Association Between Composite Dietary Antioxidant Index and Cognitive Function Among Aging Americans from NHANES 2011-2014.

Background: Antioxidant diets are considered to be protective factors for cognitive function. However, comprehensive measures of antioxidant diets are lacking. Objective: To examine the association between the Composite Dietary Antioxidant Index (CDAI) and cognitive function in the elderly. Methods: This cross-sectional study included a total of 2,456 participants (≥60 years old) from NHANES 2011-2014. Calculation of CDAI based on 6 minerals and vitamins (manganese, selenium, zinc, vitamins A, C, and E). Cognitive function was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning sub-test, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). We also created a composite cognitive z-score to represent global cognition. The statistical analyses we used included multiple linear regression analyses, subgroup analyses, curve-fitting analyses, and threshold effects analyses. Results: After controlling for demographic characteristics, lifestyle factors, and disease history, multivariate linear regression analyses showed that increased CDAI was positively associated with scores on global cognitive function and each cognitive domain (p < 0.05), with subgroup analyses suggesting that this association was more pronounced in stroke patients (p for interaction < 0.05). Curve-fitting analyses and threshold effect analyses showed saturation effects between CDAI and CREAD Test, AFT, and composite Z-score, and an inverted U-shaped relationship with DSST, with inflection points of -1.89, 0.79, 1.13, and 1.77, respectively. Conclusions: Our findings support that higher levels of CDAI are correlated with significantly elevated cognitive function. Maintaining CDAI in an appropriate range may contribute to cognitive health in elderly.

Race, disadvantage, and violence: A spatial exploration of macrolevel covariates of police-involved homicides within and between US counties.

Efforts to explore the macrolevel determinants of police-involved homicides have expanded in recent years due in part to increased scrutiny and media attention to such events, and increased data availability of these events through crowdsourced databases. However, little empirical research has examined the spatial determinants of such events. The present study extends the extant macrolevel research on police-involved homicides by employing an underutilized spatial econometric model, the spatial Durbin model (SDM), to assess the direct and indirect county effects of racial threat, economic threat, social disorganization, and community violence on police killings within and between US counties from 2013 through 2020. Results indicate a direct inverse relationship between racial threat and police-involved homicides, no support for economic threat, and a direct positive association with two measures of social disorganization. Additionally, we find firearm availability exhibits significant direct and indirect spatial dependence on focal county police-involved homicides, reflecting spatial spillover processes. In essence, as firearm availability in neighboring counties increases, police-involved homicides within a focal county increase. The implications of these findings for racial threat, economic threat, social disorganization, and community violence are discussed.

KLF7 promotes colon adenocarcinoma progression through the PDGFB signaling pathway.

Colon adenocarcinoma (COAD) is the most common malignancy of the digestive tract, which is characterized by a dismal prognosis. No effective treatment has been established presently, thus there is an urgent need to understand the mechanisms driving COAD progression in order to develop effective therapeutic approaches and enhance clinical outcomes. In this study, we found that KLF7 is overexpressed in COAD tissues and correlated with clinicopathological features of COAD. Both gain-of-function and loss-of-function experiments have unequivocally demonstrated that overexpression of KLF7 promotes the growth and metastasis of COAD in vitro and in vivo, while KLF7 knockdown attenuated these effects. Mechanistically, our findings reveal that KLF7 can specifically bind to the promoter region of PDGFB (TGGGTGGAG), thus promoting the transcription of PDGFB and increasing its secretion. Subsequently, secreted PDGFB facilitates the progression of COAD by activating MAPK/ERK, PI3K/AKT, and JAK/STAT3 signaling pathways through PDGFRß. Additionally, we found that sunitinib can block PDGFB signaling and inhibit COAD progression, offering a promising therapeutic strategy for COAD treatment.

Integrated Multi-omics Analyses Identify CDCA5 as a Novel Biomarker Associated with Alternative Splicing, Tumor Microenvironment, and Cell Proliferation in Colon Cancer Via Pan-cancer Analysis.

Background: CDCA5 has been reported as a gene involved in the cell cycle, however current research provides little details. Our goal was to figure out its functions and probable mechanisms in pan-cancer. Methods: Pan-cancer bulk sequencing data and web-based analysis tools were applied to analyze CDCA5's correlations with the gene expression, clinical prognosis, genetic alterations, promoter methylation, alternative splicing, immune checkpoints, tumor microenvironment and enrichment. Real­time PCR, cell clone formation assay, CCK-8 assay, cell proliferation assay, migration assay, invasion assay and apoptosis assay were used to evaluate the effect of CDCA5 silencing on colon cancer cell lines. Results: CDCA5 is highly expressed in most tumors, which has been linked to a poor prognosis. Immune checkpoints analysis revealed that CDCA5 was associated with the immune gene CD276 in various tumors. Single-cell analysis showed that CDCA5 correlated with proliferating T cell infiltration in COAD. Enrichment analysis demonstrated that CDCA5 may modify cell cycle genes to influence p53 signaling. The examination of DLD1 cells revealed that CDCA5 increased the proliferation and blocked cell apoptosis. Conclusion: This study contributes to the knowledge of the role of CDCA5 in carcinogenesis, highlighting the prognostic potential and carcinogenic involvement of CDCA5 in pan-cancer.

An L-shaped association between composite dietary antioxidant index and stroke: Evidence from NHANES 2011-2020.

OBJECTIVES: Antioxidant diets are considered to be protective factors against stroke. However, comprehensive measurement and evaluation of antioxidant diets are lacking. This study aimed to investigate the correlation between the Composite Dietary Antioxidant Index (CDAI) and stroke in adults. MATERIALS AND METHODS: In this study, based on the National Health and Nutrition Examination Survey (NHANES) 2011-2020 data, multivariate logistic regression, smoothing curve fitting, and threshold effect analysis were used to explore the relationship between CDAI and stroke. Subgroup analyses and interaction tests were conducted to assess the stability of this association within the population. RESULTS: Among 12,922 U.S. adults, there was a significant negative correlation between CDAI and the prevalence of stroke. In the fully adjusted model, the risk of stroke was reduced by 4 % for each 1-unit increase in CDAI (OR [95% CI] = 0.96 [0.93, 0.99]). Participants in the highest quartile of the CDAI had a 37 % lower risk of stroke than those in the lowest quartile (OR [95% CI] = 0.63 [0.47, 0.84]). This negative correlation remained stable across subgroups. Furthermore, the study revealed an L-shaped association between CDAI and stroke through smoothing curve fitting. The threshold effect analysis further identified the inflection point as -1.55. CONCLUSIONS: This study revealed an L-shaped relationship between CDAI and stroke. Keeping CDAI in the proper range may help prevent stroke in the general population.

Spinal interleukin-16 mediates inflammatory pain via promoting glial activation.

Proinflammatory cytokines are crucial contributors to neuroinflammation in the development of chronic pain. Here, we identified il16, which encodes interleukin-16 (IL-16), as a differentially expressed gene in spinal dorsal horn of a complete Freund's Adjuvant (CFA) inflammatory pain model in mice by RNA sequencing. We further investigated whether and how IL-16 regulates pain transmission in the spinal cord and contributes to the development of inflammatory pain hypersensitivity. RNA sequencing and bioinformatics analysis revealed elevated IL-16 transcript levels in the spinal dorsal horn after CFA injection. This increase was further confirmed by qPCR, immunofluorescence, and western blotting. Knockdown of IL-16 by intrathecal injection of IL-16 siRNA not only attenuated CFA-induced mechanical and thermal pain hypersensitivity, but also inhibited enhanced c-fos expression and glial activation in the spinal dorsal horn in male mice injected with CFA. Moreover, exogenous IL-16 induced nociceptive responses and increased c-fos expression and glial activation in spinal dorsal horn. This effect was largely impaired when CD4, the binding receptor for IL-16, was inhibited. In addition, CD4 expression was upregulated in the spinal dorsal horn after CFA injection and CD4 was present in microglia and in contact with astrocytes and activated spinal neurons. Taken together, these results suggest that enhanced IL-16-CD4 signaling triggers pain and activates microglia and astrocytes in the spinal dorsal horn, thus contributing to inflammatory pain. IL-16 may serve as a promising target for the treatment of inflammatory pain.

Parental Perspectives on Barriers to Pediatric Oral Health Care: Associations with Children's And Families' Characteristics.

PURPOSE: The purpose of this study was to identify barriers to oral health services experienced by children and evaluate variation across demographic and socioeconomic population groups. METHODS: The data were collected from 1,745 parents/legal guardians who responded to a web-based survey regarding their children's access to health services in 2019. Descriptive statistics and binary and multinomial logistic models were used to examine barriers to needed dental care and factors contributing to differential experiences with those barriers. RESULTS: A quarter of children of responding parents experienced at least one barrier to oral health care, most commonly cost-related barriers. Child-guardian relationship type, having a pre-existing health condition, and dental insurance type increased the risk of encountering certain barriers two-to four-fold. Children with a diagnosed emotional, developmental, or behavioral condition (odds ratio [OR] equals 1.77, dental anxiety; OR equals 4.09, unavailability of needed services) and those with a Hispanic parent/guardian (OR equals 2.44, lack of insurance; OR equals 3.03, insurance not paying for needed services) were more likely to encounter various barriers than other children. The number of siblings, parent/guardian's age, education level, and oral health literacy were also associated with different barriers. The likelihood of encountering multiple barriers was over three times higher for children with a pre-existing health condition (OR equals 3.56; 95 percent confidence interval equals 2.30 to 5.50). CONCLUSIONS: This study highlighted the significance of cost-related barriers to oral health care and suggested disparities in access among children with disparate personal and family backgrounds.

Assessment of Diagnosis, Prognosis and Immune Infiltration Response to the Expression of the Ferroptosis-Related Molecule HAMP in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Hepcidin antimicrobial peptide (HAMP) is a key factor in maintaining iron metabolism, which may induce ferroptosis when upregulated. However, its prognostic value and relation to immune infiltrating cells remains unclear. METHODS: This study analyzed the expression levels of HAMP in the Oncomine, Timer and Ualcan databases, and examined its prognostic potential in KIRC with R programming. The Timer and GEPIA databases were used to estimate the correlations between HAMP and immune infiltration and the markers of immune cells. The intersection genes and the co-expression PPI network were constructed via STRING, R programming and GeneMANIA, and the hub genes were selected with Cytoscape. In addition, we analyzed the gene set enrichment and GO/KEGG pathways by GSEA. RESULTS: Our study revealed higher HAMP expression levels in tumor tissues including KIRC, which were related to poor prognosis in terms of OS, DSS and PFI. The expression of HAMP was positively related to the immune infiltration level of macrophages, Tregs, etc., corresponding with the immune biomarkers. Based on the intersection genes, we constructed the PPI network and used the 10 top hub genes. Further, we performed a pathway enrichment analysis of the gene sets, including Huntington's disease, the JAK-STAT signaling pathway, ammonium ion metabolic process, and so on. CONCLUSION: In summary, our study gave an insight into the potential prognosis of HAMP, which may act as a diagnostic biomarker and therapeutic target related to immune infiltration in KIRC.

A novel link between chronic inflammation and humanin regulation in children.

Objective: Children with inflammatory bowel disease (IBD) often suffer from poor bone growth and impaired bone health. Humanin is a cytoprotective factor expressed in bone and other tissues and we hypothesized that humanin levels are suppressed in conditions of chronic inflammation. To address this, humanin levels were analyzed in serum samples from IBD patients and in ex vivo cultured human growth plate tissue specimens exposed to IBD serum or TNF alone. Methods: Humanin levels were measured by ELISA in serum from 40 children with IBD and 40 age-matched healthy controls. Growth plate specimens obtained from children undergoing epiphysiodesis surgery were cultured ex vivo for 48 hours while being exposed to IBD serum or TNF alone. The growth plate samples were then processed for immunohistochemistry staining for humanin, PCNA, SOX9 and TRAF2 expression. Dose-response effect of TNF was studied in the human chondrocytic cell line HCS-2/8. Ex vivo cultured fetal rat metatarsal bones were used to investigate the therapeutic effect of humanin. Results: Serum humanin levels were significantly decreased in children with IBD compared to healthy controls. When human growth plate specimens were cultured with IBD serum, humanin expression was significantly suppressed in the growth plate cartilage. When cultured with TNF alone, the expression of humanin, PCNA, SOX9, and TRAF2 were all significantly decreased in the growth plate cartilage. Interestingly, treatment with the humanin analog HNG prevented TNF-induced bone growth impairment in cultured metatarsal bones. Conclusion: Our data showing suppressed serum humanin levels in IBD children with poor bone health provides the first evidence for a potential link between chronic inflammation and humanin regulation. Such a link is further supported by the novel finding that serum from IBD patients suppressed humanin expression in ex vivo cultured human growth plates.

TNF overexpression and dexamethasone treatment impair chondrogenesis and bone growth in an additive manner.

Children with chronic inflammation are often treated with glucocorticoids (GCs) and many of them experience growth retardation. It is poorly understood how GCs interact with inflammatory cytokines causing growth failure as earlier experimental studies have been performed in healthy animals. To address this gap of knowledge, we used a transgenic mouse model where human TNF is overexpressed (huTNFTg) leading to chronic polyarthritis starting from the first week of age. Our results showed that femur bone length and growth plate height were significantly decreased in huTNFTg mice compared to wild type animals. In the growth plates of huTNFTg mice, increased apoptosis, suppressed Indian hedgehog, decreased hypertrophy, and disorganized chondrocyte columns were observed. Interestingly, the GC dexamethasone further impaired bone growth, accelerated chondrocyte apoptosis and reduced the number of chondrocyte columns in huTNFTg mice. We conclude that TNF and dexamethasone separately suppress chondrogenesis and bone growth when studied in an animal model of chronic inflammation. Our data give a possible mechanistic explanation to the commonly observed growth retardation in children with chronic inflammatory diseases treated with GCs.

Precision Killing of Sinoporphyrin Sodium-Mediated Photodynamic Therapy against Malignant Tumor Cells.

Photodynamic therapy (PDT) has significant advantages in the treatment of malignant tumors, such as high efficiency, minimal invasion and less side effects, and it can preserve the integrity and quality of the organs. The power density, irradiation time and photosensitizer (PS) concentration are three main parameters that play important roles in killing tumor cells. However, until now, the underlying relationships among them for PDT outcomes have been unclear. In this study, human malignant glioblastoma U-118MG and melanoma A375 cells were selected, and the product of the power density, irradiation time and PS concentration was defined as the total photodynamic parameter (TPP), in order to investigate the mechanisms of PS sinoporphyrin sodium (DVDMS)-mediated PDT (DVDMS-PDT). The results showed that the survival rates of the U-118MG and A375 cells were negatively correlated with the TPP value in the curve, and the correlation exactly filed an e-exponential function. Moreover, according to the formula, we realized controllable killing effects of the tumor cells by randomly adjusting the three parameters, and we finally verified the accuracy and repeatability of the formula. In conclusion, the establishment and implementation of a newly functional relationship among the PDT parameters are essential for predicting PDT outcomes and providing personalized precise treatment, and they are contributive to the development of PDT dosimetry.

Multiple circRNAs regulated by QKI5 conjointly spongemiR-214-3p to antagonize bisphenol A-inducedspermatocyte toxicity.

Although circular RNAs (circRNAs) are found to play important roles in many pathophysiological processes, the canonical theory that they act as microRNA sponges is now more and more challenged, given that most circRNAs only have few binding sites in a particular microRNA. Our previous study revealed that some up-regulated circRNAs play protective roles in bisphenol A (BPA)-induced toxicity in GC-2 germ cells. Here by CCK-8 assay, apoptosis assay, qRT-PCR and western blot analysis, we further discover that circRNAs (represented by circDcbld2, circMapk1 and circTbcld20) can cooperatively sponge miR-214-3p and then up-regulate AKT1 in ameliorating BPA-induced reproductive toxicity. They share binding sites with miR-214-3p and collectively reinforce the sponging effects. In addition, the upstream regulation mechanism, proven by bioinformatics analysis and in vitro gain- and loss-of-function study, shows that down-regulation of RNA binding protein QKI5 after BPA exposure can increase the expressions of these protective circRNAs, and thus activate the cell protective process. The QKI5-circDcbld2/circMapk1/circTblcd20-miR-214-3p-AKT1 axis ameliorates the toxic effect of BPA on GC-2 cells. Many other circRNAs up-regulated upon BPA treatment and QKI5 down-regulation also show binding sites with miR-214-3p. Thus the above axis may also be extrapolated to other circRNAs. Our results enrich the context of circRNA sponge mode and may provide new ideas in future multiple nucleic acid therapy.

Highly efficient organic long persistent luminescence based on host-guest doping systems.

Recently, organic long persistent luminescence (OLPL) has attracted widespread attention as a new luminescence pathway initiated by the exciplex. However, the low quantum yield, few alternative molecules and high fabrication cost seriously slow down the development of OLPL materials. Herein, a series of simple multi-guest/host OLPL materials with a high quantum yield are reported by doping four phenothiazine derivative guest molecules into 9H-xanthen-9-one host matrices. The F-substituted phenothiazine derivative doping system displays highly efficient emission with 46.3% quantum yield in air. Meanwhile, these OLPL materials provide broad opportunities for further application in the field of heat resistance due to their highly efficient luminescence at high temperatures.

A sensing platform based on zinc-porphyrin derinative in hexadecyl trimethyl ammonium bromide (CTAB) microemulsion for highly sensitive detection of theophylline.

A new porphyrin-based sensing platform in hexadecyl trimethyl ammonium bromide (CTAB) microemulsion is developed for highly sensitive detection of theophylline. In this sensing system, the zinc-porphyrin-cinnamic acid conjugate (Zn-TPPCA) works as fluorescence probe while theophylline can decrease fluorescence intensity of the probe. Further studies indicate the linear relationship between the fluorescence quenching value and the concentration of theophylline within a given range. And the introduction of CTAB microemulsion can greatly enhance sensibility and stability of this detecting system and facilitate the detection of theophylline. On the basis above, a highly sensitive sensing platform for theophylline is created with a low limit of detection (LOD) of 0.0083 µg mL-1 under the optimal detection conditions. And further application of this method in determination of commercially available theophylline preparation shows excellent results. Subsequent studies on quenching mechanism indicate that static quenching appears between Zn-TPPCA and theophylline. Therefore, this work provides not only a highly sensitive method for determination of theophylline but also further evidence for creation of biosensors for drugs with porphyrin derivatives.

Examining spatial inequality in COVID-19 positivity rates across New York City ZIP codes.

We aim to understand the spatial inequality in Coronavirus disease 2019 (COVID-19) positivity rates across New York City (NYC) ZIP codes. Applying Bayesian spatial negative binomial models to a ZIP-code level dataset (N = 177) as of May 31st, 2020, we find that (1) the racial/ethnic minority groups are associated with COVID-19 positivity rates; (2) the percentages of remote workers are negatively associated with positivity rates, whereas older population and household size show a positive association; and (3) while ZIP codes in the Bronx and Queens have higher COVID-19 positivity rates, the strongest spatial effects are clustered in Brooklyn and Manhattan.

Correlation between sleep characteristics and cognitive decline in the elderly people: A cross-sectional study in China.

STUDY OBJECTIVES: In this study, we conducted a cross-sectional analysis of the sleep characteristics in the elderly Chinese people to comprehensively investigate the association between sleep and cognitive function in the elderly people. We aimed to evaluate the most important demographic factors, conventional physiological indices and living habits that may influence sleep. METHODS: We surveyed 2901 elderly people (age ≥60 years old) face-to-face from 1 July to 31 December 2017, who were recruited from 17 communities of the Pudong New Area (Shanghai, China) by probability proportional to size. The Pittsburgh sleep quality index (PSQI) scale was used to describe the sleep features of each participant. Cognitive assessment was performed using the mini-mental state examination (MMSE) scale, Montreal cognitive assessment (MoCA) and the clinical dementia rating (CDR) scale. Those factors which potentially influence sleep and consequentially may impact cognition in the elderly people were evaluated, and the correlations of sleep characteristics and cognitive function were explored by the linear regression analysis. RESULTS: Altogether, there were 1287 (44.4%) people taking part in the investigation. Sleep quality was significantly correlated with MMSE and MoCA total scores. Healthy sleep (especially enough sleep) was correlated with better cognitive functions. Besides recognised relative factors (such as age, sex and living alone), the number of children was found to be a strong risk factor of poor sleep. Anxiety before sleep and light/noise interference significantly damaged sleep while an exercise routine was associated with better sleep. Moderate levels of reading, watching TV and household work were correlated with superior sleep quality. CONCLUSION: In conclusion, sleep characteristics correlate with cognitive decline in the elderly people, and they can be influenced by multiple demographic factors and living habits. To improve sleep quality, it may be important to change sleep environment, to be relax, to increase physical exercise and recreational activities moderately.

Androgen-dependent miR-125a-5p targets LYPLA1 and regulates global protein palmitoylation level in late-onset hypogonadism males.

Late-onset hypogonadism (LOH) is defined as a clinical and biochemical syndrome with multiple symptoms caused by testosterone deficiency in aging males. An in-depth exploration of the molecular mechanism underlying LOH development is insufficient. We previously identified miR-125a-5p as a dysregulated microRNA in LOH patients and potential diagnostic biomarker for LOH. The present study demonstrated that plasma miR-125a-5p was upregulated after testosterone supplementation in both LOH patients and castrated mice, and positively associated with the testosterone concentrations, suggesting direct regulation of miR-125a-5p expression by testosterone. Androgen response element in the promoter of miR-125a-5p was subsequently identified. Target gene screening and confirmation verified that LYPLA1, encoding acyl-protein thioesterase 1 which catalyzed protein depalmitoylation process, was a target gene of miR-125a-5p. Furthermore, in cells cultured with testosterone deprivation and organs from castrated mice, testosterone deficiency led to decreased global protein palmitoylation level. In aging males, global protein palmitoylation in peripheral blood showed a notable decline in LOH patients contrast to the normal elderly males. And the palmitoylation level was positively correlative with serum testosterone concentrations. Our results suggested that testosterone could regulate global palmitoylation level through miR-125a-5p/LYPLA1 signaling pathway. Given that protein palmitoylation is pivotal for protein function and constitutes the pathogenesis of various diseases, testosterone/miR-125a-5p/LYPLA1 may contribute to the molecular mechanism underlying multiple symptoms caused by testosterone deficiency in LOH patients, and aberrant global palmitoylation could be a potential biomarker for LOH.

The association of age-related differences in serum total testosterone and sex hormone-binding globulin levels with the prevalence of diabetes.

BACKGROUND: Age-related differences of sex hormones are traditionally considered detrimental to certain diseases particularly in middle-aged and elderly males, however, it is imprudent to conclude without elucidating the influences of other age-related pathophysiology apart from reproductive aging. We sought to examine serum testosterone and sex hormone-binding globulin (SHBG) levels from different decades of life and their associations with the prevalence of diabetes in each respective decade. MATERIALS AND METHODS: A total of 6296 males participated in this multicenter cross-sectional study, aged between 40-79 years. Information on diabetes and associated risk factors were obtained by questionnaires. Serum total testosterone (TT), SHBG and calculated free testosterone (fT) were determined. RESULTS: Age-related stable level of TT even with significantly lower level of fT did not result in a higher age-related odds of diabetes. Whereas, age-related higher SHBG level was associated with a lower age-related odds of diabetes [-5.88 % (p = 0.038), -14.28 % (p = 0.003) and -23.53 % (p = 0.001) for males aged 50-59, 60-69, 70-79 years, respectively]. Also, the combined age-related differences of TT and SHBG levels were found associated with a lower age-related odds of diabetes [-2.21 % (p = 0.040), -8.16 % (p = 0.025) and -14.37 % (p = 0.002) for males aged 50-59, 60-69, 70-79 years, respectively]. CONCLUSIONS: The differences in hormonal levels of each age group category showed a negative association with the prevalence of diabetes in middle-aged and elderly males, however, this association could be deterred in the presence of obesity.

Prisons as Schools: Inmates' Participation in Vocational and Academic Programs in Chinese Prisons.

Although the idea of criminal rehabilitation in China has a long history, research on offender rehabilitation in contemporary China is limited. Although Chinese scholars generally agree that rehabilitation through correctional education helps inmates with social reintegration and reduces recidivism, few have examined factors associated with prisoners' participation in such programs. Building on relevant theory and studies in Western societies, this study examines how Chinese prisoners' participation in vocational and academic programs is associated with a range of push and pull factors. Our research questions are addressed with binary and multinomial logistic regressions based on a unique prisoner data set collected in Zhejiang, China. Results show that some factors found to affect inmate participation in the West failed to demonstrate significant relationships with participation among Chinese prisoners. Furthermore, factors most significantly associated with participation appear to be incarceration related, such as prison visits, prison phone calls, and sentence lengths. We conclude with a discussion of the implications of our results.

Humanin is a novel regulator of Hedgehog signaling and prevents glucocorticoid-induced bone growth impairment.

Glucocorticoids (GCs) are frequently used to treat chronic disorders in children, including inflammation and cancer. Prolonged treatment with GCs is well known to impair bone growth, an effect linked to increased apoptosis and suppressed proliferation in growth plate chondrocytes. We hypothesized that the endogenous antiapoptotic protein humanin (HN) may prevent these effects. Interestingly, GC-induced bone growth impairment and chondrocyte apoptosis was prevented in HN overexpressing mice, HN-treated wild-type mice, and in HN-treated cultured rat metatarsal bones. GC-induced suppression of chondrocyte proliferation was also prevented by HN. Furthermore, GC treatment reduced Indian Hedgehog expression in growth plates of wild-type mice but not in HN overexpressing mice or HN-treated wild-type animals. A Hedgehog (Hh) antagonist, vismodegib, was found to suppress the growth of cultured rat metatarsal bones, and this effect was also prevented by HN. Importantly, HN did not interfere with the desired anti-inflammatory effects of GCs. We conclude that HN is a novel regulator of Hh signaling preventing GC-induced bone growth impairment without interfering with desired effects of GCs. Our data may open for clinical studies exploring a new possible strategy to prevent GC-induced bone growth impairment by cotreating with HN.-Zaman, F., Zhao, Y., Celvin, B., Mehta, H. H., Wan, J., Chrysis, D., Ohlsson, C., Fadeel, B., Cohen, P., Sävendahl, L. Humanin is a novel regulator of Hedgehog signaling and prevents glucocorticoid-induced bone growth impairment.