Role of micronutrients in HIV infection

More than 60% of the estimated 40 million persons with HIV/AIDS worldwide live in sub-Saharan Africa, where poverty, social insecurity, food shortages and malnutrition are major problems.1 In children under the age of 5 years, who live in developing countries, malnutrition has been associated with 50% of the 10.8 million deaths mainly caused by neonatal disorders, diarrhoea, pneumonia, malaria and HIV/AIDS.2 Likewise micronutrient deficiencies are widespread and are associated with increased morbidity and mortality particularly in relation to infectious diseases.3 This review focuss on the interaction between micronutrients and HIV/AIDS and discusses recent research findings that may have important public health implications in terms of the case management of persons with HIV/AIDS Southern African Journal of HIV Medicine Vol. 6 (2) 2005: pp. 18-2

Safety and immunogenicity of TetractHib (a vaccine combining DTP vaccine and Haemophilus influenza type b conjugate vaccine) administered to infants at 6, 10 and 14 weeks of age

The safety and immunogenicity of TETRActHIB (a vaccine combining diphtheria and tetanus toxoids-pertussis vaccine (DTP) with Haemophilus influenzae type b (Hib) conjugate vaccine (polyribosyl ribitol phosphate conjugated to tetanus protein) (PRP-T)) was assessed in 131 Cape Town infants immunised at 6, 10 and 14 weeks of age. Serological responses to all component antigens were measured before the first dose and at 18 weeks of age. In addition, anti-PRP antibodies were measured at 9 and 18 months of age to determine long-term immunogenicity. The vaccine was well tolerated by infants and no significant side-effects were reported. Responses to Hib at 18 weeks of age were good in that most infants achieved a level of anti-PRP antibodies <". 0.15 μg/ml, indicative of short-term protection, and 70% achieved a level<". 1 μg/ml, indicative of long-term protection. The proportions of children with protective levels<". 0.15 μg/ml and<". 1 μg/ml were similar at 9 and 18 months of age, i.e. approximately 75% and 45%, respectively. Responses to tetanus and diphtheria toxoids were excellent and all infants achieved protective serological levels. Responses to pertussis were moderate in that approximately 65% achieved 'protective' serum levels of pertussis agglutinins, i.e. titres <". 320. In conclusion, this study has shown that the DTP /PRP-T vaccine is safe, immunogenic and well tolerated in infants immunised at 6, 10 and 14 weeks of age. TETRActHIB is therefore suitable for inclusion in the World Health Organisation Expanded Programme on Immunisation (WHO EPI) schedule

Reciprocal links between anxiety sensitivity and obsessive-compulsive symptoms in youth: a longitudinal twin study

Background: Anxiety sensitivity, the tendency to fear the symptoms of anxiety, is a key risk factor for the development anxiety disorders. Although obsessive-compulsive disorder was previously classified as an anxiety disorder, the prospective relationship between anxiety sensitivity and obsessive-compulsive symptoms (OCS) has been largely overlooked. Furthermore, a lack of genetically-informative studies means the aetiology of the link between anxiety sensitivity and OCS remains unclear. Methods: Adolescent twins and siblings (N=1,579) from the G1219 study completed self-report questionnaires two years apart assessing anxiety sensitivity, OCS, anxiety and depression. Linear regression models tested prospective associations between anxiety sensitivity and OCS, with and without adjustment for anxiety and depressive symptoms. A phenotypic cross-lagged model assessed bidirectional influences between anxiety sensitivity and OCS over time, and a genetic version of this model examined the aetiology of these associations. Results: Anxiety sensitivity was prospectively associated with changes in OCS, even after controlling for comorbid anxiety and depressive symptoms. The longitudinal relationship between anxiety sensitivity and OCS was bidirectional, and these associations were predominantly accounted for by non-shared environmental influences. Conclusions: Our findings are consistent with the notion that anxiety sensitivity is a risk factor for OCS during adolescence, but also suggest that experiencing OCS confers risk for heightened anxiety sensitivity. The reciprocal links between OCS and anxiety sensitivity over time are likely to be largely mediated by non-shared environmental experiences, as opposed to common genes. Our findings raise the possibility that interventions aimed at ameliorating anxiety sensitivity could reduce risk for OCS, and vice versa

Prognostic significance of serum inflammatory markers in esophageal cancer

Background The aim of this study was to assess the relative prognostic value of biomarkers to measure the systemic inflammatory response (SIR) and potentially improve prognostic modeling in patients undergoing potentially curative surgery for esophageal adenocarcinoma (EC). Methods Consecutive 330 patients undergoing surgery for EC between 2004 and 2018 within a regional UK cancer network were identified. Serum measurements of haemoglobin, C-reactive protein, albumin, modified Glasgow Prognostic Score (mGPS), and differential neutrophil to lymphocyte ratio (NLR) were obtained before surgery, and correlated with histopathological factors and outcomes. Primary outcome measures were disease-free (DFS) and overall survival (OS). Results Of 330 OC patients, 294 underwent potentially curative esophagectomy. Univariable DFS analysis revealed pT, pN, pTNM stage (all p < 0.001), poor differentiation (p = 0.001), vascular invasion (p < 0.001), R1 status (p < 0.001), perioperative chemotherapy (p = 0.009), CRP (p = 0.010), mGPS (p = 0.011), and NLR (p < 0.001), were all associated with poor survival. Multivariable Cox regression analysis of DFS revealed only NLR [Hazard Ratio (HR) 3.63, 95% Confidence Interval (CI) 2.11–6.24, p < 0.001] retained significance. Multivariable Cox regression analysis of OS revealed similar findings: NLR [HR 2.66, (95% CI 1.58–4.50), p < 0.001]. Conclusion NLR is an important SIR prognostic biomarker associated with DFS and OS in EC

Aetiology of Shame and its Association with Adolescent Depression and Anxiety: Results from a Prospective Twin and Sibling Study

Background Shame is considered a maladaptive self-conscious emotion that commonly co-occurs alongside depression and anxiety. Little is known, however, about the aetiology of shame and its associations with depression and anxiety. We estimated, for the first time, genetic and environmental influences on shame and on its associations with depression and anxiety in adolescence. Methods The sample was twin and sibling pairs from the Genesis 1219 Study (Time 1, N = 2,685; males 42.8%, Mage = 14.95, SD = 1.67, age range: 12–21; Time 2, N = 1618; males 39.7%, Mage = 16.97, SD = 1.64, age range: 14–23). Participants completed validated questionnaires to measure shame (at Time 1), depression and anxiety (at Times 1 and 2). Results Shame was moderately to strongly associated with concurrent depression and anxiety. Prospectively, shame was significantly associated with an increase in depression, but not anxiety. Genetic analyses revealed that shame was moderately heritable with substantial nonshared environmental influence. The associations between shame and concurrent depression and anxiety were primarily accounted for by overlapping genetic influences. Prospectively, the association between shame and later depression was primarily accounted for by genetic and nonshared environmental influences shared with earlier depression. The unique association between shame and later depression was mostly explained by common nonshared environmental influences. Conclusions The findings offer novel evidence regarding aetiology of shame—although moderately heritable, shame in adolescents may also result from nonshared environmental factors. Genetic and nonshared environmental influences contribute to the co-occurrence of shame with depression and anxiety

Risk-optimized proton therapy to minimize radiogenic second cancers

Proton therapy confers substantially lower predicted risk of second cancer compared with photon therapy. However, no previous studies have used an algorithmic approach to optimize beam angle or fluence-modulation for proton therapy to minimize those risks. The objectives of this study were to demonstrate the feasibility of risk-optimized proton therapy and to determine the combination of beam angles and fluence weights that minimizes the risk of second cancer in the bladder and rectum for a prostate cancer patient. We used 6 risk models to predict excess relative risk of second cancer. Treatment planning utilized a combination of a commercial treatment planning system and an in-house risk-optimization algorithm. When normal-tissue dose constraints were incorporated in treatment planning, the risk model that incorporated the effects of fractionation, initiation, inactivation, repopulation and promotion selected a combination of anterior and lateral beams, which lowered the relative risk by 21% for the bladder and 30% for the rectum compared to the lateral-opposed beam arrangement. Other results were found for other risk models

Physiological performance and inflammatory markers as indicators of complications after oesophageal cancer surgery

Background The extent to which physiological factors influence outcome following oesophageal cancer surgery is poorly understood. This study aimed to evaluate the extent to which cardiorespiratory fitness and selected metabolic factors predicted complications after surgery for carcinoma. Methods Two hundred and twenty‐five consecutive patients underwent preoperative cardiopulmonary exercise testing to determine peak oxygen uptake (urn:x-wiley:24749842:media:bjs550328:bjs550328-math-0001o2peak), anaerobic threshold and the ventilatory equivalent for carbon dioxide (urn:x-wiley:24749842:media:bjs550328:bjs550328-math-0002e/urn:x-wiley:24749842:media:bjs550328:bjs550328-math-0003co2). Cephalic venous blood was assayed for serum C‐reactive protein (CRP) and albumin levels, and a full blood count was done. The primary outcome measure was the Morbidity Severity Score (MSS). Results One hundred and ninety‐eight patients had anatomical resection. A high MSS (Clavien–Dindo grade III or above) was found in 48 patients (24·2 per cent) and was related to an increased CRP concentration (area under the receiver operating characteristic (ROC) curve (AUC) 0·62, P = 0·001) and lower urn:x-wiley:24749842:media:bjs550328:bjs550328-math-0004o2peak (AUC 0·36, P = 0·003). Dichotomization of CRP levels (above 10 mg/l) and urn:x-wiley:24749842:media:bjs550328:bjs550328-math-0005o2peak (below 18·6 ml per kg per min) yielded adjusted odds ratios (ORs) for a high MSS of 2·86 (P = 0·025) and 2·92 (P = 0·002) respectively. Compared with a cohort with a low Combined Inflammatory and Physiology Score (CIPS), the OR was 1·70 (95 per cent c.i. 0·85 to 3·39) for intermediate and 27·47 (3·12 to 241·69) for high CIPS (P < 0·001). Conclusion CRP and urn:x-wiley:24749842:media:bjs550328:bjs550328-math-0006o2peak were independently associated with major complications after potentially curative oesophagectomy for cancer. A composite risk score identified a group of patients with a high risk of developing complications

Twins Early Development Study: A Genetically Sensitive Investigation into Behavioral and Cognitive Development from Infancy to Emerging Adulthood

The Twins Early Development Study (TEDS) is a longitudinal twin study that recruited over 16,000 twin-pairs born between 1994 and 1996 in England and Wales through national birth records. More than 10,000 of these families are still engaged in the study. TEDS was and still is a representative sample of the population in England and Wales. Rich cognitive and emotional/behavioral data have been collected from the twins from infancy to emerging adulthood, with data collection at first contact and at ages 2, 3, 4, 7, 8, 9, 10, 12, 14, 16, 18 and 21, enabling longitudinal genetically sensitive analyses. Data have been collected from the twins themselves, from their parents and teachers, and from the UK National Pupil Database. Genotyped DNA data are available for 10,346 individuals (who are unrelated except for 3320 dizygotic co-twins). TEDS data have contributed to over 400 scientific papers involving more than 140 researchers in 50 research institutions. TEDS offers an outstanding resource for investigating cognitive and behavioral development across childhood and early adulthood and actively fosters scientific collaborations