Correlates of protection for COVID-19 vaccines are urgently needed to license additional vaccines. We measured immune responses to four COVID-19 vaccines of proven efficacy using a single serological ...platform. IgG anti-Spike antibodies were highly correlated with ID50 neutralization in a validated pseudoviral assay and correlated significantly with efficacies for protection against infection with wild-type, alpha and delta variant SARS-CoV-2 virus. The protective threshold for each vaccine was calculated for IgG anti-Spike antibody. The mean protective threshold for all vaccine studies for WT virus was 154 BAU/ml (95 %CI 42–559), and for studies with antibody distributions that enabled precise estimation of thresholds (i.e. leaving out 2-dose mRNA regimens) was 60 BAU/ml (95 %CI 35–102). We propose that the proportion of individuals with responses above the appropriate protective threshold together with the geometric mean concentration can be used in comparative non-inferiority studies with licensed vaccines to ensure that new vaccines will be efficacious.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Intramuscular injections of hypertonic saline are commonly used to induce experimental muscle pain, but reliability data on this technique are lacking. This study investigated the intra- and ...interindividual reliability of pain measures from a hypertonic saline injection into the vastus lateralis.
Fourteen healthy participants (6 female) attended three laboratory visits where they received an intramuscular injection of 1 mL hypertonic saline into the vastus lateralis. Changes in pain intensity were recorded on an electronic visual analogue scale, and pain quality was assessed after pain had resolved. Reliability was assessed with the coefficient of variation (CV), minimum detectable change (MDC) and intraclass correlation coefficient (ICC) with 95% CIs.
Mean pain intensity displayed high levels of intraindividual variability (CV = 16.3 10.5-22.0%) and 'poor' to 'very good' relative reliability (ICC = 0.71 0.45-0.88) but had a MDC of 11 8-16 au (out of 100). Peak pain intensity exhibited high levels of intraindividual variability (CV = 14.8 8.8-20.8%) with 'moderate' to 'excellent' levels of relative reliability (ICC = 0.81 0.62-0.92), whereas the MDC was 18 14-26 au. Measures of pain quality exhibited good reliability. Interindividual variability in pain measures was high (CV > 37%).
Intramuscular injections of 1 mL of hypertonic saline into the vastus lateralis display substantial levels of interindividual variability, but MDC is below the clinically important changes in pain. This model of experimental pain is suitable for studies involving repeated exposures.
Many pain research studies have performed intramuscular injections of hypertonic saline to investigate responses to muscle pain. However, the reliability of this technique is not well established. We examined the pain response over three repeated sessions of a hypertonic saline injection. The pain induced by hypertonic saline has considerable interindividual variability but has largely acceptable intraindividual reliability. Therefore, the injections of hypertonic saline to induce muscle pain are a reliable model of experimental muscle pain.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Iron deficiency and cobalamin deficiency, as sequelae to chronic gastrointestinal (GI) disease, could result in anemia and increased morbidity in cats with chronic enteropathies.
Objective
...To evaluate iron deficiency in cats with chronic GI disease and its relationship with hypocobalaminemia, anemia, and disease severity.
Animals
Twenty client‐owned cats with primary GI disease.
Methods
Prospective, cross‐sectional study. Cats were enrolled at the time of evaluation for chronic GI disease, after exclusion of comorbidities. CBC with reticulocyte indices, iron metabolism (serum iron and ferritin concentrations, total iron binding capacity TIBC), serum methylmalonic acid (MMA), cobalamin, and folate concentrations, pancreatic lipase and trypsin‐like immunoreactivity, and disease severity were evaluated.
Results
Anemia (hematocrit <30%), iron deficiency, and cobalamin deficiency were diagnosed in 4/20, 7/20, and 8/20 cats, respectively. Hematocrit (rs = −.45; P < .05) and body condition score (rs = −.60; P < .01) negatively correlated with MMA. Median TIBC was lower in cats with increased vs normal MMA (218 μg/mL; range, 120‐466 μg/mL vs 288 μg/mL; range, 195‐369 μg/mL; P = .02). Hematocrit (rs = .51; P = .02), reticulocyte MCV (rs = .52; P = .02), reticulocyte hemoglobin content (rs = .71; P < .001), and percent transferrin saturation (rs = .79; P < .0001) positively correlated with serum iron concentration.
Conclusions and Clinical Importance
Functional iron deficiency was common in cats with chronic GI disease. Associations between hypocobalaminemia, iron parameters, and hematologic parameters warrant further investigation on the impact of iron deficiency on chronic GI disease morbidity in cats.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Perspectives on autism and psychiatric conditions are affected by a mix of scientific and social influences. Evolutionary psychiatry (EP) and the neurodiversity movement are emerging paradigms that ...reflect these distinct influences, with the former grounded in scientific theory and the latter driven by political and social principles. Despite their separate foundations, there is a significant overlap between EP and neurodiversity that has not been explored. Specifically, both paradigms reframe disorders as natural cognitive differences rather than disease; expand the concept of "normal" beyond that implied in modern psychiatry; focus on relative strengths; recognize that modern environments disadvantage certain individuals to cause functional impairment; emphasize cognitive variation being socially accommodated and integrated rather than treated or cured; and can help reduce stigmatization. However, in other ways, they are distinct and sometimes in conflict. EP emphasizes scientific explanation, defines "dysfunction" in objective terms, and differentiates heterogenous cases based on underlying causes (e.g. autism due to de novo genetic mutations). The neurodiversity movement emphasizes social action, removes barriers to inclusion, promotes inclusive language, and allows unrestricted identification as neurodivergent. By comparing and contrasting these two approaches, we find that EP can, to some extent, support the goals of neurodiversity. In particular, EP perspectives could be convincing to groups more responsive to scientific evidence and help achieve a middle ground between neurodiversity advocates and critics of the movement.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Traditional evolutionary theory invoked natural and sexual selection to explain species- and sex-typical traits. However, some heritable inter-individual variability in behaviour and ...psychology – personality – is probably adaptive. Here we extend this insight to common psychopathological traits. Reviewing key findings from three background areas of importance – theoretical models, non-human personality and evolved human social dynamics – we propose that a combination of social niche specialisation, negative frequency-dependency, balancing selection and adaptive developmental plasticity should explain adaptation for individual differences in psychology – ‘specialised minds’ – explaining some variance in personality and psychopathology trait dimensions, which share various characteristics. We suggest that anthropological research of behavioural differences should be extended past broad demographic factors (age and sex) to include individual specialisations. As a first step towards grounding psychopathology in ancestral social structure, we propose a minimum plausible prevalence, given likely ancestral group sizes, for negatively frequency-dependent phenotypes to be maintained as specialised tails of adaptive distributions – below the calculated prevalence, specialisation is highly unlikely. For instance, chronic highly debilitating forms of autism or schizophrenia are too rare for such explanations, whereas attention-deficit-hyperactivity disorder and broad autism phenotypes are common enough to have existed in most hunter-gatherer bands, making adaptive explanations more plausible.
We conducted a psychometric synthesis of the internal consistency reliability and internal structure of scores on the English versions of the Patient Health Questionnaire-9 (PHQ-9) and Generalized ...Anxiety Disorder-7 (GAD-7) in publications between 2012 and 2022. Results supported acceptable-to-strong reliability and validity evidence of scores among a number of samples.
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BFBNIB, DOBA, NUK, PILJ, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hormone assessment is typically recommended for awake, unsedated dogs. However, one of the most commonly asked questions from veterinary practitioners to the endocrinology laboratory is how sedation ...impacts cortisol concentrations and the adrenocorticotropic hormone (ACTH) stimulation test. Butorphanol, dexmedetomidine, and trazodone are common sedatives for dogs, but their impact on the hypothalamic-pituitary-adrenal axis (HPA) is unknown. The objective of this study was to evaluate the effects of butorphanol, dexmedetomidine, and trazodone on serum cortisol concentrations.
Twelve healthy beagles were included in a prospective, randomized, four-period crossover design study with a 7-day washout. ACTH stimulation test results were determined after saline (0.5 mL IV), butorphanol (0.3 mg/kg IV), dexmedetomidine (4 µg/kg IV), and trazodone (3-5 mg/kg PO) administration.
Compared to saline, butorphanol increased basal (median 11.75 µg/dL (range 2.50-23.00) (324.13 nmol/L; range 68.97-634.48)
1.27 µg/dL (0.74-2.10) (35.03 nmol/L; 20.41-57.93);
< 0.0001) and post-ACTH cortisol concentrations (17.05 µg/dL (12.40-26.00) (470.34 nmol/L; 342.07-717.24)
13.75 µg/dL (10.00-18.90) (379.31 nmol/L; 275.96-521.38);
≤ 0.0001). Dexmedetomidine and trazodone did not significantly affect basal (1.55 µg/dL (range 0.75-1.55) (42.76 nmol/L; 20.69-42.76);
= 0.33 and 0.79 µg/dL (range 0.69-1.89) (21.79 nmol/L; 19.03-52.14);
= 0.13, respectively,
saline 1.27 (0.74-2.10) (35.03 nmol/L; 20.41-57.93)) or post-ACTH cortisol concentrations (14.35 µg/dL (range 10.70-18.00) (395.86 nmol/L; 295.17-496.55); (P = 0.98 and 12.90 µg/dL (range 8.94-17.40) (355.86 nmol/L; 246.62-480);
= 0.65), respectively,
saline 13.75 µg/dL (10.00-18.60) (379.31 nmol/L; 275.86-513.10).
Butorphanol administration should be avoided prior to ACTH stimulation testing in dogs. Further evaluation of dexmedetomidine and trazodone's effects on adrenocortical hormone testing in dogs suspected of HPA derangements is warranted to confirm they do not impact clinical diagnosis.
More than half the global population has been exposed to SARS-CoV-2. Naturally induced immunity influences the outcome of subsequent exposure to variants and vaccine responses. We measured anti-spike ...IgG responses to explore the basis for this enhanced immunity.
A prospective cohort study of mothers in a South African community through ancestral/beta/delta/omicron SARS-CoV-2 waves (March 2020-February 2022). Health seeking behaviour/illness were recorded and post-wave serum samples probed for IgG to Spike (CoV2-S-IgG) by ECLISA. To estimate protective CoV2-S-IgG threshold levels, logistic functions were fit to describe the correlation of CoV2-S-IgG measured before a wave and the probability for seroconversion/boosting thereafter for unvaccinated and vaccinated adults.
Despite little disease, 176/339 (51·9%) participants were seropositive following wave 1, rising to 74%, 89·8% and 97·3% after waves 2, 3 and 4 respectively. CoV2-S-IgG induced by natural exposure protected against subsequent SARS-CoV-2 infection with the greatest protection for beta and least for omicron. Vaccination induced higher CoV2-S-IgG in seropositive compared to naïve vaccinees. Amongst seropositive participants, proportions above the 50% protection against infection threshold were 69% (95% CrI: 62, 72) following 1 vaccine dose, 63% (95% CrI: 63, 75) following 2 doses and only 11% (95% CrI: 7, 14) in unvaccinated during the omicron wave.
Naturally induced CoV2-S-IgG do not achieve high enough levels to prevent omicron infection in most exposed individuals but are substantially boosted by vaccination leading to significant protection. A single vaccination in those with prior immunity is more immunogenic than 2 doses in a naïve vaccinee and may provide adequate protection.
UK NIH GECO award (GEC111), Wellcome Trust Centre for Infectious Disease Research in Africa (CIDRI), Bill & Melinda Gates Foundation, USA (OPP1017641, OPP1017579) and NIH H3 Africa (U54HG009824, U01AI110466. HZ is supported by the SA-MRC. MPN is supported by an Australian National Health and Medical Research Council Investigator Grant (APP1174455). BJQ is supported by a grant from the Bill and Melinda Gates Foundation (OPP1139859). Stefan Flasche is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant number 208812/Z/17/Z).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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DEAD/H box helicases are implicated in lung cancer but have not been systematically investigated for their clinical significance and function. In this study, we aimed to evaluate the ...potential of DEAD/H box helicases as prognostic biomarkers and therapeutic targets in lung cancer by integrated bioinformatic analysis of multivariate large-scale databases. Survival and differential expression analysis of these helicases enabled us to identify four biomarkers with the most significant alterations. These were found to be the negative prognostic factors DDX11, DDX55 and DDX56, and positive prognostic factor DDX5. Pathway enrichment analysis indicates that MYC signalling is negatively associated with expression levels of the DDX5 gene while positively associated with that of DDX11, DDX55 and DDX56. High expression levels of the DDX5 gene is associated with low mutation levels of TP53 and MUC16, the two most frequently mutated genes in lung cancer. In contrast, high expression levels of DDX11, DDX55 and DDX56 genes are associated with high levels of TP53 and MUC16 mutation. The tumour-infiltrated CD8 + T and B cells positively correlate with levels of DDX5 gene expression, while negatively correlate with that of the other three DEAD box helicases, respectively. Moreover, the DDX5-associated miRNA profile is distinguished from the miRNA profiles of DDX11, DDX55 and DDX56, although each DDX has a different miRNA signature. The identification of these four DDX helicases as biomarkers will be valuable for prognostic prediction and targeted therapeutic development in lung cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Pseudoaneurysm formation following cerebrovascular blunt trauma is a rarely experienced complication with an incidence rate of less than 1 %.•In craniofacial trauma, pseudoaneurysm formation is not ...apparent on physical examination due to its deep location and usually presents as persistent nasal bleeding.•A low threshold for diagnosing and treating such entities is essential for controlling the hemorrhage and preventing morbidity and mortality.•Endovascular embolization provides immediate blood control should be included as a primary treatment option or as an adjunct to the surgical approach.
Facial fractures, specifically orbitozygomatic and zygomaticomaxillary complex fractures, are well-documented and common injuries. Pseudoaneurysm formation following cerebrovascular blunt trauma is a rarely experienced complication with an incidence rate of less than 1% with only a few cases reported in the literature. Traumatic pseudoaneurysm formation of the sphenopalatine artery (SPA), the deepest branch of the maxillary artery, is extremely rare due to the deep location of the SPA and its protection from bony landmarks. In craniofacial trauma, pseudoaneurysm formation is not apparent on physical examination due to its deep location and usually presents as persistent nasal bleeding. SPA pseudoaneurysms can present as complications of surgical osteotomies, endoscopic sinus surgeries, facial trauma, or even as a progression of nasopharyngeal cancer. Endovascular embolization provides, safe, quick, and effective treatment while minimizing the morbidity of extensive surgical exposure. In this case report we describe a sphenopalatine artery pseudoaneurysm formation post trauma to provide insight to these rare entities and highlight the importance of early detection and treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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