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The article presents a report from the U.S. Centers of Disease Control and Prevention regarding the incidence of tuberculosis (TB) cases reported in the U.S. Statistics show a 3.8% decline in the number of TB cases between 2007 and 2008. The 4.2 cases per 100,000 people are the lowest on record. The data was collected by the National TB Surveillance System. Foreign born persons and ethnic minorities continue to bear a disproportionate burden of TB cases in the U.S. Trends in the number of multidrug-resistant TB (MDR TB) cases are analyzed.

Acute undifferentiated febrile illness (AUFI) is often undiagnosed in Thailand, resulting in delayed or ineffective treatment. We compared the demographic, exposure history, and clinical characteristics of AUFI patients with laboratory evidence of bacterial and nonbacterial pathogens. Patients aged 2-80 years presenting to 12 hospitals in Nakhon Phanom and Tak provinces were enrolled from April 2017 through May 2020. Interviews were conducted and blood, urine, and sputum were collected for culture as well as rapid diagnostic and molecular testing. A total of 1,263 patients tested positive for one or more bacterial, viral, or parasitic pathogens and were included in the analysis. Multivariable logistic regression was performed to compare factors associated with bacterial infections versus nonbacterial infections. Bacterial infections were more commonly identified in participants from Nakhon Phanom than Tak. Bacterial infections were independently associated with several factors including age ≥50 years (adjusted odds ratio [95% CI]): (4.18 [2.85-6.14]), contact with farm animals (1.82 [1.29-2.57]), antibiotic use within 72 hours of hospital presentation (2.37 [1.50-3.74]), jaundice (2.31 [1.15-4.63]), existing comorbidities (2.77 [1.93-3.96]), contact with febrile individuals (0.42 [0.31-0.57]), muscle pain (0.44 [0.31-0.64]), and rash (0.45 [0.29-0.70]). Bacterial infections were also associated with longer hospitalization (2.75 [2.08-3.64]) and lower odds of recovery at the time of discharge (0.14 [0.07-0.31]). Consideration of patient characteristics and signs/symptoms may help to inform targeted laboratory testing for suspected infectious etiologies. Understanding factors associated with bacterial and non-bacterial causes of AUFI may aid diagnosis and judicious use of antibiotics in resource-limited settings.

Background: In response to the 2015-2016 Zika virus (ZIKV) outbreak and the causal relationship established between maternal ZIKV infection and adverse infant outcomes, we conducted a cohort study to estimate the incidence of ZIKV infection in pregnancy and assess its impacts in women and infants., Methodology/principal Findings: From May 2018-January 2020, we prospectively followed pregnant women recruited from 134 participating hospitals in two non-adjacent provinces in northeastern Thailand. We collected demographic, clinical, and epidemiologic data and blood and urine at routine antenatal care visits until delivery. ZIKV infections were confirmed by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Specimens with confirmed ZIKV underwent whole genome sequencing. Among 3,312 women enrolled, 12 (0.36%) had ZIKV infections, of which two (17%) were detected at enrollment. Ten (83%, 3 in 2nd and 7 in 3rd trimester) ZIKV infections were detected during study follow-up, resulting in an infection rate of 0.15 per 1,000 person-weeks (95% CI: 0.07-0.28). The majority (11/12, 91.7%) of infections occurred in one province. Persistent ZIKV viremia (42 days) was found in only one woman. Six women with confirmed ZIKV infections were asymptomatic until delivery. Sequencing of 8 ZIKV isolates revealed all were of Asian lineage. All 12 ZIKV infected women gave birth to live, full-term infants; the only observed adverse birth outcome was low birth weight in one (8%) infant. Pregnancies in 3,300 ZIKV-rRT-PCR-negative women were complicated by 101 (3%) fetal deaths, of which 67 (66%) had miscarriages and 34 (34%) had stillbirths. There were no differences between adverse fetal or birth outcomes of live infants born to ZIKV-rRT-PCR-positive mothers compared to live infants born to ZIKV-rRT-PCR-negative mothers., Conclusions/significance: Confirmed ZIKV infections occurred infrequently in this large pregnancy cohort and observed adverse maternal and birth outcomes did not differ between mothers with and without confirmed infections., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Neuronal mitochondria play important roles beyond ATP generation, including Ca 2+ uptake, and therefore have instructive roles in synaptic function and neuronal response properties. Mitochondrial morphology differs significantly between the axon and dendrites of a given neuronal subtype, but in CA1 pyramidal neurons (PNs) of the hippocampus, mitochondria within the dendritic arbor also display a remarkable degree of subcellular, layer-specific compartmentalization. In the dendrites of these neurons, mitochondria morphology ranges from highly fused and elongated in the apical tuft, to more fragmented in the apical oblique and basal dendritic compartments, and thus occupy a smaller fraction of dendritic volume than in the apical tuft. However, the molecular mechanisms underlying this striking degree of subcellular compartmentalization of mitochondria morphology are unknown, precluding the assessment of its impact on neuronal function. Here, we demonstrate that this compartment-specific morphology of dendritic mitochondria requires activity-dependent, Ca 2+ and Camkk2-dependent activation of AMPK and its ability to phosphorylate two direct effectors: the pro-fission Drp1 receptor Mff and the recently identified anti-fusion, Opa1-inhibiting protein, Mtfr1l. Our study uncovers a signaling pathway underlying the subcellular compartmentalization of mitochondrial morphology in dendrites of neurons in vivo through spatially precise and activity-dependent regulation of mitochondria fission/fusion balance., (© 2024. The Author(s).)

Public Health Emergency Operations Centers (PHEOCs) are the critical units to lead communications, information sharing, and resource mobilisation during national and international health emergencies, and are key components for maintaining global health security. This assessment sought to examine the coordination mechanisms between national and sub-national PHEOCs in Thailand, Cambodia, Lao People's Democratic Republic, and Malaysia (TCLM countries) during the COVID-19 pandemic. Information was collected on PHEOC structures, functions, and cross-border communications in three stages: a literature review of national PHEOC and emergency preparedness capacities; questionnaire responses from stakeholders to describe PHEOC activity at the national level; and meetings with emergency response staff in five border provinces of Thailand to assess communications between sub-national PHEOCs across country borders. The findings showed that each of the countries has demonstrated a commitment to strengthening their national PHEOCs and improving cross-border communication in the face of the COVID-19 pandemic. Strong existing relationships between TCLM countries assisted in activating a coordinated pandemic response, but gaps remain in efficient data sharing, workforce capacity, and the utilisation of consistent communication platforms among countries. Lessons learned from the pandemic can be used to further strengthen countries' preparedness for future health emergencies, in line with International Health Regulations (2005) and regional plans to build health security in the Southeast Asia region. This assessment provides TCLM countries with the opportunity to address weaknesses in national and international PHEOC capacities. It may be used alongside existing guidelines to prepare the region for a stronger response to future global and regional health emergencies., Competing Interests: Disclosure statement No potential conflict of interest was reported by the authors.

We evaluated effectiveness of personal protective measures against severe acute respiratory disease coronavirus 2 (SARS-CoV-2) infection. Our case-control study included 211 cases of coronavirus disease (COVID-19) and 839 controls in Thailand. Cases were defined as asymptomatic contacts of COVID-19 patients who later tested positive for SARS-CoV-2; controls were asymptomatic contacts who never tested positive. Wearing masks all the time during contact was independently associated with lower risk for SARS-CoV-2 infection compared with not wearing masks; wearing a mask sometimes during contact did not lower infection risk. We found the type of mask worn was not independently associated with infection and that contacts who always wore masks were more likely to practice social distancing. Maintaining >1 m distance from a person with COVID-19, having close contact for <15 minutes, and frequent handwashing were independently associated with lower risk for infection. Our findings support consistent wearing of masks, handwashing, and social distancing to protect against COVID-19.

The HIV epidemic in Thailand is concentrated in key populations, with the highest rates in men who have sex with men (MSM) and transgender women (TG). Previous studies of HIV incidence in these groups have been limited mostly to Bangkok. We measured HIV incidence in MSM and TG in four provinces and evaluated factors associated with incident infections to inform public health prevention efforts. An analysis was conducted using data collected during a prospective observational cohort study during April 2015-May 2018 in outpatient clinics in five hospitals across four provinces in Thailand. MSM and TG aged ≥18 years, who were not known to be HIV-infected, and who reported anal intercourse with a male or TG without a condom in the past six months were enrolled. Participants were followed-up every 6 months for 18 months with questionnaires and HIV testing. A total of 40 HIV seroconversions occurred during follow-up, resulting in an HIV incidence of 3.5 per 100 person-years (95% CI 2.5, 4.8). Multivariate analyses indicated that identifying as gay (adjusted hazard ratio [AHR] 4.9; 95% CI 1.7-14.2), having receptive anal sex in the past six months (AHR 3.6; 95% CI 1.4-9.5), using alcohol (AHR 3.3; 95% CI 1.3-8.3), and taking alkyl nitrites (AHR 4.4; 95% CI 1.7-11.2) in the past six months were all independently associated with HIV infection. Overall this study found a lower HIV incidence in the highest risk population in Thailand compared with similar studies in Bangkok. Accelerated prevention efforts are needed to make the goal of 'zero new infections' possible in Thailand.

Background: Health care workers are at high risk for tuberculosis (TB). China, a high burden TB country, has no policy on medical surveillance for TB among healthcare workers. In this paper, we evaluate whether China's national TB diagnostic guidelines could be used as a framework to screen healthcare workers for pulmonary TB disease in a clinical setting in China., Methods: Between April-August 2010, healthcare workers from 28 facilities in Inner Mongolia Autonomous Region, China were eligible for TB screening, comprised of symptom check, chest X-ray and tuberculin skin testing. Healthcare workers were categorized as having presumptive, confirmed, or clinically-diagnosed pulmonary TB, using Chinese national guidelines., Results: All healthcare workers (N=4347) were eligible for TB screening, of which 4285 (99%) participated in at least one TB screening test. Of the healthcare workers screened, 2% had cough for ≥ 14 days, 3% had a chest X-ray consistent with TB, and 10% had a tuberculin skin test induration ≥ 20 mm. Of these, 124 healthcare workers were identified with presumptive TB (i.e., cough for ≥ 14 days in the past 4 weeks or x-ray consistent with TB). Twelve healthcare workers met the case definition for clinically-diagnosed pulmonary TB, but none were diagnosed with TB during the study period., Conclusion: A substantial proportion of healthcare workers in Inner Mongolia had signs, symptoms, or test results suggestive of TB disease that could have been identified using national TB diagnostic guidelines as a screening framework. However, achieving medical surveillance in China will require a framework that increases the ease, accuracy, and acceptance of TB screening in the medical community. Routine screening with improved diagnostics should be considered to detect tuberculosis disease among healthcare workers and reduce transmission in health care settings in China., Competing Interests: HCWs provided written informed consent to participate in TB screening. The Chinese Ethical Committee for Tuberculosis Operational Research and the China Center for Disease Control and Prevention approved this project.Not applicable.None of the authors have a commercial or other financial interest associated with the information presented.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Mycobacterium africanum is endemic to West Africa and causes tuberculosis (TB). We reviewed reported cases of TB in the United States during 2004-2013 that had lineage assigned by genotype (spoligotype and mycobacterial interspersed repetitive unit variable number tandem repeats). M. africanum caused 315 (0.4%) of 73,290 TB cases with lineage assigned by genotype. TB caused by M. africanum was associated more with persons from West Africa (adjusted odds ratio [aOR] 253.8, 95% CI 59.9-1,076.1) and US-born black persons (aOR 5.7, 95% CI 1.2-25.9) than with US-born white persons. TB caused by M. africanum did not show differences in clinical characteristics when compared with TB caused by M. tuberculosis. Clustered cases defined as >2 cases in a county with identical 24-locus mycobacterial interspersed repetitive unit genotypes, were less likely for M. africanum (aOR 0.1, 95% CI 0.1-0.4), which suggests that M. africanum is not commonly transmitted in the United States.

Background: Kenya recently transitioned from a paper to an electronic system for recording and reporting of tuberculosis (TB) data., Methods: During September-October 2013, the data quality of the new system was evaluated through an audit of data in paper source documents and in the national electronic system, and an analysis of all 99 281 cases reported in 2012., Results: While the new electronic system overall is robust, this assessment demonstrated limitations in the concordance and completeness of data reaching the national level., Conclusions: Additional oversight and training in data entry are needed to strengthen TB surveillance data quality in Kenya., (Published by Oxford University Press on behalf of the European Public Health Association 2015. This work is written by US Government employees and is in the public domain in the US.)

Background: WHO recommends screening for TB and evaluation for isoniazid preventive therapy (IPT) based on evidence that they reduce TB-related morbidity and mortality among HIV-infected persons. In Vietnam, an IPT pilot was implemented in two provinces; TB screening, treatment and outcomes were evaluated to inform the adoption and scale-up of IPT., Methods: During April 2008 to March 2010, eligible HIV-infected persons aged >15 years, with no previous or current TB treatment, alcohol abuse or liver disease were screened for TB. If TB disease was ruled out based on symptoms, chest x-rays and sputum smears, isoniazid was administered for 9 months., Results: Among 1281 HIV-infected persons who received initial eligibility screening, 520 were referred to and evaluated at district TB clinics for TB disease or IPT eligibility. Active TB was diagnosed in 17 patients and all were started on treatment. Of 520 patients evaluated, 416 (80.0%) initiated IPT: 382 (91.8%) completed IPT, 17 (4.1%) stopped treatment, 8 (1.9%) died, 3 (0.7%) developed TB during IPT and 6 (1.4%) had unknown outcomes. No severe adverse events were reported., Conclusions: IPT treatment completion was high; no serious complications occurred. Improving and expanding intensified case-finding and IPT should be considered in Vietnam., (Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Setting: The Uganda National Tuberculosis Reference Laboratory (NTRL) in Kampala., Objective: The proportion of poor quality specimens received for drug susceptibility testing (DST) at the NTRL and factors contributing to poor specimen quality were assessed., Design: A cross-sectional study was conducted of sputum samples received at the NTRL from patients at high risk for multidrug-resistant tuberculosis (MDR TB) during July-October 2013. Demographic, clinical, and bacteriological data were abstracted from laboratory records. A poor quality sample failed to meet any one of four criteria: ≥3 milliliter (ml) volume, delivered within 72 hours, triple packaged, and non-salivary appearance., Results: Overall, 365 (64%) of 556 samples were of poor quality; 89 (16%) were not triple packaged, 44 (8%) were <3 mls, 164 (30%) were not delivered on time, and 215 (39%) were salivary in appearance. Poor quality specimens were more likely to be collected during the eighth month of TB treatment (OR = 2.5, CI = 1.2 - 5.1), from the East or Northeast zones (OR = 2.2, CI = 1.1 - 4.8), and from patients who previously defaulted from treatment (OR = 1.9, CI = 1.1 - 3.2)., Conclusion: The majority of sputum samples had poor quality. Additional efforts are needed to improve quality of samples collected at the end of treatment, from East and Northeast zones, and from patients who had previously defaulted., Competing Interests: Conflict of Interest None of the authors have a commercial or other financial interest associated with the information presented in this manuscript.

Objectives: We used race-corrected data and comprehensive diagnostic codes to better compare HIV and tuberculosis (TB) mortality from 1999 to 2009 between American Indian/Alaska Natives (AI/ANs) and Whites., Methods: National Vital Statistics Surveillance System mortality data were adjusted for AI/AN racial misclassification through linkage with Indian Health Service registration records. We compared average annual 1990 to 2009 HIV and TB death rates (per 100,000 people) for AI/AN persons with those for Whites; Hispanics were excluded., Results: Although death rates from HIV in AI/AN persons were significantly lower than those in Whites from 1990 to 1998 (4.2 vs 7.0), they were significantly higher than those in Whites from 1999 to 2009 (3.6 vs 2.0). Death rates from TB in AI/AN persons were significantly higher than those in Whites, with a significant disparity during both 1990 to 1998 (3.3 vs 0.3) and 1999 to 2009 (1.5 vs 0.1)., Conclusions: The decrease in death rates from HIV and TB was greater among Whites, and death rates remained significantly higher among AI/AN individuals. Public health interventions need to be prioritized to reduce the TB and HIV burden and mortality in AI/AN populations.

Background: An unprecedented number of nationwide tuberculosis (TB) prevalence surveys will be implemented between 2010 and 2015, to better estimate the burden of disease caused by TB and assess whether global targets for TB control set for 2015 are achieved. It is crucial that results are analysed using best-practice methods., Objective: To provide new theoretical and practical guidance on best-practice methods for the analysis of TB prevalence surveys, including analyses at the individual as well as cluster level and correction for biases arising from missing data., Analytic Methods: TB prevalence surveys have a cluster sample survey design; typically 50-100 clusters are selected, with 400-1000 eligible individuals in each cluster. The strategy recommended by the World Health Organization (WHO) for diagnosing pulmonary TB in a nationwide survey is symptom and chest X-ray screening, followed by smear microscopy and culture examinations for those with an abnormal X-ray and/or TB symptoms. Three possible methods of analysis are described and explained. Method 1 is restricted to participants, and individuals with missing data on smear and/or culture results are excluded. Method 2 includes all eligible individuals irrespective of participation, through multiple missing value imputation. Method 3 is restricted to participants, with multiple missing value imputation for individuals with missing smear and/or culture results, and inverse probability weighting to represent all eligible individuals. The results for each method are then compared and illustrated using data from the 2007 national TB prevalence survey in the Philippines. Simulation studies are used to investigate the performance of each method., Key Findings: A cluster-level analysis, and Methods 1 and 2, gave similar prevalence estimates (660 per 100,000 aged ≥ 10 years old), with a higher estimate using Method 3 (680 per 100,000). Simulation studies for each of 4 plausible scenarios show that Method 3 performs best, with Method 1 systematically underestimating TB prevalence by around 10%., Conclusion: Both cluster-level and individual-level analyses should be conducted, and individual-level analyses should be conducted both with and without multiple missing value imputation. Method 3 is the safest approach to correct the bias introduced by missing data and provides the single best estimate of TB prevalence at the population level.

Objective: Between December 2005 and November 2007, a cluster of 11 tuberculosis (TB) cases emerged in Jackson County, Mississippi. We investigated the potential sources of disease transmission and epidemiologic links in this cluster to prevent future transmission in the community., Materials and Methods: Cases of TB reported in Jackson County from December 2005 to November 2007 having matching genotypes or social links to patients with matching genotypes were included in the investigation. We interviewed patients, reviewed medical records, and performed contact investigations., Results: The combined genotyping and epidemiologic data pointed to ongoing TB transmission in this rural community. A combination of patient-specific and programmatic factors, including substance use, delays in TB diagnosis, nonadherence, and TB program staffing cuts, contributed to this outbreak in the context of the 2004 and 2005 Atlantic hurricane seasons., Conclusions: To eliminate Mycobacterium tuberculosis transmission in this setting, recommendations for the TB program include enhanced coordination with substance abuse programs, community and provider education, and increased outreach capacity.

Objectives: We examined trends and epidemiology of tuberculosis (TB) across racial/ethnic groups to better understand TB disparities in the United States, with particular focus on American Indians/Alaska Natives (AI/ANs) and Native Hawaiians/other Pacific Islanders (NH/PIs)., Methods: We analyzed cases in the U.S. National Tuberculosis Surveillance System and calculated TB case rates among all racial/ethnic groups from 2003 to 2008. Socioeconomic and health indicators for counties in which TB cases were reported came from the Health Resources and Services Administration Area Resource File., Results: Among the 82,836 TB cases, 914 (1.1%) were in AI/ANs and 362 (0.4%) were in NH/PIs. In 2008, TB case rates for AI/ANs and NH/PIs were 5.9 and 14.7 per 100,000 population, respectively, rates that were more than five and 13 times greater than for non-Hispanic white people (1.1 per 100,000 population). From 2003 to 2008, AI/ANs had the largest percentage decline in TB case rates (-27.4%) for any racial/ethnic group, but NH/PIs had the smallest percentage decline (-3.5%). AI/ANs were more likely than other racial/ethnic groups to be homeless, excessively use alcohol, receive totally directly observed therapy, and come from counties with a greater proportion of people living in poverty and without health insurance. A greater proportion of NH/PIs had extrapulmonary disease and came from counties with a higher proportion of people with a high school diploma., Conclusions: There is a need to develop flexible TB-control strategies that address the social determinants of health and that are tailored to the specific needs of AI/ANs and NH/PIs in the U.S.

Setting: Latvia has one of the highest rates of multidrug-resistant tuberculosis (MDR-TB) globally. Clinical management of MDR-TB requires lengthy multidrug regimens that often cause adverse events., Design: We retrospectively reviewed records of patients who began MDR-TB treatment between 2000 and 2004. Treatment-related adverse events and factors associated with experiencing adverse events were evaluated. We also examined the frequency of and reasons for changing drug regimens., Results: Among 1027 cases, 807 (79%) experienced at least one adverse event, with a median of three events per case. The most commonly reported events were nausea (58%), vomiting (39%) and abdominal pain (24%). More serious events, such as psychiatric episodes (13%), hepatitis (9%) and renal failure (4%), were relatively frequent. A change in drug dose due to an adverse event occurred in 201 (20%) cases, while 661 (64%) had at least one drug discontinued temporarily or permanently. Being older, female, having bilateral lung cavities and a greater number of TB symptoms at baseline were associated with an increased number of events., Conclusion: Adverse events were prevalent among MDR-TB cases treated in Latvia, with over two thirds requiring discontinuation of at least one drug. MDR-TB patients who are female, older or have severe TB disease should be closely monitored for treatment-related adverse events.

Chronic stress has been shown in animal models to result in altered dendritic morphology of pyramidal neurons of the medial prefrontal cortex (mPFC). It has been hypothesized that the stress-induced dendritic retractions and spine loss lead to disrupted connectivity that results in stress-induced functional impairment of mPFC. While these alterations were initially viewed as a neurodegenerative event, it has recently been established that stress induced dendritic alterations are reversible if animals are given time to recover from chronic stress. However, whether spine growth accompanies dendritic extension remains to be demonstrated. It is also not known if recovery-phase dendritic extension allows for re-establishment of functional capacity. The goal of this study, therefore, was to characterize the structural and functional effects of chronic stress and recovery on the infralimbic (IL) region of the rat mPFC. We compared neuronal morphology of IL layer V pyramidal neurons from male Sprague-Dawley rats subjected to 21 days of chronic restraint stress (CRS) to those that experienced CRS followed by a 21 day recovery period. Layer V pyramidal cell functional capacity was assessed by intra-IL long-term potentiation (LTP) both in the absence and presence of SKF38393, a dopamine receptor partial agonist and a known PFC LTP modulator. We found that stress-induced IL apical dendritic retraction and spine loss co-occur with receptor-mediated impairments to catecholaminergic facilitation of synaptic plasticity. We also found that while post-stress recovery did not reverse distal dendritic retraction, it did result in over extension of proximal dendritic arbors and spine growth as well as a full reversal of CRS-induced impairments to catecholaminergic-mediated synaptic plasticity. Our results support the hypothesis that disease-related PFC dysfunction is a consequence of network disruption secondary to altered structural and functional plasticity and that circuitry reestablishment may underlie elements of recovery. Accordingly, we believe that pharmacological treatments targeted at preventing dendritic retraction and spine loss or encouraging circuitry re-establishment and stabilization may be advantageous in the prevention and treatment of mood and anxiety disorders.

How dietary restriction (DR) increases lifespan and decreases disease burden are questions of major interest in biomedical research. Here we report that hypothalamic expression of CREB-binding protein (CBP) and CBP-binding partner Special AT-rich sequence binding protein 1 (SATB-1) is highly correlated with lifespan across five strains of mice, and expression of these genes decreases with age and diabetes in mice. Furthermore, in Caenorhabditis elegans, cbp-1 is induced by bacterial dilution DR (bDR) and the daf-2 mutation, and cbp-1 RNAi specifically in adults completely blocks lifespan extension by three distinct protocols of DR, partially blocks lifespan extension by the daf-2 mutation but not of cold, and blocks delay of other age-related pathologies by bDR. Inhibiting the C. elegans ortholog of SATB-1 and CBP-binding partners daf-16 and hsf-1 also attenuates lifespan extension by bDR, but not other protocols of DR. In a transgenic Abeta42 model of Alzheimer's disease, cbp-1 RNAi prevents protective effects of bDR and accelerates Abeta42-related pathology. Furthermore, consistent with the function of CBP as a histone acetyltransferase, drugs that enhance histone acetylation increase lifespan and reduce Abeta42-related pathology, protective effects completely blocked by cbp-1 RNAi. Other factors implicated in lifespan extension are also CBP-binding partners, suggesting that CBP constitutes a common factor in the modulation of lifespan and disease burden by DR and the insulin/IGF1 signaling pathway., Competing Interests: The authors have declared that no competing interests exist.