Sleep disorders related to nutrition and digestive diseases: a neglected clinical condition.

Sleep disturbances often result from inappropriate lifestyles, incorrect dietary habits, and/or digestive diseases. This clinical condition, however, has not been sufficiently explored in this area. Several studies have linked the circadian timing system to the physiology of metabolism control mechanisms, energy balance regulation, and nutrition. Sleep disturbances supposedly trigger digestive disorders or conversely represent specific clinical manifestation of gastrointestinal (GI) diseases. Poor sleep may worsen the symptoms of GI disorders, affecting the quality of life. Conversely, short sleep may influence dietary choices, as well as meal timing, and the circadian system drives temporal changes in metabolic patterns. Emerging evidence suggests that patients with inappropriate dietary habits and chronic digestive disorders often sleep less and show lower sleep efficiency, compared with healthy individuals. Sleep disturbances may thus represent a primary symptom of digestive diseases. Further controlled trials are needed to fully understand the relationship between sleep disturbances, dietary habits, and GI disorders. It may be also anticipated that the evaluation of sleep quality may prove useful to drive positive interventions and improve the quality of life in a proportion of patients. This review summarizes data linking sleep disorders with diet and a series of disease including gastro-esophageal reflux disease, peptic disease, functional gastrointestinal disorders, inflammatory bowel diseases, gut microbiota alterations, liver and pancreatic diseases, and obesity. The evidence supporting the complex interplay between sleep dysfunction, nutrition, and digestive diseases is discussed.

Resistance mesenteric arteries display hypercontractility in the resolution time of Strongyloides venezuelensis infection.

The blood flow in the mesenteric region is crucial for nutrient absorption and immune response in the gastrointestinal tract. The presence of nematodes or their excreted/secreted products seems to provoke vascular dysfunction. However, it is unclear whether and how the intestinal nematodes with habitat in the intestinal niche could affect the mesenteric vascular resistance. In this study, male Wistar rats were infected with 2000 larvae of S. venezuelensis, and experiments were conducted at 0 (non-infected control), 10 or 30 days post-infection (DPI). Eggs were counted in rats' feces and adult worms recovered from the small intestine. Second- or third-order mesenteric arteries were extracted for concentration-response curves (CRC) to phenylephrine [PE; in the presence or absence of L-NAME or indomethacin] and acetylcholine. The number of eggs and adult worms were significantly higher in the 10 DPI group than those of 30 DPI group. Augmented PE-induced contraction was seen after 30 DPI compared to 10 DPI or control group. Hypercontractility to PE was partially prevented by L-NAME and wholly abolished by indomethacin incubation. Endothelium-dependent relaxation and endothelial nitric oxide synthase expression were unchanged among groups. COX-1 and COX-2 display a different pattern of expression over the infection. Hypercontractility observed in mesenteric resistance arteries in the resolution time of S. venezuelensis infection may represent systemic damage, which can generate significant cardiovascular and gastrointestinal repercussions.

Neglected tropical diseases and infectious illnesses: potential targeted peptides employed as hits compounds in drug design.

Neglected Tropical Diseases (NTDs) and infectious illnesses, such as malaria, tuberculosis and Zika fever, represent a major public health concern in many countries and regions worldwide, especially in developing ones. They cause thousands of deaths per year, and certainly compromise the life of affected patients. The drugs available for therapy are toxic, have considerable adverse effects, and are obsolete, especially with respect to resistance. In this context, targeted peptides are considered promising in the design of new drugs, since they have specific action and reduced toxicity. Indeed, there is a rising interest in these targeted compounds within the pharmaceutical industry, proving their importance to the Pharmaceutical Sciences field. Many have been approved by the Food and Drug Administration (FDA) to be used as medicines, plus there are more than 300 peptides currently in clinical trials. The main purpose of this review is to show the most promising potential targeted peptides acting as hits molecules in NTDs and other infectious illnesses. We hope to contribute to the discovery of medicines in this relatively neglected area, which will be extremely useful in improving the health of many suffering people.

Paediatric visceral leishmaniasis: a retrospective study on clinical manifestations, demographic features and laboratory findings of hospitalised cases in Iran between 2006 and 2016.

Visceral leishmaniasis (VL) is a neglected disease. Our retrospective study describes 38 clinical and epidemiological characteristics of VL in patients admitted to a paediatric hospital in Tehran, Iran, who came from different geographical regions, indicating that the disease has spread to most parts of the country. Some 76.3% of the children documented suffered with symptoms of the disease for two months before admission.

Apraxia, Neglect, and Agnosia.

PURPOSE OF REVIEW: In part because of their striking clinical presentations, disorders of higher nervous system function figured prominently in the early history of neurology. These disorders are not merely historical curiosities, however. As apraxia, neglect, and agnosia have important clinical implications, it is important to possess a working knowledge of the conditions and how to identify them. RECENT FINDINGS: Apraxia is a disorder of skilled action that is frequently observed in the setting of dominant hemisphere pathology, whether from stroke or neurodegenerative disorders. In contrast to some previous teaching, apraxia has clear clinical relevance as it is associated with poor recovery from stroke. Neglect is a complex disorder with many different manifestations that may have different underlying mechanisms. Neglect is, in the author's view, a multicomponent disorder in which impairment in attention and arousal is a major contributor. Finally, agnosias come in a wide variety of forms, reflecting impairments ranging from low-level sensory processing to access to stored knowledge of the world (semantics). SUMMARY: The classic behavioral disorders reviewed here were of immense interest to early neurologists because of their arresting clinical phenomenology; more recent investigations have done much to advance the neuroscientific understanding of the disorders and to reveal their clinical relevance.

Promoting awareness of neonatal menstruation.

Neonatal uterine bleeding (NUB) has been carefully studied in the past through case reports, small series, clinical cohort studies, pathology investigations of fetal and neonatal. Following a historical recount, this review summarizes biological mechanisms conditioning NUB, starting from the persistence till birth of an 'ontogenetic progesterone resistance' (OPR), causing decreased responsiveness of target tissues to bioavailable progesterone. Several pregnancy-related conditions, such as preeclampsia, fetal growth restriction, prematurity, post-maturity and even Rhesus or ABO incompatibility, influence the occurrence of NUB. It seems therefore that the phenomenon is precipitated by chronic fetal distress. When present, OPR may persists until telarche; as a consequence, if pregnancy occurs in early teenage, the disorder known as "defective deep placentation" may ensue, increasing the risk of obstetrical syndromes. In the presence of NUB, retrograde shedding into the peritoneal cavity of endometrial stem/progenitor and niche cells may occur. There, given the right environment, these cells can survive and become activated at the time of telarche, causing the specific phenotype of early-onset endometriosis. In conclusion, neonatal menstruation is a fetal distress indicator and can alter the incidence of a variety of pathological conditions later in life. For this reason, it should be carefully recorded and the parents informed.

Financing and collaboration on research and development for nodding syndrome.

BACKGROUND: Nodding syndrome is a neurological disease with no known cure or treatment, impacting children aged 3-18 years old, mainly in East Africa. Children progressively develop varying degrees of cognitive impairment which may lead to severe wasting, a vegetative state and, eventually, death. Despite its 50-year existence, little is known about its cause, risk factors and prognosis. It is a disease where markets will not provide solutions because the patients are both too few and too poor, making it especially neglected. Open source innovation has been recommended as an approach to neglected disease research in order to maximize available funding through greater collaboration and openness to results. Nodding syndrome is a useful case to examine the relevance of open source innovation. METHODS: We assessed the magnitude of research related to nodding syndrome, its availability, financing and the amount of collaboration. We surveyed researchers regarding their motivations, attitudes toward open source innovation concepts and barriers to greater collaboration. RESULTS: Little research is occurring for nodding syndrome, but it is openly available and researchers are highly collaborative. The disease is largely unknown, which is partly attributed to WHO not classifying nodding syndrome as a neglected tropical disease and not including it in any formal programme. Impacted countries, particularly Uganda, demonstrate a strong degree of ownership through both authorship and research financing. Nodding syndrome researchers have been allocated a total of €5 million from 2013 to 2019 in grant funding. Annual financing, due to three new grants, doubled from 2014 to 2015. CONCLUSIONS: Nodding syndrome, a disease previously ignored by the international community, is starting to receive greater attention, although financing remains modest. If infectious, a larger epidemic could take the world by surprise. Open source innovation can likely help by sharing research protocols (to avoid duplication) and early research results (to adjust to the findings of others). The existing scientists have already endorsed open source innovation, but increased financing is needed. The support of just a few high-income countries could reap a large impact.

Podoconiosis treatment in northern Ethiopia (GoLBet): study protocol for a randomised controlled trial.

BACKGROUND: Podoconiosis is one of the forgotten types of leg swelling (elephantiasis) in the tropics. Unlike the other, better-known types of leg swelling, podoconiosis is not caused by any parasite, virus or bacterium, but by an abnormal reaction to minerals found in the clay soils of some tropical highland areas. Non-governmental Organizations (NGOs) have been responsible for the development of simple treatment methods without systematic evaluation of its effectiveness. It is essential that a large scale, fully controlled, pragmatic trial of the intervention is conducted. We aim to test the hypothesis that community-based treatment of podoconiosis lymphoedema reduces the frequency of acute dermatolymphangioadenitis episodes ('acute attacks') and improves other clinical, social and economic outcomes. METHODS/DESIGN: This is a pragmatic, individually randomised controlled trial. We plan to randomly allocate 680 podoconiosis patients from the East Gojjam Zone in northern Ethiopia to one of two groups: 'Standard Treatment' or 'Delayed Treatment'. Those randomised to standard treatment will receive the hygiene and foot-care intervention from May 2015 for one year, whereas those in the control arm will be followed through 2015 and be offered the intervention in 2016. The trial will be preceded by an economic context survey and a Rapid Ethical Assessment to identify optimal methods of conveying information about the trial and the approaches to obtaining informed consent preferred by the community. The primary outcome will be measured by recording patient recall and using a simple, patient-held diary that will be developed to record episodes of acute attacks. Adherence to treatment, clinical stage of disease, quality of life, disability and stigma will be considered secondary outcome measures. Other outcomes will include adverse events and economic productivity. Assessments will be made at baseline and at 3, 6, 9 and 12 months thereafter. DISCUSSION: The evidence is highly likely to inform implementation of the new master plan for integrated control of Neglected Tropical Diseases (NTDs), in which podoconiosis is identified as one of eight NTDs prioritised for control. Potentially, an estimated 3 million patients in Ethiopia will therefore benefit from the results of this trial. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number. REGISTRATION NUMBER: ISRCTN67805210. Date of registration: 24 January 2013.

Neurologic manifestations of the neglected tropical diseases.

BACKGROUND: The World Health Organization has identified 17 neglected tropical diseases (NTDs) that disproportionately affect the world's poorest populations. The neurologic aspects of many of these NTDs have received relatively little attention. METHODS: A review was performed in PubMed (MedLine) for each NTD by disease name, name of its causative organism, and neurology, neurosurgery, neurologist, brain, spinal cord, peripheral nerve, muscle, nervous system, encephalitis, meningitis, encephalopathy, stroke, neuropathy, and myopathy (1968-Sept. 2013). The Oxford Center for Evidence-based Medicine guidelines were used to determine the level of evidence of neurological involvement and treatment based on the reports identified. RESULTS: Neurologic manifestations were reported for all NTDs except yaws. Neurologic involvement was described in systematic reviews for four NTDs (Chagas disease, echinococcosis, rabies, cysticercosis) (levels 2a-3a), retrospective cohort studies for six (dengue, human African trypanosomiasis, leishmaniasis, leprosy, onchocerciasis, schistosomiasis) (levels 2b-3b), case series for one (foodborne trematodiasis) (level 4), and case reports for five (Buruli ulcer, dracunculiasis, filariasis, soil-transmitted helminthes, and trachoma). Level 1 evidence for treatment of neurologic manifestations of NTDs was found for human African trypanosomiasis, leprosy, and cysticercosis and level 2 evidence exists for treatment of neurologic involvement in Chagas disease. For the remaining NTDs, treatment of neurologic complications is described in case series and case reports only. CONCLUSIONS: Neurologic manifestations of NTDs cause significant morbidity and mortality, although limited evidence exists on how best to treat these neurologic complications. Increased awareness of neurologic manifestations of the NTDs can increase their early identification and treatment, contributing to ongoing elimination and eradication campaigns.

The Impact of Nurses on Neglected Tropical Disease Management.

Although Neglected Tropical Diseases (NTDs) are largely endemic in the developing nations of Africa, Asia, and South and Central America, they are reemerging with increasing frequency in developed countries. Their diagnosis, treatment, and control are an increasing public health concern that requires a different awareness by health care providers. Neglected tropical diseases (NTDs) are chronic infectious diseases which disproportionately burden poor, rural, and marginalized populations with significant mortality and high morbidity (disability, disfigurement, impaired childhood growth and cognitive development, increased vulnerability to coinfection) that reinforces their poverty. What can we learn from the nurses in developing countries already battling NTD's that could be useful in the developed world? This article provides an overview of distribution, pathophysiology, symptoms, and management of 13 NTDs, with particular attention to the role of nurses in delivering cost-effective integrated interventions. Case studies of schistosomiasis, Chagas disease, and leishmaniasis address recognition and treatment of infected individuals in developed nations where NTD infection is limited primarily to immigrants and travelers.

The impact of community health workers (CHWs) on Buruli ulcer in sub-Saharan Africa: a systematic review.

UNLABELLED: Buruli ulcer (BU) is a cutaneous neglected tropical disease caused by Mycobacterium ulcerans. Participation of Community Health Workers (CHWs) is an integral part of the management of BU, yet their impact has not been systematically evaluated in sub-Saharan Africa. METHODS: Our objectives were to summarize the evidence on the impact of CHWs on the control of BU in sub-Saharan Africa by looking at their recruitment, training, non-governmental support and performance. We searched the following electronic databases from January 1998 to July 2012: Medline, EMBASE (Excerpta Medica Database), The Cochrane Library, Google Scholar, CINAHL (Cumulative Index to Nursing and Allied Health Literature), WHOLIS (World Health Organization Library Database), LILACS (Latin American and Caribbean Literature on Health Sciences) and contacted experts in the field. There were no restrictions to language or publication status. All study designs that could provide the information we sought were eligible, provided the studies were conducted in sub-Saharan Africa. Critical appraisal of all identified citations was done independently by two authors to establish the possible relevance of the articles for inclusion in the review. Of 195 hits, 17 papers met the inclusion criteria. For the management of Buruli Ulcer, CHWs are often recruited from the communities they will serve. Communities play a role in CHW selection. Larger numbers of CHWs are needed in order to improve the detection and management of cases. One of the major obstacles to the control of BU is inadequate and poorly- equipped health facilities in the affected areas. Evidence from this review suggests that CHW programmes can have large impacts on the control of BU in sub-Saharan Africa. Large-scale rigorous studies, including RCTs, are needed to assess whether the CHWs programs promote equity and access.

Multidisciplinary approach to R&D in vitiligo, a neglected skin disease.

A global interest in therapies for neglected diseases is rising, but traditional biopharma research and development (R&D) process is prohibitively expensive to justify cost of their development. Vitiligo is a multifactorial orphan disease that affects at minimum 35 million people worldwide, yet no therapeutic solutions exist. The present authors describe a budget-minded pursuit of the new therapy development for vitiligo, which includes a multidiscipline collaboration and effective bridging between academic research, biobanking, and bioinformatics. The present authors anticipate that the present authors' "theoretically induced and empirically guided" discovery process will enable development of more leads, with a much greater probability of success and under tighter budgets compared with those of the biopharma company. Ultimately, the multidisciplinary approach described below facilitates the collaborative development of personalized treatments for different patient subpopulations in vitiligo and other neglected diseases.

Neglected femoral neck fractures in adults.

PURPOSE: To assess treatment outcomes in adults with neglected femoral neck fractures, and propose a treatment protocol based on bone quality measured by the Singh index. METHODS: 16 men and 6 women aged 18 to 48 (mean, 33) years presented with neglected (>3 weeks old) femoral neck fractures. Those with good bone quality (Singh index, >3) underwent closed reduction and valgus osteotomy and fixation with 120º double angle blade plates (group 1, n=8), whereas those with poor bone quality (Singh index, >3) and/or communition of the posterior femoral neck underwent fibular grafting and internal fixation with one or two 7-mm cannulated cancellous screws (group 2, n=14). Functional outcome was assessed at the 6-month follow-up, according to modified Askin and Bryan criteria. RESULTS: The mean delay in surgery was 12 (range, 4-21) weeks. Patients were followed up for a mean of 19 (range, 12-24) months. The mean time to union was 20 (range, 12-52) weeks. The mean time to full weight bearing was 18 (range, 12-40) weeks. All patients achieved bone union except one in group 1 who had non-union and breakage of the blade plate at week 20 and underwent total hip arthroplasty. Other complications included slippage of fibular graft (n=1), delayed union (n=1), avascular necrosis of the femoral head (n=2), limb length discrepancy (n=3), and superficial infection (n=1). Functional outcome was excellent in 2 patients, good in 17, and poor in 3. CONCLUSION: Valgus osteotomy and double angle blade plate fixation, and fibular grafting and cancellous screw fixation appeared to be appropriate treatments for neglected femoral neck fractures in adults.