Miracle-dz/UniFAR-FTUs huggingface dataset:
Transparency and Access to Full Information for the Fatal or Serious Toxicity Risks, Low Efficacy and High Price of Deferasirox, Could Increase the Prospect of Improved Iron Chelation Therapy Worldwide

The risks of using a drug causing fatalities and irreversible organ damage outweigh its benefits, especially if safer and more effective therapies are available. The toxicity and efficacy profile of deferasirox has been previously reviewed and additional toxic side effects of imminent concern for the safety of patients have recently been included from information based on the manufacturers’ and regulatory authorities clinical trial and post marketing monitoring reports (1–3). Porter et al. have a different risk and benefit assessment on iron chelation therapy and especially deferasirox, which is not shared by others (1,2,4–6). In the conclusion of their letter, Porter et al. admit that there are unanswered questions about the tolerability, efficacy and safety of deferasirox, a view shared by the Food and Drug Administration (FDA) of the USA, and many others who require more clinical data demonstrating deferasirox’s long term safety and efficacy (6,7). However, while deferasirox was provisionally approved pending further investigations and following fast-track orphan drug procedures by the FDA in November 2005, irreversible renal failure fatalities were reported in June 2006, the publication of which coincided immediately after its provisional approval by the European Union (EU) authorities. In the same report,
Mineralization initiation of MC3T3‐E1 preosteoblast is suppressed under simulated microgravity condition

Microgravity decreases the differentiation of osteoblast. However, as this process is multistage and complex, the mechanism by which microgravity inhibits osteoblast differentiation is still unclear. We have previously found that 24 h acute treatment of simulated microgravity (SM) with a random positioning machine (RPM) significantly inhibited the differentiation of preosteoblasts and have explored whether osteoblasts show different response to microgravity condition at other stages, such as the mineralizing‐stage. Murine MC3T3‐E1 preosteoblasts induced for osteogenic differentiation for seven days were cultured either under normal gravity or SM conditions for 24 h. SM treatment significantly suppressed mineralized nodule formation. Alkaline phosphatase (ALP) activity was dramatically decreased, and the expression of ALP gene was downregulated. Expression of well‐known markers and regulators for osteoblasts differentiation, including osteocalcin (OC), type I collagen α1 (Col Iα1), dentin matrix protein 1 (DMP1) and runt‐related transcription factor 2 (Runx2), were downregulated. Western blot analysis showed that the phosphorylated extracellular signal‐regulated kinase (p‐ERK) level was lower under SM condition. Thus, the initiation of osteoblast mineralization is suppressed by SM condition, and the suppression may be through the regulation of ALP activity and the osteogenic gene expression. ERK signaling might be involved in this process. These results are relevant to the decrease of osteoblast maturation and bone formation under microgravity condition.
Characterizing the obesogenic environment: the state of the evidence with directions for future research

Despite the explosion of obesogenic environment research within the last decade, consensus on what constitutes the very environment we are trying to measure has not yet been reached. This presents a major challenge towards our understanding of environmental research for obesity, and the development of a desperately needed contextualized evidence base to support action and policies for curbing this epidemic. Specifically, we lack the application of a cohesive definition or framework, which creates the potential for confusion regarding the role of the environment, misinterpretation of research findings and missed opportunities with respect to possible avenues for environmentally based interventions. This scoping review identified primary studies and relevant reviews examining factors related to body mass index, diet and/or physical activity with respect to the obesogenic environment. Using a comprehensive framework for conceptualizing the obesogenic environment, the Analysis Grid for Environments Linked to Obesity (ANGELO), we identified 146 primary studies, published between January 1985 and January 2008, that could be characterized according to the dimensions of ANGELO. Gaps in the literature were clearly identified at the level of the macro‐environment, and the political and economic micro‐environments, highlighting key areas where further research is warranted if we are to more fully understand the role of the obesogenic environment.
Hemoglobin Variant Profiles among Brazilian Quilombola Communities

Abstract Brazilian Quilombolas are communities composed of African-derived populations that have their territories guaranteed by the Brazilian Constitution. The present study investigated the hemoglobin (Hb) variants among these population groups. This study was conducted in a total of 2843 individuals of Brazilian Quilombola communities of the Bahia, Pará, and Piauí states. All the participants had their Hb profiles evaluated. The Hb S (HBB: c.20A>T) variant was described in all the studied localities. However, the individuals in Bahia State had the highest frequency of the Hb C (HBB: c.19G>A) variant; individuals from Piauí State had a higher frequency of the Hb D-Punjab (HBB: c.364G>C) variant compared to the other states, and individuals from Pará State only carried the Hb S variant. The present study revealed a specific distribution of Hb variants that could represent different waves of African influence in these Brazilian populations.
The role of children's bone marrow mesenchymal stromal cells in the ex vivo expansion of autologous and allogeneic hematopoietic stem cells

The recognition of the role of Mesenchymal Stromal Cells (MSC) in hematopoiesis, as part of the bone marrow microenvironment, renewed the interest for cord blood (CB) ex vivo expansion as a source of HSC for transplantation. MSC from children are recognized to have different biological properties compared to the ones from adults. The current study focuses on the evaluation of the effects of children's bone marrow MSC on the ex vivo expansion capacity of both allogeneic cord blood and autologous bone marrow (BM) CD34+ hematopoietic stem cells (HSCs) when used as a cell feeder layer with or without recombinant cytokines. Our results showed that children's bone marrow‐derived MSC expand more primitive populations in co culture with CD34 and that the expansion is further enhanced when the culture is supplemented with growth factors. No additive effect was seen either with the early‐ or late‐acting growth factors' cocktails used. Biological features of CB hematopoietic progenitors seem to make them more suitable than their BM counterparts for ex vivo expansion. Clinical implementation will be facilitated by methodological standardization and guidelines' establishment.
Defining overweight and obesity in pre‐school children: IOTF reference or WHO standard?

Two international datasets are used to define overweight and obesity in pre‐school children: the International Obesity Task Force (IOTF) reference and the WHO standard. This study compares the performance of the two datasets in defining overweight and obesity in 24–60 months old children. This was done by plotting the IOTF cut‐offs against WHO curves and by comparing the prevalence of overweight and obesity, as defined by the IOTF reference and by the WHO standard, using 2001 data from the Czech Republic. The IOTF cut‐off for overweight in 24–60 months old children goes from 1.7 to 1.1 z‐scores on the WHO chart, and for obesity it shifts with age from 2.7 to 2.2 z‐scores. As a consequence, at 5 years of age the prevalence of overweight in Czech girls is 3.4% using the WHO and 15.3% using the IOTF definition. These discrepancies are due to the choice of cut‐offs and to the different criteria used to select the sample for the IOTF reference and the WHO standard. Research is urgently needed to identify, for the WHO standard, BMI cut‐offs associated with an increased risk of overweight and obesity, and associated health outcomes later in life.
Gastrointestinal targets to modulate satiety and food intake

This review discusses the role of enteroendocrine cells in the gastrointestinal tract as chemoreceptors that sense intraluminal contents and induce changes in food intake through the release of signalling substances, such as satiety hormones. Recent evidence supports the concept that chemosensing in the gut involves G protein‐coupled receptors (GPCRs) that are known to mediate gustatory signals in the oral cavity. GPCRs can be grouped into several families, depending on the stimuli to which they respond, e.g. proteins, amino acids, carbohydrates, fatty acids, or tastants. Sensing of these stimuli by GPCRs results in hormone secretions of enteroendocrine cells, which participate in the control of food intake. A better understanding of the stimuli that induce the strongest binding with these receptors, and thus induce a strong release of hormones, can be a very useful strategy for the development of novel foods in the treatment of obesity.
Formulation and Comparative Characterization of Chitosan, Gelatin, and Chitosan–Gelatin-Coated Liposomes of CPT-11–HCl

Liposomes containing phosphatidylcholine and cholesterol (uncoated) and coated by chitosan, gelatin, and combination of chitosan and gelatin were prepared by the modified ethanol injection method. The aim of this work was to formulate and characterize liposomes of camptothecin (CPT)-11–HCl (Irinotecan HCl) containing chitosan, gelatin, and both polymers as coating materials; and also to increase its circulation longevity when compared with the free drug while maintaining the agent in its active lactone form. Size, shape, zeta potential, encapsulation efficiency, stability study, in vitro, and in vivo release study were used for characterization of liposomes. The size of liposomes was in the order of uncoated < chitosan coated < gelatin coated < combination of chitosan and gelatin coated. The zeta potential of liposomes was in the order of combination of chitosan and gelatin coated > chitosan coated > gelatin coated > uncoated. The formulations showed the long-term stability. The encapsulation efficiency of liposomes was in order of combination of chitosan and gelatin coated > gelatin coated > chitosan coated > uncoated. The in vitro and in vivo release of drug was observed in the order of combination chitosan and gelatin coated > gelatin coated > chitosan coated > uncoated.
The characterization and comparison of spray-dried mannitol samples

Background: Following the production of spray-dried mannitol powders, it is essential that the polymorphic content of each individual product is completely characterized. The implications of the polymorphic behavior of mannitol are immense. The appearance or disappearance of a crystalline form within a dosage form can have costly repercussions and lead to a dosage form being withdrawn. Method: In this study, commercially available and laboratory-produced spray-dried mannitol products were characterized to establish the polymorphic content of each. Their polymorphic behavior was also characterized after laboratory scale pharmaceutical processes. Thermal analysis employed differential scanning calorimetry, thermogravimetric analysis, and isothermal microcalorimetry. Structural analysis of the samples was obtained using X-ray powder diffraction and Fourier transform Raman spectroscopy. Results: Structural analysis revealed that α- and β- polymorphic forms were present in the commercial samples and some contained a mixture of polymorphs. Reprocessing employing spray drying indicated α- to β- polymorphic transitions occurred within some of the samples. Conclusion: It is essential that preformulation studies where spray-dried mannitol products are to be employed must take into account its polymorphic behavior upon supply, processing, and subsequent storage.
Novel cyclodextrin-based film formulation intended for buccal delivery of atenolol

Background: Unknown influence of cyclodextrin on the properties of the film formulation aimed for buccal application. Aim: Development and characterization of a novel bioadhesive film formulation for buccal atenolol delivery containing drug/cyclodextrin inclusion. Method: Interaction between atenolol and randomly methylated β-cyclodextrin (RAMEB) in solution was studied by phase solubility studies. The complex in solid state was prepared by the freeze-drying method and characterized by differential scanning calorimetry and Fourier-transformed infrared spectroscopy (FTIR). The drug, free or in complex form, was incorporated into polymeric films prepared by the casting method using ethylcellulose (EC), polyvinyl alcohol (PVA), and hydroxypropyl methylcellulose (HPMC). The prepared film formulations were characterized in terms of swelling, bioadhesion, and in vitro drug release. Results: The formation of a stabile inclusion complex (Ks = 783.4 ± 21.6 M−1) in 1:1 molar stoichiometry was confirmed in solution and in solid state. The swelling properties of films were predominated by the type of polymer used in the formulation. In vitro bioadhesive properties of the films were well correlated with the swelling properties of the polymers used in the formulation. Although incorporation of the drug, free or in complex form, decreased the bioadhesion of the films, PVA- and HPMC-based formulations retained suitable bioadhesive properties. Higher atenolol solubility upon complexation with RAMEB increased the drug dissolution rate under conditions designed to be similar to those on the buccal mucosa, but it has decreased the drug release rate from the PVA and HPMC film formulation, leading to a sustained drug release pattern. In the case of EC-based films, RAMEB promoted drug release. Other parameters that influenced the drug release rate were associated with the structure of the polymer used in the formulation, swelling characteristics of the films, and the interaction between atenolol and hydrophilic polymers that was demonstrated by FTIR analysis. Conclusion: Incorporation of atenolol in the form of an inclusion complex into hydrophilic films may be an appropriate strategy to prepare a suitable formulation for buccal drug delivery.
Innovations in health and demographic surveillance systems to establish the causal impacts of HIV policies

Purpose of reviewHealth and demographic surveillance systems (HDSS), in conjunction with HIV treatment cohorts, have made important contributions to our understanding of the impact of HIV treatment and treatment-related interventions in sub-Saharan Africa. The purpose of this review is to describe and discuss innovations in data collection and data linkage that will create new opportunities to establish the impacts of HIV treatment, as well as policies affecting the treatment cascade, on population health and economic and social outcomes. Recent findingsNovel approaches to routine collection of biomarkers, behavioural data, spatial data, social network information, migration events and mobile phone records can significantly strengthen the potential of HDSS to generate exposure and outcome data for causal analysis of HIV treatment impact and policies affecting the HIV treatment cascade. Additionally, by linking HDSS data to health service administration, education and welfare service records, researchers can substantially broaden opportunities to establish how HIV treatment affects health and economic outcomes when delivered through public sector health systems and at scale. SummaryAs the HIV treatment scaleup in sub-Saharan Africa enters its second decade, it is becoming increasingly important to understand the long-term causal impacts of large-scale HIV treatment and related policies on broader population health outcomes, such as noncommunicable diseases, as well as on economic and social outcomes, such as family welfare and children's educational attainment. By collecting novel data and linking existing data to public sector records, HDSS can create near-unique opportunities to contribute to this research agenda.
Intermittent versus daily calorie restriction: which diet regimen is more effective for weight loss?

Dietary restriction is an effective strategy for weight loss in obese individuals. The most common form of dietary restriction implemented is daily calorie restriction (CR), which involves reducing energy by 15–60% of usual caloric intake every day. Another form of dietary restriction employed is intermittent CR, which involves 24 h of ad libitum food consumption alternated with 24 h of complete or partial food restriction. Although both diets are effective for weight loss, it remains unknown whether one of these interventions produces superior changes in body weight and body composition when compared to the other. Accordingly, this review examines the effects of daily CR versus intermittent CR on weight loss, fat mass loss and lean mass retention in overweight and obese adults. Results reveal similar weight loss and fat mass loss with 3 to 12 weeks' intermittent CR (4–8%, 11–16%, respectively) and daily CR (5–8%, 10–20%, respectively). In contrast, less fat free mass was lost in response to intermittent CR versus daily CR. These findings suggest that these diets are equally as effective in decreasing body weight and fat mass, although intermittent CR may be more effective for the retention of lean mass.
Time use and physical activity: a shift away from movement across the globe

Technology linked with reduced physical activity (PA) in occupational work, home/domestic work, and travel and increased sedentary activities, especially television viewing, dominates the globe. Using detailed historical data on time allocation, occupational distributions, energy expenditures data by activity, and time‐varying measures of metabolic equivalents of task (MET) for activities when available, we measure historical and current MET by four major PA domains (occupation, home production, travel and active leisure) and sedentary time among adults (>18 years). Trends by domain for the United States (1965–2009), the United Kingdom (1961–2005), Brazil (2002–2007), China (1991–2009) and India (2000–2005) are presented. We also project changes in energy expenditure by domain and sedentary time (excluding sleep and personal care) to 2020 and 2030 for each of these countries. The use of previously unexplored detailed time allocation and energy expenditures and other datasets represents a useful addition to our ability to document activity and inactivity globally, but highlights the need for concerted efforts to monitor PA in a consistent manner globally, increase global PA and decrease sedentary behavior. Given the potential impact on weight gain and other cardiometabolic health risks, the differential declines in MET of activity and increases in sedentary time across the globe represent a major threat to global health.
Self-Management of Upper Limb Recovery after Stroke: How Effectively Do Occupational Therapists and Physiotherapists Train Clients and Carers?

Aim: A self-management approach to upper limb management following stroke has received little attention in the literature. The aim of the study was to investigate the impact of occupational therapists' and physiotherapists' standard practice on clients' and carers' self-management of upper limb recovery. Method: Fifteen clients, 7 carers, 11 occupational therapists and 7 physiotherapists were recruited. Therapists described five self-administered tasks they expected clients and carers were doing, using the Goal Attainment Scale (GAS). For each task, clients' and carers' performances were then evaluated using the GAS and their self-efficacy was rated on a 10-point Likert scale. A survey questionnaire investigated their perceptions of the training provided, with respect to a self-management approach. Results: At least a quarter of the self-administered tasks related to upper limb activity, strengthening and secondary prevention were performed below therapists' expectations. In contrast, mean self-efficacy ratings across these tasks were high (clients = 7.8–9.5, carers = 8.5–8.9). Seventy per cent of the self-management training strategies listed in the survey questionnaire were considered missing by more than 40% of carers. Conclusion: There is a need for therapy resources that enhance the content and delivery of self-management training related to upper limb management following stroke, particularly for carers.
Developing a neonatal HIV vaccine: insights from macaque models of pediatric HIV/AIDS

Purpose of reviewThis review analyzes recent findings from nonhuman primate models of HIV/AIDS that are most relevant to developing active neonatal vaccine strategies against HIV breast milk transmission. We focus on studies published from 2005 to early 2007 that have characterized simian immunodeficiency virus or simian/human immunodeficiency virus transmission and the efficacy of HIV vaccine strategies in neonatal macaques. Recent findingsNonhuman primate models of natural HIV breast milk transmission recapitulate many features of infection in human infants; however, the variation in timing and overall low rate of infection in these models precludes their use in conducting vaccine studies. Oral inoculation of infant macaques with defined viral inocula results in reliable transmission and is an efficient model for evaluating neonatal HIV vaccine strategies. All HIV vaccine strategies tested in neonatal macaques are immunogenic, but only a subset of these vaccines confer significant protection against virus acquisition or simian AIDS after oral challenge. SummaryCandidate HIV vaccine strategies can elicit virus-specific humoral and cell-mediated immune responses in newborn primates; however, vaccine immunogenicity in infant macaques is not a reliable criterion for predicting a vaccine's efficacy against oral virus challenge exposure.
TOXIC EFFECTS FROM BISMUTH SUBNITRATE: WITH REPORTS OF CASES TO DATE

Toxic effects from the use of bismuth subnitrate in medicine and surgery are so rare that until recently physicians have regarded its administration as perfectly harmless. Schuler 1 and Bardeleben 2 have pronounced its action non-toxic. The latter treated 100 extensive burns by dusting them with bismuth subnitrate and observed no unpleasant symptoms therefrom. Professor Muhlig 3 administered 20 gm. daily for a prolonged period without producing any poisonous effect. It was, therefore, not surprising that when radiographers began to use bismuth subnitrate for the purpose of obtaining radiographs of the stomach and intestines, they had no hesitancy in administering large doses, and boasted of the safety with which as much as 40 gm. in one dose could be administered. Cases of poisoning resulting from the administration of bismuth subnitrate have been reported as early as 1793, but these were thought to be due to the impurities in the drug,