Validity and utility of urinary CXCL10/Cr immune monitoring in pediatric kidney transplant recipients

Individualized posttransplant immunosuppression is hampered by suboptimal monitoring strategies. To validate the utility of urinary CXCL10/Cr immune monitoring in children, we conducted a multicenter prospective observational study in children <21 years with serial and biopsy-associated urine samples (n = 97). Biopsies (n = 240) were categorized as normal (NOR), rejection (>i1t1; REJ), indeterminate (IND), BKV infection, and leukocyturia (LEU). An independent pediatric cohort of 180 urines was used for external validation. Ninety-seven patients aged 11.4 ± 5.5 years showed elevated urinary CXCL10/Cr in REJ (3.1, IQR 1.1, 16.4; P < .001) and BKV nephropathy (median = 5.6, IQR 1.3, 26.9; P < .001) vs. NOR (0.8, IQR 0.4, 1.5). The AUC for REJ vs. NOR was 0.76 (95% CI 0.66–0.86). Low (0.63) and high (4.08) CXCL10/Cr levels defined high sensitivity and specificity thresholds, respectively; validated against an independent sample set (AUC = 0.76, 95% CI 0.66–0.86). Serial urines anticipated REJ up to 4 weeks prior to biopsy and declined within 1 month following treatment. Elevated mean CXCL10/Cr was correlated with first-year eGFR decline (ρ = −0.37, P ≤ .001), particularly when persistently exceeding ≥4.08 (ratio = 0.81; P < .04). Useful thresholds for urinary CXCL10/Cr levels reproducibly define the risk of rejection, immune quiescence, and decline in allograft function for use in real-time clinical monitoring in children.     

Sex-Positivity,Medical Mistrust,and PrEP Conspiracy Beliefs Among HIV-Negative Cisgender Black Sexual Minority Men in Atlanta,Georgia

Because the public health response to the disproportionate HIV burden faced by Black sexual minority men (BSMMM) has focused on sexual risk reduction and disease prevention, other vital components of sexual health (e.g., intimacy, pleasure, benefits of sex) have been often overlooked. Sex-positive describes a more open, holistic approach toward sex and sexuality that prioritizes these other components, though such an approach is rarely applied to BSMM's sexual health. For sex-positive BSMM, risk/preventive discourse may foster or exacerbate medical mistrust as a reaction to the dissonance between how these men view sexual health and how the medical establishment views it, which may discourage sexual healthcare-seeking. We assessed sex-positivity and its association with medical mistrust and PrEP conspiracy beliefs among 206 HIV-negative cisgender BSMM in Atlanta, Georgia. We performed exploratory factor analytic procedures on responses to a sex-positivity scale, followed by multivariable linear regressions to determine sex-positivity’s associations with medical mistrust and PrEP conspiracy beliefs. We extracted two sex-positivity factors: sexual freedom (α?=?0.90), reflecting openness toward casual sex and rejection of sexual mores, and essence of sex (α?=?0.77), reflecting the intimate, relational, and pleasurable qualities of sex. Sexual freedom was independently associated with perceived provider deception (β?=?0.19, CI?=?0.04, 0.34). Essence of sex was independently associated with PrEP conspiracy beliefs (β?=?0.16, CI?=?0.02, 0.31) and marginally associated with perceived provider deception (β?=?0.14, CI?=???0.00, 0.29). Healthcare providers and public health practitioners may cultivate greater trust with BSMM by incorporating a sex-positive approach into patient/participant interactions, clinical decision-making, and interventions. Improving access to sexual pleasure acknowledges BSMM’s right to optimal, holistic sexual health.

     

Toward A Typology of Identity Gaps in “Non-Normative” Sexual Partner Communication

Archives of Sexual Behavior - The present study presents a typology of identity gaps (Hecht, 1993), or cognitive, affective, and behavioral discrepancies between and among different parts of the...     

Black–white racial disparities in household food insecurity from 2005 to 2014, Canada

ObjectivesTo understand the differential vulnerability to household food insecurity of the Black population as compared with white counterparts in Canada.MethodsUsing data for households with Black and white respondents in pooled Canadian Community Health Survey cycles from 2005 to 2014, the 18-question Household Food Security Survey Module was analyzed (N = 491,400). Bivariate and multivariate logistic and multinomial regression models were run using respondent’s race, immigration status, and six well-established predictors of household food insecurity in the general population. Additional multivariable logistic regression models were run, with race interacted with each predictor individually to yield predicted probabilities.ResultsThe weighted prevalence of household food insecurity was 10.0% for white respondents and 28.4% for Black respondents. The odds of Black households being food-insecure as compared with white households fell from 3.56 (95% CI: 3.30–3.85) to 1.88 (95% CI: 1.70–2.08) with adjustment for household socio-demographic characteristics. In contrast with white households, there was relative homogeneity of risk of food insecurity among Black subgroups defined by immigration status, household composition, education, and province of residence. Homeownership was associated with lower probabilities of food insecurity for Black and white households, but the probability among Black owners was similar to that for white renters (14.7% vs. 14.3%). Black households had significantly higher predicted probabilities of food insecurity than their white counterparts across all main sources of household income except child benefits and social assistance.ConclusionBeing racialized as Black appears to be an overriding factor shaping vulnerability to food insecurity for the Black population in Canada. Future research and public policy on food insecurity should seriously consider the role of racism at the systemic and institutional levels.     

Extracellular vesicles released from irradiated neonatal mouse cheek tissue increased cell survival after radiation

Alopecia is one of the common symptoms after high-dose radiation exposure. In our experiments, neonatal mice that received 7 Gy X-ray exhibited defects in overall hair growth, except for their cheeks. This phenomenon might suggest that some substances were secreted and prevented hair follicle loss in the infant tissues around their cheeks after radiation damage. In this study, we focused on exosome-like vesicles (ELV) secreted from cheek skin tissues and back skin tissues, as control, and examined their radiation protective effects on mouse fibroblast cell lines. We observed that ELV from irradiated cheek skin showed protective effects from radiation. Our results suggest that ELV from radiation-exposed cheek skin tissue is one of the secreted factors that prevent hair follicle loss after high-dose radiation.     

A new species of Stephanostomum Looss, 1899 (Digenea, Acanthocolpidae) with a bizarre oral sucker: S. adlardi sp. nov. from the common coral trout Plectropomus leopardus (Lacepède, 1802) (Perciformes, Serranidae) from Lizard Island, Great Barrier Reef

A new species of Acanthocolpidae, Stephanostomum adlardi is described from the serranid Plectropomus leopardus from Lizard Island in the northern Great Barrier Reef. It differs from all previously described acanthocolpids in the structure of the oral sucker which is extended into dorsal and ventral lobes each bearing a row of spines. A phylogenetic tree estimated from combined nuclear small and partial large ribosomal RNA gene sequences shows that, despite the unusual oral sucker structure, the species is a true member of the genus Stephanostomum. The molecular results also suggest that Monostephanostomum nolani is derived from within Stephanostomum.     

Chromatin architectural proteins

The accessibility of eukaryotic DNA is dependent upon the hierarchical level of chromatin organization. These include (1) intra-nucleosome interactions, (2) inter-nucleosome interactions and (3) the influence of non-histone chromatin architectural proteins. There appears to be interplay between all these levels, in that one level can override another or that two or more can act in concert. In the first level, the stability of the nucleosome itself is dependent on the number and type of contacts between the core histones and the surrounding DNA, as well as protein–protein interactions within the core histone octamer. Core histone variants, post-translational modifications of the histones, and linker histones binding to the DNA all influence the organization and stability of the nucleosome. When nucleosomes are placed end-to-end in linear chromatin arrays, the second level of organization is revealed. The amino terminal tails of the histone proteins make contacts with adjacent and distant nucleosomes, both within the fiber and between different fibers. The third level of organization is imposed upon these ‘intrinsic’ constraints, and is due to the influence of chromatin binding proteins that alter the architecture of the underlying fiber. These chromatin architectural proteins can, in some cases, bypass intrinsic constraints and impart their own topological affects, resulting in truly unique, supra-molecular assemblages that undoubtedly influence the accessibility of the underlying DNA. In this review we will provide a brief summary of what has been learned about the intrinsic dynamics of chromatin fibers, and survey the biology and architectural affects of the handful of chromatin architectural proteins that have been identified and characterized. These proteins are likely only a small subset of the architectural proteins encoded within the eukaryotic genome. We hope that an increased understanding and appreciation of the contribution of these proteins to genome accessibility will hasten the identification and characterization of more of these important regulatory factors.     

Effects of lorazepam upon recollective experience in recognition memory

The effects of lorazepam (2 mg) and placebo upon recognition memory with and without conscious recollection were assessed in a cross-over study with normal volunteers. When recognising a word from study lists presented before and 1, 3 and 5 h after drug administration, subjects were required to indicate whether they could consciously recollect the word's prior occurrence or recognised it on the basis of knowing; in the absence of conscious recollection. Lorazepam only impaired word recognition which was accompanied by conscious recollection, and further, the level of this impairment correlated significantly with each of three different indices of subjects' arousal at the time of presentation of each list. Recognition in the absence of conscious recollection was not impaired but somewhat heightened by lorazepam, and these effects did not significantly relate to any index of arousal. These findings are interpreted as providing further support for the notion that recognition entails two distinct components, one based on contextual and associative information and related to conscious recollection, the other possibly based on a traceless perceptual or semantic memory system and related to feelings of knowing in the absence of conscious recollection. Implications are drawn for a contextual-encoding/retrieval account of lorazepam-induced amnesia.     

Interactions between imidazoline compounds and sulphonylureas in the regulation of insulin secretion

1. Imidazoline α₂-antagonist drugs such as efaroxan have been shown to increase the insulin secretory response to sulphonylureas from rat pancreatic B-cells. We have investigated whether this reflects binding to an islet imidazoline receptor or whether α₂-adrenoceptor antagonism is involved.
2. Administration of (±)-efaroxan or glibenclamide to Wistar rats was associated with a transient increase in plasma insulin. When both drugs were administered together, the resultant increase in insulin levels was much greater than that obtained with either drug alone.
3. Use of the resolved enantiomers of efaroxan revealed that the ability of the compound to enhance the insulin secretory response to glibenclamide resided only in the α₂-selective-(+)-enantiomer; the imidazoline receptor-selective-(−)-enantiomer was ineffective.
4. In vitro, (+)-efaroxan increased the insulin secretory response to glibenclamide in rat freshly isolated and cultured islets of Langerhans, whereas (−)-efaroxan was inactive. By contrast, (+)-efaroxan did not potentiate glucose-induced insulin secretion but (−)-efaroxan induced a marked increase in insulin secretion from islets incubated in the presence of 6 mM glucose.
5. Incubation of rat islets under conditions designed to minimize the extent of α₂-adrenoceptor signalling (by receptor blockade with phenoxybenzamine; receptor down-regulation or treatment with pertussis toxin) abolished the capacity of (+)-and (±)-efaroxan to enhance the insulin secretory response to glibenclamide. However, these manoeuvres did not alter the ability of (±)-efaroxan to potentiate glucose-induced insulin secretion.
6. The results indicate that the enantiomers of efaroxan exert differential effects on insulin secretion which may result from binding to effector sites having opposite stereoselectivity. Binding of (−)-efaroxan (presumably to imidazoline receptors) results in potentiation of glucose-induced insulin secretion, whereas interaction of (+)-efaroxan with a second site leads to selective enhancement of sulphonylurea-induced insulin release.