HTLV-1 bZIP Factor-Induced Reprogramming of Lactate Metabolism and Epigenetic Status Promote Leukemic Cell Expansion.

Acceleration of glycolysis is a common trait of cancer. A key metabolite, lactate, is typically secreted from cancer cells because its accumulation is toxic. Here, we report that a viral oncogene, HTLV-1 bZIP factor (HBZ), bimodally upregulates TAp73 to promote lactate excretion from adult T-cell leukemia-lymphoma (ATL) cells. HBZ protein binds to EZH2 and reduces its occupancy of the TAp73 promoter. Meanwhile, HBZ RNA activates TAp73 transcription via the BATF3-IRF4 machinery. TAp73 upregulates the lactate transporters MCT1 and MCT4. Inactivation of TAp73 leads to intracellular accumulation of lactate, inducing cell death in ATL cells. Furthermore, TAp73 knockout diminishes the development of inflammation in HBZ-transgenic mice. An MCT1/4 inhibitor, syrosingopine, decreases the growth of ATL cells in vitro and in vivo. MCT1/4 expression is positively correlated with TAp73 in many cancers, and MCT1/4 upregulation is associated with dismal prognosis. Activation of the TAp73-MCT1/4 pathway could be a common mechanism contributing to cancer metabolism. SIGNIFICANCE: An antisense gene encoded in HTLV-1, HBZ, reprograms lactate metabolism and epigenetic modification by inducing TAp73 in virus-positive leukemic cells. A positive correlation between TAp73 and its target genes is also observed in many other cancer cells, suggesting that this is a common mechanism for cellular oncogenesis. This article is featured in Selected Articles from This Issue, p. 337.

Social phobia among long-term internally displaced persons: An epidemiological study of adults in two internally displaced person settlements in Sudan.

BACKGROUND: Despite the high worldwide prevalence and association with other mental disorders and disability, only few studies are available on social phobia in low-income countries. AIMS: This study aims to assess the prevalence, socio-demographic correlates and comorbidity of social phobia and its association with disability among long-term internally displaced persons (IDPs) in one urban and one rural area in Central Sudan. METHODS: This cross-sectional study was implemented in two IDP areas in Central Sudan. Data were collected during face-to-face interviews using structured questionnaires to assess socio-demographic factors and the Mini International Neuropsychiatric Interview (MINI) to determine psychiatric diagnoses. A total of 1,876 adults were enrolled from both study areas. RESULTS: The overall lifetime prevalence of social phobia was 14.2%, with higher rates among IDPs in the rural area and among those who were less educated. Social phobia was associated with other mental disorders in both study areas. Disability and prolonged displacement increased the risk of having social phobia in the rural area. CONCLUSION: Further work needs to be done to improve our understanding and to establish proper interventions in dealing with social phobia, other common mental disorders and disability among long-term IDPs in these impoverished areas.

The use of vital signs as predictors for serious bacterial infections in children with acute febrile illness in a pediatric emergency setting in Sudan.

Distinguishing children with serious infections from those with milder, self-limiting febrile illnesses remains a daily challenge in primary care and hospital emergency department. Measurement of vital signs is recommended as part of this assessment. To determine whether vital signs can predict children with serious bacterial infections, we studied the data of children aged 1 month to < 16 years presented who with acute febrile illness to a Pediatric emergency department in Sudan. Sample size was 150 patients. The severity of infection was classified as serious or not serious bacterial infection. Vital signs and oxygen saturation were recorded and compared to the final outcome of these children. Data analyzed bivariably and multivariably using regression analysis. Ten percent of patients were classified as having serious bacterial infection. Tachycardia and tachypnea were the most sensitive and specific in predicting serious bacterial infections with (80%, 86.6 % sensitivity) and (97.4%, 83.7% specificity), respectively. High temperature, severe hypoxemia and hypotension were the least sensitive but highly specific signs of serious bacterial infections. As a conclusion, vital signs can be used to differentiate children with serious bacterial infections from those with non-serious bacterial infections in pediatric emergency departments and has comparable sensitivity to more complicated triage systems.

The mental health of internally displaced persons: an epidemiological study of adults in two settlements in Central Sudan.

AIMS: There is a scarcity of data on mental health problems among Sudanese internally displaced persons (IDPs). This study aims to assess the prevalence of mental disorders of IDPs in Sudan, and to determine and compare the association between mental disorders and socio-demographic variables between the rural and urban long-term IDP populations. METHODS: This cross-sectional study was implemented in two IDP areas in Central Sudan. Data were collected during face-to-face interviews using structured questionnaires to assess socio-demographic factors and the Mini International Neuropsychiatric Interview (MINI) to determine psychiatric diagnoses. A total of 1,876 adults were enrolled from both study areas. RESULTS: The overall prevalence of having any mental health disorder in the IDP population was 52.9%. The most common disorders were major depressive disorder (24.3%), generalized anxiety disorder (23.6%), social phobia (14.2%) and post-traumatic stress disorder (12.3%). Years of displacement and education were associated with different mental disorders between the two areas, and there were no gender differences in prevalence of mental disorders in either area. CONCLUSION: This study shows high prevalence rates of mental disorders in both urban and rural IDP populations in Sudan, indicating a need to explore the circumstances for these high rates and to develop appropriate responses.