Sweet liking predicts liking and familiarity of some alcoholic beverages, but not alcohol intake: A population study using a split-sample approach.

Sweetness has been proposed to be an important quality in the decision to consume alcohol, and strong preferences for sweet tastes have been associated with alcohol abuse. However, alcohol is characterized by a number of other sensory properties, including astringency and bitterness that may drive preference and consumption. Spinelli et al. (2021) classified individuals into three sweet-sensory liking clusters (High Sweet-Liking, Moderate Sweet-Liking, and Inverted-U) that differed in their sweetness optima and sensory-liking patterns (relationship between liking and sweetness, bitterness and astringency perception in a food model). The current paper replicates the sweet sensory-liking clusters in a new set of participants (n = 1976), and extends the predicted value of these clusters examining their relationship to wine and other types of alcoholic beverages by gender using a split-sample approach on a total of over 3000 adults. The sweet sensory-liking clusters had a predictive relationship for the familiarity and liking of some alcoholic beverages characterized by stronger tastes, but not weekly alcohol intake levels. Thus, although sweet sensory-liking clusters may be associated with the type of beverages and frequency with which a person will drink and enjoy a type of alcoholic beverage, they are poor predictors of the quantity of alcohol that a person ingests over the course of a week.

Selective replication and vertical transmission of Ebola virus in experimentally infected Angolan free-tailed bats.

The natural reservoir of Ebola virus (EBOV), agent of a zoonosis burdening several African countries, remains unidentified, albeit evidence points towards bats. In contrast, the ecology of the related Marburg virus is much better understood; with experimental infections of bats being instrumental for understanding reservoir-pathogen interactions. Experiments have focused on elucidating reservoir competence, infection kinetics and specifically horizontal transmission, although, vertical transmission plays a key role in many viral enzootic cycles. Herein, we investigate the permissiveness of Angolan free-tailed bats (AFBs), known to harbour Bombali virus, to other filoviruses: Ebola, Marburg, Taï Forest and Reston viruses. We demonstrate that only the bats inoculated with EBOV show high and disseminated viral replication and infectious virus shedding, without clinical disease, while the other filoviruses fail to establish productive infections. Notably, we evidence placental-specific tissue tropism and a unique ability of EBOV to traverse the placenta, infect and persist in foetal tissues of AFBs, which results in distinct genetic signatures of adaptive evolution. These findings not only demonstrate plausible routes of horizontal and vertical transmission in these bats, which are expectant of reservoir hosts, but may also reveal an ancillary transmission mechanism, potentially required for the maintenance of EBOV in small reservoir populations.

Responsiveness to warning sensations and anxiety-related psychological traits modulate individual differences in preference for vegetable foods with varied sensory properties.

The innate aversion to warning sensations is an important barrier to the acceptance of vegetable food often characterized by bitter and sour tastes, and astringency. Large individual variations exist in preference for this food category. The present study aimed at exploring differences in demographics, anthropometrics, taste responsiveness, personality traits and attitudes in consumers differing in their preference for vegetable food with varied levels of warning sensations. A panel of Italian consumers (n = 718; 53.6% women, age 18-74 years) self-reported familiarity with, preference for and choice of vegetables with high and low levels of warning sensations. Two clusters were identified: High Warning-Vegetable Consumers (HWVC, n = 464) and Low-Warning Vegetable Consumers (LWVC, n = 254). HWVC showed higher familiarity with and preference for vegetables as a whole and higher choice of vegetables characterized by warning sensations than LWVC. HWVC were more represented by older and normal weight individuals as compared to LWVC. Differences among clusters in liking for and perception of a phenol-enriched plant-based food model specifically developed to induce different levels of bitterness, sourness and astringency were found. HWVC rated bitterness, sourness, and astringency lower and liking higher than LWVC. Scores in anxiety-related psychological traits were lower while attitudes to healthy and high-quality food choice were higher in HWVC than in LWVC. The results of the present study depicted a coherent interplay among several person-related dimensions in modulating preference for vegetable foods. Higher responsiveness to warning sensations, higher level of anxiety-related traits, lower importance assigned to food healthy/quality aspects and younger age all acted as barriers to exposure and acceptance of vegetable food and call for a multidimensional approach to promote the consumption of this food category.

Inoculation route-dependent Lassa virus dissemination and shedding dynamics in the natural reservoir - Mastomys natalensis.

Lassa virus (LASV), a Risk Group-4 zoonotic haemorrhagic fever virus, affects sub-Saharan African countries. Lassa fever, caused by LASV, results in thousands of annual deaths. Although decades have elapsed since the identification of the Natal multimammate mouse (Mastomys natalensis) as a natural reservoir of LASV, little effort has been made to characterize LASV infection in its reservoir. The natural route of infection and transmission of LASV within M. natalensis remains unknown, and the clinical impact of LASV in M. natalensis is mostly undescribed. Herein, using an outbred colony of M. natalensis, we investigate the replication and dissemination dynamics of LASV in this reservoir following various inoculation routes. Inoculation with LASV, regardless of route, resulted in a systemic infection and accumulation of abundant LASV-RNA in many tissues. LASV infection in the Natal multimammate mice was subclinical, however, clinical chemistry values were transiently altered and immune infiltrates were observed histologically in lungs, spleens and livers, indicating a minor disease with coordinated immune responses are elicited, controlling infection. Intranasal infection resulted in unique virus tissue dissemination dynamics and heightened LASV shedding, compared to subcutaneous inoculation. Our study provides important insights into LASV infection in its natural reservoir using a contemporary infection system, demonstrating that specific inoculation routes result in disparate dissemination outcomes, suggesting intranasal inoculation is important in the maintenance of LASV in the natural reservoir, and emphasizes that selection of the appropriate inoculation route is necessary to examine aspects of viral replication, transmission and responses to zoonotic viruses in their natural reservoirs.

The problem with assumptions: Revisiting "The dark figure of sexual recidivism".

What is the actual rate of sexual recidivism given the well-known fact that many crimes go unreported? This is a difficult and important problem, and in "The dark figure of sexual recidivism," Nicholas Scurich and Richard S. John (2019) attempt to make progress on it by "estimat[ing] actual recidivism rates . . . given observed rates of reoffending" (p. 171). In this article, we show that the math in their probabilistic model is flawed, but more importantly, we demonstrate that their conclusions follow ineluctably from their empirical assumptions and the unrepresentative empirical research they cite to benchmark their calculations. Scurich and John contend that their analysis undermines what they call the "orthodoxy in academic circles" (p. 173) of low sexual recidivism rates among individuals convicted of sexual offenses, but we underscore that their article does not analyze data in the traditional sense; instead, it just interprets past scholarly work through the use of strong assumptions in a way that, for practitioners, is likely to be opaque and misleading (and, for us, strays into speculation, argument, or advocacy and away from objective research). Our simple calculations show that their findings are highly sensitive to their assumptions, and we conclude that courts and others should recognize Scurich and John's work for what it is-a set of complex hypotheticals that are no more reliable than what judges and lawyers accomplish on their own by simply recognizing the basic problem that not all sexual offenses are reported.

Clostridium perfringens Produces an Adhesive Pilus Required for the Pathogenesis of Necrotic Enteritis in Poultry.

Clostridium perfringens type G strains cause necrotic enteritis (NE) in poultry, an economically important disease that is a major target of in-feed antibiotics. NE is a multifactorial disease, involving not only the critically important NetB toxin but also additional virulence and virulence-associated factors. We previously identified a C. perfringens chromosomal locus (VR-10B) associated with disease-causing strains that is predicted to encode a sortase-dependent pilus. In the current study, we sought to provide direct evidence for the production of a pilus by C. perfringens and establish its role in NE pathogenesis. Pilus structures in virulent C. perfringens strain CP1 were visualized by transmission electron microscopy (TEM) of immunogold-labeled cells. Filamentous structures were observed extending from the cell surface in wild-type CP1 but not from isogenic pilin-null mutant strains. In addition, immunoblotting of cell surface proteins demonstrated that CP1, but not the null mutant strains, produced a high molecular weight ladder-like pattern characteristic of a pilus polymer. Binding to collagen types I, II, and IV was significantly reduced (Tukey's test, P < 0.01) in all three pilin mutants compared to CP1 and could be specifically blocked by CnaA and FimA antisera, indicating that these pilins participate in adherence. Furthermore, fimA and fimB null mutants were both severely attenuated in their ability to cause disease in an in vivo chicken NE challenge model. Together, these results provide the first direct evidence for the production of a sortase-dependent pilus by C. perfringens and confirm its critical role in NE pathogenesis and collagen binding.IMPORTANCE In necrotic enteritis (NE), an intestinal disease of chickens, Clostridium perfringens cells adhere tightly to damaged intestinal tissue, but the factors involved are not known. We previously discovered a cluster of C. perfringens genes predicted to encode a pilus, a hair-like bacterial surface structure commonly involved in adherence. In the current study, we have directly imaged this pilus using transmission electron microscopy (TEM). We also show that inactivation of the pilus genes stops pilus production, significantly reducing the bacterium's ability to bind collagen and cause disease. Importantly, this is the first direct evidence for the production of a sortase-dependent pilus by C. perfringens, revealing a promising new target for developing therapeutics to combat this economically important disease.

Configural memory of a blending aromatic mixture reflected in activation of the left orbital part of the inferior frontal gyrus.

Blending aromatic mixtures components naturally fuse to form a unique odor - a configuration- qualitatively different from each component's odor. Repeated exposure to the components either in the mixture or separately, favors respectively, configural and elemental processings. The neural bases of such processes are still unknown. We examined the brain correlates of the experienced-induced configural processing of a well-known model of binary blending odor mixture, the aromatic pineapple blending (AB, ethyl maltol + ethyl isobutyrate). Before fMRI recording, half of the participants were repeatedly exposed to the mixture (AB, group Gmix), with the other half exposed to its separate components (A and B; Gcomp). During the fMRI recording, all participants were stimulated with the mixture (AB) and the components (A and B). Finally, participants rated the number of odors perceived for each stimulus. Gmix perceived the AB mixture as less complex than did Gcomp. While Gcomp perceived the mixture as more complex than its components, Gmix did not. These results show the presence of experience-induced configural or elemental processing of the AB mixture in each group. Contrasting the brain activity of Gcomp and Gmix, when stimulated with AB, revealed higher activation in the left orbital part of the inferior frontal gyrus. This result sheds light on this area's function, commonly found activated in olfactory studies, and closely connected with the lateral orbitofrontal cortex. We discuss the role of this area as a mediator of configural percepts between temporal and orbitofrontal areas involved in configural memory processes.

Veterinary antimicrobial stewardship in North America.

Major changes are occurring in veterinary antimicrobial stewardship (AMS) in food animals in Canada and the USA. Advances have been ending the use of medically important antimicrobials (MIAs) as growth promoters and bringing all MIAs for food animals under veterinary prescription in Canada (2018) or MIAs in feed or water under veterinary prescription (2017) in the USA. The USA proposes bringing all MIAs for food and companion animals under veterinary oversight, to reduce the duration of preventive use for food animals and to develop a strategy for companion animals. Both countries are taking a 'One Health' approach as part of their national strategies on addressing AMS. Federal state or province jurisdictional issues have impeded development and implementation of regulation-based stewardship approaches. Veterinary regulatory bodies in some of the larger states and provinces are active in AMS. Both the American and Canadian veterinary medical associations are independently heavily engaged in promoting AMS, as are, variably, the different veterinary 'specialty' groups. Regulatory changes and market demand are markedly reducing the use of antimicrobials in food animals. The promotion of veterinary AMS is happening at an increasing pace.

Immunization with subunits of a novel pilus produced by virulent Clostridium perfringens strains confers partial protection against necrotic enteritis in chickens.

Necrotic enteritis (NE) is an economically important disease of broiler chickens that is caused primarily by Clostridium perfringens strains that produce the NetB toxin. It is controlled in North America principally through the application of in-feed antimicrobials, but alternative control methods, such as vaccination, are urgently needed. We previously identified a cluster of C. perfringens genes prevalent in disease-causing strains, denominated VR-10B, that is predicted to encode a pilus. The current study evaluated the ability of three predicted pilin structural subunits (CnaA, FimA, FimB) to protect against NE in two immunization studies. In the first study, young broiler chickens were immunized twice intramuscularly (i.m.) with CnaA or FimA, which resulted in only a weak serum antibody response, and no reduction in the severity of intestinal lesions following experimental challenge with C. perfringens strain CP1. In the second study, chickens were injected subcutaneously (s.c.) with CnaA, FimB, or a combination of all three proteins, on days 7, 14 and 19, which resulted in a marked antibody response specific to each antigen. Chickens immunized with either CnaA or FimB had significantly reduced NE lesion severity, whereas immunization with all three proteins in combination did not provide protection. Western blot experiments using serum from immunized birds were also performed, providing the first experimental evidence to suggest that this locus may in fact encode a functional pilus structure.

Evaluation of Therapeutics for Advanced-Stage Heart Failure and Other Severely-Debilitating or Life-Threatening Diseases.

Severely-debilitating or life-threatening (SDLT) diseases include conditions in which life expectancy is short or quality of life is greatly diminished despite available therapies. As such, the medical context for SDLT diseases is comparable to advanced cancer and the benefit vs. risk assessment and development of SDLT disease therapeutics should be similar to that of advanced cancer therapeutics. A streamlined development approach would allow patients with SDLT conditions earlier access to therapeutics and increase the speed of progression through development. In addition, this will likely increase the SDLT disease therapeutic pipeline, directly benefiting patients and reducing the economic and societal burden of SDLT conditions. Using advanced-stage heart failure (HF) as an example that illustrates the concepts applicable to other SDLT indications, this article proposes a streamlined development paradigm for SDLT disease therapeutics and recommends development of aligned global regulatory guidance.

Relationships between food neophobia and food intake and preferences: Findings from a sample of New Zealand adults.

Food neophobia (FN) has been shown to be a strong influence on food preferences using primarily small data sets. This has limited the explanatory power of FN and the extent to which it can be related to other factors that influence food choice. To address these limitations, we collected Food Neophobia Scale data from 1167 adults from New Zealand over a 45-month period. Participants also completed a 112-item food preference questionnaire and a self-report 24 h, a 145 item food intake recall survey, and the Food Choice Questionnaire (FCQ). As a way of providing a structure to the food intake and preference data, in each case the food items were condensed into patterns described in terms of the foods/beverages with highest factor loadings. We then determined the impact of season and participant age, gender, education and income on these factors, as well as the interaction of these variables with FN scores, divided into tertiles. FN was a strong influence on both intake frequency and preferences in the majority of the intake/preference factor patterns. When significant associations with FN were established, both frequency of intake and preference was lower among high FN individuals. Notably, the effect of FN on food preferences was evident on many commonplace foods making up the diet, suggesting that high FN individuals like food overall less than do those with lower degrees of FN. Seasonal effects in food intake were demonstrated, but with smaller impact for higher levels of FN. While associations between FN varied according to all demographic variables, these relationships varied as a function of the intake/preference patterns. Overall, the results suggest that FN is an important barrier to dietary change and addressing diet-related health problems.

"Sometimes I feel like a pharmacist": identity and medication use among adolescents with juvenile arthritis.

BACKGROUND: Taking medicines as intended is difficult for everybody, but young people going through adolescence have greater problems than adults and younger children. One of the most important things that happen during the teenage years is the development of individual identities, which might not remain constant during this time and can be affected deeply by the diagnosis of a long-term condition. The aim of this study was to examine the relationships between identity and medication use among young people with juvenile arthritis. METHODS: A prospective qualitative study was undertaken to collect private online 'blog' style data from young people (aged 11-19 years) with juvenile arthritis, and their parents, to examine their views about their condition, identity, medication and use of health services. Participants were identified from a large paediatric hospital in the UK. RESULTS: Young people (n = 21) with a median age 14 years (range 11-17 years) posted a median (range) of 8 (1-36) blogs and parents (n = 6) posted 4 (1-12) blogs. Young people gave a strong sense of both private and public identity that was intertwined with their arthritis and treatment. It was evident that young people's self-care was intrinsically linked to their attempts to maintain a sense of individually and socially constructed definitions of normality. The act of taking medication, and the consequences (positive or negative) of that act, had an impact both personally and socially. CONCLUSIONS: Young people with juvenile arthritis reflect on their medication as a factor affecting their perception of themselves. Acknowledging the roles of both personal and social identity will be important in any strategies to support optimal medication use. This includes an understanding of the identity transformations that young people can experience and how decision-making may be affected by their attempts to retain pre-diagnosis identities and/or develop new social identities.

A prospective cohort study of endometriosis and subsequent risk of infertility.

STUDY QUESTION: Is there a temporal relationship between endometriosis and infertility? SUMMARY ANSWER: Endometriosis is associated with a higher risk of subsequent infertility, but only among women age <35 years. WHAT IS KNOWN ALREADY: Endometriosis is the most commonly observed gynecologic pathology among infertile women undergoing laparoscopic examination. Whether endometriosis is a cause of infertility or an incidental discovery during the infertility examination is unknown. STUDY DESIGN, SIZE, DURATION: This study included data collected from 58 427 married premenopausal female nurses <40 years of age from 1989 to 2005, who are participants of the Nurses' Health Study II prospective cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our exposure was laparoscopically confirmed endometriosis. Multivariate Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for infertility risk (defined as attempting to conceive for >12 months) among women with and without endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 4612 incident cases of infertility due to any cause over 362 219 person-years of follow-up. Compared with women without a history of endometriosis, women with endometriosis had an age-adjusted 2-fold increased risk of incident infertility (HR = 2.12, 95% CI = 1.76-2.56) that attenuated slightly after accounting for parity. The relationship with endometriosis was only observed among women <35 years of age (multivariate HR <35 years = 1.77, 95% CI = 1.46-2.14; multivariate HR 35-39 years = 1.20, 95% CI = 0.94-1.53; P-interaction = 0.008). Risk of primary versus secondary infertility was similar subsequent to endometriosis diagnosis. Among women with primary infertility, 50% became parous after the endometriosis diagnosis, and among all women with endometriosis, 83% were parous by age 40 years. LIMITATIONS, REASONS FOR CAUTION: We did not have information on participants' intentions to conceive, but by restricting the analytic population to married women we increased the likelihood that pregnancies were planned (and therefore infertility would be recognized). Women in our cohort with undiagnosed asymptomatic endometriosis will be misclassified as unexposed. However, the small proportion of these women are diluted among the >50 000 women accurately classified as endometriosis-free, minimizing the impact of exposure misclassification on the effect estimates. WIDER IMPLICATIONS OF THE FINDINGS: This study supports a temporal association between endometriosis and infertility risk. Our prospective analysis indicates a possible detection bias in previous studies, with our findings suggesting that the infertility risk posed by endometriosis is about half the estimates observed in cross-sectional analyses. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Institutes of Health (grant numbers: UM1 CA176726, HD52473, HD57210, T32DK007703, T32HD060454, K01DK103720). We have no competing interests to declare.

Chromosomal microarray provides enhanced targetable gene aberration detection when paired with next generation sequencing panel in profiling lung and colorectal tumors.

The development of targeted therapies based on specific genomic alterations has altered the treatment and management of lung and colorectal cancers. Chromosomal microarray (CMA) has allowed identification of copy number variations (CNVs) in lung and colorectal cancers in great detail, and next-generation sequencing (NGS) is used extensively to analyze the genome of cancers for molecular subtyping and use of molecularly guided therapies. The main objective of this study was to evaluate the utility of combining CMA and NGS for a comprehensive genomic assessment of lung and colorectal adenocarcinomas, especially for detecting drug targets. We compared the results from NGS and CMA data from 60 lung and 51 colorectal tumors. From CMA analysis, 33% were amplified, 89% showed gains, 75% showed losses and 41% demonstrated loss of heterozygosity; pathogenic variants were identified in 81% of colon and 67% lung specimens through NGS. KRAS mutations commonly occurred with loss in TP53 and there was significant loss of BRCA1 and NF1 among male patients with lung cancer. For clinically actionable targets, 23% had targetable CNVs when no pathogenic variants were detected by NGS. The data thus indicate that combining the two approaches provides significant benefit in a routine clinical setting not available by NGS alone.

Toxicokinetics and toxicity of atorvastatin in dogs.

HMG-CoA reductase inhibitors (e.g., statins) are an important clinical option to lower cholesterol and treat co-morbidities. Atorvastatin is the most prescribed statin and has obtained generic status. We recently had a clinical development program evaluating a combination of atorvastatin with a GPR119 agonist as a treatment for dyslipidemia, where toxicological evaluations in dogs were completed. There were several challenges related to selecting doses for atorvastatin, including understanding the dose-exposure relationship from different drug forms used by the innovator in their general toxicology studies, bioanalytical assays that did not separate and quantify parent from metabolites, and high variability in the systemic exposures following oral dosing. The studies in this report characterized the toxicokinetics and toxicity of atorvastatin in the dog for up to 13-weeks. Overall, there were no notable differences in the toxicokinetics of atorvastatin or the two active hydroxylated metabolites between the sexes at Week 13. However, systemic exposures were markedly lower at Week 13 compared to that observed at Week 4, suggesting induction of metabolism or reduced absorption from the gastrointestinal tract following oral dosing. Changes in laboratory chemistries included increased liver enzyme levels and lower cholesterol levels. Histopathologic evaluation revealed multifocal minimal to slight hemorrhages in the submucosa of the gallbladder; all findings were reversible. The information from these studies along with the existing clinical experience with atorvastatin can be used to design robust toxicology studies in dogs and reduce animal use.

Differential in vivo tumorigenicity of diverse KRAS mutations in vertebrate pancreas: A comprehensive survey.

Somatic activation of the KRAS proto-oncogene is evident in almost all pancreatic cancers, and appears to represent an initiating event. These mutations occur primarily at codon 12 and less frequently at codons 13 and 61. Although some studies have suggested that different KRAS mutations may have variable oncogenic properties, to date there has been no comprehensive functional comparison of multiple KRAS mutations in an in vivo vertebrate tumorigenesis system. We generated a Gal4/UAS-based zebrafish model of pancreatic tumorigenesis in which the pancreatic expression of UAS-regulated oncogenes is driven by a ptf1a:Gal4-VP16 driver line. This system allowed us to rapidly compare the ability of 12 different KRAS mutations (G12A, G12C, G12D, G12F, G12R, G12S, G12V, G13C, G13D, Q61L, Q61R and A146T) to drive pancreatic tumorigenesis in vivo. Among fish injected with one of five KRAS mutations reported in other tumor types but not in human pancreatic cancer, 2/79 (2.5%) developed pancreatic tumors, with both tumors arising in fish injected with A146T. In contrast, among fish injected with one of seven KRAS mutations known to occur in human pancreatic cancer, 22/106 (20.8%) developed pancreatic cancer. All eight tumorigenic KRAS mutations were associated with downstream MAPK/ERK pathway activation in preneoplastic pancreatic epithelium, whereas nontumorigenic mutations were not. These results suggest that the spectrum of KRAS mutations observed in human pancreatic cancer reflects selection based on variable tumorigenic capacities, including the ability to activate MAPK/ERK signaling.

Nonculture molecular techniques for diagnosis of bacterial disease in animals: a diagnostic laboratory perspective.

The past decade has seen remarkable technical advances in infectious disease diagnosis, and the pace of innovation is likely to continue. Many of these techniques are well suited to pathogen identification directly from pathologic or clinical samples, which is the focus of this review. Polymerase chain reaction (PCR) and gene sequencing are now routinely performed on frozen or fixed tissues for diagnosis of bacterial infections of animals. These assays are most useful for pathogens that are difficult to culture or identify phenotypically, when propagation poses a biosafety hazard, or when suitable fresh tissue is not available. Multiplex PCR assays, DNA microarrays, in situ hybridization, massive parallel DNA sequencing, microbiome profiling, molecular typing of pathogens, identification of antimicrobial resistance genes, and mass spectrometry are additional emerging technologies for the diagnosis of bacterial infections from pathologic and clinical samples in animals. These technical advances come, however, with 2 caveats. First, in the age of molecular diagnosis, quality control has become more important than ever to identify and control for the presence of inhibitors, cross-contamination, inadequate templates from diagnostic specimens, and other causes of erroneous microbial identifications. Second, the attraction of these technologic advances can obscure the reality that medical diagnoses cannot be made on the basis of molecular testing alone but instead through integrated consideration of clinical, pathologic, and laboratory findings. Proper validation of the method is required. It is critical that veterinary diagnosticians understand not only the value but also the limitations of these technical advances for routine diagnosis of infectious disease.