Dyskeratosis congenita (DC) is a heterogeneous inherited bone marrow failure and cancer predisposition syndrome in which germline mutations in telomere biology genes account for approximately one-half of known families. Hoyeraal Hreidarsson syndrome (HH) is a clinically severe variant of DC in which patients also have cerebellar hypoplasia and may present with severe immunodeficiency and enteropathy. We discovered a germline autosomal recessive mutation in RTEL1, a helicase with critical telomeric functions, in two unrelated families of Ashkenazi Jewish (AJ) ancestry. The affected individuals in these families are homozygous for the same mutation, R1264H, which affects three isoforms of RTEL1. Each parent was a heterozygous carrier of one mutant allele. Patient-derived cell lines revealed evidence of telomere dysfunction, including significantly decreased telomere length, telomere length heterogeneity, and the presence of extra-chromosomal circular telomeric DNA. In addition, RTEL1 mutant cells exhibited enhanced sensitivity to the interstrand cross-linking agent mitomycin C. The molecular data and the patterns of inheritance are consistent with a hypomorphic mutation in RTEL1 as the underlying basis of the clinical and cellular phenotypes. This study further implicates RTEL1 in the etiology of DC/HH and immunodeficiency, and identifies the first known homozygous autosomal recessive disease-associated mutation in RTEL1.
Patients with dyskeratosis congenita (DC), a rare inherited disease, are at very high risk of developing cancer and bone marrow failure. The clinical features of DC include nail abnormalities, skin discoloration, and white spots in the mouth. Patients with Hoyeraal-Hreidarsson syndrome (HH) have symptoms of DC plus cerebellar hypoplasia, immunodeficiency, and poor prenatal growth. DC and HH are caused by defects in telomere biology; improperly maintained telomeres are thought to be a major contributor to carcinogenesis. In half the cases of DC, the causative mutation is unknown. By studying families affected by DC for whom a causative mutation has not yet been identified, we have discovered a homozygous germline mutation in RTEL1, a telomere maintenance gene that, if mutated, can result in HH. The mutations result in the inability of the RTEL1 protein to function properly at the telomere, and underscore its important role in telomere biology.
Blast-induced traumatic brain injury has emerged as a “signature injury” in combat casualty care. Present combat helmets are designed primarily to protect against ballistic and blunt impacts, but the current issue with helmets is protection concerning blasts. In order to delineate the blast wave attenuating capability of the Advanced Combat Helmet (ACH), a finite element (FE) study was undertaken to evaluate the head response against blast loadings with and without helmet using a partially validated FE model of the human head and ACH. Four levels of overpressures (0.27–0.66 MPa) from the Bowen’s lung iso-damage threshold curves were used to simulate blast insults. Effectiveness of the helmet with respect to head orientation was also investigated. The resulting biomechanical responses of the brain to blast threats were compared for human head with and without the helmet. For all Bowen’s cases, the peak intracranial pressures (ICP) in the head ranged from 0.68 to 1.8 MPa in the coup cortical region. ACH was found to mitigate ICP in the head by 10–35%. Helmeted head resulted in 30% lower average peak brain strains and product of strain and strain rate. Among three blast loading directions with ACH, highest reduction in peak ICP (44%) was due to backward blasts whereas the lowest reduction in peak ICP and brain strains was due to forward blast (27%). The biomechanical responses of a human head to primary blast insult exhibited directional sensitivity owing to the different geometry contours and coverage of the helmet construction and asymmetric anatomy of the head. Thus, direction-specific tolerances are needed in helmet design in order to offer omni-directional protection for the human head. The blasts of varying peak overpressures and durations that are believed to produce the same level of lung injury produce different levels of mechanical responses in the brain, and hence “iso-damage” curves for brain injury are likely different than the Bowen curves for lung injury.
traumatic brain injury; primary blast; finite element model; advanced combat helmet model; human head model; intracranial pressure; brain strain and strain rate; head protection
Wait times in cancer diagnosis and treatment may significantly affect a patient’s treatment outcome, prognosis and quality of life. The purpose of this study was to capture wait time intervals for patients with prostate cancer treated with radiotherapy (RT) at the Odette Cancer Centre, Toronto, Ontario, Canada and to compare patients diagnosed in a rapid diagnostic unit (RDU) versus the usual community referral process.
Patients agreed to participate in the study during their RT planning sessions. A semi-structured interview and chart abstraction was conducted to record key wait time milestones.
A total of 87 patients participated in the study: 44 RDU patients and 43 community patients. The median overall wait time intervals from suspicion of prostate cancer to RT was 138 and 183 days, respectively (p = 0.046). There were statistically significant differences observed for other key wait time intervals favouring the RDU cohort: suspicion to decision-to-treat (DTT; p = 0.012), urologist visit to diagnosis (p = 0.0094), diagnosis to DTT (p = 0.018), and diagnosis to treatment (p = 0.016). Risk category and Gleason sum was independently predictive of longer intervals from diagnosis to DTT.
Wait time intervals from suspicion to treatment are significantly shorter for prostate cancer patients in 2011 to 2012 than in 2003 when patients were diagnosed and referred in the community setting. A prostate-specific RDU further reduced a number of key wait time intervals supporting more multidisciplinary RDUs for common diseases. Further work needs to be done to identify why delays are occurring and to develop new processes to minimize delays.
To assess the relative importance of four different measures of HIV-related stigma in predicting psychological problems among children affected by HIV in rural China.
Cross-sectional data were collected from 755 orphans (i.e., children who lost one or both of their parents to HIV), 466 vulnerable children (children who were living with HIV-infected parents), and 404 comparison children who were from the same community and did not have HIV-related illness or death in their families. Four HIV-related stigma measures include perceived public stigma against people living with HIV/AIDS (PLWHA), perceived public stigma against children affected by HIV (orphans and vulnerable children), personal stigmatizing attitudes against PLWHA, and enacted stigma among children affected by HIV. Psychological problems included depression and adjustment problems.
Various measures of HIV-related stigma independently and differentially contribute to children psychological problems. Enacted stigma and children's perceived public stigma against PLWHA or children affected by HIV are generally stronger predictors of psychological problems than their own feelings or attitudes towards PLWHA.
Various aspects of HIV-related stigma are important for us to understand the perception, attitudes, and experience of children affected by HIV, including both children experiencing HIV-related parental illness and death in their own family and children who were living in the communities hardly hit by HIV. Future health promotion and psychological care efforts for children affected by HIV need to consider the effect of various forms of HIV-related stigma on these children's psychosocial well-being and mobilize the community resources to mitigate the negative effect of HIV-related stigma on PLWHA and their children.
Perceived stigma; Personal stigma; Enacted stigma; HIV; Children; China
The mechanism by which endogenous progenitor cells contribute to functional and beneficial effects in stem cell therapy remains unknown.
Utilizing a novel 31P magnetic resonance spectroscopy–2-dimensional chemical shift imaging method, this study examined the heterogeneity and bioenergetic consequences of postinfarction left ventricular (LV) remodeling and the mechanisms of endogenous progenitor cell contribution to the cellular therapy.
Methods and Results
Human embryonic stem cell–derived vascular cells (hESC-VCs) that stably express green fluorescent protein and firefly luciferase (GFP+/Luc+) were used for the transplantation. hESC-VCs may release various cytokines to promote angiogenesis, prosurvival, and antiapoptotic effects. Both in vitro and in vivo experiments demonstrated that hESC-VCs effectively inhibit myocyte apoptosis. In the mouse model, a fibrin patch–based cell delivery resulted in a significantly better cell engraftment rate that was accompanied by a better ejection fraction. In the swine model of ischemia-reperfusion, the patch-enhanced delivery of hESC-VCs resulted in alleviation of abnormalities including border zone myocardial perfusion, contractile dysfunction, and LV wall stress. These results were also accompanied by a pronounced recruitment of endogenous c-kit+ cells to the injury site. These improvements were directly associated with a remarkable improvement in myocardial energetics, as measured by a novel in vivo 31P magnetic resonance spectroscopy–2-dimensional chemical shift imaging technology.
The findings of this study demonstrate that a severely abnormal heterogeneity of myocardial bioenergetics in hearts with postinfarction LV remodeling can be alleviated by the hESC-VCs therapy. These findings suggest an important therapeutic target of peri-scar border zone and a promising therapeutic potential for using hESC-VCs together with the fibrin patch–based delivery system.
myocardial infarction; stem cells; metabolism; ischemia; swine
Clear cell renal cell carcinoma (ccRCC) is the major and aggressive subtype of renal cell carcinoma. It is known to derive its histologic appearance from accumulation of abundant lipids and glycogens. The cell death-inducing DFF45-like effector (CIDE) family has been characterized as the lipid droplet proteins involved in the metabolism of lipid storage droplets. The purpose of this study was to evaluate the expression of CIDE proteins in ccRCC cells and to investigate their prognostic significance. We examined consecutive patients with sporadic ccRCC, who underwent nephrectomy, to measure their mRNA and protein expression of CIDE proteins. We found that Cidec and ADRP expression were significantly up-regulated in ccRCC, compared with normal kidney tissues. Cideb was down-regulated. We also found that Cideb was expressed more in low-grade ccRCC than in high-grade tumors. To further clarify the relationship between Cideb expression and patient prognosis, we evaluated 57 ccRCC patients followed up for 120 months. Reduced ccRCC Cideb expression was associated with a higher Fuhrman nuclear grade. Patients with high Cideb expression had better overall survival rate than those with low expression (p < 0.05). Cideb expression was an independent predictor of survival (p = 0.001). Although the biologic function of Cideb in ccRCC remains unknown, the expression level of Cideb might be a novel predictor of prognosis in ccRCC.
Electronic supplementary material
The online version of this article (doi:10.1007/s11010-013-1605-y) contains supplementary material, which is available to authorized users.
Cideb; Lipid droplet; Clear cell renal cell carcinoma; Metabolism
The genetics of lymphoma susceptibility reflect the marked heterogeneity of diseases that comprise this broad phenotype. However, multiple subtypes of lymphoma are observed in some families, suggesting shared pathways of genetic predisposition to these pathologically distinct entities. Using a two-stage GWAS, we tested 530,583 SNPs in 944 cases of lymphoma, including 282 familial cases, and 4,044 public shared controls, followed by genotyping of 50 SNPs in 1,245 cases and 2,596 controls. A novel region on 11q12.1 showed association with combined lymphoma (LYM) subtypes. SNPs in this region included rs12289961 near LPXN, (PLYM = 3.89×10−8, OR = 1.29) and rs948562 (PLYM = 5.85×10−7, OR = 1.29). A SNP in a novel non-HLA region on 6p23 (rs707824, PNHL = 5.72×10−7) was suggestive of an association conferring susceptibility to lymphoma. Four SNPs, all in a previously reported HLA region, 6p21.32, showed genome-wide significant associations with follicular lymphoma. The most significant association with follicular lymphoma was for rs4530903 (PFL = 2.69×10−12, OR = 1.93). Three novel SNPs near the HLA locus, rs9268853, rs2647046, and rs2621416, demonstrated additional variation contributing toward genetic susceptibility to FL associated with this region. Genes implicated by GWAS were also found to be cis-eQTLs in lymphoblastoid cell lines; candidate genes in these regions have been implicated in hematopoiesis and immune function. These results, showing novel susceptibility regions and allelic heterogeneity, point to the existence of pathways of susceptibility to both shared as well as specific subtypes of lymphoid malignancy.
B-cell lymphomas comprise several diseases representing aberrant proliferations of immune cells at various stages of maturation. It might be expected that dissimilar subtypes of lymphoma will have different etiologic and pathogenic mechanisms, reflecting the distinct histologic and clinical characteristics of these diseases. This study aims to define both shared as well as specific genetic risk factors for lymphoma. Utilizing a genome-wide approach, we discovered novel locations in the genome associated with risk for lymphoid malignancies. Common variants in these regions, on chromosome 11q12.1 and 6p23, were each associated with a modest modification of risk for lymphoma. These regions harbor several genes of biological importance in lymphoid maturation and function. We also further characterized the HLA region at 6p21.32, previously associated with lymphoma risk and thought to be important in immune function. Some of the associated SNP markers were specific for one common subtype of lymphoma, e.g. follicular lymphoma. However, others were associated with combined subsets of disease, suggesting that there are both shared and subtype-specific associations between common genetic variants and human lymphoid cancer. Secondary analyses showed that the two novel regions harbor candidates that are biologically relevant and that regulate cell development and hematopoiesis.
In this paper, we have reported that paper-like graphene-Ag composite films could be prepared by a facile and novel chemical reduction method at a large scale. Using ascorbic acid as a reducing agent, graphene oxide films dipped in Ag+ aqueous solutions can be easily reduced along with the decoration of different sizes of Ag particles distributed uniformly. The results reveal that the obtained films exhibit improved mechanical properties with the enhancement of tensile strength and Young's modulus by as high as 82% and 136%, respectively. The electrical properties of graphene-Ag composite films were studied as well, with the sheet resistance of which reaching lower than approximately 600 Ω/□. The graphene-Ag composite films can be expected to find interesting applications in the area of nanoelectronics, sensors, transparent electrodes, supercapacitors, and nanocomposites.
Graphene; Ag particles; Composite films; Graphene oxide; In situ reduction; Graphene paper; Electrical properties; Mechanical properties
Perhaps one of the most significant achievements in modern science is the discovery of human induced pluripotent stem cells (hiPSCs), which have paved the way for regeneration therapy using patients’ own cells. Cardiomyocytes differentiated from hiPSCs (hiPSC-CMs) could be used for modelling patients with heart failure, for testing new drugs, and for cellular therapy in the future. However, the present cardiomyocyte differentiation protocols exhibit variable differentiation efficiency across different hiPSC lines, which inhibit the application of this technology significantly. Here, we demonstrate a novel myocyte differentiation protocol that can yield a significant, high percentage of cardiac myocyte differentiation (>85%) in 2 hiPSC lines, which makes the fabrication of a human cardiac muscle patch possible. The established hiPSCs cell lines being examined include the transgene integrated UCBiPS7 derived from cord blood cells and non-integrated PCBC16iPS from skin fibroblasts. The results indicate that hiPSC-CMs derived from established hiPSC lines respond to adrenergic or acetylcholine stimulation and beat regularly for greater than 60 days. This data also demonstrates that this novel differentiation protocol can efficiently generate hiPSC-CMs from iPSC lines that are derived not only from fibroblasts, but also from blood mononuclear cells.
A modified Marmarou impact acceleration model was developed to study the mechanical responses induced by this model and their correlation to traumatic axonal injury (TAI). Traumatic brain injury (TBI) was induced in 31 anesthetized male Sprague-Dawley rats (392±13 g) by a custom-made 450-g impactor from heights of 1.25 m or 2.25 m. An accelerometer and angular rate sensor measured the linear and angular responses of the head, while the impact event was captured by a high-speed video camera. TAI distribution along the rostro-caudal direction, as well as across the left and right hemispheres, was determined using β-amyloid precursor protein (β-APP) immunocytochemistry, and detailed TAI injury maps were constructed for the entire corpus callosum. Peak linear acceleration 1.25 m and 2.25 m impacts were 666±165 g and 907±501 g, respectively. Peak angular velocities were 95±24 rad/sec and 124±48 rad/sec, respectively. Compared to the 2.25-m group, the observed TAI counts in the 1.25-m impact group were significantly lower. Average linear acceleration, peak angular velocity, average angular acceleration, and surface righting time were also significantly different between the two groups. A positive correlation was observed between normalized total TAI counts and average linear acceleration (R2=0.612, p<0.05), and time to surface right (R2=0.545, p<0.05). Our study suggested that a 2.25-m drop in the Marmarou model may not always result in a severe injury, and TAI level is related to the linear and angular acceleration response of the rat head during impact, not necessarily the drop height.
corpus callosum; head impact acceleration model; linear and angular head motion; rat; traumatic axonal injury
Doping an impure element with a larger atomic volume into crystalline structure of buck crystals is normally blocked because the rigid crystalline structure could not tolerate a larger distortion. However, this difficulty may be weakened for nanocrystalline structures. Diamonds, as well as many semiconductors, have a difficulty in effective doping. Theoretical calculations carried out by DFT indicate that vanadium (V) is a dopant element for the n-type diamond semiconductor, and their several donor state levels are distributed between the conduction band and middle bandgap position in the V-doped band structure of diamond. Experimental investigation of doping vanadium into nanocrystalline diamond films (NDFs) was first attempted by hot filament chemical vapor deposition technique. Acetone/H2 gas mixtures and vanadium oxytripropoxide (VO(OCH2CH2CH3)3) solutions of acetone with V and C elemental ratios of 1:5,000, 1:2,000, and 1:1,000 were used as carbon and vanadium sources, respectively. The resistivity of the V-doped NDFs decreased two orders with the increasing V/C ratios.
Nanocrystalline diamond; Vanadium dopant; Donor state levels; Structural distortion toleration
Mesenchymal stem cells (MSCs) are potent immunoregulators and have shown clinical utility in suppressing immunity. MSC function is modulated by cytokines, since inflammatory cytokines, such as IFNγ concomitant with TNFα, induce their immunoregulatory capability. Here, we show that IFNγ and TNFα act synergistically to induce high levels of expression of IL-6 and several other immune-related molecules in MSCs in vitro. We further found that, while either IFNγ or TNFα alone induced minor expression of C/EBPβ in MSCs, this transcription factor was dramatically upregulated when these cytokines were added together. A causal relationship between C/EBPβ upregulation and IL-6 expression was demonstrated by siRNA knockdown of C/EBPβ. C/EBPβ knockdown also inhibited the synergistic expression of CXCL1, iNOS, and CCL5 in response to concomitant IFNγ and TNFα . We conclude that C/EBPβ is a key transcription factor in synergistic gene upregulation by IFNγ and TNFα Importantly, C/EBPβ similarly mediated synergistic gene induction in response to IFNγ accompanied by IL-1β or LPS, suggesting that synergy between IFNγ and other stimuli share C/EBPβ as common mechanism. Furthermore, while STAT1 is critical in IFNγ signaling, we found that STAT1 knockdown in MSCs did not affect C/EBPβ expression or the synergistic induction of IL-6 and CXCL1 by IFNγ and TNFα. Thus, C/EBPβ is not regulated by STAT1. These results demonstrate the importance of cytokine interactions in MSC immunobiology, a better understanding of which will allow improved clinical application of these cells.
C/EBP beta; Mesenchymal stem cells; IFN-γ; TNF
When parents die of or are infected with HIV, children might have to leave their own household and be displaced to other living arrangement and some may even be displaced multiple times. The objective of this study is to examine the association between household displacement and health risk behaviors among AIDS orphans (children who have lost one or both of their parents to HIV/AIDS) and vulnerable children (children living with HIV-infected parents) in rural China.
The sample consisted of 1015 children (549 AIDS orphans, 466 vulnerable children) in family-based care. The children were assigned to three displacement groups according to the number of household displacement (i.e., none, once, at least twice) after their parents became ill or died of AIDS. Cigarette smoking, alcohol use, violence, public property destruction, suicidal ideation, and suicide attempt were used to assess the health risk behaviors of these children. Both bivariate and multivariate tests were used to assess the differences in health risk behaviors among displacement groups.
The findings indicated that children who were displaced at least twice were more likely to report a higher frequency of public property destruction and suicide ideation than those who were never displaced or displaced once. Multivariate analysis revealed that public property destruction, suicide ideation and suicide attempt were significantly associated with the household displacement among these children, controlling for gender, age, child status (AIDS orphans vs. vulnerable children) and the duration of household displacement.
Results in the current study suggest that a stable living environment was important for both AID orphans and vulnerable children in communities of high prevalence of HIV/AIDS. The government, community and other agencies need to make efforts to avoid frequent household displacement among these children after the HIV-related infection or death of their parents.
HIV/AIDS; Health risk behaviors; Children; Household displacement; China
Cu2O p-type semiconductor hollow porous microspheres have been prepared by using a simple soft-template method at room temperature. The morphology of as-synthesized samples is hollow spherical structures with the diameter ranging from 200 to 500 nm, and the surfaces of the spheres are rough, porous and with lots of channels and folds. The photocatalytic activity of degradation of methyl orange (MO) under visible light irradiation was investigated by UV-visible spectroscopy. The results show that the hollow porous Cu2O particles were uniform in diameters and have an excellent ability in visible light-induced degradation of MO. Meanwhile, the growth mechanism of the prepared Cu2O was also analyzed. We find that sodium dodecyl sulfate acted the role of soft templates in the synthesis process. The hollow porous structure was not only sensitive to the soft template but also to the amount of reagents.
Cu2O; Hollow porous microspheres; Photocatalytic; Visible light
Computer models of the head can be used to simulate the events associated with traumatic brain injury (TBI) and quantify biomechanical response within the brain. Marmarou’s impact acceleration rodent model is a widely used experimental model of TBI mirroring axonal pathology in humans. The mechanical properties of the low density polyurethane (PU) foam, an essential piece of energy management used in Marmarou’s impact device, has not been fully characterized. The foam used in Marmarou’s device was tested at seven strain rates ranging from quasi-static to dynamic (0.014 ~ 42.86 s−1) to quantify the stress-strain relationships in compression. Recovery rate of the foam after cyclic compression was also determined through the periods of recovery up to three weeks. The experimentally determined stress-strain curves were incorporated into a material model in an explicit Finite Element (FE) solver to validate the strain rate dependency of the FE foam model. Compression test results have shown that the foam used in the rodent impact acceleration model is strain rate dependent. The foam has been found to be reusable for multiple impacts. However the stress resistance of used foam is reduced to 70% of the new foam. The FU_CHANG_FOAM material model in an FE solver has been found to be adequate to simulate this rate sensitive foam.
rodent head impact acceleration device; traumatic brain injury; low density polyurethane foam; compression test; rate dependency; finite element modeling
We previously reported that the biological activity of analogues of desmosdumotin B (1) was dramatically changed depending on the B-ring system. A naphthalene B-ring analogue 3 exerted potent in vitro activity against a diverse panel of human tumor cell lines with GI50 values of 0.8–2.1 μM. In contrast, 1-analogues with a phenyl B-ring showed unique selective activity against P-glycoprotein (P-gp) overexpressing multidrug resistance cell line. We have now prepared and evaluated 1-analogues with bicyclic or tricyclic aromatic B-ring systems as in vitro inhibitors of human cancer cell line proliferation. Among all synthesized derivatives, 21 with a benzo[b]thiophenyl B-ring was highly active, with GI50 values of 0.06–0.16 μM, and this activity was not influenced by overexpression of P-gp. Furthermore, 21 inhibited tubulin assembly in vitro with an IC 50 value of 2.0 μM and colchicine binding by 78% as well as cellular microtubule polymerization and spindle formation.
There is an estimated 100 000 children orphaned by AIDS in China, but data on the care arrangement of these orphans are limited. In this study, we examine the relationship between AIDS orphans’ care arrangement and their psychosocial well-being among a sample of AIDS orphans in rural China. A total of 296 children who lost both parents to AIDS participated in the study, including 176 in orphanages, 90 in kinship care and 30 in community-based group homes. All participants completed a cross-sectional survey assessing their traumatic symptoms, physical health and schooling. Data reveal that the AIDS orphans in group homes reported the best outcomes in three domains of psychosocial well-being, followed by those in the orphanages and then the kinship care. The differences in psychosocial well-being among the three groups of children persist after controlling for key demographic characteristics. The findings suggest that the appropriate care arrangement for AIDS orphans should be evaluated within the specific social and cultural context where the orphans live. In resource-poor regions or areas stricken hardest by the AIDS epidemic, kinship care may not sufficiently serve the needs of AIDS orphans. Community-based care models, with appropriate government and community support preserving the family style and low child-to-caregiver ratio may constitute an effective and sustainable care model for the best interest of the AIDS orphans in developing countries.
AIDS orphans; care arrangement; psychosocial well-being; China; resource-poor regions
Previous studies suggested a rapid increase of HIV prevalence among MSM in China in recent years, from 0.4% in 2004 to 5.8% in 2008. However, some MSM had never been tested for HIV. In order to expand the accessibility to HIV testing, understanding HIV testing behavior and barriers among MSM is important. Using data collected from 307 young migrant MSM (aged 18–29 years) in 2009 in Beijing, we aimed to identify psychological and structural barriers to HIV testing. MSM were recruited through peer outreach, informal social networks, internet outreach, and venue-based outreach. Participants completed a confidential self-administered questionnaire. Results show that about 72% of MSM had ever had HIV testing. Logistic regression analysis indicated that the HIV testing behavior was associated with sexual risk behaviors (e.g., multiple sexual partners, inconsistent condom use for anal sex) and history of STDs. Eighty four MSM (28%) who had never had HIV testing reported that the psychological barriers mainly were perceived low risk of HIV infection and fears of being stigmatized. The structural barriers reported included inconvenience of doing test and lack of confidentiality. Future HIV prevention programs should be strengthened among MSM to increase their awareness of HIV risk. Efforts are needed to increase access to quality and confidential HIV testing among MSM and reduce stigma against MSM.
MSM; HIV testing; HIV Prevention; Stigma; China
The purpose of this study is to compare psychological symptoms among double AIDS orphans (i.e., children who lost both of their parents to HIV/AIDS) who were in the care of different family-based caregivers (i.e., surviving parent, grandparents, other relatives, & non-relatives) before they were replaced in orphanages.
The participants include 176 double AIDS orphans from four AIDS orphanages in rural China. Prior to being replaced in AIDS orphanages, these children had received family-based care by different caregivers, which included surviving parent (38%), grandparents (22%), other relatives (19%) and non-relatives (22%). The psychological measures include traumatic symptoms, depression, and loneliness. Both bivariate and multivariate analyses suggested that children who were previously cared for by non-relatives scored significantly higher in traumatic symptoms, depression and loneliness scales than children who were previously cared for by their surviving parent, grandparents, and other relatives. The children in the care of grandparents reported the best scores on all psychological measures among children in the care of non-parent relatives. Multivariate analysis, controlling for children’s gender, age, length in orphanages, number of household replacements, and total duration of replacement, revealed that the type of caregivers was significantly associated with psychological problems.
Results in the current study suggest that children under the care of their grandparents reported the best psychological outcomes when their parents were unable to care for them because of AIDS. Appropriate psychological support and counseling services are needed for AIDS orphans who were either currently or previously under non-relative family-based care in China.
China; AIDS orphans; psychological symptoms; family-based care
The controlled cortical impact (CCI) model has been extensively used to study region-specific patterns of neuronal injury and cell death after a focal traumatic brain injury. Although external parameters such as impact velocity and depth of penetration have been defined in this injury model, little is known about the intracranial mechanical responses within cortical and subcortical brain regions where neuronal loss is prevalent. At present, one of the best methods to determine the internal responses of the brain is finite element (FE) modeling. A previously developed and biomechanically validated detailed three-dimensional FE rat brain model, consisting of 255,700 hexahedral elements and representing all essential anatomical features of a rat brain, was used to study intracranial responses in a series of CCI experiments in which injury severity ranged from mild to severe. A linear relationship was found between the percentage of the neuronal loss observed in vivo and the FE model-predicted maximum principal strain (R2 = 0.602). Interestingly, the FE model also predicted some risk of injury in the cerebellum, located remote from the point of impact, with a 25% neuronal loss for the “severe” impact condition. More research is needed to examine other regions that do not have histological data for comparison with FE model predictions before this injury mechanism and the associated injury threshold can be fully established.
brain biomechanics; controlled cortical impact; finite element models; traumatic brain injury
In this study, we examine migrant stigma and its effect on social capital reconstruction among rural migrants who possess legal rural residence but live and work in urban China. After a review of the concepts of stigma and social capital, we report data collected through in-depth interviews with 40 rural migrant workers and 38 urban residents recruited from Beijing, China. Findings from this study indicate that social stigma against rural migrants is common in urban China and is reinforced through media, social institutions and their representatives, and day-to-day interactions. As an important part of discrimination, stigma against migrant workers creates inequality, undermines trust, and reduces opportunities for interpersonal interactions between migrants and urban residents. Through these social processes, social stigma interferes with the reconstruction of social capital (including bonding, bridging and linking social capital) for individual rural migrants as well as for their communities. The interaction between stigma and social capital reconstruction may present as a mechanism by which migration leads to negative health consequences. Results from this study underscore the need for taking measures against migrant stigma and alternatively work toward social capital reconstruction for health promotion and disease prevention among this population.
Social capital; Stigma; Rural migrants; China
(1) examine the psychometric properties of two parallel measures of HIV-related stigma (i.e., perceived public stigma and children’s personal stigma against PLWHA) among these children; (2) examine whether expressions of stigma measures differ by child’s sex, developmental stage, family SES, or orphanhood status (i.e., AIDS orphans, vulnerable children, and comparison children); and (3) examine the association between HIV-related stigma and children’s psychosocial adjustments among these children.
Cross-sectional data were collected from 755 AIDS orphans (children who had lost one or both their parents to AIDS), 466 vulnerable children who lived with HIV-infected parents, and 404 comparison children who did not experience HIV-related illness and death in their families. The measures included perceived public stigma, personal stigma, depressive symptoms, loneliness, self-esteem, future expectations, hopefulness about the future, and perceived control over the future.
Both stigma scales were positively associated with psychopathological symptoms (e.g., depression, loneliness) and negatively associated with psychosocial wellbeing (e.g., self-stigma, positive future expectation, hopefulness about future, and perceived control over the future). Both stigma measures contribute to children’s psychosocial problems independent of their orphanhood status and other key demographic factors.
Community-wide stigma reduction and psychological support should be part of the care efforts for children affected by AIDS. Stigma reduction efforts should not only target the stigma against PLWHA but also possible stigma against the entire community (e.g., villages) with a high prevalence of HIV/AIDS. The stigma reduction efforts also needs to be appropriate for children’s age, gender, family SES and AIDS experience in the family. Future research should explore individual and contextual factors such as social support, coping and attachment in mitigating the negative effect of stigma among these children.
Quantitative high-throughput screening (qHTS) assays are increasingly being used to inform chemical hazard identification. Hundreds of chemicals have been tested in dozens of cell lines across extensive concentration ranges by the National Toxicology Program in collaboration with the National Institutes of Health Chemical Genomics Center.
Our goal was to test a hypothesis that dose–response data points of the qHTS assays can serve as biological descriptors of assayed chemicals and, when combined with conventional chemical descriptors, improve the accuracy of quantitative structure–activity relationship (QSAR) models applied to prediction of in vivo toxicity end points.
We obtained cell viability qHTS concentration–response data for 1,408 substances assayed in 13 cell lines from PubChem; for a subset of these compounds, rodent acute toxicity half-maximal lethal dose (LD50) data were also available. We used the k nearest neighbor classification and random forest QSAR methods to model LD50 data using chemical descriptors either alone (conventional models) or combined with biological descriptors derived from the concentration–response qHTS data (hybrid models). Critical to our approach was the use of a novel noise-filtering algorithm to treat qHTS data.
Both the external classification accuracy and coverage (i.e., fraction of compounds in the external set that fall within the applicability domain) of the hybrid QSAR models were superior to conventional models.
Concentration–response qHTS data may serve as informative biological descriptors of molecules that, when combined with conventional chemical descriptors, may considerably improve the accuracy and utility of computational approaches for predicting in vivo animal toxicity end points.
acute toxicity; animal testing; computational toxicology; quantitative high-throughput screening; QSAR
Patients experiencing lower body pain resulting from bone metastases have greater levels of functional interference than those with upper body pain. The purpose of this study was to assess the levels of interference caused by pain after treatment with conventional radiotherapy using the Brief Pain Inventory (BPI) and to validate this tool for telephone use. After radiotherapy, a total of 159, 129, and 106 patients completed the BPI over the telephone at months 1, 2, and 3, respectively. Cronbach's alpha, confirmatory factor analysis, and discriminant validity tests were performed to assess the validity of the BPI. One-way ANOVA was used to compare BPI scores. There was no statistically significant difference in functional interference among patients after treatment. Internal consistency of the BPI was high. Functional interference may be inherently higher in patients with pain in the lower body. Telephone use of the BPI is reliable and recommended in this population.
Objective To assess the relationship between parental HIV/AIDS and psychosocial adjustment of children in rural central China. Methods Participants included 296 double AIDS orphans (children who had lost both their parents to AIDS), 459 single orphans (children who had lost one parent to AIDS), 466 vulnerable children who lived with HIV-infected parents, and 404 comparison children who did not experience HIV/AIDS-related illness and death in their families. The measures included depressive symptoms, loneliness, self-esteem, future expectations, hopefulness about the future, and perceived control over the future. Results AIDS orphans and vulnerable children consistently demonstrated poorer psychosocial adjustment than comparison children in the same community. The level of psychosocial adjustment was similar between single orphans and double orphans, but differed by care arrangement among double orphans. Conclusion The findings underscore the urgency and importance of culturally and developmentally appropriate intervention efforts targeting psychosocial problems among children affected by AIDS and call for more exploration of risk and resilience factors, both individual and contextual, affecting the psychosocial wellbeing of these children.
care arrangement; China; HIV/AIDS; orphans; psychosocial adjustment; vulnerable children