Senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment.

The potential of immune checkpoint inhibitors (ICI) may be limited in situations where immune cell fitness is impaired. Here, we show that the efficacy of cancer immunotherapies is compromised by the accumulation of senescent cells in mice and in the context of therapy-induced senescence (TIS). Resistance to immunotherapy is associated with a decrease in the accumulation and activation of CD8 T cells within tumors. Elimination of senescent cells restores immune homeostasis within the tumor micro-environment (TME) and increases mice survival in response to immunotherapy. Using single-cell transcriptomic analysis, we observe that the injection of ABT263 (Navitoclax) reverses the exacerbated immunosuppressive profile of myeloid cells in the TME. Elimination of these myeloid cells also restores CD8 T cell proliferation in vitro and abrogates immunotherapy resistance in vivo. Overall, our study suggests that the use of senolytic drugs before ICI may constitute a pharmacological approach to improve the effectiveness of cancer immunotherapies.

Care needs assessment of older adults with dementia in a semi-rural district in Vietnam: A community-based cross-sectional study.

BACKGROUND: The increasing needs of people living with dementia (PLWD) in Vietnam present an enormous public health challenge. Vietnam is an understudied country, and little is known regarding the overall unmet needs of caregivers or the demographic risk factors associated with unmet caregiving needs. This study aimed to determine the burden of unmet care needs of community-dwelling PLWD and identify sociodemographic risks associated with unmet care needs. METHODS: A cross-sectional study in a rural area facing urbanisation in Hanoi, Vietnam recruited PWLD-caregiver dyads with multistage sampling. We utilised the Camberwell Assessment of Need for the Elderly (CANE) instrument to evaluate care needs across four domains. Caregivers rated PLWD needs, with higher scores indicating greater unmet needs. The Mann-Whitney test was employed for comparing two groups, while the Kruskal-Wallis test was used for comparisons involving more than two groups in the analysis, and a P-value of less than 0.05 was considered statistically significant. RESULTS: Among 90 PLWD participating in the study, the overall mean care needs score was 11.6 ± 4.3, with only 16.2% of PLWD having their care needs met. Environmental and physical needs were more frequently met than psychological or social needs. Only 48.0% and 43.9% of environmental and physical needs were met respectively, and a meagre 20.9% and 23.6% for psychological and social needs. Unmet care needs were more frequent for PWLD who were female, single or divorced, had lower monthly household income, or who were in more advanced stages of dementia, as indicated by Clinical Dementia Rating scores ≥1. CONCLUSIONS: Unmet needs for PWLD are common. Increased caregiver education, resources, and services in Vietnam are urgently required to improve the quality of life for this population.

Effect of Red Mud and Rice Husk Ash-Based Geopolymer Composites on the Adsorption of Methylene Blue Dye in Aqueous Solution for Wastewater Treatment.

In this study, geopolymer originating from locally industrial byproducts as red mud (RM) was successfully prepared in the presence of different loadings of rice husk ash (RHA) used for the adsorption of methylene blue (MB) in wastewater. During geopolymerization, various mixing amounts between RM and RHA were conducted when the weight ratio of binder solution/activated alkali-metal solution (Na2SiO3/ NaOH 7 M) was 2.5 and the curing temperature was set at 60 °C for 24 h. As a result, the surface area value of the prepared geopolymer composited with RHA at 0 and 60% was increased from 19.2 to 29.5 m2/g, while the BJH pore size of the prepared geopolymer was reduced to 6.68 and 5.76 nm, respectively. In the dye removal test, higher additions of RHA in the RM-geopolymer maintained better retention of the MB ion due to the increase in the adsorption binding site. The maximum uptake amount of dyes performed at pH 8 was changed from 6.59 to 10.74 mg/g, while RHA was from 0 to 60% after 180 min of immersion in MB solution. The adsorption isotherms well obeyed the Langmuir model, as the relative coefficient R2 was 0.999. Based on these, the initial agricultural waste as RHA and industrial byproducts as RM were valued as functional materials used for dye treatment in wastewater.

Reference intervals of complete blood count and coagulation tests in Vietnamese pregnant women.

BACKGROUND: Pregnancy has major effects that make hematology parameters outside of normal reference ranges. Therefore, we conducted this study to establish reference intervals for Vietnamese pregnant women. METHODS: From June 2023 to Augst 2023, blood samples from 879 eligible pregnant women were run on DxH 900 hematology analyzer and ACL TOP 550 coagulation analyzer. The tested parameters are prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), white blood cell (WBC) and its differentials (neutrophils, lymphocytes, monocytes, eosinophils and basophils), red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), RBC distribution width (RDW), RBC distribution width standard deviation (RDW-SD), platelet count (PLT), mean platelet volume (MPV). A non-parametric method was used to establish the 2.5th and 97.5th percentile reference intervals. RESULTS: PT, APTT decrease but fibrinogen increases during pregnancy. Physiological adaptations of pregnancy result in a decrease in RBC count, but an increase in WBC count and no changes in platelet count. The reference intervals for PT (seconds), APTT (seconds), fibrinogen (mg/dL), in the first trimester were 10.30-12.88, 25.40-35.46, 280.28-559.00, in the second trimester were 9.80-11.66, 24.05-33.23, 347.75-593.35, in the third trimester were 9.60-11.40, 23.40-31.80, 330.28-628.56, respectively. The reference intervals for main hematology parameters which are WBC (× 109/L), RBC (× 1012/L), HGB (g/dL), HCT (%), PLT (× 109/L) in the first trimester were 6.33-15.24, 3.73-5.32, 10.33-13.95, 32.22-42.29, 169.66-413.88, in the second trimester were 6.99-15.55, 3.33-4.98, 9.71-13.17, 30.26-40.07, 172.34-372.19, in the third trimester were 6.22-14.14, 3.54-4.98, 9.80-13.97, 31.11-42.70, 151.30-417.14, respectively. CONCLUSIONS: Most established referenced intervals from each trimester differ from other trimesters. These trimester-specific reference ranges for Vietnamese pregnant women will aid clinicians in entepreting parameters and help other laboratories adopt these ranges after validating. TRIAL REGISTRATION: This study is registered at www. CLINICALTRIALS: gov as NCT05929326.

Diagnostic Performance of Multispectral SWIR Transillumination and Reflectance Imaging for Caries Detection.

The aim of this clinical study was to compare the diagnostic performance of dual short wavelength infrared (SWIR) occlusal transillumination and reflectance multispectral imaging with conventional visual assessment and radiography for caries detection on premolars scheduled for extraction for orthodontics reasons. Polarized light microscopy (PLM) and micro-computed tomography (microCT) performed after tooth extraction were used as gold standards. The custom-fabricated imaging probe was 3D-printed and the imaging system employed a SWIR camera and fiber-optic light sources emitting light at 1300 nm for occlusal transillumination and 1600 nm for reflectance measurements. Teeth (n = 135) on 40 test subjects were imaged in vivo using the SWIR imaging prototype in the study and teeth were extracted after imaging. Our study demonstrates for the first time that near-simultaneous real-time transillumination and reflectance video can be successfully acquired for caries detection. Both SWIR imaging modalities had markedly higher sensitivity for lesions on proximal and occlusal surfaces compared to conventional methods (visual and radiographic). Reflectance imaging at 1600 nm had higher sensitivity and specificity than transillumination at 1300 nm. The combined SWIR methods yielded higher specificity but the combined sensitivity was lower than for each individual method.

Disclosure of HIV status and associated clinical outcomes of children and adolescents living with HIV in Asia.

Disclosure of HIV status is an important part of pediatric care. We studied disclosure and clinical outcomes in a multi-country Asian cohort of children and adolescents with HIV. Those 6-19 years of age who initiated combination antiretroviral therapy (cART) between 2008 and 2018, and who had at least one follow-up clinic visit were included. Data up to December 2019 were analyzed. Cox and competing risk regression analyses were used to assess the effect of disclosure on disease progression (WHO clinical stage 3 or 4), loss to follow-up (LTFU; > 12 months), and death. Of 1913 children and adolescents (48% female; median [IQR] age 11.5 [9.2-14.7] years at last clinic visit), 795 (42%) were disclosed to about their HIV status at a median age of 12.9 years (IQR: 11.8-14.1). During follow-up, 207 (11%) experienced disease progression, 75 (3.9%) were LTFU, and 59 (3.1%) died. There were lower hazards of disease progression (adjusted hazard ratio [aHR] 0.43 [0.28-0.66]) and death (aHR 0.36 [0.17-0.79]) for those disclosed to compared with those who were not. Disclosure and its appropriate implementation should be promoted in pediatric HIV clinics in resource-limited settings.

Active Surveillance of Root Caries in Vivo with CP-OCT.

The active surveillance of root caries lesions to monitor potential remineralization or decay progression is challenging for the clinician, due to unreliable diagnostic information. The conventional visual and tactile methods for assessing the lesion activity are not reliable, and the clinician is often unable to determine if the lesion is progressing or has been arrested. An important marker of an arrested lesion is a highly mineralized transparent surface zone (TSL) that forms when the mineral is deposited in the outer layer of the lesion. The purpose of this study was to determine if cross-polarization optical coherence tomography (CP-OCT) could be used to detect changes in the lesion severity and activity during active monitoring. In total, 18 subjects with 22 suspected active root caries lesions were evaluated using CP-OCT at the baseline, 3 months, and 6 months. All subjects were instructed to use a high fluoride dentifrice at the baseline. The results showed that CP-OCT was able to discriminate the active from the arrested lesions by identifying the presence of a TSL on arrested lesions. The results also indicated that the mean TSL thickness increased significantly (p < 0.05) for the nine lesion areas. In addition, CP-OCT was able to show the progression of demineralization, erosion, and changes in gingival contours in scanned areas. CP-OCT was valuable for monitoring the activity and severity of root caries lesions in vivo. CP-OCT can be used to assess the activity of root caries lesions at a single time point by detecting the presence of a TSL at the lesion surface indicative of the lesion arrest.

Investigating Effects of COVID-19 Pandemic on the Mental Health of Nursing Students During Remote Learning: An Experience from Dong A University, Vietnam.

Introduction: There was a radically changed in nursing education during the nationwide lockdown due to the COVID-19 outbreaks. The transition to remote learning stressed nursing students in many countries, particularly in Vietnam. However, there is still lacking a novel study to describe the mental characteristics of nursing students in detail. Objectives: To assess the mental health of nursing students, including stress, anxiety, and depression, and to identify the related factors to their mental health during the online study period because of the COVID-19 pandemic. Methods: A cross-sectional survey was conducted on 540 nursing students at Dong A university using a socio-demographic questionnaire, the Depression, Anxiety, and Stress Scale - 21 Items (DASS-21). Data were analyzed by descriptive statistics and tests, including Mann-Whitney, Kruskal-Wallis, and Spearman's correlation to identify the related factors. Results: In total 540 participants, nursing students reported stress (N = 120, 22.2%), anxiety (n = 195, 36.1%), and depression symptoms (n = 135, 23.1%). There was a significant relationship between age, work status, married status, number of children, stress, anxiety, and depression (P < 0.01). In addition, our study showed a negative correlation between frequency of physical activity, perceived health and stress (r = -0.117; p < 0.01, r = -0.127, p < 0.01), anxiety (r = -0.133; p < 0.01, r = -0.112, p < 0.01), depression (r = -0.134; p < 0.01, r = -0.135, p < 0.01). A significant relationship was observed between e-learning space and Internet status with mental health (p < 0.05). Especially, there was no association between average online learning time, academic workload, stress, anxiety, and depression (p > 0.05). However, the authors found a positive association between perceived level of stress related to evaluative activities and stress, anxiety, depression (r = 0.120, p < 0.01; r = 0.089, p < 0.05; r = 0.088, p < 0.05). Conclusion: Nursing students suffered stress, anxiety, and depression during online learning due to the COVID-19 pandemic in the presence of some related factors. Therefore, this study may increase more attention of universities, families, and governments to reduce the stress of nursing students during distance education.

Formation and Evaluation of Complete Blood Count Proficiency Testing Program.

Introduction: The haematology external quality assessment (EQA) scheme is the most commonly used service of quality assurance. The provision of complete blood count (CBC) materials must meet the quality requirements at a reasonable cost. These requirements are the most significant challenges for EQA organisers in Vietnam. This study's objective was to evaluate the homogeneity, long-term stability, and peer-group performance of 10-parameter stabilised CBC EQA samples. Methods: The CBC EQA material was prepared using the following steps, including (1) adjusting levels of stabilised erythrocyte, leukocyte, and platelet samples, (2) mixing those cells into batches at three levels, and (3) dispensing and storing them at 2-6 °C. A set of 10 and 30 specimens were randomly chosen from each batch to study the homogeneity and long-term stability following ISO 13528:2015. In total, 166 samples at two levels were randomly distributed to 40 participants, which reported 83 automatic cell counters among six automated analyser models in the CBC EQA program. Results: The 10-parameter stabilised CBC EQA materials at three levels became homogeneous and stable in 12 weeks when preserved at 2-6 °C. Meanwhile, for five parameters (RBC, Hb, MCH, MCV, and MPV), this process was prolonged for up to 16 weeks in stock condition. In terms of peer-group performance, the CV (%) values increased at the low concentration for almost all parameters, especially in platelet counts. Conclusions: The stabilised CBC EQA samples prepared using the partial fixation method with aldehyde and gutaraldehyde in this study meet the ISO 13528:2015 requirements of homogeneity and long-term stability for the CBC EQA scheme. Analytical performance evaluation should categorise participant methods into peer groups.

Autologous humanized mouse models of iPSC-derived tumors enable characterization and modulation of cancer-immune cell interactions.

Modeling the tumor-immune cell interactions in humanized mice is complex and limits drug development. Here, we generated easily accessible tumor models by transforming either primary skin fibroblasts or induced pluripotent stem cell-derived cell lines injected in immune-deficient mice reconstituted with human autologous immune cells. Our results showed that fibroblastic, hepatic, or neural tumors were all efficiently infiltrated and partially or totally rejected by autologous immune cells in humanized mice. Characterization of tumor-immune infiltrates revealed high expression levels of the dysfunction markers Tim3 and PD-1 in T cells and an enrichment in regulatory T cells, suggesting rapid establishment of immunomodulatory phenotypes. Inhibition of PD-1 by Nivolumab in humanized mice resulted in increased immune cell infiltration and a slight decrease in tumor growth. We expect that these versatile and accessible cancer models will facilitate preclinical studies and the evaluation of autologous cancer immunotherapies across a range of different tumor cell types.

The Intracerebroventricular Injection of Murine Mesenchymal Stromal Cells Engineered to Secrete Epidermal Growth Factor Does Not Prevent Loss of Neurogenesis in Irradiated Mice.

Decreased neurogenesis after brain exposure to ionizing radiation is linked to neurocognitive impairments. Using transgenic mouse models, we previously showed that abrogation of radiation-induced senescence, or apoptosis, can partially rescue neurogenesis in the subventricular and hippocampus regions. Here, we evaluate whether the injection of recombinant epidermal growth factor (rEGF) or mesenchymal stromal cells (MSC) engineered to secrete EGF (MSC-EGF) can preserve neurogenesis. Using doublecortin (Dcx) expression and BrdU incorporation assays, we found that the injection of rEGF into the subventricular zone (SVZ) promotes neurogenesis, despite increasing apoptosis, in the brain of irradiated mice. The effect of rEGF was mostly localized, as Dcx expression was not induced in the hippocampus region and limited in the contralateral SVZ. Surprisingly, the injection of bone marrow-derived MSC alone, or secreting EGF, did not result in increased neurogenesis despite the fact that part of the MSC survived a few weeks after injection. Our results suggest that only a supraphysiological concentration of rEGF can promote neurogenesis, likely through a direct mitogenic effect.

Dual short wavelength infrared transillumination/reflectance mode imaging for caries detection.

SIGNIFICANCE: We have developed a clinical probe capable of acquiring near-simultaneous short-wavelength infrared (SWIR) reflectance and occlusal transillumination images of lesions on tooth proximal and occlusal surfaces. We hypothesize that dual images will aid in differentiating between shallow and deep occlusal lesions and reduce the potential of false positives (FPs). AIM: The aim of this study was to test the performance of the dual reflectance and occlusal transillumination probe on extracted teeth prior to commencing clinical studies. APPROACH: The dual probe was 3D printed and the imaging system uses an InGaAs camera and broadband superluminescent diode light sources that emit broadband light at 1300 nm for occlusal transillumination and 1600-nm light for cross-polarization reflectance. The diagnostic performance of the dual probe was assessed using 120 extracted teeth with approximal and occlusal lesions. Reflectance and transillumination images were fused into single images to enhance the contrast between sound and lesion areas. The lesion contrast in both modes did not increase significantly with either the lesion depth or the distance from the occlusal surface for approximal lesions. In addition, the diagnostic performance of radiography, the individual reflectance and transillumination images, dual images, and fused images were compared using micro-computed tomography as the gold standard. RESULTS: Reflectance imaging at 1600 nm yielded the highest diagnostic accuracy for lesions on both occlusal and proximal surfaces while radiography yielded the lowest number of FPs. CONCLUSION: This study demonstrates that simultaneous acquisition of both reflectance and transillumination SWIR images is possible with a single clinical device.

Effects of B2O3 doping on the crystalline structure and performance of DC-magnetron-sputtered, transparent ZnO thin films.

The transparent-conducting performance is estimated through figure-of-merit (FOM) value. To improve poor FOM value of pure ZnO thin films, boron (B) as a donor impurity was doped into the films. Direct-current magnetron sputtering was used to prepare B-doped ZnO (BZO) thin films from sintered ZnO targets with variable B2O3 content changing from 0 to 2 wt. %. The x ray diffraction analysis confirmed the preferably c-axis-oriented structure of hexagonal wurtzite ZnO host. The results also showed variation in the film structure versus the B2O3 content through calculations of crystal size and residual stress. Depending on the B2O3 content, a competition of interstitial and substitutional B3+ ions induced more stress or relaxation in lattice structure of the films. At 1% B2O3, the BZO thin film had the best crystalline characterization with the lowest stress and large crystal size. In consequence, the BZO 1% film obtained the lowest resistivity of 2.7×10-3Ωcm, average transmittance of 82.1%, and the best FOM value of 18.8×102Ω-1cm-1. The transparent-conducting performance of the ZnO thin films deposited by direct-current (DC) magnetron sputtering was significantly enhanced through B doping. The good-performance BZO film at 1% B2O3 is believed to be of use as electrodes in thin-film solar cells.

SWIR, Thermal and CP-OCT imaging probes for the in vivo assessment of the activity of root caries lesions.

New imaging technologies are needed for the clinical assessment of lesions on root surfaces. It is not sufficient to simply detect caries lesions; methods are needed to assess lesion depth, structural composition and activity to determine if chemical intervention has the potential to be effective and if remineralization has occurred. Lesions were monitored using CP-OCT during lesion dehydration to assess the lesion structure and any shrinkage. Thermal imaging at 6-10 µm wavelengths and short wavelength-IR imaging at 1450-1750-nm were used to monitor thermal emission during lesion dehydration to assess lesion activity. Imaging probes were custom fabricated for clinical use. We present the first clinical results of a small feasibility study employing CP-OCT, thermal and SWIR imaging to assess lesion activity in vivo on thirty test subjects with suspected root caries lesions.

Community-wide Screening for Tuberculosis in a High-Prevalence Setting.

BACKGROUND: The World Health Organization has set ambitious targets for the global elimination of tuberculosis. However, these targets will not be achieved at the current rate of progress. METHODS: We performed a cluster-randomized, controlled trial in Ca Mau Province, Vietnam, to evaluate the effectiveness of active community-wide screening, as compared with standard passive case detection alone, for reducing the prevalence of tuberculosis. Persons 15 years of age or older who resided in 60 intervention clusters (subcommunes) were screened for pulmonary tuberculosis, regardless of symptoms, annually for 3 years, beginning in 2014, by means of rapid nucleic acid amplification testing of spontaneously expectorated sputum samples. Active screening was not performed in the 60 control clusters in the first 3 years. The primary outcome, measured in the fourth year, was the prevalence of microbiologically confirmed pulmonary tuberculosis among persons 15 years of age or older. The secondary outcome was the prevalence of tuberculosis infection, as assessed by an interferon gamma release assay in the fourth year, among children born in 2012. RESULTS: In the fourth-year prevalence survey, we tested 42,150 participants in the intervention group and 41,680 participants in the control group. A total of 53 participants in the intervention group (126 per 100,000 population) and 94 participants in the control group (226 per 100,000) had pulmonary tuberculosis, as confirmed by a positive nucleic acid amplification test for Mycobacterium tuberculosis (prevalence ratio, 0.56; 95% confidence interval [CI], 0.40 to 0.78; P<0.001). The prevalence of tuberculosis infection in children born in 2012 was 3.3% in the intervention group and 2.6% in the control group (prevalence ratio, 1.29; 95% CI, 0.70 to 2.36; P = 0.42). CONCLUSIONS: Three years of community-wide screening in persons 15 years of age or older who resided in Ca Mau Province, Vietnam, resulted in a lower prevalence of pulmonary tuberculosis in the fourth year than standard passive case detection alone. (Funded by the Australian National Health and Medical Research Council; ACT3 Australian New Zealand Clinical Trials Registry number, ACTRN12614000372684.).

Author Correction: L1 drives IFN in senescent cells and promotes age-associated inflammation.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Restored immune cell functions upon clearance of senescence in the irradiated splenic environment.

Some studies show eliminating senescent cells rejuvenate aged mice and attenuate deleterious effects of chemotherapy. Nevertheless, it remains unclear whether senescence affects immune cell function. We provide evidence that exposure of mice to ionizing radiation (IR) promotes the senescent-associated secretory phenotype (SASP) and expression of p16INK4a in splenic cell populations. We observe splenic T cells exhibit a reduced proliferative response when cultured with allogenic cells in vitro and following viral infection in vivo. Using p16-3MR mice that allow elimination of p16INK4a -positive cells with exposure to ganciclovir, we show that impaired T-cell proliferation is partially reversed, mechanistically dependent on p16INK4a expression and the SASP. Moreover, we found macrophages isolated from irradiated spleens to have a reduced phagocytosis activity in vitro, a defect also restored by the elimination of p16INK4a expression. Our results provide molecular insight on how senescence-inducing IR promotes loss of immune cell fitness, which suggest senolytic drugs may improve immune cell function in aged and patients undergoing cancer treatment.

L1 drives IFN in senescent cells and promotes age-associated inflammation.

Retrotransposable elements are deleterious at many levels, and the failure of host surveillance systems for these elements can thus have negative consequences. However, the contribution of retrotransposon activity to ageing and age-associated diseases is not known. Here we show that during cellular senescence, L1 (also known as LINE-1) retrotransposable elements become transcriptionally derepressed and activate a type-I interferon (IFN-I) response. The IFN-I response is a phenotype of late senescence and contributes to the maintenance of the senescence-associated secretory phenotype. The IFN-I response is triggered by cytoplasmic L1 cDNA, and is antagonized by inhibitors of the L1 reverse transcriptase. Treatment of aged mice with the nucleoside reverse transcriptase inhibitor lamivudine downregulated IFN-I activation and age-associated inflammation (inflammaging) in several tissues. We propose that the activation of retrotransposons is an important component of sterile inflammation that is a hallmark of ageing, and that L1 reverse transcriptase is a relevant target for the treatment of age-associated disorders.

Seroprevalence of Hepatitis B Among HIV-infected Children and Adolescents Receiving Antiretroviral Therapy in the TREAT Asia Pediatric HIV Observational Database.

BACKGROUND: Hepatitis B (HBV)-HIV coinfection is associated with liver inflammation, which can progress to liver fibrosis/cirrhosis and hepatocellular carcinoma. We determined HBV seroprevalence in children and adolescents participating in the TREAT Asia Pediatric HIV Observational Database. METHODS: A multisite cross-sectional study was conducted in HIV-infected patients currently <25 years old receiving antiretroviral treatment (ART) who had HBV surface antigen (HBsAg), or HBV surface antibody (anti-HBs) or HBV core antibody (anti-HBc) tested during 2012-2013. HBV coinfection was defined as having either a positive HBsAg test or being anti-HBc positive and anti-HBs negative, reflective of past HBV infection. HBV seroprotection was defined as having a positive anti-HBs test. RESULTS: A total of 3380 patients from 6 countries (Vietnam, Thailand, Cambodia, Malaysia, Indonesia and India) were included. The current median (interquartile range) age was 11.2 (7.8-15.1) years. Of the 2755 patients (81.5%) with HBsAg testing, 130 (4.7%) were positive. Of 1558 (46%) with anti-HBc testing, 77 (4.9%) were positive. Thirteen of 1037 patients with all 3 tests were anti-HBc positive and HBsAg and anti-HBs negative. One child was positive for anti-HBc and negative for anti-HBs but did not have HBsAg tested. The prevalence of HBV coinfection was 144/2759 (5.2%) (95% confidence interval: 4.4-6.1). Of 1093 patients (32%) with anti-HBs testing, 257 (23.5%; confidence interval: 21.0-26.0) had positive tests representing HBV seroprotection. CONCLUSIONS: The estimated prevalence of HBV coinfection in this cohort of Asian HIV-infected children and adolescents on ART was 5.2%. The majority of children and adolescents tested in this cohort (76.5%) did not have protective HBV antibody. The finding supports HBV screening of HIV-infected children and adolescents to guide revaccination, the use of ART with anti-HBV activity and future monitoring.

INK4a/ARF Expression Impairs Neurogenesis in the Brain of Irradiated Mice.

Brain neurogenesis is severely impaired following exposure to ionizing radiation (IR). We and others have shown that the expression of the tumor suppressor gene p16INK4a is increased in tissues exposed to IR and thus hypothesized that its expression could limit neurogenesis in the irradiated brain. Here, we found that exposure to IR leads to persistent DNA damage and the expression of p16INK4a in the hippocampus and subventricular zone regions. This was accompanied by a decline in neurogenesis, as determined by doublecortin expression and bromodeoxyuridine incorporation, an effect partially restored in Ink4a/arf-null mice. Increased neurogenesis in the absence of INK4a/ARF expression was independent of apoptosis and activation of the microglia. Moreover, treatment of irradiated mice with a superoxide dismutase mimetic or clearance of p16INK4a-expressing cells using mouse genetics failed to increase neurogenesis. In conclusion, our results suggest that IR-induced p16INK4a expression is a mechanism that limits neurogenesis.