Primary squamous cell carcinoma of lung in a 13-year-old boy: a case report

We are reporting a very rare case of primary bronchogenic squamous cell carcinoma (SCC) with bone metastasis in a 13-year-old boy. A brief review of the English literature on this rare neoplasm in childhood is presented

Unknotting night-time muscle cramp: a survey of patient experience, help-seeking behaviour and perceived treatment effectiveness

Background: Night-time calf cramping affects approximately 1 in 3 adults. The aim of this study was to explore the experience of night-time calf cramp; if and where people seek treatment advice; and perceived treatment effectiveness. Methods: 80 adults who experienced night-time calf cramp at least once per week were recruited from the Hunter region, NSW, Australia through newspaper, radio and television advertisements. All participants completed a pilot-tested survey about muscle cramp. Quantitative data were analysed with independent-sample t-tests, Chi square tests and Fisher’s tests. Qualitative data were transcribed and sorted into categories to identify themes. Results: Median recalled age of first night-time calf cramp was 50 years. Most participants recalled being awoken from sleep by cramping, and experiencing cramping of either calf muscle, calf-muscle soreness in the days following cramp and cramping during day-time. Despite current therapies, mean usual pain intensity was 66 mm on a 100 mm visual analogue scale. Participants described their cramps as being ‘unbearable’, ‘unmanageable’ and ‘cruel’. One participant stated that ‘sometimes I just wish I could cut my legs open’ and another reported ‘getting about 2h sleep a night due to cramps’. Most participants had sought advice about their night-time calf cramps from a health professional. Participants identified 49 different interventions used to prevent night-time calf cramp. Of all treatment ratings, 68% described the intervention used to prevent cramp as being ‘useless’ or of ‘a little help’. Of 14 participants who provided additional information regarding their use of quinine, eight had a current prescription of quinine for muscle cramp at the time of the survey. None had been asked by their prescribing doctor to stop using quinine. Conclusion: Night time calf cramps typically woke sufferers from sleep, affected either leg and caused ongoing pain. Most participants experienced little or no relief with current therapies used to prevent muscle cramp. Most people who were taking quinine for muscle cramp were unaware that the Australian Therapeutic Goods Administration withdrew support of quinine for muscle cramp in 2004 due to the risk of thrombocytopaenia. Case-control studies are required to identify therapeutic targets so that clinical trials can evaluate safe interventions to prevent recurrent cramp

Impaired Glymphatic Function and Pulsation Alterations in a Mouse Model of Vascular Cognitive Impairment

ACKNOWLEDGMENTS Schematic diagrams in Figures 2, 8 are created withBiorender.com. FUNDING We gratefully acknowledge the grant support from the Alzheimer’s Society (152 (PG-157); 290 (AS-PG-15b-018); 228 (AS-DTC-2014-017), 314 (AS –PhD-16-006), and Alzheimer’s Research United Kingdom (ART-PG2010-3; ARUK-PG2013- 22; ARUK-PG2016B-6), and The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (G0700704/84698). ML and JB are funded by an Alzheimer’s Society Scotland Doctoral Training Programme and RS Macdonald Trust. ML was also funded by a China Scholarship Council (CSC)/University of Edinburgh scholarship.Peer reviewedPublisher PD

Predictive factors for sustained pain after (sub)acute osteoporotic vertebral fractures:Combined results from the VERTOS II and VERTOS IV trial

PURPOSE: Osteoporotic vertebral compression fractures are treated conservatively or in selected cases with percutaneous vertebroplasty (PV). The purpose of this retrospective analysis is to determine predictive factors for a high visual analogue scale (VAS) pain score after conservative, sham or PV and is based on previously published randomized trials. METHODS: The VERTOS II compared conservative versus PV, and VERTOS IV compared sham versus PV treatment. The conservative group received pain medication. The sham and PV group received subcutaneous lidocaine/bupivacaine. In addition, the PV group received cementation, which was simulated in the sham group. Nineteen different predictors of high (≥ 5) versus low ( 8, long-term baseline pain, mild/severe Genant and new fractures. CONCLUSIONS: Statistically significant more patients had a high pain score at 12 months in the sham and conservative group when compared with the PV group. Five predictors were identified for sustained high local back pain, regardless of the received treatment. Patients with moderate fracture deformity were less likely to have high pain scores at 12 months if they received PV than if they had sham or conservative therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00270-022-03170-7

An empirical evaluation of camera trap study design: How many, how long and when?

Abstract Camera traps deployed in grids or stratified random designs are a well‐established survey tool for wildlife but there has been little evaluation of study design parameters. We used an empirical subsampling approach involving 2,225 camera deployments run at 41 study areas around the world to evaluate three aspects of camera trap study design (number of sites, duration and season of sampling) and their influence on the estimation of three ecological metrics (species richness, occupancy and detection rate) for mammals. We found that 25–35 camera sites were needed for precise estimates of species richness, depending on scale of the study. The precision of species‐level estimates of occupancy (ψ) was highly sensitive to occupancy level, with 0.75) species, but more than 150 camera sites likely needed for rare (ψ < 0.25) species. Species detection rates were more difficult to estimate precisely at the grid level due to spatial heterogeneity, presumably driven by unaccounted habitat variability factors within the study area. Running a camera at a site for 2 weeks was most efficient for detecting new species, but 3–4 weeks were needed for precise estimates of local detection rate, with no gains in precision observed after 1 month. Metrics for all mammal communities were sensitive to seasonality, with 37%–50% of the species at the sites we examined fluctuating significantly in their occupancy or detection rates over the year. This effect was more pronounced in temperate sites, where seasonally sensitive species varied in relative abundance by an average factor of 4–5, and some species were completely absent in one season due to hibernation or migration. We recommend the following guidelines to efficiently obtain precise estimates of species richness, occupancy and detection rates with camera trap arrays: run each camera for 3–5 weeks across 40–60 sites per array. We recommend comparisons of detection rates be model based and include local covariates to help account for small‐scale variation. Furthermore, comparisons across study areas or times must account for seasonality, which could have strong impacts on mammal communities in both tropical and temperate sites

Azithromycin Mass Treatment for Trachoma Control: Risk Factors for Non-Participation of Children in Two Treatment Rounds

The World Health Organization advocates at least three mass drug administrations (MDAs) with antibiotics when the prevalence of follicular trachoma (TF) is greater than 10% in children under age ten. Full child participation is necessary for maximizing the impact of trachoma control programs. The present paper identifies guardian, household, and program risk factors for households with a child who never participated in two annual rounds of MDAs with azithromycin. In comparison to households with full child participation, guardians with at least one child who never participated had a higher burden of familial responsibility, as represented by reporting ill family members, more children, and were younger in age. In addition, guardians of persistent non-participants seemed less well connected in the community, in terms of reliance on others and not knowing who their assigned community treatment assistants (CTAs) were. These guardians were assigned to CTAs who had a wide geographic dispersion of their assigned households. By developing programs with local groups to find and encourage participation in at-risk households, program managers may have the greatest impact on preventing persistent child non-participation. Increasing the number of distribution days and reducing CTAs' travel time may further prevent non-participation

Experimental Philosophical Bioethics

There is a rich tradition in bioethics of gathering empirical data to inform, supplement, or test the implications of normative ethical analysis. To this end, bioethicists have drawn on diverse methods, including qualitative interviews, focus groups, ethnographic studies, and opinion surveys to advance understanding of key issues in bioethics. In so doing, they have developed strong ties with neighboring disciplines such as anthropology, history, law, and sociology. Collectively, these lines of research have flourished in the broader field of “empirical bioethics” for more than 30 years (Sugarman & Sulmasy 2010). More recently, philosophers from outside the field of bioethics have similarly employed empirical methods—drawn primarily from psychology, the cognitive sciences, economics, and related disciplines—to advance theoretical debates. This approach, which has come to be called experimental philosophy (or x-phi), relies primarily on controlled experiments to interrogate the concepts, intuitions, reasoning, implicit mental processes, and empirical assumptions about the mind that play a role in traditional philosophical arguments (Knobe et al. 2012). Within the moral domain, for example, experimental philosophy has begun to contribute to long-standing debates about the nature of moral judgment and reasoning; the sources of our moral emotions and biases; the qualities of a good person or a good life; and the psychological basis of moral theory itself (Alfano, Loeb, & Plakias 2018). We believe that experimental philosophical bioethics—or “bioxphi”—can similarly explain how it is distinct from empirical bioethics more broadly construed, and attempt to characterize how it might advance theory and practice in this area

Exploiting members of the BAHD acyltransferase family to synthesize multiple hydroxycinnamate and benzoate conjugates in yeast

BACKGROUND: BAHD acyltransferases, named after the first four biochemically characterized enzymes of the group, are plant-specific enzymes that catalyze the transfer of coenzyme A-activated donors onto various acceptor molecules. They are responsible for the synthesis in plants of a myriad of secondary metabolites, some of which are beneficial for humans either as therapeutics or as specialty chemicals such as flavors and fragrances. The production of pharmaceutical, nutraceutical and commodity chemicals using engineered microbes is an alternative, green route to energy-intensive chemical syntheses that consume petroleum-based precursors. However, identification of appropriate enzymes and validation of their functional expression in heterologous hosts is a prerequisite for the design and implementation of metabolic pathways in microbes for the synthesis of such target chemicals. RESULTS: For the synthesis of valuable metabolites in the yeast Saccharomyces cerevisiae, we selected BAHD acyltransferases based on their preferred donor and acceptor substrates. In particular, BAHDs that use hydroxycinnamoyl-CoAs and/or benzoyl-CoA as donors were targeted because a large number of molecules beneficial to humans belong to this family of hydroxycinnamate and benzoate conjugates. The selected BAHD coding sequences were synthesized and cloned individually on a vector containing the Arabidopsis gene At4CL5, which encodes a promiscuous 4-coumarate:CoA ligase active on hydroxycinnamates and benzoates. The various S. cerevisiae strains obtained for co-expression of At4CL5 with the different BAHDs effectively produced a wide array of valuable hydroxycinnamate and benzoate conjugates upon addition of adequate combinations of donors and acceptor molecules. In particular, we report here for the first time the production in yeast of rosmarinic acid and its derivatives, quinate hydroxycinnamate esters such as chlorogenic acid, and glycerol hydroxycinnamate esters. Similarly, we achieved for the first time the microbial production of polyamine hydroxycinnamate amides; monolignol, malate and fatty alcohol hydroxycinnamate esters; tropane alkaloids; and benzoate/caffeate alcohol esters. In some instances, the additional expression of Flavobacterium johnsoniae tyrosine ammonia-lyase (FjTAL) allowed the synthesis of p-coumarate conjugates and eliminated the need to supplement the culture media with 4-hydroxycinnamate. CONCLUSION: We demonstrate in this study the effectiveness of expressing members of the plant BAHD acyltransferase family in yeast for the synthesis of numerous valuable hydroxycinnamate and benzoate conjugates

Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations.

Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57 phosphatidylcholines (PC), 20 lysophosphatidylcholines (LPC), 27 phosphatidylethanolamines (PE), and 16 PE-based plasmalogens (PLPE), as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10(-204)) and 10 loci for sphingolipids (smallest P-value = 3.10×10(-57)). After a correction for multiple comparisons (P-value<2.2×10(-9)), we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1) and two with sphingolipids (PLD2 and APOE) explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3) suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE) mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2) to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our study identified nine novel phospho- and sphingolipid loci, substantially increasing our knowledge of the genetic basis for these traits