Glycolytic potential and ultimate muscle pH values in red deer (Cervus elaphus) and fallow deer (Dama dama)

The ultimate pH value of meat (measured at approx. 24 hours post slaughter) gives information about the technological quality, i.e. shelf life, colour, water-holding properties and tenderness and is a direct consequence of muscle glycogen (energy) levels at slaughter. It may therefore also indicate whether or not the animal has been exposed to stressful energy depleting events prior to slaughter. In the present study, 141 animals (130 red deer (Cervus elaphus) and 11 fallow deer (Dama dama) were included to investigate the relationship between ultimate pH and residual glycogen concentration in red deer and fallow deer M. longissimus. In addition, the muscle glycogen content and ultimate pH values in three red deer muscles (Mm. triceps brachii, longissimus and biceps femoris) were studied. M. triceps brachii had higher ultimate pH and lower glycogen content compared with the other two studied muscles. The frequency of intermediate DFD (5.8≤ pH<6.2) was 5.4% in red deer M. longissimus, compared with 9.1% in fallow deer, while the frequency of DFD (pH≥ 6.2) was much lower in red deer (3.8%) than in fallow deer (54.5%). A curvilinear relationship between ultimate pH and total glucose concentration (glycogen and glucose) 30 min post slaughter in red deer and fallow deer M. longissimus was found. The relationship between muscle pH and lactic acid concentration however, was indicated to be linear. A significant variation in total glucose concentration at ultimate pH below 5.80 was observed, including values in the range from 18 to 123 mmol/kg wet tissue. It was concluded that further studies are needed to further explore the relationship between muscle glycogen content and technological and sensory quality attributes of meat from different deer species.Abstract in Swedish / Sammanfattning:Köttets pH-värde (mätt ca 24 timmar efter slakt) har stor betydelse för den teknologiska kvaliteten som t. ex. hållbarhet, färg, vattenhållande förmåga och mörhet. Glykogenförrådet (energinivån) i djurens muskulatur vid slakt är helt avgörande för köttets slutliga pH-värde. Därför kan pH-värdet också indikera om hanteringen av slaktdjur varit skonsam eller om stora mängder muskelenergi har förbrukats vid stress. I vår undersökning ingick 141 hjortar (130 kronhjortar (Cervus elaphus) och 11 dovhjortar (Dama dama) för att studera sambandet mellan köttets pH-värde och glykogeninnehållet i M. longissimus. Glykogeninnehåll och pH-värden i 3 muskler från kronhjort (Mm. triceps brachii, longissimus och biceps femoris) undersöktes också. M. triceps brachii hade högre pH-värde och lägre glykogeninnehåll jämfört med de två andra musklerna. Det var inte så stor skillnad i frekvensen av intermediär DFD (pH-värden mellan 5,8 og 6,2) mellan de två hjortarterna (5,4% för kronhjort och 9,1% för dovhjort), däremot var frekvensen av DFD (pH-värden över 6,2) mycket låg hos kronhjort (3,8%) jämfört med dovhjort (54,5%). Det fanns ett kurvlinjärt samband mellan slutligt pH-värde i köttet och total glukoskoncentration (glykogen + glukos) mätt i M. longissimus 30 min efter slakt för både kron- och dovhjort. Ett linjärt samband mellan pH-värde och koncentration av mjölksyra i M. longissimus kunde också visas. Vi fann en mycket stor varitation i glukoskoncentration (18−123 mmol/kg våtvikt) när köttets pH-värdet var 5,8 eller lägre. Det behövs fler undersökningar för att vidare klargöra sambanden mellan glykogeninnehåll i muskulaturen och teknologisk och sensorisk kvalitet i olika typer av hjortkött

Determining Sequential Micellization Steps of Bile Salts With Multi-cmc Modeling

Hypothesis Bile salts exhibit complex concentration-dependent micellization in aqueous solution, rooted in a long-standing hypothesis of increasing size in bile aggregation that has historically focused on the measurement of only one CMC detected by a given method, without resolving successive stepwise aggregates. Whether bile aggregation is continuous or discrete, at what concentration does the first aggregate form, and how many aggregation steps occur, all remain as open questions. Experiments Bile salt critical micelle concentrations (CMCs) were investigated with NMR chemical shift titrations and a multi-CMC phase separation modeling approach developed herein. The proposed strategy is to establish a correspondence of the phase separation and mass action models to treat the first CMC; subsequent micellization steps, involving larger micelles, are then treated as phase separation events. Findings The NMR data and the proposed multi-CMC model reveal and resolve multiple closely spaced sequential preliminary, primary, and secondary discrete CMCs in dihydroxy and trihydroxy bile salt systems in basic (pH 12) solutions with a single model of one NMR data set. Complex NMR data are closely explained by the model. Four CMCs are established in deoxycholate below 100 mM (298 K, pH 12): 3.8 ± 0.5 mM, 9.1 ± 0.3 mM, 27 ± 2 mM, and 57 ± 4 mM, while three CMCs were observed in multiple bile systems, also under basic conditions. Global fitting leverages the sensitivity of different protons to different aggregation stages. In resolving these closely spaced CMCs, the method also obtains chemical shifts of these spectroscopically inaccessible (aka dark) states of the distinct micelles

Measuring the context of care in an Australian acute care hospital: a nurse survey

BACKGROUND: This study set out to achieve three objectives: to test the application of a context assessment tool in an acute hospital in South Australia; to use the tool to compare context in wards that had undergone an evidence implementation process with control wards; and finally to test for relationships between demographic variables (in particular experience) of nurses being studied (n = 422) with the dimensions of context. METHODS: The Alberta Context Tool (ACT) was administered to all nursing staff on six control and six intervention wards. A total of 217 (62%) were returned (67% from the intervention wards and 56% from control wards). Data were analysed using Stata (v9). The effect of the intervention was analysed using nested (hierarchical) analysis of variance; relationships between nurses' experience and context was examined using canonical correlation analysis. RESULTS: Results confirmed the adaptation and fit of the ACT to one acute care setting in South Australia. There was no difference in context scores between control and intervention wards. However, the tool identified significant variation between wards in many of the dimensions of context. Though significant, the relationship between nurses' experience and context was weak, suggesting that at the level of the individual nurse, few factors are related to context. CONCLUSIONS: Variables operating at the level of the individual showed little relationship with context. However, the study indicated that some dimensions of context (e.g., leadership, culture) vary at the ward level, whereas others (e.g., structural and electronic resources) do not. The ACT also raised a number of interesting speculative hypotheses around the relationship between a measure of context and the capability and capacity of staff to influence it.Timothy J. Schultz and Alison L. Kitso

DNA polymerase δ-dependent repair of DNA single strand breaks containing 3′-end proximal lesions

Base excision repair (BER) is the major pathway for the repair of simple, non-bulky lesions in DNA that is initiated by a damage-specific DNA glycosylase. Several human DNA glycosylases exist that efficiently excise numerous types of lesions, although the close proximity of a single strand break (SSB) to a DNA adduct can have a profound effect on both BER and SSB repair. We recently reported that DNA lesions located as a second nucleotide 5′-upstream to a DNA SSB are resistant to DNA glycosylase activity and this study further examines the processing of these ‘complex’ lesions. We first demonstrated that the damaged base should be excised before SSB repair can occur, since it impaired processing of the SSB by the BER enzymes, DNA ligase IIIα and DNA polymerase β. Using human whole cell extracts, we next isolated the major activity against DNA lesions located as a second nucleotide 5′-upstream to a DNA SSB and identified it as DNA polymerase δ (Pol δ). Using recombinant protein we confirmed that the 3′-5′-exonuclease activity of Pol δ can efficiently remove these DNA lesions. Furthermore, we demonstrated that mouse embryonic fibroblasts, deficient in the exonuclease activity of Pol δ are partially deficient in the repair of these ‘complex’ lesions, demonstrating the importance of Pol δ during the repair of DNA lesions in close proximity to a DNA SSB, typical of those induced by ionizing radiation

Genomic Testing in Localized Prostate Cancer Can Identify Subsets of African Americans With Aggressive Disease

BACKGROUND: Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting. METHODS: This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score. RESULTS: The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non-African American men). A higher proportion of African American men with National Comprehensive Cancer Network-classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non-African American men. Self-identified African American men were twice more likely than non-African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes. CONCLUSIONS: Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Vampires in the village Žrnovo on the island of Korčula: following an archival document from the 18th century

Središnja tema rada usmjerena je na raščlambu spisa pohranjenog u Državnom arhivu u Mlecima (fond: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) koji se odnosi na događaj iz 1748. godine u korčulanskom selu Žrnovo, kada su mještani – vjerujući da su se pojavili vampiri – oskvrnuli nekoliko mjesnih grobova. U radu se podrobno iznose osnovni podaci iz spisa te rečeni događaj analizira u širem društvenom kontekstu i prate se lokalna vjerovanja.The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village Žrnove on the island of Korčula in Croatia opened tombs on the local cemetery in the fear of the vampires treating. This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant