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An endoscopic capsule is a miniaturized ingestible video camera used to acquire images of the gastrointestinal tract wirelessly. Being morphologically equivalent to any ingestible pill, they can be simply swallowed. Endoscopic capsules therefore present an inviting alternative to the traditional endoscope for the examination of the gastrointestinal tract as well for therapeutic purposes. Endoscopic capsules are considered a disruptive technology, as they have revolutionized the examination of the gastrointestinal tract in a relatively short time. The implementation of an active locomotion system can improve the performance of a capsule and, in the solution proposed in this paper, allows providing the capsule the needed power for therapeutic purposes. Alternative therapeutic solutions, based on optical solutions and capsule endoscopy can be applied to patients affected by Helicobacter pylori, a bacterium of the stomach that affects about half of the world population, mainly in developing countries. The infection can be asymptomatic or associated with slight symptomatology. In some cases, it can take to major pathologies or death. The literature reports results deriving from recent applications of photodynamic treatments to H. pylori. Specific wavelengths have been found to exhibit photo-killing capabilities toward the bacterium. Some solutions have been proposed based on the use of endoscopic devices and capsules capable of administering photodynamic therapy inside the stomach. The proposed treatments, however, are invasive and insufficient to achieve long-term eradication. In this work, the administration of photodynamic therapy is proposed, aimed at the eradication of H. pylori by means of an active endoscopic capsule with LED emission. The capsule design, in addition to the therapeutic module aimed at administering an appropriate light intensity at specific wavelengths already demonstrated in the literature, integrates an active locomotion system aimed at maximizing the efficiency of the treatment.

Hemogenic endothelium (HE) undergoes endothelial-to-hematopoietic transition (EHT) to generate blood, a process that requires progressive down-regulation of endothelial genes and induction of hematopoietic ones. Previously, we have shown that the transcription factor HoxA3 prevents blood formation by inhibiting Runx1 expression, maintaining endothelial gene expression and thus blocking EHT. In the present study, we show that HoxA3 also prevents blood formation by inhibiting Notch pathway. HoxA3 induced upregulation of Jag1 ligand in endothelial cells, which led to cis-inhibition of the Notch pathway, rendering the HE nonresponsive to Notch signals. While Notch activation alone was insufficient to promote blood formation in the presence of HoxA3, activation of Notch or downregulation of Jag1 resulted in a loss of the endothelial phenotype which is a prerequisite for EHT. Taken together, these results demonstrate that Notch pathway activation is necessary to downregulate endothelial markers during EHT.

Sanfilippo syndrome is a fatal childhood neurodegenerative disorder involving neuroinflammation among multiple pathologies. We hypothesized that anakinra, a recombinant interleukin-1 receptor antagonist, could improve neurobehavioral and functional symptoms owing to its capacity to treat neuroinflammation. This phase 1/2 trial aimed to test the safety, tolerability and effects of anakinra on neurobehavioral, functional and quality-of-life outcomes in patients and their caregivers. The primary outcome was the percent of participants requiring a dose increase at week 8 or week 16. Secondary efficacy outcomes included a multi-domain responder index (MDRI). Twenty-three participants (6–26 years of age) were enrolled. Twenty continued treatment to week 8, and 15 (75%) required an increased dose at week 8 or week 16. There was an improvement in at least one domain in the MDRI in 18 of 21 (86%) at week 8 and in 15 of 16 (94%) at week 36. Seven participants withdrew (intolerability of daily injections and lost to follow-up) before week 36. Adverse events occurred in 22 of 23 (96%) participants, most commonly mild injection site reactions. No serious adverse events were related to anakinra. In conclusion, anakinra was safe and associated with improved neurobehavioral and functional outcomes, supporting continued investigation of anakinra in Sanfilippo syndrome and other mucopolysaccharidoses. ClinicalTrials.gov identifier: NCT04018755 . In a phase 1/2 trial, the recombinant interleukin-1 receptor antagonist anankira was safe and associated with clinically meaningful improvements in neurobehavioral and quality-of-life outcomes in patients with Sanfilippo syndrome.

In anticipation of the revision of the 1985 Food and Agricultural Organization/World Health Organization/United Nations University (FAO/ WHO/UNU) Expert Consultation Report on 'Energy and Protein Requirements', recent scientific knowledge on the principles underlying the estimation of energy requirement is reviewed. This paper carries out a historical review of the scientific rationale adopted by previous FAO/WHO technical reports on energy requirement, discusses the concepts used in assessing basal metabolic rate (BMR), energy expenditure, physical activity level (PAL), and examines current controversial areas. Recommendations and areas of future research are presented. The database of the BMR predictive equations developed by the 1985 FAO/WHO/UNU Expert Consultation Report on Energy and Protein Requirements needs updating and expansion, applying strict and transparent selection criteria. The existence of an ethnic/tropical factor capable of affecting BMR is not supported by the available evidence. The factorial approach for the calculation of energy requirement, as set out in the 1985 report, should be retained. The estimate should have a normative rather than a prescriptive nature, except for the allowance provided for extra physical activity for sedentary populations, and for the prevention of non-communicable chronic diseases. The estimate of energy requirement of children below the age of 10 years should be made on the basis of energy expenditure rather than energy intake. The evidence of the existence of an ethnic/tropical factor is conflicting and no plausible mechanism has as yet been put forward.

Background A close association between HIV infection and the development of cancer exists. Although the advent of highly active antiretroviral therapy has changed the epidemiology of AIDS-associated malignancies, a better understanding on how HIV can induce malignant transformation will help the development of novel therapeutic agents. Methods HIV has been reported to induce the expression of DNMT1 in vitro , but still no information is available about the mechanisms regulating DNMT expression in HIV-related B-cell lymphomas. In this paper, we investigated the expression of DNMT family members (DNMT1, DNMT3a/b) in primary cases of aggressive B-cell lymphomas of HIV-positive subjects. Results Our results confirmed the activation of DNMT1 by HIV in vivo , and reported for the first time a marked up-regulation of DNMT3a and DNMT3b in HIV-positive aggressive B-cell lymphomas. DNMT up-regulation in HIV-positive tumors correlated with down-regulation of specific microRNAs, as the miR29 family, the miR148-152 cluster, known to regulate their expression. Literature reports the activation of DNMTs by the human polyomavirus BKV large T-antigen and adenovirus E1a, through the pRb/E2F pathway. We have previously demonstrated that the HIV Tat protein is able to bind to the pocket proteins and to inactivate their oncosuppressive properties, resulting in uncontrolled cell proliferation. Therefore, we focused on the role of Tat, due to its capability to be released from infected cells and to dysregulate uninfected ones, using an in vitro model in which Tat was ectopically expressed in B-cells. Conclusions Our findings demonstrated that the ectopic expression of Tat was per se sufficient to determine DNMT up-regulation, based on microRNA down-regulation, and that this results in aberrant hypermethylation of target genes and microRNAs. These results point at a direct role for Tat in participating in uninfected B-cell lymphomagenesis, through dysregulation of the epigenetical control of gene expression.

There has been a dramatic improvement in the health of European children and adults since 1900. These improvements were remarkable in the first half of the century, with a progressive fall in the death of children and pregnant women and substantial increases in life expectancy. This century's early health changes were not the result of the provision of medical services, the discovery of drugs and antibiotics, or even the increasing capacity to immunise children against an ever greater range of infectious diseases. They resulted from improvements in the diet, in the housing, occupational and social conditions of workers and their families. Since World War II, with modern living conditions, the general year-around availability of a huge variety of foods, expanding immunisation and improving health care through the health services, with modern therapeutic techniques and new drugs, life expectancy continues to increase in many European countries. These are great public health achievements which should not be overlooked by policy makers and indeed the public.

The study was conducted to assess the effect of definition of episode on diarrhoeal morbidity and to develop a means of adjusting estimates of morbidity for the definition of episode used. This paper reports on a cohort study of 374 children, aged 9-32 months, in three African countries, which recorded frequency and consistency of stool over a seven-month period. Different definitions of episode were applied to these data to assess their effect on annualized diarrhoeal morbidity. Adjustment factors were then derived that corrected morbidity for non-standard definitions of episode. Applying non-standard definitions of episode gave estimates of an annualized number of episodes between 38% and 137% of the internationally-accepted definition. Researchers should be encouraged to use the standard definition of episode of diarrhoea and to use appropriate field protocols. Where this is not possible, correction factors should be applied, particularly where estimates of diarrhoeal morbidity are pooled in systematic reviews.