Sex drives colonic mucin sialylation in wild mice.

Mucin protein glycosylation is important in determining biological properties of mucus gels, which form protective barriers at mucosal surfaces of the body such as the intestine. Ecological factors including: age, sex, and diet can change mucus barrier properties by modulating mucin glycosylation. However, as our understanding stems from controlled laboratory studies in house mice, the combined influence of ecological factors on mucin glycosylation in real-world contexts remains limited. In this study, we used histological staining with 'Alcian Blue, Periodic Acid, Schiff's' and 'High-Iron diamine' to assess the acidic nature of mucins stored within goblet cells of the intestine, in a wild mouse population (Mus musculus). Using statistical models, we identified sex as among the most influential ecological factors determining the acidity of intestinal mucin glycans in wild mice. Our data from wild mice and experiments using laboratory mice suggest estrogen signalling associates with an increase in the relative abundance of sialylated mucins. Thus, estrogen signalling may underpin sex differences observed in the colonic mucus of wild and laboratory mice. These findings highlight the significant influence of ecological parameters on mucosal barrier sites and the complementary role of wild populations in augmenting standard laboratory studies in the advancement of mucus biology.

Dynamic Protective Factors Relevant to Sexual Offending.

PURPOSE OF REVIEW: Focusing on protective factors rather than risk factors potentially better aligns assessment with strengths-based treatment. We examine research into the assessment of protective factors to see whether it can play this role relative to sexual offending. RECENT FINDINGS: Structured asses sment of protective factors is well developed relative to violent offending but only recently studied relative to sexual offending. Nevertheless, multiple measures of protective factors have now been trialed with men who have committed sexual offenses and shown to predict reduced recidivism. Although research into individual scales is limited, overlapping content between scales suggests that protective factors aligning with constructs of Resilience, Adaptive Sexuality, and Prosocial Connection and Reward are all relevant to sexual offending. Protective factors relevant to sexual offending are sufficiently well identified that they can usefully be used for treatment need assessment, treatment planning during therapy, and case management. They can also make some contribution to risk assessment. The Structured Assessment of PROtective Factors against Sexual Offending (SAPROF-SO) is currently the most comprehensive measure of protective factors relevant to sexual offending.

Morphologically intact airways in lung fibrosis have an abnormal proteome.

Honeycombing is a histological pattern consistent with Usual Interstitial Pneumonia (UIP). Honeycombing refers to cystic airways located at sites of dense fibrosis with marked mucus accumulation. Utilizing laser capture microdissection coupled mass spectrometry (LCM-MS), we interrogated the fibrotic honeycomb airway cells and fibrotic uninvolved airway cells (distant from honeycomb airways and morphologically intact) in specimens from 10 patients with UIP. Non-fibrotic airway cell specimens from 6 patients served as controls. Furthermore, we performed LCM-MS on the mucus plugs found in 6 patients with UIP and 6 patients with mucinous adenocarcinoma. The mass spectrometry data were subject to both qualitative and quantitative analysis and validated by immunohistochemistry. Surprisingly, fibrotic uninvolved airway cells share a similar protein profile to honeycomb airway cells, showing deregulation of the slit and roundabout receptor (Slit and Robo) pathway as the strongest category. We find that (BPI) fold-containing family B member 1 (BPIFB1) is the most significantly increased secretome-associated protein in UIP, whereas Mucin-5AC (MUC5AC) is the most significantly increased in mucinous adenocarcinoma. We conclude that fibrotic uninvolved airway cells share pathological features with fibrotic honeycomb airway cells. In addition, fibrotic honeycomb airway cells are enriched in mucin biogenesis proteins with a marked derangement in proteins essential for ciliogenesis. This unbiased spatial proteomic approach generates novel and testable hypotheses to decipher fibrosis progression.

Emotional intelligence in incarcerated sexual offenders with sexual sadism.

Emotional intelligence (EI) is defined by the ability to perceive, manage, and reason about emotions in oneself and others. Studies have reported deficits in EI abilities among certain antisocial populations such as individuals with psychopathy, and enhanced performance among sexual offenders. Despite EI's relevance to offending behaviour, the association between EI and paraphilic offending has been under-studied. We examined the association between EI, sexual offending, and sexual sadism in 80 incarcerated men with sexual offenses and 207 incarcerated men with non-sexual offences. EI was assessed using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Sadism was measured using the Severe Sexual Sadism Scale (SeSaS). Results showed that SeSaS scores were positively associated with Strategic EI (the ability to understand and manage emotions), but were not significantly related to Experiential EI. This may reflect core characteristics of sexual sadism including domination and manipulation, challenging the prevalent notion that higher EI is invariably positive.

Mucin networks: Dynamic structural assemblies controlling mucus function.

Contrary to first appearances, mucus structural biology is not an oxymoron. Though mucus hydrogels derive their characteristics largely from intrinsically disordered, heavily glycosylated polypeptide segments, the secreted mucin glycoproteins that constitute mucus undergo an orderly assembly process controlled by folded domains at their termini. Recent structural studies revealed how mucin complexes promote disulphide-mediated polymerization to produce the mucus gel scaffold. Additional protein-protein and protein-glycan interactions likely tune the mesoscale properties, stability, and activities of mucins. Evidence is emerging that even intrinsically disordered glycosylated segments have specific structural roles in the production and properties of mucus. Though soft-matter biophysical approaches to understanding mucus remain highly relevant, high-resolution structural studies of mucins and other mucus components are providing new perspectives on these vital, protective hydrogels.

High-fat diet-induced resistance to helminth infection via alternative induction of type 2 immunity.

Gastrointestinal nematode infections cause morbidity and socioeconomic loss in the most deprived communities. The shift in the context of obesity has led to spatial overlap with endemic gastrointestinal nematode regions resulting in the emergence of a novel comorbidity. Despite this, the impact of a high-fat diet (HFD) on immune-regulated protection against gastrointestinal infections remains largely unknown. We employed the murine model of nematode infection, Trichuris muris, to investigate the effect of an HFD on the immune response against chronic infection. Surprisingly, diet-induced obesity drove parasite expulsion in both single and repeated trickle low doses of T. muris eggs. Mechanistically, an HFD increased the expression of the ST2 receptor on CD4+ T cells, priming an enhanced type 2 helper T (Th2) cell cytokine production following interleukin (IL)-33 stimulation ex vivo. Despite IL-33-/- mice demonstrating that IL-33 is not critical for host protective immunity to T. muris under a conventional diet, HFD-fed T-cell deplete mice adoptively transferred with ST2-/- CD4 T cells were unable to expel a T. muris infection unlike those transferred with ST2-sufficient cells. Collectively, this study demonstrates that an HFD primes CD4+ T cells to utilize the IL-33-ST2 axis in a novel induction of type 2 immunity, providing insights into the emerging comorbidities of obesity and nematode infection.

Attending to the Positive: A Retrospective Validation of the Structured Assessment of Protective Factors-Sexual Offence Version.

Sexual recidivism risk assessment tools focus almost exclusively on risk factors associated with increased rates of recidivism and do not attend to protective factors that might mitigate reoffense risk. The present study investigated the predictive validity of the Structured Assessment of Protective Factors - Sexual Offence version (SAPROF-SO), developed to assess hypothesised protective factors against sexual recidivism in adult males. The SAPROF-SO pilot version contains 24 items across two domains: Personal and Professionally Provided Support. SAPROF-SO scores were rated retrospectively from a review of archived case files of 210 men with convictions for child sexual offenses, using the SAPROF-SO pilot manual and a supplementary retrospective scoring guide developed for the current study. SAPROF-SO Total and Personal domain scores were significantly predictive of sexual recidivism after an average follow-up period of 12.24 years (AUC = .81), and to a lesser extent, violent and general recidivism. SAPROF-SO Total and Personal scores additionally provided significant incremental validity over Static-99R scores in the prediction of sexual recidivism. Results support the predictive validity of protective factors for reduced sexual recidivism and invite future research examining how to integrate the SAPROF-SO alongside contemporary sexual recidivism risk assessment tools.

Reliability and Factor Structure of the Sex Offender Treatment Intervention and Progress Scale.

Assessment of risk of sexual recidivism has progressed from tools containing only static factors to tools including dynamic (i.e., changeable) risk factors. The psychometric properties and factor structure of one such scale, the Sex Offender Treatment Intervention and Progress Scale (SOTIPS) were explored. Seven hundred and thirty-one men assigned probation for sexual crimes in New York City and Maricopa County, Arizona were administered SOTIPS three times: intake into probation, six months later, and six months after that. SOTIPS showed good internal consistency (Time 1 ω = .87, Time 2 ω = .89, and Time 3 ω = .91), and acceptable inter-rater reliability (for the 26 cases rated in the same month, ICC =.821). An exploratory factor analysis did not result in the original factor structure proposed by the developers; instead, SOTIPS showed two factors: sexual risk and antisocial opposition. This factor structure required the averaging of two items to avoid collinearity. SOTIPS showed temporal invariance indicating that its factor structure and its association to underlying latent variables are consistent over time.

Mucus aberrant properties in CF: Insights from cells and animal models.

Cystic fibrosis (CF), an autosomal genetic disorder caused by the dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, is characterized by mucus accumulation in the lungs, the intestinal tract, and the pancreatic ducts. Mucins are high-molecular-weight glycoproteins that govern the biochemical and biophysical properties of mucus. In the CF lung, increased mucus viscoelasticity is associated with decreased mucociliary clearance and defects in host defense mechanisms. The link between defective ion channel and abnormal mucus properties has been investigated in studies involving cell and animal models. In this review article, we discuss recent progress toward understanding the different regions and cells that express CFTR in the airways and how mucus is produced and cleared from the lungs. In addition, we reflect on animal models that provided insights into the organization and the role of the mucin network and how mucus and antimicrobial activities act in concert to protect the lungs from invading pathogens.

Long Term Recidivism Rates Among Individuals at High Risk to Sexually Reoffend.

Preventive detention provisions in the US and Canada assume we can identify, in advance, individuals at high risk for sexual recidivism. To test this assumption, 377 adult males with a history of sexual offending were followed for 20 years using Canadian national criminal history records and Internet searches. Using previously collected information, a high risk/high need (HRHN) subgroup was identified based on an unusually high levels of criminogenic needs (n = 190, average age of 38 years; 83% White, 13% Indigenous, 4% other). A well above average subgroup of 99 individuals was then identified based on high Static-99R (6+) and Static-2002R (7+) scores. In the HRHN group, 40% reoffended sexually. STATIC HRHN norms overestimated sexual recidivism at 5 years (Static-99R, E/O = 1.44; Static-2002R, E/O = 1.72) but were well calibrated for longer follow-up periods (20 years: Static-99R, E/0 = 1.00; Static-2002R, E/O = 1.16). The overall sexual recidivism rate for the well above average subgroup was 52.1% after 20 years, and 74.3% for any violent recidivism. The highest risk individuals (top 1%) had rates in the 60%-70% range. We conclude that some individuals present a high risk for sexual recidivism, and can be identified using currently available methods.

Factors associated with repeat sexual offending among U.S. military veterans compared to civilians.

Although veterans have lower incarceration rates than civilians, large national surveys find higher rates of incarceration for sexual offenses among veterans compared to non-veterans. However, little is known about the factors associated with repeat sexual offending among veterans. This study examines characteristics of veterans who committed sexual offenses and how they differ from civilians with those offenses. It also examined if the factors that differ between veterans and civilians who have a history of repeat sexual offenses and those who do not. Based on previous research related to risk in veterans, we expected there may be veteran-specific risk factors. This study used the Survey of Inmates in State and Federal Correctional Facilities. Predictors were identified through a review of the literature regarding sexual offense risk assessment and justice-involved veterans. Risk factors were examined using logistic regression analysis. In a multivariate logistic regression, there were significant interactions between veteran status and age, race, and education in the prediction of repeat offense status. Prior incarceration for a non-sexual offense was also associated with repeat offense status. Findings suggests that civilian risk factors are relevant to veteran risk assessment, an important finding that can help inform intervention and risk management with veterans.

Defining the early stages of intestinal colonisation by whipworms.

Whipworms are large metazoan parasites that inhabit multi-intracellular epithelial tunnels in the large intestine of their hosts, causing chronic disease in humans and other mammals. How first-stage larvae invade host epithelia and establish infection remains unclear. Here we investigate early infection events using both Trichuris muris infections of mice and murine caecaloids, the first in-vitro system for whipworm infection and organoid model for live helminths. We show that larvae degrade mucus layers to access epithelial cells. In early syncytial tunnels, larvae are completely intracellular, woven through multiple live dividing cells. Using single-cell RNA sequencing of infected mouse caecum, we reveal that progression of infection results in cell damage and an expansion of enterocytes expressing of Isg15, potentially instigating the host immune response to the whipworm and tissue repair. Our results unravel intestinal epithelium invasion by whipworms and reveal specific host-parasite interactions that allow the whipworm to establish its multi-intracellular niche.

The lipophilic cyclic peptide cyclosporin A induces aggregation of gel-forming mucins.

Cyclic peptides are good candidates for orally delivered therapeutics, however, issues remain in their development due to low intestinal permeability. Although some of the biological factors have been reported that regulate intestinal permeation of cyclic peptides, the influence of the mucus barrier, a major hurdle to epithelial drug delivery, on cyclic peptide bioavailability is unclear. In this study, we show that the lipophilic cyclic peptide, cyclosporin A (CsA), interacted with, and likely induced aggregation, of polymeric, gel-forming mucins (MUC2, MUC5AC and MUC5B) which underpin the mucus gel-networks in the gastrointestinal tract. Under similar conditions, two other cyclic peptides (daptomycin and polymyxin B) did not cause mucin aggregation. Using rate-zonal centrifugation, purified MUC2, MUC5AC and MUC5B mucins sedimented faster in the presence of CsA, with a significant increase in mucins in the pellet fraction. In contrast, mucin sedimentation profiles were largely unaltered after treatment with daptomycin or polymyxin B. CsA increased MUC5B sedimentation was concentration-dependent, and sedimentation studies using recombinant mucin protein domains suggests CsA most likely causes aggregation of the relatively non-O-glycosylated N-terminal and C-terminal regions of MUC5B. Furthermore, the aggregation of the N-terminal region, but not the C-terminal region, was affected by pH. CsA has partially N-methylated amide groups, this unique molecular structure, not present in daptomycin and polymyxin B, may potentially be involved in interaction with gel-forming mucin. Taken together, our results indicate that the interaction of gel-forming mucins with the cyclic peptide CsA is mediated at the N- and C-terminal domains of mucin polymers under physiological conditions. Our findings demonstrate that the mucus barrier is an important physiological factor regulating the intestinal permeation of cyclic peptides in vivo.

Why are individuals over age 60 still committed as sexually violent persons?

Civilly committed sexually violent persons (SVPs) are a select group of individuals designated as high risk for future sexual violence. Despite risk reduction in older age, SVP programs are seeing aging client populations, with many individuals remaining committed after age 60 (60+). Recent research found a sexual recidivism rate of 7.5% for 60+ individuals released from an SVP civil commitment program. The current paper follows up by examining reasons why individuals remain committed after age 60. It compares SVPs discharged after age 60 to those who are 60+ but remain civilly committed. Results of bivariate analyses reveal older SVPs who remain committed have significantly higher actuarial risk scores and are more likely to be of minority race. Multivariate logistic regression analyses found actuarial risk scores (Static-99R) predicted continued commitment, after controlling for other relevant variables. Barriers to community reintegration and suggestions for multi-disciplinary case management for older SVPs are discussed.

Understanding the Latent Structure of Dynamic Risk: Seeking Empirical Constraints on Theory Development Using the VRS-SO and the Theory of Dynamic Risk.

The present study is part of a larger project aiming to more closely integrate theory with empirical research into dynamic risk. It seeks to generate empirical findings with the dynamic risk factors contained in the Violence Risk Scale-Sexual Offense version (VRS-SO) that might constrain and guide the further development of Thornton's theoretical model of dynamic risk. Two key issues for theory development are (a) whether the structure of pretreatment dynamic risk factors is the same as the structure of the change in the dynamic risk factors that occurs during treatment, and (b) whether theoretical analysis should focus on individual dynamic items or on the broader factors that run through them. Factor analyses and item-level prediction analyses were conducted on VRS-SO pretreatment, posttreatment, and change ratings obtained from a large combined sample of men (Ns = 1,289-1,431) convicted and treated for sexual offenses. Results indicated that the latent structure of pretreatment dynamic risk was best described by a three-factor model while the latent structure of change items was two dimensional. Prediction analyses examined the degree to which items were predictive beyond prediction obtained from the broader factor that they loaded on. Results showed that for some items, their prediction appeared to be largely carried by the three broad factors. In contrast, other items seem to operate as funnels through which the broader factors' predictiveness flowed. Implications for theory development implied by these results are identified.

Hormonal response to perceived emotional distress in incarcerated men with sexual sadism.

Sexual sadists derive pleasure from humiliation, domination and infliction of pain on victims. They display increased penile arousal and activation of brain regions involved in sexual arousal and emotional states when viewing stimuli depicting individuals in physical distress. Neuroactive hormones modulate these regions, but it is unknown if sexual sadists also have endocrine responses to depictions of individuals in distress. The present study examined endocrine responses, elicited by viewing a video depicting an individual in extreme emotional distress, in incarcerated adult male sexual offenders (n = 23) with varying levels of sadistic traits. Sadism, was measured by the Severe Sexual Sadism Scale (SeSaS). Testosterone (T), adrenocorticotropic hormone (ACTH), and oxytocin (OT) were assayed before and after participants watched a video depicting an individual in emotional distress. T responses to the video were significantly and positively associated with SeSaS scores. There were no significant associations between sexual sadism and OT or ACTH. Our findings provide physiological evidence of atypical processing of distress cues in sadism consistent with the role of testosterone in sexual arousal and aggressive behaviors. These findings have implications for the evaluation and treatment of sexual sadists.

Sputum biomarkers during acute severe asthma attacks in children-a case-control study.

AIM: To study sputum mediator profiles pattern in children with acute severe asthma, compared with stable asthma and healthy controls. The mechanisms of acute severe asthma attacks, such as biomarkers cascades and immunological responses, are poorly understood. METHODS: We conducted a prospective observational case-control study of children aged 5 to 17 years, who presented to hospital with an asthma attack. Children with stable asthma were recruited during outpatient asthma clinic visits. Control children without an asthma diagnosis were recruited from surgical wards. Sputum mediator profiles were measured, and sputum leukocyte differential cell counts were generated. RESULTS: Sputum data were available in 48 children (acute asthma; n = 18, stable asthma; n = 17, healthy controls; n = 13). Acute-phase biomarkers and neutrophil attractants such as IL-6 and its receptor, IL-8 and cytokines linked with bacterial signals, including TNF-R1 and TNF-R2, were elevated in asthma attacks versus stable asthma and healthy controls. T-cell attractant cytokines, associated with viral infections, such as CCL-5, CXCL-10 and CXCL-11, and CXCL-9 (secreted from eosinophils after a viral trigger) were also raised. CONCLUSION: Mediator profiles consistent with bacterial and viral respiratory infections, and T2 inflammation markers co-exist in the sputum of children with acute severe asthma attacks.

Vitamin D Status and Physical Activity during Wintertime in Forensic Inpatients-A Randomized Clinical Trial.

This study aimed to gain deeper knowledge about the relationship between vitamin D and physical activity in a sample of forensic inpatients. Sixty-seven male forensic inpatients participated. Participants were randomly assigned into an Intervention group (vitamin D) or a Control group (placebo). The Physical Activity-Rating (PA-R) questionnaire was used to measure physical activity from January to May. Vitamin D status was measured as 25-hydroxy vitamin D (25-OHD) pre- and post-intervention. The results revealed that vitamin D status at post-test was positively correlated with physical activity, but there was no effect of vitamin D supplementation looking at the two randomized groups. However, controlling for body mass index (BMI), the results showed an effect of BMI and a main effect of groups with a higher level of physical activity in the Intervention group. No interaction effects were found. Participants were also assigned into High and Low vitamin D groups based on the vitamin D status at post-test; i.e., the upper (75.1 nmol/L) and lower quartile (46.7 nmol/L). T-tests revealed that participants with a vitamin D status above 75 nmol/L showed significantly higher levels of physical activity than participants with a vitamin D status below 46.7 nmol/L. Thus, a vitamin D status above 75 nmol/L seems to be an optimal level.

Assembly and organization of the N-terminal region of mucin MUC5AC: Indications for structural and functional distinction from MUC5B.

Elevated levels of MUC5AC, one of the major gel-forming mucins in the lungs, are closely associated with chronic obstructive lung diseases such as chronic bronchitis and asthma. It is not known, however, how the structure and/or gel-making properties of MUC5AC contribute to innate lung defense in health and drive the formation of stagnant mucus in disease. To understand this, here we studied the biophysical properties and macromolecular assembly of MUC5AC compared to MUC5B. To study each native mucin, we used Calu3 monomucin cultures that produced MUC5AC or MUC5B. To understand the macromolecular assembly of MUC5AC through N-terminal oligomerization, we expressed a recombinant whole N-terminal domain (5ACNT). Scanning electron microscopy and atomic force microscopy imaging indicated that the two mucins formed distinct networks on epithelial and experimental surfaces; MUC5B formed linear, infrequently branched multimers, whereas MUC5AC formed tightly organized networks with a high degree of branching. Quartz crystal microbalance-dissipation monitoring experiments indicated that MUC5AC bound significantly more to hydrophobic surfaces and was stiffer and more viscoelastic as compared to MUC5B. Light scattering analysis determined that 5ACNT primarily forms disulfide-linked covalent dimers and higher-order oligomers (i.e., trimers and tetramers). Selective proteolytic digestion of the central glycosylated region of the full-length molecule confirmed that MUC5AC forms dimers and higher-order oligomers through its N terminus. Collectively, the distinct N-terminal organization of MUC5AC may explain the more adhesive and unique viscoelastic properties of branched, highly networked MUC5AC gels. These properties may generate insight into why/how MUC5AC forms a static, "tethered" mucus layer in chronic muco-obstructive lung diseases.

Mucus.

Mucus is a slimy hydrogel that lines the mucosal surfaces in our body, including the intestines, stomach, eyes, lungs and urogenital tract. This glycoprotein-rich network is truly the jack of all trades. As a barrier, it lubricates surfaces, protects our cells from physical stress, and selectively allows the passage of nutrients while clearing out pathogens and debris. As a home to our microbiota, it supports a level of microbial diversity that is unattainable with most culture methods. As a reservoir of complex carbohydrate structures called glycans, it plays critical roles in controlling cell adhesion and signaling, and it alters the behavior and spatial distribution of microbes. On top of all this, mucus regulates the passage of sperm during fertilization, heals wounds, helps us smell, and prevents the stomach from digesting itself, to name just a few of its functions. Given these impressive features, it is no wonder that mucus crosses boundaries of species and kingdoms - mucus gels are made by organisms ranging from the simplest metazoans to corals, snails, fish, and frogs. It is also no surprise that mucus is exploited in everyday applications, including foods, cosmetics, and other products relevant to medicine and industry.