Effects of local and systemic treatment with human natural killer-1 mimetic peptide (HNK-1) after ventral root avulsion and reimplantation in mice.

Background: Spinal ventral root injuries generate significant motoneuron degeneration, which hinders full functional recovery. The poor prognosis of functional recovery can be attributed to the use or combination of different therapeutic approaches. Several molecules have been screened as potential treatments in combination with surgical reimplantation of the avulsed roots, the gold standard approach for such injuries. Among the studied molecules, human natural killer-1 (HNK-1) stands out as it is related to the stimulation of motor axon outgrowth. Therefore, we aimed to comparatively investigate the effects of local administration of an HNK-1 mimetic peptide (mp-HNK-1) and systemic treatment with ursolic acid (UA), another HNK-1 mimetic, after ventral root avulsion and reimplantation with heterologous fibrin biopolymer (HFB). Methods: Female mice of the isogenic strain C57BL/6JUnib were divided into five experimental groups: Avulsion, Reimplantation, mp-HNK-1 (in situ), and UA (systemic treatment). Mice were evaluated 2 and 12 weeks after surgery. Functional assessment was performed every four days using the Catwalk platform. Neuronal survival was analyzed by cytochemistry, and glial reactions and synaptic coverage were evaluated by immunofluorescence. Results: Treatment with UA elicited long-term neuroprotection, accompanied by a decrease in microglial reactions, and reactive astrogliosis. The neuroprotective effects of UA were preceded by increased glutamatergic and GABAergic inputs in the ventral spinal cord two weeks after injury. However, a single application of mp-HNK-1 had no significant effects. Functional analysis showed that UA treatment led to an improvement in motor and sensory recovery. Conclusion: Overall, the results indicate that UA is neuroprotective, acting on glial cells and synaptic maintenance, and the combination of these findings led to a better functional recovery.

Exploring Changes in Patient Safety Incidents During the COVID-19 Pandemic in a Canadian Regional Hospital System: A Retrospective Time Series Analysis.

OBJECTIVES: The COVID-19 pandemic has placed unprecedented strain on healthcare systems and may have consequential impacts on patient safety incidents (PSIs). The primary objective of this study was to examine the impact of the COVID-19 pandemic on PSIs reported in Niagara Health. METHODS: Flexible Farrington models were used to retrospectively detect weeks from January to September 2020 where PSI counts were significantly above expected counts. Incident counts were adjusted to weekly inpatient-days. Outcomes included overall incident numbers, incidents by category, and incidents by ward type. RESULTS: The overall number of PSIs across Niagara Health did not increase during the first wave of the COVID-19 pandemic. However, significant increases in falls were observed, suggesting that other types of incidents decreased. Falls increased by 75% from February to March 2020, coinciding with the onset of the first wave of the pandemic. Further investigation by unit type revealed that the number of falls increased specifically on internal medicine and complex continuing care wards. CONCLUSIONS: Despite no observed changes in overall number, significant composition shifts in PSIs occurred during the first wave of the COVID-19 pandemic, with increased falls on internal medicine and complex continuing care wards. Possible explanations include restrictions on patient visitation, reduced patient contact/supervision, and/or personal protective equipment requirements. Providers should maintain a particularly high vigilance for patient falls during pandemic outbreaks, and hospitals should consider targeting resources to higher-risk locations. The results of this study reinforce the need for ongoing pandemic PSI monitoring and rapidly adaptive responses to new patient safety concerns.

Predicting Survival After VA-ECMO for Refractory Cardiogenic Shock: Validating the SAVE Score.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used increasingly to support patients who are in cardiogenic shock. Due to the risk of complications, prediction models may aid in identifying patients who would benefit most from VA-ECMO. One such model is the Survival After Veno-Arterial Extracorporeal Membrane Oxygenation (SAVE) score. Therefore, we wanted to validate the utility of the SAVE score in a contemporary cohort of adult patients. METHODS: Retrospective data were extracted from electronic health records of 120 patients with cardiogenic shock supported with VA-ECMO between 2011 and 2018. The SAVE score was calculated for each patient to predict survival to hospital discharge. We assessed the SAVE score calibration by comparing predicted vs observed survival at discharge. We assessed discrimination with the area under the receiver operating curve using logistic regression. RESULTS: A total of 45% of patients survived to hospital discharge. Survivors had a significantly higher mean SAVE score (-9.3 ± 4.1 in survivors vs -13.1 ± 4.4, respectively; P = 0.001). SAVE score discrimination was adequate (c = 0.77; 95% confidence interval 0.69-0.86; P < 0.001). SAVE score calibration was limited, as observed survival rates for risk classes II-V were higher in our cohort (II: 67% vs 58%; III: 78% vs 42%; IV: 61% vs 30%; and V: 29% vs 18%). CONCLUSIONS: The SAVE score underestimates survival in a contemporary North American cohort of adult patients with cardiogenic shock. Its inaccurate performance could lead to denying ECMO support to patients deemed to be too high risk. Further studies are needed to validate additional predictive models for patients requiring VA-ECMO.

CONTEXTE: L'oxygénation extracorporelle veino-artérielle (ECMO-VA) est de plus en plus utilisée comme assistance pour les patients qui sont en choc cardiogène. En raison du risque de complications, des modèles de prédiction peuvent aider à déterminer quels patients bénéficieraient le plus d'une ECMO-VA. Le score SAVE (Survival After Veno-Arterial Extracorporeal Membrane Oxygenation) est un modèle de ce genre. Par conséquent, nous voulions valider l'utilité du score SAVE dans une cohorte contemporaine de patients adultes. MÉTHODOLOGIE: Des données rétrospectives ont été extraites de dossiers médicaux électroniques de 120 patients atteints d'un choc cardiogène ayant reçu une ECMO-VA entre 2011 et 2018. Le score SAVE a été calculé pour chaque patient afin de prédire la survie au congé de l'hôpital. Nous avons évalué la calibration du score SAVE en comparant la survie prédite au moment du congé et la survie observée. Nous avons évalué la discrimination par l'aire sous la courbe opérationnelle chez le receveur en faisant appel à la régression logistique. RÉSULTATS: Au total, 45 % des patients ont survécu au congé de l'hôpital. Les survivants affichaient un score SAVE moyen considérablement plus élevé (­9,3 ± 4,1 chez les survivants vs ­13,1 ± 4,4; p = 0,001). La discrimination par le score SAVE était adéquate (c = 0,77; intervalle de confiance à 95 % : 0,69 à 0,86; p < 0,001). La calibration du score SAVE était limitée, car les taux pour les classes de risque II à V étaient plus élevés dans notre cohorte (II : 67 % vs 58 %; III : 78 % vs 42 %; IV : 61 % vs 30 %; et V : 29 % vs 18 %). CONCLUSIONS: Le score SAVE sous-estime la survie dans une cohorte nord-américaine contemporaine de patients adultes atteints d'un choc cardiogène. L'inexactitude de ses résultats pourrait faire en sorte qu'une assistance par ECMO serait refusée à des patients jugés comme présentant un risque élevé. D'autres études sont nécessaires pour valider d'autres modèles de prédiction pour les patients ayant besoin d'une ECMO-VA.

Fluctuating asymmetry of finger lengths, digit ratio (2D:4D), and tattoos: A pre-registered replication and extension of Koziel et al. (2010).

BACKGROUND: Tattoos bring risks yet no obvious evolutionary benefit. Koziel et al. (2010) reported increased fluctuating symmetry (a proxy for low developmental instability) in tattooed men, suggesting they could serve as fitness indicators. AIMS: We replicate and extend the findings of Koziel et al. by examining fluctuating asymmetry of finger lengths and digit ratio (2D:4D) (a putative indicator of prenatal testosterone exposure) as predictors of adult tattoo prevalence. STUDY DESIGN: We used an online survey with a correlational design. SUBJECTS: Participants were recruited from the UK and Poland via university participant pools and social media. Data were available for presence/absence of tattoos and at least one predictor variable (composite Fluctuating Asymmetry [cFA], right-hand digit ratio [R2D:4D] and left-hand digit ratio [L2D:4D]) for n = 186 males and n = 997 females. OUTCOME MEASURES: We firstly assessed presence/absence of tattoos; when at least one tattoo was present, we also examined overall number and highest visibility. RESULTS: Greater cFA was associated with lower likelihood of having tattoos in males, though in females greater cFA was associated with higher numbers of tattoos. R2D:4D and L2D:4D correlated negatively with number of tattoos in males, and a positive correlation between L2D:4D and number of tattoos was observed in females. However, these latter findings did not remain significant after controlling for covariates. CONCLUSIONS: Tattoos may act as fitness indicators in males, though this explanation appears not to extend to females. Prenatal testosterone may also play a role, though doubt is cast on this premise because 2D:4D effects did not remain statistically significant after controlling for covariates.

Patient-Centred Outcomes in Anaemia and Renal Disease: A Systematic Review.

BACKGROUND: Anaemia is a nearly universal complication of chronic kidney disease (CKD). Erythropoiesis-stimulating agents (ESAs) have been demonstrated to improve clinical outcomes and quality of life (QOL) in renal patients with anaemia. Patient-reported outcome measures (PROMs) are increasingly being used to evaluate the patient-centred impact of medical therapy. Here, we describe a systematic review of studies that evaluated patient-centred outcomes (PCOs) in renal patients undergoing anaemia treatment. METHODS: We conducted a search of Medline (Ovid), EMBASE (Ovid), PsychINFO, and CINAHL databases for studies published until March 2018 that investigated an intervention to treat anaemia in renal patients and used at least one PROM. We also performed a quality assessment for all included studies. Statistical analyses characterized each study, PROMs used, the quality of PCO reporting, and the association between haematological outcomes and PCOs. RESULTS: Of the 3,533 studies identified in the database search, 21 met all eligibility criteria. Fourteen (67%) of the studies were randomized-controlled trials. Most studies (81%) investigated CKD patients, 14% investigated post-renal transplant patients and 5% assessed patients with heart disease on haemodialysis. The most common anaemia intervention, used in 95% of studies, was ESAs. Forty-three percent of studies utilized one PROM, most commonly the SF-36, a measure of QOL not specifically created for use in nephrology patients. About a third of studies selectively reported PROM subscales, rather than reporting all subscales. Notable biases among included studies included lack of blinding, selective outcome reporting, and lack of power estimates for PCOs. We did not find a statistically significant association between improvements in haemoglobin and QOL. CONCLUSIONS: Future studies employing anaemia and nephrology-specific PROMs and conducted with greater rigour, standardization in the research methods, and reporting of PCOs in renal populations will improve understanding of PCOs in this patient group and hopefully improve patient outcomes and experiences.

Using Small Peptide Segments of Amyloid-ß and Humanin to Examine their Physical Interactions.

BACKGROUND: Amyloid fibrils in Alzheimer's disease are composed of amyloid-ß (Aß) peptides of variant lengths. Humanin (HN), a 24 amino acid residue neuroprotective peptide, is known to interact with the predominant Aß isoform in the brain, Aß (1-40). METHODS: Here, we constructed smaller segments of Aß and HN and identified residues in HN important for both HN-HN and HN-Aß interactions. Peptides corresponding to amino acid residues 5- 15 of HN, HN (5-15), HN (5-15, L11S), where Leu11 was replaced with Ser, and residues 17-28 of Aß, Aß (17-28), were synthesized and tested for their ability to block formation of the complex between HN and Aß (1-40). RESULTS: Co-immunoprecipitation and binding kinetics showed that HN (5-15) was more efficient at blocking the complex between HN and Aß (1-40) than either HN (5-15, L11S) or Aß (17-28). Binding kinetics of these smaller peptides with either full-length HN or Aß (1-40) showed that HN (5- 15) was able to bind either Aß (1-40) or HN more efficiently than HN (5-15, L11S) or Aß (17-28). Compared to full-length HN, however, HN (5-15) bound Aß (1-40) with a weaker affinity suggesting that while HN (5-15) binds Aß, other residues in the full length HN peptide are necessary for maximum interactions. CONCLUSION: L11 was more important for interactions with Aß (1-40) than with HN. Aß (17-28) was relatively ineffective at binding to either Aß (1-40) or HN. Moreover, HN, and the smaller HN (5-15), HN (5-15 L11S), and Aß (17-28) peptides, had different effects on regulating Aß (1-40) aggregation kinetics.

Patient-Centered Outcomes in the Management of Anemia: A Scoping Review.

Anemia is a frequently diagnosed condition that may be a symptom of or complication of many illnesses affecting patients of all demographics. Anemia can lead to both worsened clinical outcomes and reduced quality of life. Patient-reported outcome measures (PROMs) are methodological tools used to capture the impact of disease on patient well-being. Use of PROMs in medical research is becoming more common as it is increasingly recognized that disease outcomes of interest to researchers and clinicians are not always consistent with patients' greatest concerns related to their diseases. We conducted a scoping review to characterize the studies that have evaluated patient-centered outcomes using PROMs in patients undergoing treatment for anemia. We conducted a search of Medline (Ovid), EMBASE (Ovid), PsychINFO, and CINAHL databases for studies published until January 2017 that investigated an intervention to treat anemia in any patient population and used at least 1 PROM to evaluate patient-centered outcomes. A descriptive synthesis was performed to characterize the PROMs used and to evaluate the quality of patient-centered outcome (PCO) reporting. Of the 3224 studies identified in the initial search, 130 met all eligibility criteria. We found that the population most frequently studied was oncology patients (46.2% of studies). The therapy for anemia evaluated in the most studies was erythropoietin-stimulating agents (77.7% of studies). The most commonly used PROM was the Functional Assessment of Cancer Therapy/Functional Assessment of Chronic Illness Therapy tool (46.9%), and the majority of studies used only 1 PROM tool (53.1%). We found significant variability in the quality of PCO reporting across all included studies. Improved methodologic rigor in the assessment of PCOs in anemia management is needed in future studies.

Application of an Enzymatic Extract from Aspergillus niger as Coagulant for Cheddar Cheese Manufacture

Abstract The coagulation of milk by a serin protease from Aspergillus niger NRRL3 was studied by rheology. Cheddar-type cheese was manufactured using 3.5% (v/v) of fungal enzymatic extract and fermentation-produced chymosin was used as control coagulant. Full composition and ripening of both kinds of Cheddar cheese were studied. Differences in the proteolysis of caseins, not only during cheese manufacture but also during ripening, affected cheese composition, texture and peptide profile. Microbial development during ripening was not affected by the coagulant used.

Mineral fortification modifies physical and microstructural characteristics of milk gels coagulated by a bacterial enzymatic pool.

An enzymatic pool from the Amazonian bacterium Bacillus sp. P7 was used as milk coagulant. Discovery of novel coagulants is of great interest in dairy industry for the development of new textures in cheese. Color, mechanical and microstructural characterization of milk gels induced by the bacterial enzymatic pool was carried out. Effect of mineral fortification on these characteristics was studied. Whiter gels with smaller pore diameters were obtained in the presence of Ca2+ or Mg2+. These characteristics seemed to be influenced by the effect of ionic strength on casein structure which was also evidenced by digital texture features analysis. On the other hand, specific affinity of the assayed cations for milk proteins showed to be important in the development of the mechanical texture of the gels. Firmness and fracture force of milk gels obtained in the presence of Zn2+ or Ca2+ were higher than in the presence of Mg2+ and Na2+.

Milk protein suspensions enriched with three essential minerals: Physicochemical characterization and aggregation induced by a novel enzymatic pool.

Structural changes of casein micelles and their aggregation induced by a novel enzymatic pool isolated from Bacillus spp. in the presence of calcium, magnesium or zinc were investigated. The effect of cations on milk protein structure was studied using fluorescence and dynamic light scattering. In the presence of cations, milk protein structure rearrangements and larger casein micelle size were observed. The interaction of milk proteins with zinc appears to be of a different nature than that with calcium or magnesium. Under the experimental conditions assayed, the affinity of each cation for some groups present in milk proteins seems to play an important role, besides electrostatic interaction. On the other hand, the lowest aggregation times were achieved at the highest calcium and zinc concentrations (15 mM and 0.25 mM, respectively). The study found that the faster the aggregation of casein micelles, the less compact the gel matrix obtained. Cation concentrations affected milk protein aggregation kinetics and the structure of the aggregates formed.

Physicochemical study of the formation of complexes between pancreatic proteases and polyanions.

The formation of insoluble complexes between proteins and oppositely charged polyelectrolytes was assessed. Two pancreatic enzymes: trypsin and chymotrypsin, and two anionic synthetic polyelectrolytes: polyacrylate and polyvinylsulfonate, were used for the study at the pH range between 3.00 and 5.00. Two different titration curve shapes, representing two insoluble complexes formation mechanisms, were found. The turbidity of enzyme-polyelectrolyte mixtures is related to the increase either in the size or in the quantity of the insoluble complexes. Ionic strength destabilized insoluble complex formation. Finally, the kinetics of the process of insoluble complex formation at different conditions was studied.