Anger and disgust shape judgments of social sanctions across cultures, especially in high individual autonomy societies.

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.

Therapeutic drug monitoring of clozapine in human serum by high-throughput paper spray mass spectrometry.

Introduction: Monitoring the atypical antipsychotic drug clozapine is crucial to ensure patient safety. This article showcases a high-throughput analytical method for measuring clozapine and its primary metabolite norclozapine (N-desmethylclozapine) in serum using paper spray mass spectrometry (PS-MS). Objectives: This study aimed to assess the viability of a PS-MS method for the rapid measurement of clozapine and norclozapine in human serum samples as an alternative to liquid chromatography mass spectrometry (LC-MS). Methods: Serum samples were processed by protein precipitation followed by deposition of the supernatant containing labelled internal standards onto paper spray substrates mounted in cartridges. Analytes were then analyzed using a triple quadrupole mass spectrometer equipped with a commercial paper spray ionization source. The results obtained from the patient samples were compared to those from a validated LC-MS assay. Results: PS-MS calibrations for clozapine and norclozapine were linear (R2 > 0.99) over five days. Between-run precision was below 8 %, and within-run precision did not exceed 10 %. When compared to a validated LC-MS method, the mean bias for 39 patient samples was -9% for clozapine and -1% for norclozapine, with no outliers. Mass spectrometry ion ratio comparisons indicated no interference for patient samples above the lower limit of quantification. There was less than 7 % change in the measured concentrations of both analytes over five days for samples dried on paper substrates. Notably, virtually no maintenance of the MS source was required during this study. Conclusion: This study illustrates the potential of PS-MS for serum drug monitoring in the clinical laboratory.

Potential of dietary polyphenols for protection from age-related decline and neurodegeneration: a role for gut microbiota?

Many epidemiological studies have shown the beneficial effects of a largely plant-based diet, and the strong association between the consumption of a Mediterranean-type diet with healthy aging including a lower risk of cognitive decline. The Mediterranean diet is characterized by a high intake of olive oil, fruits and vegetables and is rich in dietary fiber and polyphenols - both of which have been postulated to act as important mediators of these benefits. Polyphenols are large molecules produced by plants to protect them from environmental threats and injury. When ingested by humans, as little as 5% of these molecules are absorbed in the small intestine with the majority metabolized by the gut microbiota into absorbable simple phenolic compounds. Flavan-3-ols, a type of flavonoid, contained in grapes, berries, pome fruits, tea, and cocoa have been associated with many beneficial effects on several risk factors for cardiovascular disease, cognitive function and brain regions involved in memory formation. Both preclinical and clinical studies suggest that these brain and heart benefits can be attributed to endothelial vascular effects and anti-inflammatory properties among others. More recently the gut microbiota has emerged as a potential modulator of the aging brain and intriguingly polyphenols have been shown to alter microbiota composition and be metabolized by different microbial species. However, there is a need for well controlled studies in large populations to identify predictors of response, particularly given the vast inter-individual variation of human gut microbiota.

Improving vitamin D content in pork meat by UVB biofortification.

Vitamin D deficiency is prevalent worldwide and identification of alternative food-based strategies are urgently warranted. In two studies, 12-week old crossbred pigs (Duroc x (Large White x Landrace)) were exposed daily to narrowband UVB radiation for ∼10 weeks or control (no UVB exposure) until slaughter. In Study 1 (n = 48), pigs were exposed to UVB for 2 min and in Study 2 (n = 20), this duration was tripled to 6 min. All pigs were fed the maximum permitted 2000 IU vitamin D3/kg feed. Loin meat was cooked prior to vitamin D LC-MS/MS analysis. In Study 1, pork loin vitamin D3 did not differ between groups. Study 2 provided longer UVB exposure time and resulted in significantly higher loin vitamin D3 (11.97 vs. 6.03 µg/kg), 25(OH)D3 (2.09 vs. 1.65 µg/kg) and total vitamin D activity (22.88 vs. 14.50 µg/kg) concentrations, compared to control (P < 0.05). Pigs remained healthy during both studies and developed no signs of erythema. Biofortification by UVB radiation provides an effective strategy to further safely increase the naturally occurring vitamin D content of pork loin, alongside feed supplementation.

Bioavailability of vitamin D biofortified pork meat: results of an acute human crossover study in healthy adults.

Vitamin D intakes are concerningly low. Food-based strategies are urgently warranted to increase vitamin D intakes and subsequently improve 25-hydroxyvitamin D (25(OH)D) concentrations. This acute randomised three-way crossover study investigated the efficacy of vitamin D biofortified pork derived from pigs exposed to UVB light to increase serum 25(OH)D3 concentrations, compared to a dose-matched vitamin D3 supplement and control pork in adults (n = 14). Blood samples were obtained at baseline and then 1.5, 3, 6, 9 and 24 h postprandially. There was a significant effect of time (p < 0.01) and a significant treatment*time interaction (p < 0.05). UV pork and supplement significantly increased within-group serum 25(OH)D3 concentrations over timepoints (p < 0.05) (max. change 0.9 nmol/L (2.2%) UV pork, 1.5 nmol/L (3.5%) supplement, 0.7 nmol/L (1.9%) control). Vitamin D biofortified pork modestly increased 25(OH)D3 concentrations and produced a similar response pattern as a dose-matched vitamin D supplement, but biofortification protocols should be further optimised to ensure differentiation from standard pork.

Quantum limits of position-sensitive photodiodes.

The split photodiode and the lateral effect photodiode are two popular detectors for measuring beam displacement. For small displacements of a Gaussian beam, which is the case of interest here, they are often seen as equivalent and used interchangeably, giving a signal proportional to the displacement. We show theoretically and experimentally that in the limit of low technical noise, where the signal to noise ratio is dominated by the shot noise of the light, the lateral effect photodiode produces a better signal to noise ratio than the split photodiode, owing to its optimum spatial detector response. This quantum advantage can be practically exploited in spite of the intrinsic thermal noise of the lateral effect photodiode.

Selectivity of upper limb posterior root muscle reflexes via cervicothoracic spinal cord stimulation.

Recent studies have reported that transcutaneous spinal stimulation (tSCS) may facilitate improved upper limb motor function in those with incomplete tetraplesia. However, little is known about how tSCS engages upper limb motor pools. This study aimed to explore the extent to which discrete upper limb motor pools can be selectively engaged via altering stimulus location and intensity. 14 participants with intact nervous systems completed two test visits, during which posterior root-muscle reflexes (PRMR) were evoked via a 3x3 cathode matrix applied over the cervicothoracic spine. An incremental recruitment curve at C7 vertebral level was initially performed to attain minimal threshold intensity (MTI) in each muscle. Paired pulses (1ms square monophasic with inter-pulse interval of 50ms) were subsequently delivered at a frequency of 0.25Hz at two intensities (MTI and [Formula: see text]) across all nine locations. in a random order. Evoked response to the 1st (PRMR1) and 2nd (PRMR2) stimuli were recorded from four upper limb muscles. A significant effect of spinal level was observed in all muscles for PRMR1 with greater responses recorded more caudally. Unexpectedly, contralateral cathode placement significantly increased PRMR1 in Biceps Brachii (P=0.012), Flexor Carpi Radialis (P=0.035) and Abductor Pollicis Brevis (P=0.001). Post-activation depression (PAD) was also significantly increased with contralateral cathode placement in Biceps Brachii (P=0.001), Triceps Brachii (P=0.012) and Flexor Carpi Radialis (P=0.001). These results suggest that some level of unilateral motor pool selectivity may be attained via altering stimulus intensity and location during cervicothoracic tSCS.

Effect of Initial Knee angle and Arm Facilitation on biomechanics of the Sit-to-Stand movement.

Spinal cord injuries cause loss of muscle function and subsequently reduce independence. Therapeutic interventions such as transcutaneous spinal cord stimulation are increasingly being used to help improve motor functioning however, a comprehensive understanding of the biomechanical elements of movement may help optimize stimulation protocols. Twenty healthy participants completed five sit-to-stand (STS) transitions while initial knee angle and arm facilitation were altered. Electromyography (EMG) activation of four lower limb muscles and centre of pressure dynamics were recorded. Acute initial knee angles resulted in a change in duration of phases within the STS, and restrictive arm positioning caused the time to completion to increase (p=0.04). Muscle activation patterns across phases were compared and showed significant differences between phases in both the Tibialis Anterior and Rectus Femoris (p<0.006). Acute initial knee angles were also found to significantly increase Biceps Femoris activation across multiple phases (p=0.034). Altering the starting position and limb movement result in vastly different temporal and muscular strategies to complete the STS. Thus, joint angle and upper limb facilitation should be considered when designing rehabilitative interventions for clinical cohorts.

Impact of cooking on vitamin D3 and 25(OH)D3 content of pork products.

Little is known regarding the impact of cooking on vitamin D content in pork, despite meat being a major contributor to vitamin D intakes. This paper investigated the effect of household cooking (pan-fry/roast/grill/sous-vide/sauté), on the vitamin D3 and 25-hydroxyvitamin D3 (25(OH)D3) concentration/retention in pork loin, mince and sausages. We hypothesised that vitamin D concentrations would be higher in cooked vs raw pork, and retention would differ between products. Cooking significantly increased vitamin D3 (+49 %) and 25(OH)D3 (+33 %) concentrations. All cooked loin vitamin D3 concentrations were significantly lower than mince/sausage. Vitamin D3 retention was > 100 % for all samples (102-135 %), except sauté mince (99 %) which still did not differ significantly from 100 % retention. Sous-vide cooking resulted in the highest vitamin D3 retention (135 %). Likely owing to water/fat loss, household cooking of pork results in favourable retention of vitamin D3 and 25(OH)D3. The type of pork product has greater influence than cooking method.

Perceptions of the appropriate response to norm violation in 57 societies.

Norm enforcement may be important for resolving conflicts and promoting cooperation. However, little is known about how preferred responses to norm violations vary across cultures and across domains. In a preregistered study of 57 countries (using convenience samples of 22,863 students and non-students), we measured perceptions of the appropriateness of various responses to a violation of a cooperative norm and to atypical social behaviors. Our findings highlight both cultural universals and cultural variation. We find a universal negative relation between appropriateness ratings of norm violations and appropriateness ratings of responses in the form of confrontation, social ostracism and gossip. Moreover, we find the country variation in the appropriateness of sanctions to be consistent across different norm violations but not across different sanctions. Specifically, in those countries where use of physical confrontation and social ostracism is rated as less appropriate, gossip is rated as more appropriate.

How has COVID-19 affected the treatment of osteoporosis? An IOF-NOF-ESCEO global survey.

The effects of COVID-19 have the potential to impact on the management of chronic diseases including osteoporosis. A global survey has demonstrated that these impacts include an increase in telemedicine consultations, delays in DXA scanning, interruptions in the supply of medications and reductions in parenteral medication delivery. INTRODUCTION: The COVID-19 pandemic has had profound effects on the health of the global population both directly, via the sequelae of the infection, and indirectly, including the relative neglect of chronic disease management. Together the International Osteoporosis Foundation and National Osteoporosis Foundation sought to ascertain the impact on osteoporosis management. METHODS: Questionnaires were electronically circulated to a sample of members of both learned bodies and included information regarding the location and specialty of respondents, current extent of face to face consultations, alterations in osteoporosis risk assessment, telemedicine experience, alterations to medication ascertainment and delivery and electronic health record (EHR) utilisation. Responses were collected, quantitative data analysed, and qualitative data assessed for recurring themes. RESULTS: Responses were received from 209 healthcare workers from 53 countries, including 28% from Europe, 24% from North America, 19% from the Asia Pacific region, 17% from the Middle East and 12% from Latin America. Most respondents were physicians (85%) with physician assistants, physical therapists and nurses/nurse practitioners represented in the sample. The main three specialties represented included rheumatology (40%), endocrinology (22%) and orthopaedics (15%). In terms of the type of patient contact, 33% of respondents conducted telephone consultations and 21% video consultations. Bone mineral density assessment by dual-energy X-ray absorptiometry (DXA) usage was affected with only 29% able to obtain a scan as recommended. The majority of clinicians (60%) had systems in place to identify patients receiving parenteral medication, and 43% of clinicians reported difficulty in arranging appropriate osteoporosis medications during the COVID-19 crisis. CONCLUSIONS: To conclude through surveying a global sample of osteoporosis healthcare professionals, we have observed an increase in telemedicine consultations, delays in DXA scanning, interrupted supply of medications and reductions in parenteral medication delivery.

Asymptomatic Bordetella pertussis infections in young African infants and their mothers identified within a longitudinal cohort.

Despite long-standing vaccination programs, pertussis incidence has increased in numerous countries; transmission by asymptomatic individuals is a suspected driver of this resurgence. However, unequivocal evidence documenting asymptomatic infections in adults and children is lacking due, in part, to the cross-sectional nature of most pertussis surveillance studies. In addition, modern pertussis surveillance relies on quantitative PCR (qPCR) using fixed diagnostic thresholds to identify cases. To address this gap, we present a longitudinal analysis of 17,442 nasopharyngeal samples collected from a cohort of 1,320 Zambian mother/infant pairs. Using full-range cycle threshold (CT) values from IS481 qPCR assays, we document widespread asymptomatic infections among mothers and also, surprisingly, among young infants. From an initial group of eight symptomatic infants who tested positive by qPCR, we identify frequent contemporaneous subclinical infections in mothers. Within the full cohort, we observe strong temporal correlation between low- and high-intensity qPCR signals. We compute a single time-averaged score for each individual summarizing the evidence for pertussis infection (EFI), and show that EFI strongly clusters within mother/infant pairs, and is strongly associated with clinical symptomatology and antibiotic use. Overall, the burden of pertussis here is substantially underestimated when restricting diagnostic criteria to IS481 CT≤35. Rather, we find that full-range CT values provide valuable insights into pertussis epidemiology in this population, and illuminate the infection arc within individuals. These findings have significant implications for quantifying asymptomatic pertussis prevalence and its contribution to overall transmission. Our results also expose limitations of threshold-based interpretations of qPCR assays in infectious disease surveillance.

Considerations for the design and conduct of human gut microbiota intervention studies relating to foods.

With the growing appreciation for the influence of the intestinal microbiota on human health, there is increasing motivation to design and refine interventions to promote favorable shifts in the microbiota and their interactions with the host. Technological advances have improved our understanding and ability to measure this indigenous population and the impact of such interventions. However, the rapid growth and evolution of the field, as well as the diversity of methods used, parameters measured and populations studied, make it difficult to interpret the significance of the findings and translate their outcomes to the wider population. This can prevent comparisons across studies and hinder the drawing of appropriate conclusions. This review outlines considerations to facilitate the design, implementation and interpretation of human gut microbiota intervention studies relating to foods based upon our current understanding of the intestinal microbiota, its functionality and interactions with the human host. This includes parameters associated with study design, eligibility criteria, statistical considerations, characterization of products and the measurement of compliance. Methodologies and markers to assess compositional and functional changes in the microbiota, following interventions are discussed in addition to approaches to assess changes in microbiota-host interactions and host responses. Last, EU legislative aspects in relation to foods and health claims are presented. While it is appreciated that the field of gastrointestinal microbiology is rapidly evolving, such guidance will assist in the design and interpretation of human gut microbiota interventional studies relating to foods.

A rare differential for sinusitis and visual loss.

Erdheim-Chester disease is a rare infiltrative histiocytic disorder with around 800 cases being reported worldwide. Patients most commonly present with skeletal pain, but the condition has been shown to affect multiple other organs. We describe a rare presentation in which the disease infiltrated the sinuses and affected an ex-RAF pilot's vision. After extensive investigation of the elusive diagnosis, repeating of a molecular test using polymerase chain reaction analysis allowed for identification of a mutation (BRAF V600) ultimately leading to the diagnosis of Erdheim-Chester disease.

Emerging Use of Ultra-High-Field 7T MRI in the Study of Intracranial Vascularity: State of the Field and Future Directions.

Cerebrovascular disease is a major source of mortality that commonly requires neurosurgical intervention. MR imaging is the preferred technique for imaging cerebrovascular structures, as well as regions of pathology that include microbleeds and ischemia. Advanced MR imaging sequences such as time-of-flight, susceptibility-weighted imaging, and 3D T2-weighted sequences have demonstrated excellent depiction of arterial and venous structures with and without contrast administration. While the advantages of 3T compared with 1.5T have been described, the role of ultra-high-field (7T) MR imaging in neurovascular imaging remains poorly understood. In the present review, we examine emerging neurosurgical applications of 7T MR imaging in vascular imaging of diverse conditions and discuss current limitations and future directions for this technique.

Discrimination and geo-spatial mapping of atmospheric VOC sources using full scan direct mass spectral data collected from a moving vehicle.

Volatile and semi-volatile organic compounds (S/VOCs) are ubiquitous in the environment, come from a wide variety of anthropogenic and biogenic sources, and are important determinants of environmental and human health due to their impacts on air quality. They can be continuously measured by direct mass spectrometry techniques without chromatographic separation by membrane introduction mass spectrometry (MIMS) and proton-transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS). We report the operation of these instruments in a moving vehicle, producing full scan mass spectral data to fingerprint ambient S/VOC mixtures with high temporal and spatial resolution. We describe two field campaigns in which chemometric techniques are applied to the full scan MIMS and PTR-ToF-MS data collected with a mobile mass spectrometry lab. Principal Component Analysis (PCA) has been successfully employed in a supervised analysis to discriminate VOC samples collected near known VOC sources including internal combustion engines, sawmill operations, composting facilities, and pulp mills. A Gaussian mixture model and a density-based spatial clustering of application with noise (DBSCAN) algorithm have been used to identify sample clusters within the full time series dataset collected and we present geospatial maps to visualize the distribution of VOC sources measured by PTR-ToF-MS.