Specific oral tolerance induction in childhood

Food allergy continues to be a significant public health concern for which there are no approved treatments and management strategies primarily include allergen avoidance and pharmacological measures for accidental exposures. Food allergy is thought to result from either a failure to establish oral tolerance or the breakdown of existing oral tolerance, and therefore, experimental preventative and treatment strategies are now aimed at inducing specific oral tolerance. This may occur in infancy prior to the development of food allergy through the optimal timing of dietary exposure (primary oral tolerance induction) or as a treatment for established food allergy through oral immunotherapy (secondary oral tolerance induction). Trials examining the effectiveness of early dietary allergen exposure to prevent food allergy have yielded promising results for peanut allergy but not so for other allergens, although the results of several trials are yet to be published. Although infant feeding guidelines no longer advise to avoid allergenic foods and exposure to food allergens orally is an important step in inducing food tolerance by the immune system, evidence regarding the optimal timing, dose and form of these foods into the infant's diet is lacking. Likewise, oral immunotherapy trials appear promising for inducing desensitization; however, the long-term efficacy in achieving sustained desensitization and optimal protocols to achieve this is unknown. More research is needed in this emerging field

Assessment of the Effectiveness of Ich Tam Khang as a Supportive Therapy for Chronic Heart Failure

Background: Heart failure is a chronic disease needing lifelong management. Despite the advances that have been made in the treatment of the disease, both the longevity and quality of life for those with chronic heart failure remain impaired. A more effective therapeutic approach with less negative side effects is still needed. In this study, we evaluate Ich Tam Khang (ITK), the poly-ingredient herbal and nutritional preparation with multiple physiological actions, as a supportive therapy for patients with chronic heart failure.Aims of Study: To evaluate the effectiveness and safety of Ich Tam Khang as an adjunctive treatment of chronic heart failure.Methods: A total of 60 patients with chronic congestive heart failure were enrolled in this open label, cross-sectional and prospective study. All patients were treated with a conventional regimen (digoxin, diuretics, angiotensin-converting-enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), beta blockers) for at least 4 weeks before being divided into two equal groups. In the treated patients with ITK, patients received conventional therapy plus 4 tablets ITK per day added in two divided doses. In the control patients, all patients kept the same conventional regimen without ITK. All patients were followed up for 3 months for clinical and para-clinical outcomes.Result: The symptoms of heart failure (dyspnea, palpitation, peripheral edema, neck vein distention, heptojugular reflex) decreased. Heart rate and blood pressure stabilized during treatment in the treated patients with ITK. Additionally, total cholesterol and HDL-cholesterol normalized in the patients treated with ITK. Most of echocardiography parameters in the ITK treated patients were superior to the control patients. ITK is safe and it has no side effects.Conclusion: ITK as a combination of herbal and nutritional preparation is effective in reducing heart failure symptoms, improving patient's quality of life for the patients with decompensated heart failure and reducing total cholesterol and LDL-C

Acceptance patterns and decision-making for human papillomavirus vaccination among parents in Vietnam: an in-depth qualitative study post-vaccination

BACKGROUND: The GAVI Alliance’s decision in late 2011 to invite developing countries to apply for funding for human papillomavirus (HPV) vaccine introduction underscores the importance of understanding levels of HPV vaccine acceptance in developing country settings. In this paper, we present findings from qualitative research on parents’ rationales for vaccinating or not vaccinating their daughters (vaccine acceptance) and their decision-making process in the context of an HPV vaccination demonstration project in Vietnam (2008–2009). METHODS: We designed a descriptive qualitative study of HPV vaccine acceptability among parents of girls eligible for vaccination in four districts of two provinces in Vietnam(a). The study was implemented after each of two years of vaccinations was completed. In total, 133 parents participated in 16 focus group discussions and 27 semi-structured interviews. RESULTS: Focus group discussions and in-depth interviews with parents of girls vaccinated revealed that they were generally very supportive of immunization for disease prevention and of vaccinating girls against HPV. The involvement of the National Expanded Program of Immunization in the demonstration project lent credibility to the HPV vaccine, contributing to high levels of acceptance. For parents who declined participation, concerns about side effects, the possibility that the vaccine was experimental, and the possible impact of the vaccine on future fertility rose to the surface. In terms of the decision-making process, many parents exhibited ‘active decision-making,’ reaching out to friends, family, and opinion leaders for guidance prior to making their decision. CONCLUSION: Vietnam’s HPV vaccination experience speaks to the importance of close collaboration with the government to make the most of high levels of trust, and to reduce suspicions about new vaccines that may arise in the context of vaccine introduction in developing country settings

Class based Influence Functions for Error Detection

Influence functions (IFs) are a powerful tool for detecting anomalous examples in large scale datasets. However, they are unstable when applied to deep networks. In this paper, we provide an explanation for the instability of IFs and develop a solution to this problem. We show that IFs are unreliable when the two data points belong to two different classes. Our solution leverages class information to improve the stability of IFs. Extensive experiments show that our modification significantly improves the performance and stability of IFs while incurring no additional computational cost.Comment: Thang Nguyen-Duc, Hoang Thanh-Tung, and Quan Hung Tran are co-first authors of this paper. 12 pages, 12 figures. Accepted to ACL 202

Structural Brain Alterations Associated with Rapid Eye Movement Sleep Behavior Disorder in Parkinson’s Disease

Characterized by dream-enactment motor manifestations arising from rapid eye movement (REM) sleep, REM sleep behavior disorder (RBD) is frequently encountered in Parkinson’s disease (PD). Yet the specific neurostructural changes associated with RBD in PD patients remain to be revealed by neuroimaging. Here we identified such neurostructural alterations by comparing large samples of magnetic resonance imaging (MRI) scans in 69 PD patients with probable RBD, 240 patients without RBD and 138 healthy controls, using deformation-based morphometry (p < 0.05 corrected for multiple comparisons). All data were extracted from the Parkinson’s Progression Markers Initiative. PD patients with probable RBD showed smaller volumes than patients without RBD and than healthy controls in the pontomesencephalic tegmentum, medullary reticular formation, hypothalamus, thalamus, putamen, amygdala and anterior cingulate cortex. These results demonstrate that RBD is associated with a prominent loss of volume in the pontomesencephalic tegmentum, where cholinergic, GABAergic and glutamatergic neurons are located and implicated in the promotion of REM sleep and muscle atonia. It is additionally associated with more widespread atrophy in other subcortical and cortical regions whose loss also likely contributes to the altered regulation of sleep-wake states and motor activity underlying RBD in PD patients

Assessing decentralised policy implementation in Vietnam : The case of land recovery and resettlement in the Vung Ang Economic Zone

From 2006 plans were implemented to create a deep-sea water port linked to an Economic Zone in the coastal Province of Ha Tinh, located in north central Vietnam. The multi-purpose Zone entitled ‘Vung Ang’, was to attract foreign investors, while the port would provide a link to nearby Laos and Thailand. The project obviously had large implications for the administrations at various levels of governance from Hanoi to the coastal communes and villages, but even more serious impacts on the people living in the affected areas. A large area of about 23,000 hectares was to be cleared, affecting the people of 9 communes, in some of which all inhabitants had to leave their houses and homesteads, to be relocated to completely new settlements about 10 miles inland. These tightly knit communities were not too happy with the prospect to leave their homes and land, the burial places of their ancestors, and the long term comforts of community support networks. While initial decision making process started at the highest levels of Vietnam Governance, the implementation of port and industrial park construction and the related relocation policy was delegated to Ha Tinh province, which is consistent with current decentralisation policies in Vietnam. Actual implementation was carried out by the affected District and Commune level officials – with support from the Communist Party led Mass Organisations – who were in charge of the planning and implementation of the relocation process. This entailed a complex and sensitive series of steps to inform affected households, prepare relocation areas and allocate compensation and alternative housing. This paper describes the implementation dynamics of relocation by depicting and assessing the roles of all stakeholders involved, including the impacts - for better or for worse – of the relocated households. It brings out the way local authorities dealt with affected people, including efforts linked to the ideal of grass-roots democracy. Key areas of contestation are uncovered, such as inadequate infrastructure and low compensation rates. The paper has a second objective to assess the degree to which decentralisation in Vietnam has been actually implemented, and how this affects policy making processes such as the Vung Ang port/industrial zone project. The paper concludes that the relocation policy was implemented in a fairly efficient and harmonious way – with a very intensive engagement of the entire provincial administrative machinery, but that it is too early to assess the livelihood opportunities of the relocated households

Adjunctive dexamethasone for tuberculous meningitis in HIV-positive adult

BACKGROUND Adjunctive glucocorticoids are widely used to treat human immunodeficiency virus (HIV)–associated tuberculous meningitis despite limited data supporting their safety and efficacy. METHODS We conducted a double-blind, randomized, placebo-controlled trial involving HIV-positive adults (≥18 years of age) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomly assigned to receive a 6-to-8-week tapering course of either dexamethasone or placebo in addition to 12 months of antituberculosis chemotherapy. The primary end point was death from any cause during the 12 months after randomization. RESULTS A total of 520 adults were randomly assigned to receive either dexamethasone (263 participants) or placebo (257 participants). The median age was 36 years; 255 of 520 participants (49.0%) had never received antiretroviral therapy, and 251 of 484 participants (51.9%) with available data had a baseline CD4 count of 50 cells per cubic millimeter or less. Six participants withdrew from the trial, and five were lost to follow-up. During the 12 months of follow-up, death occurred in 116 of 263 participants (44.1%) in the dexamethasone group and in 126 of 257 participants (49.0%) in the placebo group (hazard ratio, 0.85; 95% confidence interval, 0.66 to 1.10; P=0.22). Prespecified analyses did not reveal a subgroup that clearly benefited from dexamethasone. The incidence of secondary end-point events, including cases of immune reconstitution inflammatory syndrome during the first 6 months, was similar in the two trial groups. The numbers of participants with at least one serious adverse event were similar in the dexamethasone group (192 of 263 participants [73.0%]) and the placebo group (194 of 257 participants [75.5%]) (P=0.52). CONCLUSIONS Among HIV-positive adults with tuberculous meningitis, adjunctive dexamethasone, as compared with placebo, did not confer a benefit with respect to survival or any secondary end point. (Funded by the Wellcome Trust; ACT HIV ClinicalTrials.gov number, NCT03092817. opens in new tab.

2-Deoxy-D-glucose couples mitochondrial DNA replication with mitochondrial fitness and promotes the selection of wild-type over mutant mitochondrial DNA

Pathological variants of human mitochondrial DNA (mtDNA) typically co-exist with wild-type molecules, but the factors driving the selection of each are not understood. Because mitochondrial fitness does not favour the propagation of functional mtDNAs in disease states, we sought to create conditions where it would be advantageous. Glucose and glutamine consumption are increased in mtDNA dysfunction, and so we targeted the use of both in cells carrying the pathogenic m.3243A>G variant with 2-Deoxy-D-glucose (2DG), or the related 5-thioglucose. Here, we show that both compounds selected wild-type over mutant mtDNA, restoring mtDNA expression and respiration. Mechanistically, 2DG selectively inhibits the replication of mutant mtDNA; and glutamine is the key target metabolite, as its withdrawal, too, suppresses mtDNA synthesis in mutant cells. Additionally, by restricting glucose utilization, 2DG supports functional mtDNAs, as glucose-fuelled respiration is critical for mtDNA replication in control cells, when glucose and glutamine are scarce. Hence, we demonstrate that mitochondrial fitness dictates metabolite preference for mtDNA replication; consequently, interventions that restrict metabolite availability can suppress pathological mtDNAs, by coupling mitochondrial fitness and replication.publishedVersio

Hidden attractors in fundamental problems and engineering models

Recently a concept of self-excited and hidden attractors was suggested: an attractor is called a self-excited attractor if its basin of attraction overlaps with neighborhood of an equilibrium, otherwise it is called a hidden attractor. For example, hidden attractors are attractors in systems with no equilibria or with only one stable equilibrium (a special case of multistability and coexistence of attractors). While coexisting self-excited attractors can be found using the standard computational procedure, there is no standard way of predicting the existence or coexistence of hidden attractors in a system. In this plenary survey lecture the concept of self-excited and hidden attractors is discussed, and various corresponding examples of self-excited and hidden attractors are considered