IRE1α silences dsRNA to prevent taxane-induced pyroptosis in triple-negative breast cancer.

Chemotherapy is often combined with immune checkpoint inhibitor (ICIs) to enhance immunotherapy responses. Despite the approval of chemo-immunotherapy in multiple human cancers, many immunologically cold tumors remain unresponsive. The mechanisms determining the immunogenicity of chemotherapy are elusive. Here, we identify the ER stress sensor IRE1α as a critical checkpoint that restricts the immunostimulatory effects of taxane chemotherapy and prevents the innate immune recognition of immunologically cold triple-negative breast cancer (TNBC). IRE1α RNase silences taxane-induced double-stranded RNA (dsRNA) through regulated IRE1-dependent decay (RIDD) to prevent NLRP3 inflammasome-dependent pyroptosis. Inhibition of IRE1α in Trp53-/- TNBC allows taxane to induce extensive dsRNAs that are sensed by ZBP1, which in turn activates NLRP3-GSDMD-mediated pyroptosis. Consequently, IRE1α RNase inhibitor plus taxane converts PD-L1-negative, ICI-unresponsive TNBC tumors into PD-L1high immunogenic tumors that are hyper-sensitive to ICI. We reveal IRE1α as a cancer cell defense mechanism that prevents taxane-induced danger signal accumulation and pyroptotic cell death.

Probing the energetic particle environment near the Sun.

NASA's Parker Solar Probe mission1 recently plunged through the inner heliosphere of the Sun to its perihelia, about 24 million kilometres from the Sun. Previous studies farther from the Sun (performed mostly at a distance of 1 astronomical unit) indicate that solar energetic particles are accelerated from a few kiloelectronvolts up to near-relativistic energies via at least two processes: 'impulsive' events, which are usually associated with magnetic reconnection in solar flares and are typically enriched in electrons, helium-3 and heavier ions2, and 'gradual' events3,4, which are typically associated with large coronal-mass-ejection-driven shocks and compressions moving through the corona and inner solar wind and are the dominant source of protons with energies between 1 and 10 megaelectronvolts. However, some events show aspects of both processes and the electron-proton ratio is not bimodally distributed, as would be expected if there were only two possible processes5. These processes have been very difficult to resolve from prior observations, owing to the various transport effects that affect the energetic particle population en route to more distant spacecraft6. Here we report observations of the near-Sun energetic particle radiation environment over the first two orbits of the probe. We find a variety of energetic particle events accelerated both locally and remotely including by corotating interaction regions, impulsive events driven by acceleration near the Sun, and an event related to a coronal mass ejection. We provide direct observations of the energetic particle radiation environment in the region just above the corona of the Sun and directly explore the physics of particle acceleration and transport.

Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis.

BACKGROUND AND AIM: Food/environmental allergens have been associated with eosinophilic esophagitis (EoE); however, the correlation between allergy profiles and disease responsiveness to proton pump inhibitor (PPI) therapy remains unclear. We aimed to assess the association between food/environmental allergies identified on allergen testing and histologic response to PPI in patients with treatment-naive EoE. METHODS: Adults with newly diagnosed EoE who underwent formal testing for food/environmental allergies at a tertiary center were included. All patients underwent twice-daily PPI for 8 weeks with subsequent repeat endoscopy and biopsy to assess histologic response. Patients with <15 eosinophils/hpf on post-PPI mucosal biopsies were classified as responders (PPI-r-EoE), while those with ≥15 eosinophils/hpf were nonresponders (PPI-nr-EoE). RESULTS: Sixty-one patients met inclusion criteria (21 PPI-r-EoE vs 40 PPI-nr-EoE). Demographic, clinical, and endoscopic finding variables were similar between groups. Positive food allergen test was more prevalent among PPI-nr-EoE patients (82.5% vs 42.9%, P = 0.003). On multivariable analysis, positive food allergen testing remained an independent predictor for PPI nonresponse (aOR 0.15, CI: 0.04-0.58, P = 0.0006). Positive environmental allergen testing was highly prevalent, with no significant differences between groups (77.5% vs 95.2%, P = 0.14). However, higher number of positive environmental allergens (23.3% [≥5 allergens] vs 73.3% [<5 allergens], P = 0.003) and specific aeroallergens correlated with PPI-nr-EoE. CONCLUSION: Positive food allergy testing and increased environmental allergens predicted lower likelihood of histologic response to PPI in EoE. Our findings support an allergic phenotype of EoE that may less likely respond to PPI therapy. Formal allergen testing may play a role in therapy selection and tailored management in EoE.

Hospitalisation and mortality among privately insured individuals with COVID-19 in the United States: The role of intellectual disabilities and Neurogenetic disorders.

BACKGROUND: Individuals with intellectual disabilities (IDs) and neurogenetic conditions (IDNDs) are at greater risk for comorbidities that may increase adverse outcomes for this population when they have coronavirus disease 2019 (COVID-19). The study aims are to examine the population-level odds of hospitalisation and mortality of privately insured individuals with COVID-19 with and without IDNDs IDs, controlling for sociodemographics and comorbid health conditions. METHODS: This is a retrospective, cross-sectional study of 1174 individuals with IDs and neurogenetic conditions within a population of 752 237 de-identified, privately insured, US patients diagnosed with COVID-19 between February 2020 and September 2020. Odds of hospitalisation and mortality among COVID-19 patients with IDNDs adjusted for demographic characteristics, Health Resources and Services Administration region, states with Affordable Care Act and number of comorbid health conditions were analysed. RESULTS: Patients with IDNDs overall had higher rates of COVID-19 hospitalisation than those without IDNDs (35.01% vs. 12.65%, P < .0001) and had higher rates of COVID-19 mortality than those without IDNDs (4.94% vs. .88%, P < .0001). Adjusting for sociodemographic factors only, the odds of being hospitalised for COVID-19 associated with IDNDs was 4.05 [95% confidence interval (CI) 3.56-4.61]. Adjusting for sociodemographic factors and comorbidity count, the odds of hospitalisation for COVID-19 associated with IDNDs was 1.42 (95% CI 1.25-1.61). The odds of mortality from COVID-19 for individuals with IDNDs adjusted for sociodemographic factors only was 4.65 (95% CI 3.47-6.24). The odds of mortality from COVID-19 for patients with IDNDs adjusted for sociodemographic factors and comorbidity count was 2.70 (95% CI 2.03-3.60). A major finding of the study was that even when considering the different demographic structure and generally higher disease burden of patients with IDNDs, having a IDND was an independent risk factor for increased hospitalisation and mortality compared with patients without IDNDs. CONCLUSIONS: Individuals with IDNDs had significantly higher odds of hospitalisation and mortality after adjusting for sociodemographics. Results remained significant with a slight attenuation after adjusting for sociodemographics and comorbidities. Adjustments for comorbidity count demonstrated a dose-response increase in odds of both hospitalisation and mortality, illustrating the cumulative effect of health concerns on COVID-19 outcomes. Together, findings highlight that individuals with IDNDs experience vulnerability for negative COVID-19 health outcomes with implications for access to comprehensive healthcare.

Osteoarthritis consumers as co-researchers: identifying consumer insights to improve osteoarthritis management by co-designing translational research solutions.

INTRODUCTION: Co-design is a consumer-driven approach that facilitates consumer participation in creating meaningful solutions to complex problems. Poor uptake of core management strategies for osteoarthritis suggests there is a missing link in translation between research and practice. We partnered with osteoarthritis consumers as 'co-researchers' to identify translational research solutions to improve uptake of core management strategies that are grounded in lived experiences. OBJECTIVE: To transparently describe a theory-driven, generative co-design approach using an integrated conceptual framework to collaborate with consumers at the equal partnership level. DESIGN: We used co-design workshops with a non-hierarchical participatory framework. Three workshops with six co-researchers [2 female, mean age 68.7 (9.8) years, 3-30 years symptom duration] were conducted using activities to encourage creative thinking, promote deep reflection on personal/societal beliefs and minimise sensitivities around sharing personal beliefs (e.g., establishing a safe space, prompting questions, perspective-taking, counter-stereotypical exemplars). RESULTS: All six co-researchers actively participated in the workshops. Achievement of an equal collaborative partnership was evidenced by co-researchers challenging a project proposed by the research team and making alternative recommendations that have been implemented in prospective decision-making - representing a complete change in research focus driven by consumer input. A key suggested solution was to develop a scalable knowledge translation intervention that targets misconceptions about osteoarthritis and its management at the societal-level. CONCLUSIONS: Through an innovative co-design approach in partnership with co-researchers, we identified meaningful areas on which to focus translational research for osteoarthritis. Discordance between existing research priorities and novel solutions proposed by co-researchers highlights the value of co-design.

Reaching Ambulatory Older Adults with Educational Tools: Comparative Efficacy and Cost of Varied Outreach Modalities in Primary Care.

BACKGROUND: Providing patients with access to health information that can be obtained outside of an office visit is an important part of education, yet little is known about the effectiveness of outreach modalities to connect older adults to online educational tools. The objective was to identify the effectiveness and cost of outreach modalities providing online information about advance care planning (ACP) for older adults. METHODS: Six different outreach modalities were utilized to connect patients to online educational tools (ACP video decision aids). Participants were 13,582 patients aged 65 and older of 185 primary care providers with appointments over a 30-month period within a large health system in the greater New York City area. Main outcome measures were number of online video views and costs per outreach for each modality. KEY RESULTS: There were 1150 video views for 21,407 remote outreach events. Text messages, sent to the largest volume of patients (8869), had the highest outcome rate (9.6%) and were the most economical ($0.09). Characterization of phone calls demonstrated 21.7% engagement in the topic of ACP but resulted in minimal video views (<1%) and incurred the highest cost per outreach ($2.88). In-office handouts had negligible results (<1%). CONCLUSIONS: Text was the most cost-effective modality to connect older adults to an online educational tool in this pragmatic trial, though overall efficacy of all modalities was low.

Less is more: single dose versus extended antibiotic prophylaxis for transperineal prostate biopsy.

INTRODUCTION: There is an ongoing debate as to the appropriate regimen of antibiotic prophylaxis with transperineal (TP) biopsy. The objective of this study was to report the rate of infection following TP biopsy at a high-volume institution and assess the impact of single dose antibiotics at the time of biopsy versus outpatient antibiotics in preventing postprocedural infections. MATERIALS AND METHODS: Records of men undergoing TP prostate biopsy from 2012 to 2022 were reviewed. Patients were divided into two groups, those who received single dose intravenous (IV) antibiotics at the time of biopsy (n = 440) and those who received both IV antibiotics at the time of biopsy and outpatient antibiotics before/after biopsy (n = 327). Post biopsy infection was defined as at least one of the following: fever (≥ 38.3°C) with/without symptoms of urinary tract infection or positive urine culture (> 105 colony forming units) within 72 hours post biopsy. The rates of infection were compared between the two groups. RESULTS: A total of 767 biopsies were included in the study. Infection rate post TP biopsy was 1.83% (n = 14). The infection rate for patients with single dose prophylaxis was 2.05% (n = 9) and 1.53% (n = 5) for those that received the extended antibiotic regimen. No significant difference in infection rates between the different antibiotic regimens was found (p = 0.597). CONCLUSIONS: Overall rates of infection after TP prostate biopsy are very low. Our data indicate that single dose and extended regimen of antibiotic prophylaxis show similar infection rates. These findings support antibiotic stewardship and encourage further research into the appropriate regimen of prophylaxis for TP prostate biopsy.

Fundamentals of osteoarthritis: outcome evaluation with patient-reported measures and functional tests.

Evaluating outcome in osteoarthritis (OA) clinical research and practice requires reliable, valid and responsive patient-reported outcome measures (PROMs) and functional tests that reflect important problems experienced by people with OA. The goal of this work is to provide information to start to guide the reader in selecting measures for people with OA. In this narrative review, we begin by providing an overview of measurement properties that can help clinicians and researchers in making decisions about whether a measure might be appropriate for use in their research or clinical context. We then report evidence supporting the use of measures of pain (e.g., Pain Visual Analogue (VAS), Numeric Pain Rating Scale (NPRS), Intermittent and Constant Osteoarthritis Pain, PROMIS Pain Interference, and, for screening in research, the painDETECT and the Self-report Leeds Assessment of Neuropathic Symptoms and Signs) and fatigue (e.g., PROMIS-Fatigue) at a group level in clinical research. Several multi-dimensional joint-specific measures (e.g., Western Ontario McMaster Universities' Osteoarthritis Outcomes Scale, Knee/Hip Injury and Osteoarthritis Outcome Score, Oxford Hip/Knee Scale) also have evidence for group-level use. Functional tests (e.g., timed walk tests, 30 Second Chair Stand, Timed Up and Go, etc.) have measurement properties supporting their use at the group level in clinical research and at the individual patient level as do the pain VAS and NPRS. Other generic and disease-specific PROMs have been used in or could be used in OA studies but their measurement properties require further evaluation in people with OA.

Orthopedic manifestations of child abuse.

Child abuse is common in the United States but is often undetected. The incidence of this form of abuse is difficult to quantify, but children with a history of abuse are at risk of chronic health conditions. Medical providers are in the unique position of triaging trauma patients and differentiating unintentional from abusive trauma, as well as having the important position of being a mandated reporter of abuse in all states. Obtaining a detailed history and screening for risk factors can help identify children at risk of abuse. Certain orthopedic injuries may be related to abuse, which may trigger clinical suspicion and lead to further workup or intervention. By increasing awareness, through medical provider education and increased screening, earlier detection of abuse may prevent more serious injuries and consequences. This review evaluates current literature regarding the orthopedic manifestations of child abuse in hopes of increasing medical provider awareness. IMPACT: Child abuse is common in the United States but often remains undetected. Medical professionals are in the unique position of evaluating trauma patients and identifying concerns for abusive injuries. Certain orthopedic injuries may raise concern for abuse triggering clinical suspicion and further workup or intervention.

Exercise Counters the Age-Related Accumulation of Senescent Cells.

We propose the beneficial effects of exercise are in part mediated through the prevention and elimination of senescent cells. Exercise counters multiple forms of age-related molecular damage that initiate the senescence program and activates immune cells responsible for senescent cell clearance. Preclinical and clinical evidence for exercise as a senescence-targeting therapy and areas needing further investigation are discussed.

Socioeconomic Disparities in the Utilization of Total Knee Arthroplasty.

BACKGROUND: Despite strong evidence supporting the efficacy of total knee arthroplasty (TKA), studies have shown significant socioeconomic disparities regarding who ultimately undergoes TKA. The purpose of the current study is to evaluate socioeconomic factors affecting whether a patient undergoes TKA after a diagnosis of osteoarthritis. METHODS: From 2011 to 2018, claims for adult patients diagnosed with knee osteoarthritis in the New York Statewide Planning and Research Cooperative System (SPARCS) database were analyzed. International Classification of Diseases (ICD), 9/10 CM codes were used to identify the initial diagnosis for each patient. ICD 9/10 PCS codes were used to identify subsequent TKA. Logistic regression analysis was performed to determine the effect of patient factors on the likelihood of having TKA. RESULTS: Of 313,794 osteoarthritis diagnoses, 33.3% proceeded to undergo TKA. Increased age (OR 1.007, P < .0001) and workers' compensation relative to commercial insurance (OR 1.865, P < .0001) had increased odds of TKA. Compared to White race, Asian (OR 0.705, P < .0001), Black (OR 0.497, P < .0001), and "other" race (OR 0.563, P < .0001) had lower odds of TKA. Hispanic ethnicity (OR 0.597, P < .0001) had lower odds of surgery. Compared to commercial insurance, Medicare (OR 0.876, P < .0001), Medicaid (OR 0.452, P < .0001), self-pay (OR 0.523, P < .0001), and "other" insurance (OR 0.819, P < .0001) had lower odds of TKA. Increased social deprivation (OR 0.987, P < .0001) had lower odds of TKA. CONCLUSION: TKA is associated with disparities among race, ethnicity, primary insurance, and social deprivation. Additional research is necessary to identify the cause of these disparities to improve equity in orthopedic care.

Socioeconomic Disparities in the Utilization of Total Hip Arthroplasty.

BACKGROUND: There is increasing focus on highlighting disparities in both access to and equity of care in orthopedics and understanding the impact disparities have on patient health. The purpose of the present study is to evaluate socioeconomic-related factors affecting whether a patient undergoes total hip arthroplasty (THA) after a diagnosis of osteoarthritis. METHODS: From 2011 to 2018, patients ≥40 years of age diagnosed with hip osteoarthritis were identified in the New York Statewide Planning and Research Cooperative System, a comprehensive all-payer database collecting preadjudicated claims in New York State. International Classification of Diseases, Ninth Revision/Tenth Revision codes were used to identify the initial diagnosis and subsequent THA. Logistic regression analysis was performed to determine the effect of patient factors on the likelihood of undergoing THA. RESULTS: Of 142,681 hip osteoarthritis diagnoses, 48.6% proceeded to THA. Compared to non-Hispanic white patients, Asian (odds ratio [OR] 0.65, P < .0001), Black (OR 0.51, P < .0001), and "Other" race (OR 0.54, P < .0001) had lower odds of THA. Hispanic patients (OR 0.55, P < .0001) had lower odds of surgery. Compared to commercial insurance, Medicare (OR 0.83, P < .0001), Medicaid (OR 0.49, P < .0001), Self-pay (OR 0.78, P < .0001), and workers' compensation (OR 0.71, P < .0001) had lower odds of THA. Having one or more Charlson Comorbidity Index (OR 0.45, P < .0001) was associated with lower odds of THA, as was increased social deprivation (OR 0.99, P < .0001). CONCLUSION: THA is associated with disparities among race, gender, primary insurance, and social deprivation. Additional research is necessary to identify the cause of these disparities to improve equity in patient care.

Moving forward: methodological considerations for assessing corticospinal excitability during rhythmic motor output in humans.

The use of transcranial magnetic stimulation to assess the excitability of the central nervous system to further understand the neural control of human movement is expansive. The majority of the work performed to-date has assessed corticospinal excitability either at rest or during relatively simple isometric contractions. The results from this work are not easily extrapolated to rhythmic, dynamic motor outputs, given that corticospinal excitability is task-, phase-, intensity-, direction-, and muscle-dependent (Power KE, Lockyer EJ, Forman DA, Button DC. Appl Physiol Nutr Metab 43: 1176-1185, 2018). Assessing corticospinal excitability during rhythmic motor output, however, involves technical challenges that are to be overcome, or at the minimum considered, when attempting to design experiments and interpret the physiological relevance of the results. The purpose of this narrative review is to highlight the research examining corticospinal excitability during a rhythmic motor output and, importantly, to provide recommendations regarding the many factors that must be considered when designing and interpreting findings from studies that involve limb movement. To do so, the majority of work described herein refers to work performed using arm cycling (arm pedaling or arm cranking) as a model of a rhythmic motor output used to examine the neural control of human locomotion.

Development of an intervention to manage knee osteoarthritis risk and symptoms following anterior cruciate ligament injury.

INTRODUCTION: Anterior cruciate ligament (ACL) injury is a risk factor for developing knee osteoarthritis (OA). We developed an intervention to support people manage risk factors for OA. METHODS: We conducted one-on-one interviews with 20 individuals with OA symptoms 6-15 years post ACL injury and used a nominal group process during a workshop with 40 patients and healthcare professionals (HCPs) to elicit information on the intervention content and delivery characteristics (timing, HCPs, and methods). Interview data were analyzed using content analysis. Nominal group ideas with importance ratings ≥5 of 7 met criteria for inclusion. Results were integrated, considering similarities and differences. RESULTS: Eight content categories were identified: 1. understanding knee injury and expectations about recovery; 2. understanding OA risk; 3. understanding OA signs and symptoms; 4. managing OA risk; 5. managing knee OA symptoms; 6. information for influencers; 7. credible sources; and, 8. updates on new evidence and treatments. Delivery timing reflected a lifespan approach from time of injury through symptomatic knee OA management. Although multiple media for delivery were identified, introductory face-to-face discussions and opportunity for re-accessing HCPs were critical. All HCPs who treat people with ACL should be familiar with and able to deliver the intervention. CONCLUSIONS: This co-development approach identified that an intervention to support people with ACL injury to limit and manage knee OA requires content embedded within an easily accessible, multi-media delivery model with capacity for check-back with HCPs that is appealing to different age groups and personal preferences over the lifespan post injury.

Immediate outcomes following the GLA:D® program in Denmark, Canada and Australia. A longitudinal analysis including 28,370 patients with symptomatic knee or hip osteoarthritis.

OBJECTIVE: To report outcomes across three countries for patients with symptomatic knee or hip OA attending the evidence-based education and exercise therapy program Good Life with osteoArthritis from Denmark (GLA:D®). DESIGN: GLA:D® is a structured treatment program including 2-3 patient education sessions and 12 supervised exercise sessions delivered over 8 weeks by certified health care practitioners. The program was introduced in Denmark in 2013, in Canada 2015 and in Australia 2016. Absolute mean change in pain intensity, number of chair stands in 30 s, 40 m walk test time and Knee injury and Osteoarthritis Outcome Score (KOOS)/Hip dysfunction and Osteoarthritis Outcome Score (HOOS) QOL subscale scores from baseline to immediately after treatment were reported as means and 95 % CIs and proportion of responders for each country. RESULTS: Patients from the three countries improved 26-33% in mean pain intensity, 8-12% in walking speed, 18-30% in chair stand ability and 12-26% in joint-related quality of life from baseline to immediately after treatment, with no clinically relevant differences between patients with hip and knee OA. These improvements correspond with moderate to large within-group effect sizes and 43-47 % of the patients experienced clinically relevant pain reductions. CONCLUSION: About half or more of patients across the three countries were categorized as responders for pain and objective function following the implementation of GLA:D®. These findings indicate positive patient outcomes associated with GLA:D® participation across varying health care systems from implementation of guideline-based patient education and exercise therapy for knee and hip OA.

MUC1 mediates Pneumocystis murina binding to airway epithelial cells.

Previous studies have shown that Pneumocystis binds to pneumocytes, but the proteins responsible for binding have not been well defined. Mucins are the major glycoproteins present in mucus, which serves as the first line of defence during airway infection. MUC1 is the best characterised membrane-tethered mucin and is expressed on the surface of most airway epithelial cells. Although by electron microscopy Pneumocystis primarily binds to type I pneumocytes, it can also bind to type II pneumocytes. We hypothesized that Pneumocystis organisms can bind to MUC1 expressed by type II pneumocytes. Overexpression of MUC1 in human embryonic kidney HEK293 cells increased Pneumocystis binding, while knockdown of MUC1 expression by siRNA in A549 cells, a human adenocarcinoma-derived alveolar type II epithelial cell line, decreased Pneumocystis binding. Immunofluorescence labelling indicated that MUC1 and Pneumocystis were co-localised in infected mouse lung tissue. Incubation of A549 cells with Pneumocystis led to phosphorylation of ERK1/2 that increased with knockdown of MUC1 expression by siRNA. Pneumocystis caused increased IL-6 and IL-8 secretion by A549 cells, and knockdown of MUC1 further increased their secretion in A549 cells. Taken together, these results suggest that binding of Pneumocystis to MUC1 expressed by airway epithelial cells may facilitate establishment of productive infection.

Sirt4 is a mitochondrial regulator of metabolism and lifespan in Drosophila melanogaster.

Sirtuins are an evolutionarily conserved family of NAD+-dependent deacylases that control metabolism, stress response, genomic stability, and longevity. Here, we show the sole mitochondrial sirtuin in Drosophila melanogaster, Sirt4, regulates energy homeostasis and longevity. Sirt4 knockout flies have a short lifespan, with increased sensitivity to starvation and decreased fertility and activity. In contrast, flies overexpressing Sirt4 either ubiquitously or specifically in the fat body are long-lived. Despite rapid starvation, Sirt4 knockout flies paradoxically maintain elevated levels of energy reserves, including lipids, glycogen, and trehalose, while fasting, suggesting an inability to properly catabolize stored energy. Metabolomic analysis indicates several specific pathways are affected in Sirt4 knockout flies, including glycolysis, branched-chain amino acid metabolism, and impaired catabolism of fatty acids with chain length C18 or greater. Together, these phenotypes point to a role for Sirt4 in mediating the organismal response to fasting, and ensuring metabolic homeostasis and longevity.

Effects of dietary deoiled soy lecithin supplementation on milk production and fatty acid digestibility in Holstein dairy cows.

Deoiled soy lecithin is a feed additive enriched in phospholipids. Our study evaluated the effects of dietary deoiled soy lecithin supplementation on (1) milk production and composition, (2) plasma and milk fatty acid (FA) content and yield, and (3) apparent FA digestibility and absorption in lactating dairy cows fed fractionated palm fat. In a split-plot Latin square design, 16 Holstein cows (160 ± 7 days in milk; 3.6 ± 1.2 parity) were randomly allocated to a main plot receiving a corn silage and alfalfa haylage-based diet with palm fat containing either moderate (MPA) or high palmitic acid (HPA) content at 1.75% of ration dry matter (72 or 99% palmitic acid, respectively; n = 8/palm fat diet). On each palm fat diet, deoiled soy lecithin was top-dressed at 0, 0.12, 0.24, or 0.36% of ration dry matter in a replicated 4 × 4 Latin square design. Following a 14-d covariate period, lecithin supplementation spanned 14 d, with milk and blood collected during the final 3 d. Milk composition and pooled plasma markers were measured. The statistical model included the fixed effects of palm fat type, lecithin dose, period, and the interaction between palm fat type and lecithin dose. The random effect of cow nested within palm fat group was also included. Lecithin linearly decreased dry matter intake. In cows fed HPA, lecithin feeding reduced milk fat content and tended to decrease milk fat yield. Although no changes in milk yield were observed, a quadratic reduction in 3.5% fat-corrected milk was observed with increasing lecithin dose. Lecithin linearly increased energy-corrected milk efficiency in cows fed MPA. Lecithin supplementation also decreased milk urea nitrogen, relative to unsupplemented cows. The proportion of 16-carbon FA in milk fat decreased linearly with lecithin dose, whereas 18-carbon FA increased linearly. Lecithin reduced de novo FA (<16-carbon) content and tended to increase preformed FA (>16-carbon) content in a linear manner. Compared with MPA, HPA diets reduced apparent total and 16-carbon FA digestibility and absorption. Deoiled soy lecithin feeding did not modify FA digestibility or absorption. Our observations suggest that soy lecithin feeding modifies rumen digestion to reduce dry matter intake and change milk composition.

How can we realise the full potential of animal health systems for delivering development and health outcomes?

Animal health services play an essential role in supporting livestock production, with the potential to address the challenges of hunger, poverty, health, social justice and environmental health as part of the path towards the Sustainable Development Goal (SDG) defined in the United Nations, 2030 Agenda. However, the provision of animal health services remains chronically underfunded. Although the aspiration that â€Ëœno one will be left behind' is core to the SDG agenda, animal health service provision still fails to meet the basic needs of many of the poorest livestock owners. This review draws largely on experience from Tanzania and highlights the obstacles to equitable provision of animal health services, as well as identifying opportunities for improvement. Delivery models that rely on owners paying for services, whether through the private sector or public?private partnerships, can be effective for diseases that are of clear economic importance to animal keepers, particularly in more market-orientated production systems, but are currently constrained by issues of access, affordability, availability and quality. Substantial challenges remain when attempting to control diseases that exert a major burden on animal or human health but are less well recognised, as well as in the delivery of veterinary public health or other public good interventions. Here, the authors propose solutions that focus on: improving awareness of the potential for animal health services to address the SDGs, particularly those concerning public and environmental health; linking this more explicitly with advocacy for increased investment; ensuring that the voices of stakeholders are heard, particularly those of the rural poor; and embracing a cross-cutting and expanded vision for animal health services to support more adaptive development of livestock systems.

Les services de santé animale accomplissent une fonction essentielle en faveur de la production animale tout en ayant un potentiel d'action pour relever les défis de la faim, de la pauvreté, de la santé, de la justice sociale et de la santé dans la perspective des objectifs de développement durable (ODD) définis dans l'Agenda 2030 des Nations Unies. Toutefois, la prestation de services de santé animale souffre d'un sous-financement chronique. Bien que l'aspiration de « ne laisser personne pour compte ¼ soit au coeur du programme des ODD, à ce jour la prestation de services de santé animale ne parvient pas encore à répondre aux besoins fondamentaux de nombreux propriétaires de bétail parmi les plus pauvres. Les auteurs s'appuient largement sur l'expérience de la Tanzanie pour mettre en évidence les obstacles à une prestation équitable de services de santé animale, et relever des perspectives d'amélioration. Les modèles de prestation assurés dans le cadre du secteur privé ou de partenariats public-privé et reposant sur le paiement des services par les propriétaires se révèlent efficaces lorsqu'il s'agit de maladies qui ont une importance économique évidente pour les détenteurs d'animaux, en particulier dans les systèmes de production orientés vers le marché, mais ils sont actuellement limités par des problèmes d'accès, de coût, de disponibilité de l'offre et de qualité. Des difficultés encore plus grandes subsistent lorsqu'il s'agit de lutter contre des maladies moins connues bien qu'ayant un impact important sur la santé animale ou humaine, ou d'assurer des services de santé publique vétérinaire ou d'autres interventions relevant du bien public. Les auteurs proposent des solutions centrées sur : une meilleure sensibilisation concernant le potentiel des services de santé animale à réaliser les ODD, en particulier ceux qui portent sur la santé publique et la santé environnementale ; la mise en place de liens plus explicites avec les plaidoyers en faveur d'investissements accrus ; des mesures garantissant que les voix de toutes les parties prenantes soient entendues, en particulier celles des pauvres du monde rural ; l'adoption d'une stratégie transversale et de grande ampleur pour les services de santé animale en faveur d'un développement plus adaptatif des systèmes d'élevage.

Los servicios de sanidad animal cumplen una esencial función de apoyo a la producción ganadera, potencialmente útil para abordar problemas relacionados con el hambre, la pobreza, la salud, la justicia social y la salud ambiental como parte del camino hacia los Objetivos de Desarrollo Sostenible (ODS) marcados en la Agenda 2030 de las Naciones Unidas. Sin embargo, la prestación de servicios zoosanitarios está lastrada por un déficit crónico de financiación. Aunque en la base misma de los ODS late la aspiración de «no dejar a nadie atrás¼, la prestación estos servicios aún no alcanza para responder a las necesidades básicas de muchos de los propietarios de ganado más pobres. Los autores, basándose principalmente en la experiencia de Tanzania, destacan los obstáculos que dificultan una prestación equitativa de servicios zoosanitarios y señalan las posibilidades existentes para progresar al respecto. Los modelos de prestación que requieren que el propietario pague por los servicios recibidos, ya sea del sector privado o de alianzas publicoprivadas, pueden resultar eficaces en el caso de enfermedades que revisten una clara importancia económica para los productores, especialmente en sistemas productivos con una marcada orientación comercial, aunque actualmente se ven lastrados por problemas de acceso, asequibilidad, disponibilidad y calidad. Por otro lado, subsisten dificultades de gran calado a la hora de combatir enfermedades menos reconocidas, aunque estas entrañen una pesada carga sanitaria o zoosanitaria, y también a la hora de implantar medidas de salud pública veterinaria u otras intervenciones de interés público. Los autores proponen soluciones centradas en: dar mejor a conocer el potencial que encierran los servicios de sanidad animal para perseguir los ODS, sobre todo los relacionados con la salud pública y ambiental; vincular más explícitamente esto último a la labor de sensibilización para lograr inversiones más cuantiosas; hacer oír la voz de todos los interesados, en especial la de los pobres de zonas rurales; y adoptar una visión más amplia y transversal de los servicios zoosanitarios para favorecer un desarrollo más flexible de los sistemas ganaderos.

Lack of trade-offs in host offspring produced during fecundity compensation.

Host-parasite coevolution may result in life-history changes in hosts that can limit the detrimental effects of parasitism. Fecundity compensation is one such life-history response, occurring when hosts increase their current reproductive output to make up for expected losses in future reproduction due to parasitic infection. However, the potential trade-offs between this increase in quantity and the quality of offspring have been relatively unexplored. This study uses the trematode, Schistosoma mansoni, and its snail intermediate host, Biomphalaria glabrata, to better understand how this host life-history response, fecundity compensation, impacts host reproduction. Measures of host reproductive output as well as offspring hatching success and survival were collected to assess the reproductive consequences of infection. Infected snails exhibited fecundity compensation by increasing the number of eggs laid and the overall probability of laying eggs compared to uninfected snails. Parental infection status did not play a significant role in hatching or offspring survival to maturity. Offspring from a later reproductive bout demonstrated a higher hatching success rate. Overall, the lack of an apparent trade-off between quantity and quality of offspring suggests that infected parental snails invest more resources towards reproduction not only to increase reproductive output, but also to maintain the fitness of their offspring, possibly at the expense of their own longevity.