials. METHODS: Three domains of endpoints (mortality, morbidity, and organ failure) were explored through systematic literature review and a three-stage Delphi consensus process using methods consistently applied across the StEP initiative. Reliability, feasibility, and patient-centredness were assessed in round 3 of the consensus process. RESULTS: A high level of consensus was achieved for two mortality time points, 30-day and 1-yr mortality, and these two measures are recommended. No organ failure endpoints achieved threshold criteria for consensus recommendation. The Clavien-Dindo classification of complications achieved threshold criteria for consensus in round 2 of the Delphi process but did not achieve the threshold criteria in round 3 where it scored equivalently to the Post Operative Morbidity Survey. Clavien-Dindo therefore received conditional endorsement as the most widely used measure. No composite measures of organ failure achieved an acceptable level of consensus. CONCLUSIONS: Both 30-day and 1-yr mortality measures are recommended. No measure is recommended for organ failure. One measure (Clavien-Dindo) is conditionally endorsed for postoperative morbidity, but our findings suggest that no single endpoint offers a reliable and valid measure to describe perioperative morbidity that is not dependent on the quality of deli-vered care. Further refinement of current measures, or development of novel measures, of postoperative morbidity might improve consensus in this area