Care needs of people with dementia in Tanzania and associated impact on carers: A cross-sectional, observational study.

Objectives: This study aimed to understand the care needs, care arrangements and burden of care for people with dementia in Northern Tanzania. Methods: This was a cross-sectional, observational study. People with dementia and their carers (n = 53) were recruited from an outpatient clinic, and data on carer burden and independence in activities of daily living were collected. Associations with carer burden and characteristics were explored through non-parametric tests and regression analyses. Results: Thirty-six carers were female (68%). Levels of impairment in instrumental activities of daily living were high, with a median score of 38 out of 44 on the Identification and Intervention for Dementia in Elderly Africans - Instrumental Activities of Daily Living (IDEA-IADL). Carer burden was moderate with a median Zarit Burden Interview (ZBI) score of 46 out of 88. Being a female carer was associated with higher carer burden (odds ratio 3.68, 95% CI 1.04-12.99). Discussion: Carer burden was found to be higher than in previous studies based in low-and-middle income countries. Further research is needed to explore this difference, and to identify interventions to support care needs and reduce carer burden.

Differentiating Lung Nodules Due to Coccidioides from Those Due to Lung Cancer Based on Radiographic Appearance.

BACKGROUND: Coccidioidomycosis (cocci) is an endemic fungal disease that can cause asymptomatic or post-symptomatic lung nodules which are visible on chest CT scanning. Lung nodules are common and can represent early lung cancer. Differentiating lung nodules due to cocci from those due to lung cancer can be difficult and lead to invasive and expensive evaluations. MATERIALS AND METHODS: We identified 302 patients with biopsy-proven cocci or bronchogenic carcinoma seen in our multidisciplinary nodule clinic. Two experienced radiologists who were blinded to the diagnosis read the chest CT scans and identified radiographic characteristics to determine their utility in differentiating lung cancer nodules from those due to cocci. RESULTS: Using univariate analysis, we identified several radiographic findings that differed between lung cancer and cocci infection. We then entered these variables along with age and gender into a multivariate model and found that age, nodule diameter, nodule cavitation, presence of satellite nodules and radiographic presence of chronic lung disease differed significantly between the two diagnoses. Three findings, cavitary nodules, satellite nodules and chronic lung disease, have sufficient discrimination to potentially be useful in clinical decision-making. CONCLUSIONS: Careful evaluation of the three obtained radiographic findings can significantly improve our ability to differentiate benign coccidioidomycosis infection from lung cancer in an endemic region for the fungal disease. Using these data may significantly reduce the cost and risk associated with distinguishing the cause of lung nodules in these patients by preventing unnecessary invasive studies.

Population normative data for three cognitive screening tools for older adults in sub-Saharan Africa.

In sub-Saharan Africa (SSA),cognitive screening is complicated by both cultural and educational factors, and the existing normative values may not be applicable. The Identification of Dementia in Elderly Africans (IDEA) cognitive screen is a low-literacy measure with good diagnostic accuracy for dementia. OBJECTIVE: The aim of this study is to report normative values for IDEA and other simple measures [i.e., categorical verbal fluency, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) 10-word list] in representative community-dwelling older adults in SSA. METHODS: Individuals aged ≥60 years resident in 12 representative villages in Kilimanjaro, Tanzania and individuals aged ≥65 years resident within three communities in Akinyele Local Government Area, Oyo State, Nigeria underwent cognitive screening. The normative data were generated by the categories of age, sex, and education. RESULTS: A total of 3,011 people in Tanzania (i.e., 57.3% females and 26.4% uneducated) and 1,117 in Nigeria (i.e., 60.3% females and 64.5% uneducated) were screened. Individuals with higher age, lower education, and female gender obtained lower scores. The 50th decile values for IDEA were 13 (60-64 years) vs. 8/9 (above 85 years), 10-11 uneducated vs. 13 primary educated, and 11/12 in females vs. 13 in males. The normative values for 10-word list delayed recall and categorical verbal fluency varied with education [i.e., delayed recall mean 2.8 [standard deviation (SD) 1.7] uneducated vs. 4.2 (SD 1.2) secondary educated; verbal fluency mean 9.2 (SD 4.8) uneducated vs. 12.2 (SD 4.3) secondary educated], substantially lower than published high-income country values. CONCLUSIONS: The cut-off values for commonly used cognitive screening items should be adjusted to suit local normative values, particularly where there are lower levels of education.

Na África Subsaariana (ASS), a triagem cognitiva é complicada por fatores culturais e educacionais, além dos valores normativos existentes poderem não ser aplicáveis. O rastreio cognitivo Identification of Dementia in Elderly Africans (IDEA) é uma medida para níveis baixos de alfabetização com boa acurácia diagnóstica para demência. OBJETIVO: Relatar os valores normativos para a IDEA e outras medidas simples (fluência verbal categórica, a lista de 10 palavras do Consortium to Establish a Registry for Alzheimer's Disease (CERAD) em idosos residentes na comunidade, representativos da ASS. Métodos: Indivíduos com idade ≥60 residentes em 12 comunidades representativas em Kilimanjaro, Tanzânia e indivíduos com idade ≥65 anos residentes em três comunidades na área governamental de Akinyele, Estado de Oyo, Nigéria, foram submetidos à triagem cognitiva. Os dados normativos foram gerados por faixas etárias, sexo e escolaridade. RESULTADOS: Um total de 3.011 pessoas na Tanzânia (57,3% mulheres, 26,4% sem educação) e 1.117 na Nigéria (60,3% mulheres, 64,5% sem educação) foram examinadas. Os indivíduos com idade mais alta, menor escolaridade e mulheres obtiveram escores mais baixos. Os valores do percentil 50 para a IDEA foram 13 (60­64 anos) vs. 8/9 (85+ anos), 10­11 para analfabetos vs. 13 com educação primária e 11/12 em mulheres vs. 13 em homens. Os valores normativos para a evocação tardia da lista de 10 palavras e a fluência verbal categórica variaram com a educação (evocação tardia 2,8 (SD 1,7) para os sem educação, vs. 4,2 (SD 1,2) para com educação secundária; fluência verbal 9,2 (DP 4,8) para os sem educação vs. 12,2 (SD 4.3) para os com ensino médio, substancialmente inferior aos valores publicados em países de alta renda. CONCLUSÕES: Os valores de corte para testes de triagem cognitiva comumente usados devem ser ajustados para se adequar aos valores normativos locais, particularmente em níveis baixos de educação.

Population normative data for three cognitive screening tools for older adults in sub-Saharan Africa / Dados normativos populacionais para três instrumentos de triagem cognitiva para idosos na áfrica subsaariana

ABSTRACT In sub-Saharan Africa (SSA),cognitive screening is complicated by both cultural and educational factors, and the existing normative values may not be applicable. The Identification of Dementia in Elderly Africans (IDEA) cognitive screen is a low-literacy measure with good diagnostic accuracy for dementia. Objective: The aim of this study is to report normative values for IDEA and other simple measures [i.e., categorical verbal fluency, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) 10-word list] in representative community-dwelling older adults in SSA. Methods: Individuals aged ≥60 years resident in 12 representative villages in Kilimanjaro, Tanzania and individuals aged ≥65 years resident within three communities in Akinyele Local Government Area, Oyo State, Nigeria underwent cognitive screening. The normative data were generated by the categories of age, sex, and education. Results: A total of 3,011 people in Tanzania (i.e., 57.3% females and 26.4% uneducated) and 1,117 in Nigeria (i.e., 60.3% females and 64.5% uneducated) were screened. Individuals with higher age, lower education, and female gender obtained lower scores. The 50th decile values for IDEA were 13 (60-64 years) vs. 8/9 (above 85 years), 10-11 uneducated vs. 13 primary educated, and 11/12 in females vs. 13 in males. The normative values for 10-word list delayed recall and categorical verbal fluency varied with education [i.e., delayed recall mean 2.8 [standard deviation (SD) 1.7] uneducated vs. 4.2 (SD 1.2) secondary educated; verbal fluency mean 9.2 (SD 4.8) uneducated vs. 12.2 (SD 4.3) secondary educated], substantially lower than published high-income country values. Conclusions: The cut-off values for commonly used cognitive screening items should be adjusted to suit local normative values, particularly where there are lower levels of education.

RESUMO Na África Subsaariana (ASS), a triagem cognitiva é complicada por fatores culturais e educacionais, além dos valores normativos existentes poderem não ser aplicáveis. O rastreio cognitivo Identification of Dementia in Elderly Africans (IDEA) é uma medida para níveis baixos de alfabetização com boa acurácia diagnóstica para demência. Objetivo: Relatar os valores normativos para a IDEA e outras medidas simples (fluência verbal categórica, a lista de 10 palavras do Consortium to Establish a Registry for Alzheimer's Disease (CERAD) em idosos residentes na comunidade, representativos da ASS. Métodos: Indivíduos com idade ≥60 residentes em 12 comunidades representativas em Kilimanjaro, Tanzânia e indivíduos com idade ≥65 anos residentes em três comunidades na área governamental de Akinyele, Estado de Oyo, Nigéria, foram submetidos à triagem cognitiva. Os dados normativos foram gerados por faixas etárias, sexo e escolaridade. Resultados: Um total de 3.011 pessoas na Tanzânia (57,3% mulheres, 26,4% sem educação) e 1.117 na Nigéria (60,3% mulheres, 64,5% sem educação) foram examinadas. Os indivíduos com idade mais alta, menor escolaridade e mulheres obtiveram escores mais baixos. Os valores do percentil 50 para a IDEA foram 13 (60-64 anos) vs. 8/9 (85+ anos), 10-11 para analfabetos vs. 13 com educação primária e 11/12 em mulheres vs. 13 em homens. Os valores normativos para a evocação tardia da lista de 10 palavras e a fluência verbal categórica variaram com a educação (evocação tardia 2,8 (SD 1,7) para os sem educação, vs. 4,2 (SD 1,2) para com educação secundária; fluência verbal 9,2 (DP 4,8) para os sem educação vs. 12,2 (SD 4.3) para os com ensino médio, substancialmente inferior aos valores publicados em países de alta renda. Conclusões: Os valores de corte para testes de triagem cognitiva comumente usados devem ser ajustados para se adequar aos valores normativos locais, particularmente em níveis baixos de educação.

The role and profile of the informal carer in meeting the needs of people with advancing Parkinson's disease.

BACKGROUND: Many people with Parkinson's disease (PD) (PwP) require care from either informal or formal carers, due to worsening symptoms. Carer strain is a recognised consequence of caring. However there are few data on the role and profile of informal carers and if this impacts on carer strain. METHOD: People with moderate to advanced PD, with an informal carer were invited to participate. Data regarding motor and non-motor symptoms of the participant, along with demographics, tasks and duration of caring and health issues of the carer were collected. RESULTS: One-hundred and fifteen participants and their carer were recruited. Mean carer age was 70.7 years, 66.1% were female caring for a median of 16 hours per day. Over 80% provided help in housework and companionship activities, 63.2% with dressing and 49.1% with feeding. There was a significant relationship between disease stage and level of strain. Participant age, physical and cognitive disability were significantly associated with greater care need. High care need was associated with poor carer quality of life. CONCLUSIONS: The care needs of PwP are considerable. To reduce carer strain and improve quality of life, carers' needs must be considered to enable them to carry on with their vital role.

Specialist emergency care and COPD outcomes.

INTRODUCTION: In exacerbation of chronic obstructive pulmonary disease (ECOPD) requiring hospitalisation greater access to respiratory specialists improves outcome, but is not consistently delivered. The UK National Confidential Enquiry into Patient Outcome and Death 2015 enquiry showed over 25% of patients receiving acute non-invasive ventilation (NIV) for ECOPD died in hospital. On 16 June 2015 the Northumbria Specialist Emergency Care Hospital (NSECH) opened, introducing 24/7 specialty consultant on-call, direct admission from the emergency department to specialty wards and 7-day consultant review. A Respiratory Support Unit opened for patients requiring NIV. Before NSECH the NIV service included mandated training and competency assessment, 24/7 single point of access, initiation of ventilation in the emergency department, a door-to-mask time target, early titration of ventilation pressures and structured weaning. Pneumonia or hypercapnic coma complicating ECOPD have never been considered contraindications to NIV. After NSECH staff-patient ratios increased, the NIV pathway was streamlined and structured daily multidisciplinary review introduced. We compared our outcomes with historical and national data. METHODS: Patients hospitalised with ECOPD between 1 January 2013 and 31 December 2016 were identified from coding, with ventilation status and radiological consolidation confirmed from records. Age, gender, admission from nursing home, consolidation, revised Charlson Index, key comorbidities, length of stay, and inpatient and 30-day mortality were captured. Outcomes pre-NSECH and post-NSECH opening were compared and independent predictors of survival identified via logistic regression. RESULTS: There were 6291 cases. 24/7 specialist emergency care was a strong independent predictor of lower mortality. Length of stay reduced by 1 day, but 90-day readmission rose in both ventilated and non-ventilated patients. CONCLUSION: Provision of 24/7 respiratory specialist emergency care improved ECOPD survival and shortened length of stay for both non-ventilated and ventilated patients. The potential implications in respect to service design and provision nationally are substantial and challenging.

Nephron-sparing management of Xanthogranulomatous pyelonephritis presenting as spontaneous renal hemorrhage: a case report and literature review.

BACKGROUND: Xanthogranulomatous pyelonephritis (XGP) is an uncommon infectious disease of the kidney known to mimic other renal maladies. A rare presentation of this uncommon disease is spontaneous renal hemorrhage (SRH). CASE PRESENTATION: We report a case of XGP in a 58 year old woman who presented with abdominal pain, hematuria, and radiating left flank pain. CT scan was felt to be consistent with perirenal hemorrhage abutting a fat-containing renal mass. The patient was eventually taken to surgery for left partial nephrectomy. Pathology report returned as XGP, and the patient has no complications from this disease process at 8 month follow up. CONCLUSION: Our search of the literature shows XGP presenting as SRH to be a rare clinical entity. Furthermore, this is the first such case managed with a nephron-sparing approach. The "great imitator" XGP should be added to the differential for patients presenting with spontaneous renal hemorrhage.

N5 ,N10 -methylenetetrahydromethanopterin reductase from Methanocaldococcus jannaschii also serves as a methylglyoxal reductase.

In Methanocaldococcus jannaschii, methylglyoxal (MG) is required for aromatic amino acid biosynthesis. Previously, the reduction of MG to lactaldehyde in Methanocaldococcus jannaschii cell extracts using either NADPH or F420 H2 was demonstrated; however, the enzyme responsible was not identified. Using NADPH as the reductant, the unknown enzyme was purified from cell extracts of Methanocaldococcus jannaschii and determined to be the F420 -dependent N5 ,N10 -methylenetetrahydromethanopterin reductase (Mer). Here, we report that the recombinantly overexpressed Mer is able to use NADPH and MG (KM of 1.6 and 1.0 mm, respectively) to produce lactaldehyde. Additionally, Mer does not catalyze the reduction of MG to lactaldehyde in the presence of reduced Fo, the precursor of F420 .

Adaptation and validation of the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) in a low-literacy setting in sub-Saharan Africa.

OBJECTIVE: This study aimed to assess the feasibility of a low-literacy adaptation of the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) for use in rural sub-Saharan Africa (SSA) for interventional studies in dementia. No such adaptations currently exist. METHODS: Tanzanian and Nigerian health professionals adapted the ADAS-Cog by consensus. Validation took place in a cross-sectional sample of 34 rural-dwelling older adults with mild/moderate dementia alongside 32 non-demented controls in Tanzania. Participants were oversampled for lower educational level. Inter-rater reliability was conducted by two trained raters in 22 older adults (13 with dementia) from the same population. Assessors were blind to diagnostic group. RESULTS: Median ADAS-Cog scores were 28.75 (interquartile range (IQR), 22.96-35.54) in mild/moderate dementia and 12.75 (IQR 9.08-16.16) in controls. The area under the receiver operating characteristic curve (AUC) was 0.973 (95% confidence interval (CI) 0.936-1.00) for dementia. Internal consistency was high (Cronbach's α 0.884) and inter-rater reliability was excellent (intra-class correlation coefficient 0.905, 95% CI 0.804-0.964). CONCLUSION: The low-literacy adaptation of the ADAS-Cog had good psychometric properties in this setting. Further evaluation in similar settings is required.

Screening for delirium in specialist palliative care inpatient units: perceptions and outcomes.

OBJECTIVES: The UK National Institute for Health and Care Excellence (NICE) indicate that palliative care patients are at high risk of delirium and should be screened for it using the short confusion assessment method (short CAM). This study aimed to assess the perceptions of the short CAM for delirium screening amongst health-care workers in specialist palliative care inpatient units (SPCUs) and to investigate its use as a screening instrument. METHODS: Patients in 5 SPCUs in the North East of England were screened for delirium using the short CAM and a staff survey assessed the acceptability of the short-CAM in this setting. RESULTS: Of the 63 staff surveyed, 79.4% felt screening for delirium was important and 59.3% found the short CAM 'not at all' burdensome to complete. However, only 40.7% felt that the short-CAM often accurately reflected patients' conditions and none felt it always accurately reflected patients' condition. Of 298 patients screened, 20% screened positive on the short CAM. Malignant and intra-cerebral diseases were significant independent predictors of a positive screen. Hospice length of stay and in-hospice mortality were higher in those with a positive result (66.7%) than in those without (38.2%). CONCLUSIONS: Health professionals deem delirium screening to be important in SPCUs, but may not support routine use of the short CAM. This could reflect a limited perceived impact on care and lack of confidence in this tool to reflect a complex patient group.

Answering the call to address chronic pain in military service members and veterans: Progress in improving pain care and restoring health.

Chronic noncancer pain (CNCP) in military and veteran populations mirrors the experience of chronic pain in America; however, these two populations have unique characteristics and comorbid conditions such as traumatic brain injuries, postconcussive syndrome, posttraumatic stress disorder, and behavioral health disorders that complicate the diagnosis and treatment of chronic pain. Military members and veterans may also be stigmatized about their conditions and experience problems with integration back into healthy lifestyles and society as a whole following deployments and after military service. The military and veteran health care systems have made chronic pain a priority and have made substantial strides in addressing this condition through advances in practice, education, research, and health policy. Despite this progress, significant challenges remain in responding to the wide-spread problem of chronic pain. The purpose of this article is to: (a) examine the state of CNCP in military and veteran populations; (b) discuss progress made in pain practice, education, research, and health policy; and (c) examine research, evidence-based practice guidelines, and expert consensus reports that are foundational to advancing pain care and improving health for military service members and veterans with CNCP. In addition, recommendations are proposed to address this widespread health problem through the expanded use of advanced practice registered nurses, the implementation of models of care, and use of national resources to educate health care providers, support practice, and promote effective pain care.

Cognitive assessment tools in Asia: a systematic review.

BACKGROUND: The prevalence of dementia is increasing in Asia than in any other continent. However, the applicability of the existing cognitive assessment tools is limited by differences in educational and cultural factors in this setting. We conducted a systematic review of published studies on cognitive assessments tools in Asia. We aimed to rationalize the results of available studies which evaluated the validity of cognitive tools for the detection of cognitive impairment and to identify the issues surrounding the available cognitive impairment screening tools in Asia. METHODS: Five electronic databases (CINAHL, MEDLINE, Embase, Cochrane Library, and Science Direct) were searched using the keywords dementia Or Alzheimer Or cognitive impairment And screen Or measure Or test Or tool Or instrument Or assessment, and 2,381 articles were obtained. RESULTS: Thirty-eight articles, evaluating 28 tools in seven Asian languages, were included. Twenty-nine (76%) of the studies had been conducted in East Asia with only four studies conducted in South Asia and no study from northern, western, or central Asia or Indochina. Local language translations of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were assessed in 15 and six studies respectively. Only three tools (the Korean Dementia Screening Questionnaire, the Picture-based Memory Intelligence Scale, and the revised Hasegawa Dementia Screen) were derived de novo from Asian populations. These tools were assessed in five studies. Highly variable cut-offs were reported for the MMSE (17-29/30) and MoCA (21-26/30), with 13/19 (68%) of studies reporting educational bias. CONCLUSIONS: Few cognitive assessment tools have been validated in Asia, with no published validation studies for many Asian nations and languages. In addition, many available tools display educational bias. Future research should include concerted efforts to develop culturally appropriate tools with minimal educational bias.

Ofatumumab for refractory opsoclonus-myoclonus syndrome following treatment of neuroblastoma.

Opsoclonus-myoclonus syndrome (OMS) may be associated with ANNA-1 (anti-Hu) autoantibodies. The standard treatment with IVIG, steroids, and anti-CD20 monoclonal antibody may fail, and optimal therapy is unknown. A patient developed OMS with high-titer ANNA-1 following recovery from neuroblastoma. She failed standard therapy and had only transient response to rituximab. Treatment with the humanized anti-CD20 monoclonal antibody ofatumumab combined with methotrexate resulted in transient neurologic improvement and decrease of ANNA-1. This suggests that ofatumumab combined with methotrexate should further be considered OMS patients, particularly in refractory disease.

Geriatric medicine: services and training in Africa.

BACKGROUND: the population is ageing globally and developing countries are experiencing the most rapid increase in the number of older persons. By 2045 the United Nations estimate that for the first time in history more people will be over 65, than under 15, years of age. The World Health Organization predicts that deaths from non-communicable diseases will rise by 24% in Africa in the next decade. The aim of this survey was to determine the specialist medical services available for older persons and the undergraduate and postgraduate training systems in place for geriatrics in each African country. METHODS: a short survey was developed and sent to representatives from every country. Where appropriate, French and Portuguese translations were available. RESULTS: responses were received from 40/54 countries (74%). Data were obtained via an internet search for a further three countries. Out of 43, 25 countries had no geriatricians. Out of 40, 35 countries had no formal undergraduate training for medical students on geriatrics and 33 of 40 countries reported no national postgraduate training scheme for geriatrics. Having at least one geriatrician in the country was associated with a World Bank upper middle-income status (P = 0.04), but there was no significant association with the population size (P = 0.395). CONCLUSION: despite increasing numbers of older people and the increasing burden of chronic disease there are few geriatricians in Africa. Without undergraduate training, even general medical physicians will have limited knowledge of specialist geriatric needs. This is an area that will require development and investment in the future.

COX-2 expression correlates with survival in patients with osteosarcoma lung metastases.

SUMMARY: The purpose of this study was to determine whether a correlation exists between tumor cyclooxygenase (COX)-2 expression and disease-specific survival in patients with osteosarcoma lung metastases. Thirty-six patients diagnosed with osteosarcoma lung metastases between the years 1990 and 2001 were included in this retrospective study. The majority of the patients (72%) presented newly -diagnosed osteosarcoma lung metastases whereas the remaining patients (28%) presented recurrent disease. Clinicopathologic parameters were obtained from patients' clinical records. Tissue samples were obtained at the time of resection of the lung metastases and stained for COX-2 using immunohistochemistry. Samples were graded according to the intensity of COX-2 staining (grade 0: negative, grade 1: very weak, grade 2: weak, grade 3: moderate, and grade 4: strong). COX-2 staining was correlated with disease-specific survival and clinicopathologic parameters using the Jonckheere-Terpstra and the Kruskal-Wallis tests. All patients with grade 3 or 4 COX-2 expression died of osteosarcoma lung metastases. Ten percent of patients with grade 2 COX-2 expression and 29% of patients with grade 1 expression were alive and free of disease at the last follow-up. By contrast, 60% of the patients with grade 0 COX-2 expression were alive and free of disease at the last follow-up. No association between COX-2 expression and clinicopathologic parameters was found. However, COX-2 expression correlated inversely with disease-specific survival in patients with osteosarcoma lung metastases. Our data indicate that COX-2 expression in metastatic osteosarcoma may have prognostic significance.

Metabolic and immune activation effects of treatment interruption in chronic HIV-1 infection: implications for cardiovascular risk.

BACKGROUND: Concern about costs and antiretroviral therapy (ART)-associated toxicities led to the consideration of CD4 driven strategies for the management of HIV. That approach was evaluated in the SMART trial that reported an unexpected increase of cardiovascular events after treatment interruption (TI). Our goal was to evaluate fasting metabolic changes associated with interruption of antiretroviral therapy and relate them to changes of immune activation markers and cardiovascular risk. METHODOLOGY: ACTG 5102 enrolled 47 HIV-1-infected subjects on stable ART, with <200 HIV RNA copies/mL and CD4 cell count >or=500 cells/microL. Subjects were randomly assigned to continue ART for 18 weeks with or without 3 cycles of interleukin-2 (IL-2) (cycle = 4.5 million IU sc BID x 5 days every 8 weeks). After 18 weeks ART was discontinued in all subjects until the CD4 cell count dropped below 350 cells/microL. Glucose and lipid parameters were evaluated every 8 weeks initially and at weeks 2, 4, 8 and every 8 weeks after TI. Immune activation was evaluated by flow-cytometry and soluble TNFR2 levels. PRINCIPAL FINDINGS: By week 8 of TI, levels of total cholesterol (TC) (median (Q1, Q3) (-0.73 (-1.19, -0.18) mmol/L, p<0.0001), LDL, HDL cholesterol (-0.36(-0.73,-0.03)mmol/L, p = 0.0007 and -0.05(-0.26,0.03), p = 0.0033, respectively) and triglycerides decreased (-0.40 (-0.84, 0.07) mmol/L, p = 0.005). However the TC/HDL ratio remained unchanged (-0.09 (-1.2, 0.5), p = 0.2). Glucose and insulin levels did not change (p = 0.6 and 0.8, respectively). After TI there was marked increase in immune activation (CD8+/HLA-DR+/CD38+ cells, 34% (13, 43), p<0.0001) and soluble TNFR2 (1089 ng/L (-189, 1655), p = 0.0008) coinciding with the rebound of HIV viremia. CONCLUSIONS: Our data suggests that interrupting antiretroviral therapy does not reduce cardiovascular disease (CVD) risk, as the improvements in lipid parameters are modest and overshadowed by the decreased HDL levels. Increased immune cell activation and systemic inflammatory responses associated with recrudescent HIV viremia may provide a more cogent explanation for the increased cardiovascular risk associated with treatment interruption and HIV infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT00015704.

Anatomic modifications in the enteric nervous system of piebald mice and physiological consequences to colonic motor activity.

It has been assumed that in piebald lethal mice that develop megacolon, impaired colonic motor activity is restricted to the aganglionic distal colon. Peristaltic mechanical recordings, immunohistochemistry, and quantitative PCR were used to investigate whether regions of the colon, other than the aganglionic segment, may also show anatomical modifications and dysfunctional colonic motor activity. Contrary to expectations, colonic migrating motor complexes (MMCs) were absent along the whole colon of piebald lethal homozygote mice and severely impaired in heterozygote siblings. Aganglionosis was detected not only in the distal colon of piebald homozygote lethal mice (mean length: 20.4 +/- 2.1 mm) but also surprisingly in their heterozygote siblings (mean length: 12.4 +/- 1.1 mm). Unlike homozygote lethal mice, piebald heterozygotes showed no signs of megacolon. Interestingly, mRNA expression for PGP 9.5 was also dramatically reduced (by 71-99%) throughout the entire small and large bowel in both homozygote lethal and heterozygous littermates (by 67-87%). Histochemical staining confirmed a significant reduction in myenteric ganglia along the whole colon. In summary, the piebald mutation in homozygote lethal and heterozygote siblings is associated with dramatic reductions in myenteric ganglia throughout the entire colon and not limited to the distal colon as originally thought. Functionally, this results in an absence or severe impairment of colonic MMC activity in both piebald homozygote lethal and heterozygote siblings, respectively. The observation that piebald heterozygotes have an aganglionic distal colon (mean length: 12 mm) but live a normal murine life span without megacolon suggests that aganglionosis >12 mm and the complete absence of colonic MMCs may be required before any symptoms of megacolon arise.