31 Effects of dietary standardized ileal digestible (SID) lysine (Lys) levels and dietary SID tryptophan to Lys ratios on growth performance and behavior of late-nursery to finish maternal barrows

The objective was to determine the effects of dietary standardized ileal digestible (SID) lysine (Lys) levels and SID tryptophan (Trp) to Lys ratios on growth performance and behavior of late-nursery to finish maternal barrows. A total of 2,293 barrows (PIC Camborough, initially 11.9 ± 0.35 kg) were used in this trial with 96 mixed-sex pens and 23 to 25 pigs/pen. There was a total of 6 dietary phases: P1:11.9-29.5 kg; P2:29.5-49.6 kg; P3:49.6-62.6 kg; P4:62.6-80.3 kg; P5:80.3-103.3 kg; and P6:103.3-137.8 kg. Pens were blocked by body weight and randomly allotted to 1 of 6 treatments:T1: 100% Lys (dietary SID Lys levels meet PIC SID Lys recommendation) and 21.0% of SID Trp:Lys ratio; T2: 100% Lys and 18.5% of SID Trp:Lys ratio; T3: 100% Lys and 16.0% of SID Trp:Lys ratio; T4: 80% Lys (dietary SID Lys levels meet 80% of PIC SID Lys recommendation) and 21.0% of SID Trp:Lys ratio; T5: 80% Lys and 18.5% of SID Trp:Lys ratio; and T6: 80% Lys and 16.0% of SID Trp:Lys ratio for P1-P2 and then 100% Lys and 18.5% of SID Trp:Lys ratio for P3-P6. Ear lesion (EL) was monitored during P2-P5. Data were analyzed using a linear mixed model in R Studio (Version 3.5.2, R Core Team; Vienna, Austria). Pigs fed T1 and T2 showed improved average daily gain than T6 (P < 0.05), with other treatments intermediate (Table 1). Pigs fed T2 showed improved average daily feed intake as compared with T6 (P < 0.05), with other treatments intermediate. There was no evidence for significant difference on feed-to-gain ratio or mortality. Removal was significantly greater for pigs fed T6 compared with all other treatments (P < 0.05). Pigs fed T2 had significantly greater hot carcass weight than T4, with other treatments intermediate. There was no evidence for significant differences on carcass yield or lean percentage. Pig fed T6 had significantly greater incidence of EL in P2 than all other treatments (P < 0.05). Pigs fed T4 and T6 had greater incidence of EL in P3 than T1 (P < 0.05), with other treatments intermediate. Pigs fed T5 and T6 had significantly greater incidence of EL in P4 than T1, T2, and T3 (P < 0.05), with T4 intermediate. During P5, pigs fed T4 and T5 had the greatest incidence of EL (P < 0.05), while pigs fed T6 had significant greater incidence of EL than T3 (P < 0.05), with T1 and T2 intermediate. In conclusion, dietary SID Lys and SID Trp:Lys ratio less than PIC recommendation during late-nursery-to-grower phase resulted in compromised overall growth performance of maternal barrows, even with restored dietary SID Lys and SID Trp:Lys levels in finish phase. Dietary SID Lys level and/or SID Trp:Lys ratios lower than PIC recommendation may result in greater incidence of aggression behavior in maternal barrows

Characterization of Patients with Chronic Diseases and Complex Care Needs: A New High-Risk Emergent Population

Background: To analyze the prevalence and main epidemiological, clinical and outcome features of in-Patients with Complex Chronic conditions (PCC) in internal medicine areas, using a pragmatic working definition. Methods: Prospective study in 17 centers from Spain, with 97 in-hospital, monthly prevalence cuts. A PCC was considered when criteria of polypathological patient (two or more major chronic diseases) were met, or when a patient suffered one major chronic disease plus one or more of nine predefined complexity criteria like socio-familial risk, alcoholism or malnutrition among others (PCC without polypathology). A complete set of baseline features as well as 12-months survival were collected. Then, we compared clinical, outcome variables, and PROFUND index accuracy between polypathological patients and PCC without polypathology. Results: The global prevalence of PCC was 61% (40% of them were polypathological patients, and 21% PCC withouth polypathology) out of the 2178 evaluated patients. Their median age was 82 (59.5% men), suffered 2.3 ± 1.1 major diseases (heart diseases (70.5%), neurologic (41.5%), renal (36%), and lung diseases (26%)), 5.5 ± 2.5 other chronic conditions, met 2.5 ± 1.5 complexity criteria, and presented functional decline (Barthel index 55 (25-90)). Compared to polypathological patients, the subgroup of PCC without polypathology were younger, with a different pattern of major diseases and comorbidities, a better functional status, and lower 12-months mortality rates ((36.2% vs 46.8%; p = .003; OR 0.7(0.48-0.86). The PROFUND index obtained adequate calibration and discrimination power (AUC-ROC 0.67 (0.63-0.69)) in predicting 12-month mortality of PCC. Conclusion: Patients with complex chronic conditions are highly prevalent in internal medicine areas; their clinical pattern has changed in parallel to socio-epidemiological modifications, but their death-risk is still adequately predicted by PROFUND index

Sub-femto-g free fall for space-based gravitational wave observatories: LISA pathfinder results

We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2 ± 0.1 fm s−2/√Hz or (0.54 ± 0.01) × 10−15 g/√Hz, with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8 ± 0.3) fm/√Hz, about 2 orders of magnitude better than requirements. At f ≤ 0.5 mHz we observe a low-frequency tail that stays below 12 fm s−2/√Hz down to 0.1 mHz. This performance would allow for a space-based gravitational wave observatory with a sensitivity close to what was originally foreseen for LISA

Sporangiospore Size Dimorphism Is Linked to Virulence of Mucor circinelloides

Mucor circinelloides is a zygomycete fungus and an emerging opportunistic pathogen in immunocompromised patients, especially transplant recipients and in some cases otherwise healthy individuals. We have discovered a novel example of size dimorphism linked to virulence. M. circinelloides is a heterothallic fungus: (+) sex allele encodes SexP and (−) sex allele SexM, both of which are HMG domain protein sex determinants. M. circinelloides f. lusitanicus (Mcl) (−) mating type isolates produce larger asexual sporangiospores that are more virulent in the wax moth host compared to (+) isolates that produce smaller less virulent sporangiospores. The larger sporangiospores germinate inside and lyse macrophages, whereas the smaller sporangiospores do not. sexMΔ mutants are sterile and still produce larger virulent sporangiospores, suggesting that either the sex locus is not involved in virulence/spore size or the sexP allele plays an inhibitory role. Phylogenetic analysis supports that at least three extant subspecies populate the M. circinelloides complex in nature: Mcl, M. circinelloides f. griseocyanus, and M. circinelloides f. circinelloides (Mcc). Mcc was found to be more prevalent among clinical Mucor isolates, and more virulent than Mcl in a diabetic murine model in contrast to the wax moth host. The M. circinelloides sex locus encodes an HMG domain protein (SexP for plus and SexM for minus mating types) flanked by genes encoding triose phosphate transporter (TPT) and RNA helicase homologs. The borders of the sex locus between the three subspecies differ: the Mcg sex locus includes the promoters of both the TPT and the RNA helicase genes, whereas the Mcl and Mcc sex locus includes only the TPT gene promoter. Mating between subspecies was restricted compared to mating within subspecies. These findings demonstrate that spore size dimorphism is linked to virulence of M. circinelloides species and that plasticity of the sex locus and adaptations in pathogenicity have occurred during speciation of the M. circinelloides complex

Bottlenecks in the Acute Stroke Care System during the COVID-19 Pandemic in Catalonia

Introduction: The COVID-19 pandemic resulted in significant healthcare reorganizations, potentially striking standard medical care. We investigated the impact of the COVID-19 pandemic on acute stroke care quality and clinical outcomes to detect healthcare system's bottlenecks from a territorial point of view. Methods: Crossed-data analysis between a prospective nation-based mandatory registry of acute stroke, Emergency Medical System (EMS) records, and daily incidence of COVID-19 in Catalonia (Spain). We included all stroke code activations during the pandemic (March 15-May 2, 2020) and an immediate prepandemic period (January 26-March 14, 2020). Primary outcomes were stroke code activations and reperfusion therapies in both periods. Secondary outcomes included clinical characteristics, workflow metrics, differences across types of stroke centers, correlation analysis between weekly EMS alerts, COVID-19 cases, and workflow metrics, and impact on mortality and clinical outcome at 90 days. Results: Stroke code activations decreased by 22% and reperfusion therapies dropped by 29% during the pandemic period, with no differences in age, stroke severity, or large vessel occlusion. Calls to EMS were handled 42 min later, and time from onset to hospital arrival increased by 53 min, with significant correlations between weekly COVID-19 cases and more EMS calls (rho = 0.81), less stroke code activations (rho = -0.37), and longer prehospital delays (rho = 0.25). Telestroke centers were afflicted with higher reductions in stroke code activations, reperfusion treatments, referrals to endovascular centers, and increased delays to thrombolytics. The independent odds of death increased (OR 1.6 [1.05-2.4], p 0.03) and good functional outcome decreased (mRS ≤2 at 90 days: OR 0.6 [0.4-0.9], p 0.015) during the pandemic period. Conclusion: During the COVID-19 pandemic, Catalonia's stroke system's weakest points were the delay to EMS alert and a decline of stroke code activations, reperfusion treatments, and interhospital transfers, mostly at local centers. Patients suffering an acute stroke during the pandemic period had higher odds of poor functional outcome and death. The complete stroke care system's analysis is crucial to allocate resources appropriately

Clinical Use and Therapeutic Potential of IVIG/SCIG, Plasma-Derived IgA or IgM, and Other Alternative Immunoglobulin Preparations

Intravenous and subcutaneous immunoglobulin preparations, consisting of IgG class antibodies, are increasingly used to treat a broad range of pathological conditions, including humoral immune deficiencies, as well as acute and chronic inflammatory or autoimmune disorders. A plethora of Fab- or Fc-mediated immune regulatory mechanisms has been described that might act separately or in concert, depending on pathogenesis or stage of clinical condition. Attempts have been undertaken to improve the efficacy of polyclonal IgG preparations, including the identification of relevant subfractions, mild chemical modification of molecules, or modification of carbohydrate side chains. Furthermore, plasma-derived IgA or IgM preparations may exhibit characteristics that might be exploited therapeutically. The need for improved treatment strategies without increase in plasma demand is a goal and might be achieved by more optimal use of plasma-derived proteins, including the IgA and the IgM fractions. This article provides an overview on the current knowledge and future strategies to improve the efficacy of regular IgG preparations and discusses the potential of human plasma-derived IgA, IgM, and preparations composed of mixtures of IgG, IgA, and IgM

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field