Institutional outbreaks of influenza-like illnesses in the state of São Paulo: an analysis of the epidemiological profile during the COVID-19 pandemic.

OBJECTIVES: This study aimed to spatiotemporally analyze the profile of influenza-like illness (ILI) outbreaks in the state of São Paulo, Brazil, between 2020 and 2022. STUDY DESIGN: This was a cross-sectional retrospective study. METHODS: Outbreaks of ILI with final diagnoses of COVID-19, influenza, or other respiratory viruses (ORVs) recorded between January 2020 and November 2022, obtained from the Notifiable Diseases Information System (SINAN NET) Outbreak module, were analyzed. Kernel density estimates and Getis-Ord Gi∗ statistics were performed to identify spatial clusters. RESULTS: A total of 13,314 ILI outbreaks were identified, involving 130,568 cases and 2649 deaths. Of these, 104,399 (80%) were confirmed as COVID-19, 15,861 (12%) were confirmed as ORV, and 10,308 (8%) were confirmed as influenza. The year 2021 had the highest number of outbreaks and cases. Schools recorded the most outbreaks and cases, followed by long-term care facilities for older adults (LTCs). The highest average number of cases per outbreak and the highest attack rates occurred at social gatherings and prisons. Prisoners were three times more likely to contract COVID-19 during outbreaks than people in other institutions. The highest hospitalization and mortality rates for all virus types occurred in the LTC group. The occurrence and intensity of outbreaks were highly heterogeneous among the different institutions after the introduction of new SARS-CoV-2 variants in the state. CONCLUSIONS: ILI outbreaks were not randomly distributed; they clustered in specific areas. Transmissibility varied among different institutions with different responses to the COVID-19 pandemic. These results can be used as a basis for prioritizing actions and allocating resources during future pandemics.

[Survival time of HIV/AIDS cases and influencing factors in Gansu province, 1997-2018].

Objective: To understand the survival time and influencing factors of HIV/AIDS cases in Gansu province from 1997 to 2018. Methods: A retrospective cohort study was conducted to analyze the AIDS epidemic data of Gansu from 1997 to 2018 collected from the National HIV/AIDS information system. Life-span table were used to calculate survival rate, Kaplan-Meier method was used to draw the survival curves and calculate the average survival time, the Cox proportional hazard regression model were used to analyze the risk factors for death for HIV/AIDS cases. Results: Among 6 813 HIV/AIDS cases, 715 (10.5%) died, and the average survival time was 195.9 months (95%CI: 189.7-202.2). The survival rates of 12 months, 60 months, 120 months and 180 months were 91.5%, 86.1%, 79.9% and 73.8%, respectively. Cox proportional hazard regression model showed that the risk factors for death in the HIV/AIDS cases were age (≥51 years old vs. ≤25 years old, HR=1.906, 95%CI: 1.353-2.685), transmission route (blood borne and others transmission vs. heterosexual transmission, HR=1.593, 95%CI: 1.226-2.069), detection way (hospital admission detection, blood transfusion and preoperative examination vs. entry-exit health examination, pre-marital examination and physical examination of recruits, HR=5.113, 95%CI: 2.083-12.547), disease phase (AIDS phase vs. HIV infection phase: HR=4.012, 95%CI: 3.401-4.732), baseline CD(4) count (no CD(4) detected vs. CD(4) count ≥350/µl, HR=5.446, 95%CI: 3.835-7.732), antiretroviral therapy (receiving no antiretroviral therapy vs. receiving antiretroviral therapy, HR=12.019, 95%CI: 9.861-14.648). Conclusions: The average survival time of HIV/AIDS cases was above 16 years in Gansu during 1997 to 2018. Death risk of HIV/AIDS cases might be increased by age ≥51 years, hospital admission detection, blood transfusion and preoperative examination, AIDS phase of disease phase, no baseline CD(4) detected and no receiving antiretroviral therapy. It is necessary to conduct early HIV test, diagnosis and antiretroviral treatment and increase antiretroviral treatment rates and CD(4) testing rate to improve the survival of HIV/AIDS cases.

SETD5-AS1 stimulates neuron death in stroke via promoting PTEN expression.

OBJECTIVE: To investigate the specific role of long non-coding RNA (lncRNA) SETD5-AS1 in regulating stroke development, and its underlying mechanism. MATERIALS AND METHODS: Middle cerebral artery occlusion (MCAO) model and OGD/R (oxygen-glucose deprivation/reoxygenation) model were constructed for exploring the mechanism of ischemia-reperfusion injury induced by ischemic stroke. SETD5-AS1 expression in brain tissues of ischemic stroke mice and control mice was detected by quantitative Real-time-polymerase chain reaction (qRT-PCR). Proliferation and apoptosis of N2a cells were detected after transfection of overexpression plasmid or siRNA SETD5-AS1. The downstream gene of SETP5-AS1 was predicted by Starbase and PTEN was screened out. Both mRNA and protein expressions of PTEN in MCAO model and OGD/R model were detected. Furthermore, the binding condition of SETD5-AS1 and PTEN was verified by dual-luciferase reporter gene assay, RNA pull-down assay and RNA binding protein immunoprecipitation (RIP). The regulatory effect of SETD5-AS1 on PI3K/AKT pathway was detected by Western blot. RESULTS: SETD5-AS1 was highly expressed in the ischemia-reperfusion injury model. Overexpression of SETD5-AS1 in N2a cells resulted in increased apoptosis and decreased proliferation. PTEN expression was upregulated in MCAO model and OGD/R model. Dual-luciferase reporter gene assay indicated that SETD5-AS1 can promote PTEN transcription. The binding condition of SETD5-AS1 and PTEN was further verified by RNA pull-down assay and RIP. Overexpression of SETD5-AS1 in N2a cells inhibited PI3K/AKT pathway. CONCLUSIONS: SETD5-AS1 is highly expressed in the ischemia-reperfusion injury model. SETD5-AS1 participates in the development of ischemic stroke by activating PTEN and inhibiting PI3K/AKT pathway.

Effect of nicotine withdrawal on pain sensitivity in rats to mechanical stimulation and thermal stimulation.

OBJECTIVE: To establish an improved rat model of nicotine withdrawal and dependence by subcutaneous injection of pure nicotine, and observe the effect of nicotine withdrawal on the pain sensitivity in rats. MATERIALS AND METHODS: 30 SD rats were randomly divided into 5 groups with 6 rats in each group, including the control group, normal saline group (NS group), nicotine group of 3 mg/kg/d (NT3 group), nicotine group of 9 mg/kg/d (NT9 group) and nicotine group of 18 mg/kg/d (NT18 group). The 5 groups were respectively subcutaneously injected with nothing, normal saline, 1 mg/kg nicotine, 3 mg/kg nicotine and 6 mg/kg nicotine with 3 times per day for 7 consecutive days. 60 min after last injection in the 7th d, 1 mg/kg mecamylamine was subcutaneously injected. The body weight change, survival and nicotine withdrawal score of rats were observed during injection of nicotine and after withdrawal. Mechanical withdrawal threshold (MWT) and Thermal withdrawal latency (TWL) in the right hind sole of another 18 rats selected from the control group, NS group and NT9 group (6 rats from each group) were respectively tested in 7d after injection of normal saline or nicotine. RESULTS: Compared with the NT3 group, the body weight of rats in the NT9 group and NT18 group were slowly increased in 7d after injection of nicotine (p < 0.05), but were rapidly increased in 1d and 2d after withdrawal (p < 0.01). Rats in the NT9 group and NT18 group had more withdrawal symptoms after stimulation with mecamylamine (p < 0.01), but the mortality of rats in the NT18 group reached 17%. Compared with the control group, MWT in the rats of the NT9 group were significantly decreased in 1-7d after nicotine withdrawal (p < 0.01), and were particularly significantly decreased in 1d and 2d (p < 0.01); TWL was also significantly decreased (p < 0.01), and was most significantly decreased in 4d (p < 0.01). CONCLUSIONS: An improved rat model of nicotine dependence and withdrawal can be successfully established by intermittent subcutaneous injection of nicotine at 9 mg/kg/d for 7 days, and the pain sensitivity in rats is increased after nicotine withdrawal.

Epidemiological and molecular characterization of rubella virus isolated in São Paulo, Brazil during 1997-2004.

Rubella virus (RV) infection during the early stages of pregnancy can lead to serious birth defects, known as the congenital rubella syndrome (CRS). In 2003, the Pan American Health Organization (PAHO) adopted a resolution calling for the elimination of rubella and the congenital rubella syndrome (CRS) in the Americas by the year 2010. Brazil will have implemented the recommended PAHO strategy for elimination and interruption of endemic rubella virus transmission. The characterization of genotypes during the final stages of rubella elimination is important for determining whether new rubella isolates represent endemic transmission or importations. Samples (blood, urine, cerebrospinal fluid, and throat swabs) collected from patients with symptoms suggestive of rubella infection in 1997-2004 were isolated in cell culture and genotyped. Twenty-eight sequences were analyzed and two genotypes were identified: 1a and 1G. The information reported in this paper will contribute to understanding the molecular epidemiology of RV in São Paulo, Brazil.

Phylogenetic analysis of rubella virus strains during an outbreak in São Paulo, 2007-2008.

Rubella virus (RV) is an important human pathogen that causes rubella, an acute contagious disease. It also causes severe birth defects collectively known as congenital rubella syndrome when infection occurs during the first trimester of pregnancy. Here, we present the phylogenetic analysis of RV that circulated in São Paulo during the 2007-2008 outbreak. Samples collected from patients diagnosed with rubella were isolated in cell culture and sequenced. RV RNA was obtained from samples or RV-infected cell cultures and amplified by reverse transcriptase-polymerase chain reaction. Sequences were assigned to genotypes by phylogenetic analysis using RV reference sequences. Seventeen sequences were analyzed, and three genotypes were identified: 1a, 1G, and 2B. Genotypes 1a and 1G, which were isolated in 2007, were responsible for sporadic rubella cases in São Paulo. Thereafter, in late 2007, the epidemiological conditions changed, resulting in a large RV outbreak with the clear dominance of genotype 2B. The results of this study provide new approaches for monitoring the progress of elimination of rubella from São Paulo, Brazil.

Seroepidemiology of Toxoplasma infection in a metropolitan region of Brazil.

Seroprevalence data from a representative population were used to estimate the annual incidence of congenital toxoplasmosis in São Paulo Metropolitan Region (SPMR). Retrospective anti-toxoplasma IgG serological analysis was conducted to determine age-dependent seroprevalence, force of infection, average age of acquisition of infection and curve of decay of maternally derived antibodies. Seroprevalence was used to calculate the number of new infections. Toxoplasmosis in pregnant women was estimated by total number of deliveries in a given year as a proxy for the number of pregnancies per year. Toxoplasma seroprevalence was 64.9% in women of childbearing age. Average age of acquisition of toxoplasmosis was 10.74 years. The estimated annual incidence of congenital toxoplasmosis varied from 9.5 to 10.6/1000 births in the studied period. The toxoplasmosis seroprevalence model allowed a good incidence estimation of congenital disease in SPMR compared to other published data, indicating that this mathematical approach is useful in calculating the potential demand of congenital disease due to Toxoplasma gondii in a given community.

Human p16gamma, a novel transcriptional variant of p16(INK4A), coexpresses with p16(INK4A) in cancer cells and inhibits cell-cycle progression.

The INK4A locus encodes two tumor suppressor genes, p16(INK4A) and p14(ARF), transcribed using alternative exons 1alpha or 1beta spliced onto the same exons 2 and 3. Both p16(INK4A) and p14(ARF) are capable of inhibiting the cell-cycle progression, albeit in different manner; p16(INK4A) is phosphorylation of retinoblastoma (pRB) dependent while p14(ARF) is p53-dependent. In this study, we report the discovery of a novel variant of p16(INK4A), termed p16gamma, in a primary T-cell acute lymphoblastic leukemia (T-ALL) patient sample and a neuroblastoma cell line, which was expressed at both the transcriptional and translational levels. Cloning and sequencing of the p16gamma cDNA revealed that p16gamma was identical to p16(INK4A), except that it contained an in-frame insertion of 197 bp between exons 2 and 3. p16gamma expression was detected in the majority of p16(INK4A)-expressing primary T-ALL and B-ALL patient samples and other p16(INK4A)-expressing tumor samples, but was only barely detectable in some normal mononuclear cells and other non-tumor samples. Structural analysis by nuclear magnetic resonance and circular dichroism confirmed that p16gamma, like p16(INK4A), is also an ankyrin-repeat protein. Functional analysis of p16gamma revealed that p16gamma protein interacted with cyclin D-dependent kinase4 and inhibited its kinase activity. Using a luciferase reporter assay, the transfection of p16gamma repressed the E2F response, the downstream target of pRB, with an efficacy equivalent to that of p16(INK4A). Moreover p16gamma, like p16(INK4A), induced cell-cycle arrest at G(0)/G(1), and inhibited cell growth in colony formation assay.

Is waist circumference a useful measure in predicting health outcomes in the elderly?

OBJECTIVE: To examine the effect of age on the relationship between body mass index (BMI) and waist circumference (WC), and the usefulness of BMI, WC and waist-hip ratio (WHR) in predicting mortality and cardiovascular risk in the elderly population. DESIGN: Longitudinal observational study of 36 months duration. SUBJECTS AND METHOD: A stratified random sample of 2,032 Chinese subjects (990 male, 1,033 female) mean age (s.d.) 80.1 (7.5), interviewed and examined at baseline and after 36 months. Deaths and presence of diabetes mellitus and hypertension were documented. A younger data set of 1,010 subjects (500 male, 510 female), mean age (s.d.) 45.5 (11.6), was used for comparison of the BMI-WC relationship between younger and older subjects. In predicting outcomes using different values of BMI, WC and WHR, receiver operating characteristic curve analysis was used to derive cut-off values with optimal sensitivity and specificity, and the likelihood ratios for mortality, diabetes and hypertension for different anthropometric values were plotted. RESULTS: The waist circumference values corresponding to BMI values of 25 and 30 kg/m(2) were higher in elderly (92 and 103 cm for men; 88 and 99 cm for women) compared with younger subjects (85 and 97 cm for men; 78 and 88 cm for women). BMI and WC are inversely associated with mortality, in both men and women, positively associated with diabetes in men but not in women. WC was positively associated with hypertension in men and women. WHR was not associated with any outcome measures. The anthropometric measurement at the point of intersection of the likelihood curves for mortality and diabetes may be considered the optimum value, being BMI=21 kg/m(2) for men and 25 kg/m(2) for women, WC between 80 and 85 cm, and WHR 0.88-0.90. CONCLUSION: Waist measurement values for predicting health outcomes in elderly people aged 70 y and over are different compared with younger subjects, and have similar predictive accuracy compared with body mass index. Waist-hip ratio is not a useful predictor.

Lifestyle factors and health outcomes in elderly Hong Kong chinese aged 70 years and over.

BACKGROUND: Although increasing emphasis is being placed on strategies for successful aging, few studies have examined the relationship between lifestyle factors and mortality and other health outcomes in the old-old population. OBJECTIVE: To examine the impact of physical activity, dietary habits, smoking, and alcohol consumption on 3-year mortality and other health outcomes. METHODS: 2,032 Chinese subjects aged 70 years and older (mean age 80 years) were recruited territorywide by proportional random sampling and followed for 3 years. Baseline information was obtained by interview on level of physical activity, dietary habits (frequency of consumption per week of major food groups), alcohol consumption, and smoking habits. Outcome measures include mortality, self-perceived health status, frequency of hospitalization, geriatric depression score, and development of new diseases (stroke, heart disease, hypertension, diabetes mellitus, fractures). Logistic regression was used to examine the effects of lifestyle factors on each health outcome, with and without adjustment for age and baseline health status. RESULTS: The mortality risk is reduced with increasing physical activity, daily fish intake and moderate alcohol consumption, and avoidance of smoking; hospitalization is inversely associated with increasing activity; better self-perceived health is associated with moderate alcohol consumption and a non-smoking status, and there is an inverse relationship between depressive symptoms and increasing activity and moderate alcohol consumption. After adjustment for age and baseline health status, higher levels of physical activity are associated with decreased mortality and hospitalization; non-smokers have reduced mortality and a better self-perceived health, and moderate alcohol consumption is also associated with better self-perceived health. CONCLUSION: Lifestyle factors may influence health outcomes even in the old-old population.

Antibody directed against GD(2) produces mechanical allodynia, but not thermal hyperalgesia when administered systemically or intrathecally despite its dependence on capsaicin sensitive afferents.

Anti-GD(2) antibodies have been shown to be effective for immunotherapy of neuroblastoma and other GD(2) enriched malignancies. Infusion of anti-GD(2) antibodies frequently causes spontaneous pain and allodynia for the duration of the immunotherapy and occasionally longer lasting neuropathic pain. Bolus intravenous injection of anti-GD(2) in rats initiates mechanical allodynia as measured by withdrawal threshold of the hindpaws. In this study, thermal thresholds were measured prior to and for up to 6 h following systemic anti-GD(2) administration in adult rats. In addition, both thermal and mechanical thresholds were tested following intrathecal administration of anti-GD(2) and IgG(2a). Murine anti-GD(2) elicited mechanical allodynia when administered into either the vasculature or the intrathecal space. Effective systemic doses were 1--3 mg/kg as previously shown. Intrathecally, optimal doses ranged from 0.01 to 0.1 ng; a higher dose was ineffective. Thermal hyperalgesia was not observed via either route of administration. Intrathecal pretreatment 48--72 h prior to the experiment with capsaicin at doses sufficient to cause a 50% depletion of dorsal horn CGRP, caused a total blockade of the mechanical allodynia indicating an involvement of peptidergic fine afferent fibers. It is likely that the antibody reacts with an antigen on peripheral nerve and/or myelin to initiate its effect. The lack of observed thermal hyperalgesia is surprising especially in light of the capsaicin-associated blockade, however, it is consistent with several other immune system related models of pain.

p16/p14(ARF) cell cycle regulatory pathways in primary neuroblastoma: p16 expression is associated with advanced stage disease.

p16 regulates the G(1)-S cell cycle transition by inhibiting the cyclin D-cyclin-dependent kinase (CDK)4/CDK6-mediated phosphorylation of retinoblastoma protein (pRb). We examined the possible derangement of the p16-CDK/cyclin D-pRb pathway in 40 primary neuroblastomas including 18 samples in the unfavorable stages (C and D) and 22 in the favorable stages (A, B, and Ds) by PCR, reverse transcription-PCR, Western blot, and immunohistochemistry and correlated the results with clinical outcome. No samples harbored alterations of the p16 gene. Interestingly, the samples in the unfavorable stages exhibited expression of p16 mRNA and protein more frequently than those in the favorable stages [mRNA, 9 of 18 (50%) versus 2 of 22 (9%), P = 0.006; protein, 5 of 16 (31%) versus 0 of 18 (0%), P = 0.013]. Alterations of the downstream components of the pathway were infrequent. pRb was deregulated in the majority of samples investigated [27 of 33 (82%), 24 with hyperphosphorylated pRb and 3 with no pRb protein]. The phosphorylation status of pRb did not correlate with p16 protein expression, suggesting that the elevated p16 protein may not be functioning properly to regulate the pathway. Among patients of all stages, p16 expression was significantly associated with a lower overall survival. There was no overexpression of MDM2, and loss of p14(ARF) expression and p53 mutation were infrequent events. Taken together, these findings suggest that up-regulated p16 expression may represent a unique feature of aggressive neuroblastoma.

Thioredoxin expression in primary T-cell acute lymphoblastic leukemia and its therapeutic implication.

Increased expression of intracellular thioredoxin has been implicated in the inhibition of apoptosis and in a decrease in the sensitivity of the malignancies to drug-induced apoptosis. In the present studies, we analyzed expression of thioredoxin in samples from 28 children with T-cell acute lymphoblastic leukemia and analyzed their sensitivity toward inhibition of thioredoxin expression. Thioredoxin was expressed in variable amounts. Higher expression was associated with higher WBC counts. Exogenously added thioredoxin stimulated proliferation of clonogenic cells among the T-cell acute lymphoblastic leukemia samples expressing relatively lower levels of intracellular thioredoxin, whereas there was no effect on the clonogenic cells expressing high levels of thioredoxin. In addition, there was differential sensitivity of the leukemia clonogenic cells toward 1-methylpropyl 2-imidazolyl disulfide, an inhibitor of thioredoxin expression, as compared with normal hematopoietic progenitors. This suggests the possibility of using this approach for treatment. Because overexpression of thioredoxin is associated with resistance to many anticancer drugs, the inhibition of thioredoxin expression may overcome this drug resistance and probably sensitize leukemia cells to other chemotherapeutic agents.

Expression and localization of the CDC34 ubiquitin-conjugating enzyme in pediatric acute lymphoblastic leukemia.

Ubiquitin-dependent protein degradation impacts many cellular processes.However, the regulation of ubiquitin-conjugating enzymes (UBCs) in cancer is unknown. We find that the human CDC34 UBC protein is expressed at a 3-4 fold higher level (P < 0.001) in pediatric T cell than in pre-B-cell acute lymphoblastic leukemia (ALL) before treatment in two independent patient sets. The level of CDC34 mRNA was similar in both types of leukemia. CDC34 expression levels in normal resting T cells, B cells and activated T lymphocytes was comparable with pre-B-cell ALL. CDC34 protein (but not mRNA) was also increased in T-cell ALL compared with pre-B-cell ALL cell lines. The difference in expression was not attributable to mutation or associated with altered CDC34 stability. Immunohistochemistry and cellular fractionation reveals a heterogeneous CDC34 expression pattern including cells containing primarily cytoplasmic or nuclear protein. Thus, a feature of pediatric T-cell ALL is posttranscriptional up-regulation and heterogeneous localization of the human CDC34 UBC.

Preconditioning with fetal cord blood facilitates engraftment of primary childhood T-cell acute lymphoblastic leukemia in immunodeficient mice.

Childhood T-cell acute lymphoblastic leukemia (T-ALL) is one of the most common childhood cancers. It is reported that preconditioning sublethally irradiated immunodeficient NOD/SCID (nonobese diabetic/X-linked severe combined immunodeficient) mice with human cord blood mononuclear cells facilitates the engraftment, expansion, and dissemination in these mice of primary T-ALL cells obtained from patients at the time of diagnosis. Cells recovered from mouse bone marrow or spleen resembled the original leukemia cells from patients with respect to surface lineage markers and T-cell receptor Vbeta gene rearrangements. Moreover, the pattern of leukemia dissemination in mouse tissues, resulting in universally fatal leukemia, is reminiscent of the human clinical disease. In addition, the fidelity of the model to the human disease is documented with regard to the presence of morphologically identifiable human leukemia cells in mouse bone marrow and blood and the maintenance of leukemia-initiating capacity within the leukemia-engrafted mouse. Therefore, several lines of independent approaches are used to suggest that the engrafted cells are of human leukemia origin and are not derived from cord blood. The in vivo model described here should enable the study of the growth properties of primary T-ALL cells obtained from patients and should prove useful in evaluating the potential efficacy of therapeutic strategies directed toward T-ALL.

Cord blood collection before and after placental delivery: levels of nucleated cells, haematopoietic progenitor cells, leukocyte subpopulations and macroscopic clots.

The number of nucleated cells infused into the recipient of a cord blood (CB) transplant has emerged as the most important factor affecting the probability and speed of engraftment. At present, there is no international consensus on the procedure of CB collection in the maternity ward. In order to maximise the yield of viable cells in a CB unit, we aimed to investigate the efficiency of CB collection, with respect to the time of delivery of the placenta. We analysed stem and progenitor cells in terms of CD34+ cell content and colony-forming activities, lymphocyte subpopulations and the presence of macroscopic clots in 93 paired CB samples, collected before and after the delivery of the placenta. Our results demonstrated that the median concentrations of nucleated cells and total colony-forming unit (CFU) were significantly lower in CB collected after placenta delivery by 9.5% (P < 0.001) and 11.6% (P = 0.015), respectively, when compared to their counterparts collected before placental delivery. A reduction of granulocytes (P < 0.001), monocytes (P < 0.001) and CD19+ B lymphocytes (P = 0.031) was observed, with no significant change in the proportion of T cell subsets (CD4+, CD8+ cells) or activated T cells (CD25+, CD45RO+ cells) in samples collected after placenta delivery. The incidence of macroscopic clots was also higher in these samples (31% vs 1%, P < 0.001). The reduction of stem and progenitor cells correlated significantly with that of major cell populations, indicating a general cell loss, possibly due to clotting activities developed with time. Our study has documented strong evidence for recommending the collection of CB before the delivery of the placenta.

Varicella transmission in two samples of children with different social behaviour in the State of São Paulo, Brazil.

In order to establish the differences in transmission pattern of varicella-zoster virus (VZV), a comparative seroepidemiological study was carried out in two different children samples. Children aged 1-11 years, were randomly selected from state schools of São Paulo city, Brazil. Individuals aged 1-15 years were sampled by cluster from Caieiras city. Children aged 3 years or under from Caieiras were not attending school, while those from São Paulo were attending all-day nurseries or kindergarten. The presence of antibodies to VZV was analysed by ELISA technique. The force of infection and contact rate were determined by mathematical techniques. The average age of first infection was 2.87 +/- 0.14 years and 4.07 +/- 0.47 years for Sao Paulo and Caieiras, respectively. The average force of infection estimated was 0.29 year(-1) for São Paulo and was 0.26 year(-1) for Caieiras. The proportion of seropositivity and the force of infection were higher in São Paulo school children up to 3 years of age compared with Caieiras children, where the social contact starts later. In conclusion, social changes affecting contact among children may influence varicella epidemiology.

A 3-year follow-up study of social, lifestyle and health predictors of cognitive impairment in a Chinese older cohort.

BACKGROUND: Longitudinal data on the older population in the Asian setting are limited. This paper reports the factors associated with the development of cognitive impairment (CI) in a cohort of Chinese elderly aged > or =70 years. METHODS: The study cohort comprising 2030 subjects aged > or =70 years was assembled in 1991-1992 and followed for 36 months. Baseline information on cognitive function, as well as a number of social and health variables were obtained through face-to-face interview at the respondent's place of residence. The outcome variable was the development of CI among 988 cohort members who were initially free from CI, and who could be contacted at the 36-month follow-up. The instrument used to assess CI was based on the information/orientation part of the Clifton Assessment Procedure for the elderly (CAPE), using a cut-off point of 7. RESULTS: Of the men, 6.7%, but 22.2% of women had CI at 3-year follow-up. The age-adjusted annual incidence of CI was 1.52% in men, and 6.37% in women. Multivariate logistic regression analysis showed that women had a 2.5-fold increased risk of having CI, compared with men. The risk increased by about 1.5-fold with every 5-year increase in age. Slow gait time, as assessed by the 16-foot walk, was a predictor of CI in both sexes (odds ratio [OR] = 1.03 per second increase, 95% CI : 1.0-1.07). Men residing in institutions had a 4.4-fold increased risk of having CI (95% CI : 1.7-11.1) compared with those residing in community, while the OR among women was 2.5 (95% CI : 1.3-4.9). Among women, no formal education increased the risk of having CI by 3.2-fold (95% CI : 1.8-5.5). Income dependency also increased the risk of CI by about fourfold, and no exercise at baseline was associated with a twofold increased risk of CI. Incident stroke during follow-up also increased the risk of CI (OR = 8.4, 95% CI : 1.2-59.4). CONCLUSIONS: Older age and female sex were independent factors associated with CI. No formal education, slow gait time and institutionalization increased the risk of CI in both sexes. While education had a stronger effect in women, institutionalization had a stronger effect in men. Financial dependency, lack of exercise and incident stroke played a significant role in women.

In vitro sensitivity of T-cell lymphoblastic leukemia to UCN-01 (7-hydroxystaurosporine) is dependent on p16 protein status: a Pediatric Oncology Group study.

p16 regulates the cell cycle pathway by inhibiting the cyclin Ds-cyclin-dependent kinase (CDK) 4/6-mediated phosphorylation of retinoblastoma protein (pRb). Previously, we reported that most primary T-cell acute lymphoblastic leukemia (T-ALL) harbored p16 inactivation and hyperphosphorylated pRb without cyclin Ds or CDK4/6 alterations. Therefore, inhibiting CDK4/6 may be an ideal therapeutic approach for p16 (-) T-ALL. UCN-01 (7-hydroxystaurosporine) is a potent antitumor agent that exerts its effects through the inhibition of CDKs. We now report that p16 protein expression status of T-ALL cells influences their sensitivity to UCN-01. In 36 primary T-ALL cells, the IC50s of UCN-01 in the 27 p16 (-) cells (43+/-52 nM) was significantly lower than that in the 9 p16 (+) cells (258+/-260 nM). Our results suggest that agents like UCN-01 may be useful as a p16-selective therapy for T-ALL.