Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurocognitive Profiles in Children With ADHD and Their Predictive Value for Functional Outcomes

Objective: We examined whether neurocognitive profiles could be distinguished in children with ADHD and typically developing (TD) children, and whether neurocognitive profiles predicted externalizing, social, and academic problems in children with ADHD. Method: Neurocognitive data of 81 children with ADHD and 71 TD children were subjected to confirmatory factor analysis. The resulting factors were used for community detection in the ADHD and TD group. Results: Four subgroups were detected in the ADHD group, characterized by (a) poor emotion recognition, (b) poor interference control, (c) slow processing speed, or (d) increased attentional lapses and fast processing speed. In the TD group, three subgroups were detected, closely resembling Subgroups (a) to (c). Neurocognitive subgroups in the ADHD sample did not differ in externalizing, social, and academic problems. Conclusion: We found a neurocognitive profile unique to ADHD. The clinical validity of neurocognitive profiling is questioned, given the lack of associations with functional outcomes.
2-Iminobiotin for the treatment of perinatal asphyxia

Introduction: Perinatal hypoxia–ischemia (HI) continues to be a common underlying cause of brain damage. The outcomes of HI encephalopathy (HIE) are devastating and permanent, making it a major burden for the patient, the family and society. The understanding of the pathways that lead to the injury is vital for finding potential therapies. HI triggers a cascade of several detrimental insults: glutamate-mediated excitotoxicity, nitric oxide (NO) and calcium overload, oxidative stress (OS), stress signaling, inflammation and cell death. Areas covered: The reader will be introduced to the complex biological processes involved in HI injury and how these mechanisms are exploited for current and emerging therapies. Current knowledge on pathways of damage, as well as ongoing experimental therapies are reviewed, based on a comprehensive literature search employing review articles, book chapters and Medline searches. Expert opinion: Recent studies have demonstrated a protective effect of antioxidant drugs against apoptosis after cerebral ischemia and reperfusion. Iminobiotin provides long- and short-term neuroprotection hindering apoptotic pathways. As an antioxidant it acts as NO synthetase inhibitor interrupting the vicious circle and the harmful effects of excessive NO formation. More clinical trials are needed to detect safety and effectiveness of iminobiotin and to establish its dose and optimal time of action.
An EEG Investigation of the Attention-Related Impact of Mindfulness Training in Youth With ADHD: Outcomes and Methodological Considerations

Objective:The current study examined the impact of an activity-based mindfulness treatment on EEG indices of attention in youth with ADHD aged 11 to 17 years compared with a waitlist control group. Method: Pre- and post-treatment, EEG was recorded as participants completed a single-point focus rest task and two active attention tasks. Theta power, beta power, and theta/beta ratio (TBR) were calculated during each task. Results: A significant group by time by task interaction was found that indicated significant improvement in attentional ability, indexed by decreased TBR, for the treatment group but not controls. Conclusion: Findings support the benefit of mindfulness treatment for enhancing attentional control in youth with ADHD and extend the literature by providing evidence of these gains at a neural level. Findings also offer methodological support for the use of active attention tasks when examining mindfulness-related attentional gains in youth with ADHD. Directions for future research are discussed.
A national survey of food hygiene training and qualification levels in the UK food industry

The food hygiene training received and qualifications held by four different grades of food handlers were compared by means of a postal survey of 1650 businesses in the manufacturing, retail and catering sectors of the UK food industry. Significant differences ( p < 0.05) were identified between the methods of training delivery to, and qualifications held by different grades of food handlers across the three industry sectors. Business status, personnel characteristics and risk perceptions of managers all had significant effects on the methods of training used and qualification levels achieved within each industry sector. Positive attitudes towards training were expressed by most managers although follow-up face-to-face interviews revealed their concerns about the cost, time and relevancy of the training their staff received. Whilst both the uptake of training and level of food hygiene qualifications may have improved in recent years, this study highlighted the need to develop training methods that are proven to change workplace behaviour as well as imparting knowledge. This may be best achieved by consolidating food hygiene training as a fundamental part of a wider approach to food safety control based on HACCP.
Role of interleukin‐1β and tumour necrosis factor‐α in lipopolysaccharide‐induced sickness behaviour: a study with interleukin‐1 type I receptor‐deficient mice

Interleukin‐1 (IL‐1) mediates symptoms of sickness during the host response to infection. IL‐1 exerts its effects via several subtypes of receptors. To assess the role of IL‐1 receptor type I (IL‐1RI) in the sickness‐inducing effects of IL‐1, IL‐1β and the cytokine inducer lipopolysaccharide were administered to IL‐1RI‐deficient mice (IL‐1RI–/–). Sickness was assessed by depression of social exploration, anorexia, immobility and body weight loss. IL‐1RI–/– mice were resistant to the sickness‐inducing effects of IL‐1β administered intraperitoneally (2 µg/mouse) and intracerebroventricularly (2 ng/mouse), but still fully responsive to lipopolysaccharide administered intraperitoneally (2.5 µg/mouse) and intracerebroventricularly (3 ng/mouse). The sensitivity of IL‐1RI–/– mice to lipopolysaccharide was not due to a higher brain expression of proinflammatory cytokines other than IL‐1, since lipopolysaccharide‐induced expression of brain IL‐1 β, tumour necrosis factor‐α (TNF‐α) and IL‐6 transcripts were identical in IL‐1RI–/– and control mice when measured by semiquantitative reverse‐transcriptase polymerase chain reaction 1 h after treatment. Blockade of TNF‐α action in the brain by intracerebroventricular administration of a fragment of the soluble TNF receptor, TNF binding protein (3.6 µg/mouse), attenuated the depressive effects of intraperitoneal injection of lipopolysaccharide (1 µg/mouse) on behaviour in IL‐1RI–/– but not in control mice. Since IL‐1RI–/– mice were not more sensitive to intracerebroventricularly TNF‐α (50 ng) than control mice, these results indicate that IL‐1RI mediates the sickness effect of IL‐1 and that TNF‐α simply replaces IL‐1 when this last cytokine is deficient.
Beyond PSA: The Next Generation of Prostate Cancer Biomarkers

Prostate cancer biomarkers that improve upon the PSA test should address unmet clinical needs. Next-Gen Biomarkers For decades, the prostate-specific antigen (PSA) test has been used to assist in the diagnosis of prostate cancer. It has also become more prevalent in early cancer screening. Although the number of deaths related to prostate cancer has decreased, it is not clear that the PSA test has been the major factor. As Prensner and co-authors point out, the PSA test may “do more harm than good. ” This Review focuses on new ways to address unmet clinical needs in the area of biomarkers, to hopefully add to the armamentarium of diagnostic, prognostic, and predictive tools for prostate cancer, including PSA. Since the introduction of serum prostate-specific antigen (PSA) screening 25 years ago, prostate cancer diagnosis and management have been guided by this biomarker. Yet, PSA has proven controversial as a screening assay owing to several inherent limitations. The next wave of prostate cancer biomarkers has emerged, introducing new assays in serum and urine that may supplement or, in time, replace PSA because of their higher cancer specificity. This expanding universe of biomarkers has been facilitated, in large part, by new genomic technologies that have enabled an unbiased look at cancer biology. Such efforts have produced several notable success stories that involve rapidly moving biomarkers from the bench to the clinic. However, biomarker research has centered on disease diagnostics, rather than prognosis and prediction, which would address disease management. The development of biomarkers to stratify risk of prostate cancer aggressiveness at the time of screening remains the greatest unmet clinical need in prostate cancer. We review the current state of prostate cancer biomarker research, including the PSA revolution, its impact on early cancer detection, the recent advances in biomarker discovery, and the future efforts that promise to improve clinical management of this disease.
HIV-1 Reservoirs in Breast Milk and Challenges to Elimination of Breast-Feeding Transmission of HIV-1

The breast milk of HIV-infected mothers contains reservoirs of HIV, even when they are successfully treated with antiretroviral therapy; new approaches to prophylactic therapy are needed to prevent HIV transmission to their infants through breast-feeding. The breast milk of HIV-infected mothers contains reservoirs of HIV, even when they are successfully treated with antiretroviral therapy; new approaches to prophylactic therapy are needed to prevent HIV transmission to their infants through breast-feeding. By compensating for the relative immaturity of the neonatal immune system, breast milk and breast-feeding prevent deaths in children. Nevertheless, transmission of HIV-1 through breast-feeding is responsible for more than half of new pediatric HIV infections. Recent studies of possible HIV-1 reservoirs in breast milk shed new light on features that influence HIV-1 transmission through breast-feeding. The particular characteristics of breast milk CD4+ T cells that distinguish them from circulating blood lymphocytes (high frequency of cell activation and expression of memory and mucosal homing markers) facilitate the establishment of HIV-1 replication. Breast milk also contains a plethora of factors with anti-infectious, immunomodulatory, or anti-inflammatory properties that can regulate both viral replication and infant susceptibility. In addition, CD8+ T lymphocytes, macrophages, and epithelial cells in breast milk can alter the dynamics of HIV-1 transmission. Even during efficient antiretroviral therapy, a residual stable, CD4+ T cell–associated reservoir of HIV-1 is persistently present in breast milk, a likely source of infection. Only prophylactic treatment in infants—ideally with a long-acting drug, administered for the entire duration of breast-feeding—is likely to protect HIV-exposed babies against all forms of HIV transmission from breast milk, including cell-to-cell viral transfer.
Improving the range of contraceptive choices in rural Ethiopia

Background : Despite the reality of a high unmet need, the utilization of family planning services in Ethiopia could be described as very low. Besides this, the knowledge and practice of family planning is limited merely to the usage of shorter-term contraceptive methods. Therefore, there is a need to expand access to family planning services in rural Ethiopia by making available more choices to family planning clients. Objective : The aim of this study is to examine the pattern of family planning method mix overtime and to assess the impact of combining strategies, such as community and facility based approaches, in improving access to family planning services and choices. Methods : A cross-sectional, descriptive study was conducted in September 2000 in Tehuledere woreda, in South Wollo zone, Amhara Regional State. A census was done on all clients who live in 15 kebeles in the woreda and who used long-term and permanent family planning methods which included IUD, Norplant and male and female sterilization methods and were interviewed. Results : Among the 218 family planning clients interviewed, 11 (5%) were males who had undergone vasectomy. Almost 81% of the clients using long-term and permanent methods were in the age group of 25-44 years. The mean age was 34.2 years with a range of 18-70 years and the mean number of children ever born to the study subjects was 5.6 with a range of 0-14 children. Knowledge of modern family planning methods was found to be over 90%, the majority (73.9%) of the respondents getting information on family planning from the community based reproductive health (CBRH) program. Fifty two percent have undergone voluntary surgical contraception, followed by Norplant (39.0%) and IUD (8.7%). Among the major reasons mentioned for the use of the current family planning methods were limiting family size (45.9%), spacing (27.5%), and side effects of the previous method (12.4%). For most clients (90.8%) the source of information for their current use is the CBRH program. Conclusions : Improving the usage of wide range of contraceptive method mix improves the quality of family planning services rendered to the community and ensures sustainability of the services. A coordinated effort among facility based and community based providers can assist in ensuring client choices and improving the method mix. The Ethiopian Journal of Health Development Vol. 20 (2) 2006: 74-78
Supravital-stained wet film study of fine needle aspirates: A reliable supplementary diagnostic procedure

Background: Fine needle aspiration cytology (FNAC) is a simple, rapid, reliable, and cost-effective method in diagnosing mass lesions. In spite of its advances and advantages, conventional Hematoxyline and Eosin (H and E)-stained wet-fixed smear of FNAC fails to achieve 100% accuracy. To improve the accuracy of cytodiagnosis, toludine blue (TB)-stained wet film preparation of fine needle aspirates is supplemented along with conventional wet-fixed smear. We have assessed the morphology and accuracy of supravital-stained (TB) wet film study of FNAC, which has not been previously reported. Materials and Methods: A total of 197 fine needle aspirates from various body sites were studied both in supravital toludine blue (TB)-stained wet film and hematoxylin and eosin (H and E)-stained wet-fixed smear preparation. The results were interpreted with final diagnosis made by histopathological study, clinical, radiological follow-up and were statistically analyzed. Results: For the entire series, TB-stained wet film study gave a sensitivity of 93.7%, a specificity of 98%, a positive predictive value (PPV) of 96.6%, a negative predictive value (NPV) of 96.9%, and an efficacy of 96.3%. H and E-stained wet smear study revealed a sensitivity of 86.2%, specificity of 97.9%, PPV of 95.4%, NPV of 93.4%, and an efficacy of 93.2%. The combined wet film and wet smear study results showed a sensitivity of 98%, specificity of 99.2%, PPV of 98.4%, NPV of 98.9%, and an efficacy of 98.6%. The decreased sensitivity of wet smear study due to inadequate cellularity, loss of cell sample during fixation and staining, artifactual morphological distortion were minimized by supplementary wet film study and that yielded high accuracy rate. Conclusion: Wet film study gave a good cytomorphological picture and this immediate interpretation was useful for assessing the adequacy of material. False negative and false positive reports were reduced significantly when we combined this toludine blue-stained wet film study and wet smear study. Therefore, it could be regularly undertaken as a supplementary diagnostic procedure for wet smear to improve the diagnostic accuracy.
Pharmacological Characterization of Receptor Redistribution and β-Arrestin Recruitment Assays for the Cannabinoid Receptor 1

Receptor redistribution and β-arrestin recruitment assays provide a G-protein-subtype-independent method to measure ligand-stimulated activation of G-protein-coupled receptors. In particular β-arrestin assays are becoming an increasingly popular tool for drug discovery. The authors have compared a high-content-imaging-based Redistribution® assay and 2 nonimaging-based β-arrestin recruitment assays, Tango™ and PathHunter ™, for the cannabinoid receptor 1. Inasmuch as all 3 assays use receptors that are modified at the C-terminus, the authors verified their pharmacology via detection of Gαi coupling of the receptor in cAMP assays using reference ligands. The potencies and efficacies of the cannabinoid receptor agonists CP55,940 and WIN55,212-2 correlated well between the 3 assays, and are comparable with the measured ligand binding affinities. The inverse agonist SR141716 decreased basal signal in all 3 assays, but only in the Tango bla assay a reliable EC50 could be determined for this compound, suggesting that Tango is the most suitable assay for the identification of new inverse agonists. Both the Redistribution and the PathHunter assay could discriminate partial agonists from full agonists, whereas in the Tango assay partial agonists behaved as full agonists. Only the PathHunter cells allowed detection of cannabinoid receptor activation via β-arrestin recruitment and Gαi-protein-mediated inhibition of cAMP, thus enabling the identification of biased ligands that differ in these cellular effects. The characteristics and limitations of the different assays are discussed. (Journal of Biomolecular Screening 2009:811-823)
Practical experience with TCP over GPRS

We present the results of a series of experiments used to characterise the performance of a GPRS (General Packet Radio Service) wireless data network, hence highlighting issues that software architects should consider when designing applications to run over this soon to be widely-deployed service. In summary, we show that packet round trip time (RTTs) are large (>1000 ms) and can be highly variable, packet losses are relatively rare, and that available bandwidth can be quite variable. These network characteristics do not interact well with current TCP implementations. We show how it takes many seconds before a new TCP connection can expand its congestion window to make use of the full bandwidth available, leading to very poor performance of protocols like HTTP. Beyond the point of full bandwidth utilisation, TCP continues to expand the window needlessly, resulting in excessive queueing at the GPRS router. This leads to greatly inflated RTTs (10s of seconds) and hence poor interactive response and slow recovery should loss occur. We show how a simple transparent proxy interposed between the fixed and GPRS networks can be used to significantly improve TCP connection performance, particularly for activities like Web browsing.
Decade-Long Safety and Function of Retroviral-Modified Chimeric Antigen Receptor T Cells

Adoptively transferred chimeric antigen receptor T cells have stable stem cell–like persistence for at least a decade and more than 500 years of patient safety. Standing the Test of Time Retroviral vectors were once the mainstay of gene transfer because they could stably integrate into the host genome. However, some patients in early trials developed leukemia because of insertional mutagenesis. Now, Scholler et al. report that retroviral vector–mediated gene transfer in T cells may not have the same safety concerns, and that these cells may persist over a decade in patients. The authors followed patients from three clinical trials who received T cells transduced with gammaretroviruses carrying a chimeric antigen receptor. They found that these cells were present in recipients over a decade after infusion at levels higher than those induced by standard vaccines. These cells were still functional, had stable levels of engraftment, and did not require host immunosuppression before transplant. Moreover, the authors found no evidence of integration-induced immortalization, with no observable enrichment of integration sites near genes involved in growth control or transformation. Thus, the safety of retroviral vectors may be cell type–specific, opening up engineered T cells as a delivery platform for therapeutics. The success of adoptive T cell gene transfer for treatment of cancer and HIV is predicated on generating a response that is both durable and safe. We report long-term results from three clinical trials to evaluate gammaretroviral vector–engineered T cells for HIV. The vector encoded a chimeric antigen receptor (CAR) composed of CD4 linked to the CD3ζ signaling chain (CD4ζ). CAR T cells were detected in 98% of samples tested for at least 11 years after infusion at frequencies that exceeded average T cell levels after most vaccine approaches. The CD4ζ transgene retained expression and function. There was no evidence of vector-induced immortalization of cells; integration site distributions showed no evidence of persistent clonal expansion or enrichment for integration sites near genes implicated in growth control or transformation. The CD4ζ T cells had stable levels of engraftment, with decay half-lives that exceeded 16 years, in marked contrast to previous trials testing engineered T cells. These findings indicate that host immunosuppression before T cell transfer is not required to achieve long-term persistence of gene-modified T cells. Further, our results emphasize the safety of T cells modified by retroviral gene transfer in clinical application, as measured in >500 patient-years of follow-up. Thus, previous safety issues with integrating viral vectors are hematopoietic stem cell or transgene intrinsic, and not a general feature of retroviral vectors. Engineered T cells are a promising form of synthetic biology for long-term delivery of protein-based therapeutics. These results provide a framework to guide the therapy of a wide spectrum of human diseases.
The Osmolyte Trimethylamine N-Oxide (TMAO) Increases the Proteolytic Activity of Botulinum Neurotoxin Light Chains A, B, and E

Botulism, the disease caused by botulinum neurotoxins (BoNTs), secreted by the spore-forming, anaerobic bacteria Clostridium botulinum, has been associated with food poisoning for centuries. In addition, the potency of BoNTs coupled with the current political climate has produced a threat of intentional, malicious poisoning by these toxins. The ability to detect and measure BoNTs in complex matrixes is among the highest research priorities. However, the extreme potency of these toxins necessitates that assays be capable of detecting miniscule quantities of these proteins. Thus, signal-boosting strategies must be employed. A popular approach uses the proteolytic activity of the BoNT light chain (LC) to catalyze the cleavage of synthetic substrates; reaction products are then analyzed by the analytical platform of choice. However, BoNT LCs are poor catalysts. In this study, the authors used the osmolyte trimethylamine N-oxide (TMAO) to increase the proteolytic activities of BoNT LCs. Their data suggest that concentrated solutions of TMAO induce complete folding of the LCs, resulting in increased substrate affinity and enhanced enzyme turnover. The authors observed increases in catalysis for BoNT serotypes A, B, and E, and this increased proteolytic activity translated into substantial increases in analytical assay sensitivity for these medically relevant toxins.
Intratumor Heterogeneity: Seeing the Wood for the Trees

Intratumor genetic heterogeneity impedes development of new therapeutics and biomarkers that predict drug response. Most advanced solid tumors remain incurable, with resistance to chemotherapeutics and targeted therapies a common cause of poor clinical outcome. Intratumor heterogeneity may contribute to this failure by initiating phenotypic diversity enabling drug resistance to emerge and by introducing tumor sampling bias. Envisaging tumor growth as a Darwinian tree with the trunk representing ubiquitous mutations and the branches representing heterogeneous mutations may help in drug discovery and the development of predictive biomarkers of drug response.