A haplotype in the dipeptidyl peptidase 4 gene impacts glycemic-related traits of Brazilian older adults.

Dipeptidyl peptidase 4 (DPP4) regulates various physiological pathways and has a pivotal role in glucose homeostasis. The objective of this study was to verify the association of a haplotype constituted by two single nucleotide polymorphisms (rs2268894 and rs6741949) in the DPP4 gene with type 2 diabetes mellitus (T2DM) and fasting glycemia-related variables in a sample of Brazilian older adults, taking serum levels and enzymatic activity of DPP4 into account. Clinical, biochemical, and anthropometric characteristics as well as DPP4 serum levels and enzymatic activity were determined in 800 elderly (≥60 years old) individuals. Assessment of polymorphic sites was performed by real-time PCR whereas haplotypes were inferred from genotypic frequencies. Statistical analyses compared measures and proportions according to T2DM diagnosis and DPP4 haplotypic groups. The most common haplotype consisted of the T-rs2268894/G-rs6741949 string, which was 20% more frequent among non-diabetics. Considering non-diabetic patients alone, carriers of the T/G haplotype had significantly lower levels of blood glucose, insulin, HOMA-IR index, and DPP4 activity. Among diabetic patients, the T/G haplotype was associated with lower DPP4 levels whereas glycemic scores were not affected by allelic variants. Our results suggested that the genetic architecture of DPP4 affects the glycemic profile and DPP4 serum levels and activity among elderly individuals according to the presence or absence of T2DM, with a possible implication of the T/G haplotype to the risk of T2DM onset.

A haplotype in the dipeptidyl peptidase 4 gene impacts glycemic-related traits of Brazilian older adults

Dipeptidyl peptidase 4 (DPP4) regulates various physiological pathways and has a pivotal role in glucose homeostasis. The objective of this study was to verify the association of a haplotype constituted by two single nucleotide polymorphisms (rs2268894 and rs6741949) in the DPP4 gene with type 2 diabetes mellitus (T2DM) and fasting glycemia-related variables in a sample of Brazilian older adults, taking serum levels and enzymatic activity of DPP4 into account. Clinical, biochemical, and anthropometric characteristics as well as DPP4 serum levels and enzymatic activity were determined in 800 elderly (≥60 years old) individuals. Assessment of polymorphic sites was performed by real-time PCR whereas haplotypes were inferred from genotypic frequencies. Statistical analyses compared measures and proportions according to T2DM diagnosis and DPP4 haplotypic groups. The most common haplotype consisted of the T-rs2268894/G-rs6741949 string, which was 20% more frequent among non-diabetics. Considering non-diabetic patients alone, carriers of the T/G haplotype had significantly lower levels of blood glucose, insulin, HOMA-IR index, and DPP4 activity. Among diabetic patients, the T/G haplotype was associated with lower DPP4 levels whereas glycemic scores were not affected by allelic variants. Our results suggested that the genetic architecture of DPP4 affects the glycemic profile and DPP4 serum levels and activity among elderly individuals according to the presence or absence of T2DM, with a possible implication of the T/G haplotype to the risk of T2DM onset.

Social media for students' sleep health promotion - a health intervention report during COVID -19.

The COVID-19 pandemic has affected sleep health. Students' sleep health is essential for the performance of neuro-cognitive processes, as well as mental and physical balance. We assume the COVID19 pandemic has modified some sleep habits by prompting environmental and social interaction changes. In this study we surveyed a sample of 300 Brazilian students, with internet access, resident in the Federal District. They completed a questionnaire over two weeks in March 2020, i.e. the second and third week of the social isolation policy enacted in the Federal District due to COVID19. Valid responses from students aged18-24 years were analyzed. The sample was mostly female; 76,3% reported somnolence during the day, 70,2% anxiety and 87,8% worse sleep associated with stress and/or anxiety, which indicated the variables for an educational health intervention design in this context. Further, 53.2% made no effort to avoid screens before sleeping; 73.9% to avoid using the bed for work or watching television and 83.1% to avoid consuming heavy foods before sleeping. We then created an Instagram profile, @comodormimos, which focused on the main sleep issues revealed by participants in the survey. Posts on the profile were based on sleep-related subjects: sleep processes, sleep hygiene practices for students; sleep stages, function and regulation; and sleep-wake circadian rhythms. The profile gained 307 followers, mostly women (61,7%), 18-24 years old. We concluded that the Covid-10 pandemic period increased harmful sleep behavior in students. Further studies are needed to understand the impact of the COVID-19 pandemic on student sleep health.

Avaliação da toxicidade aguda do extrato das cascas de Pithecellobium cochliocarpum (Gomez) Macbr / Evaluation of acute toxicity of the Pithecellobium cochliocarpum (Gomez) Macbr bark extract

O uso popular, e mesmo o tradicional, não são suficientes para validar as plantas medicinais como medicamentos eficazes e seguros. Para melhor entendimento, é necessário avaliar a relação risco/benefício de seu uso, por meio de estudos toxicológicos. O objetivo desta pesquisa foi estimar a toxicidade aguda do extrato etanólico das cascas secas de Pithecellobium cochliocarpum (Gomez) Macbr através da obtenção da dose letal (DL50) em roedores, e da Concentração letal (CL50) frente à Artemia salina Leach. Foram realizados experimentos por via oral e intraperitoneal utilizando camundongos fêmeas albinos Swiss (Mus musculus) (n=6). Por via oral foram administradas 3 doses (1.000, 3.000 e 5.000 mg Kg-1) e por via entraperitoneal, 5 doses (155, 160, 176, 345,6 e 414,72 Kg-1). Os sinais comportamentais foram avaliados durante uma hora após a administração do extrato, ficando em observação até 48 horas. O número de óbitos foi quantificado para posterior cálculo da DL50. A administração por via intraperitoneal foi realizada em intervalo de 5 minutos para cada animal. Nos ensaios de toxicidade por via oral a solução foi introduzida por via intragástrica através de cânula metálica acoplada a seringa (gavagem) no mesmo intervalo de tempo utilizado pela via intraperitoneal. Os animais do grupo de administração oral apresentaram algumas reações, porém não letais até a dose de 5.000 mg Kg-1. A DL50 para a via intraperitoneal foi 257, 49 mg Kg-1 (muito tóxico, grau 4) (Schuartsman, 1980). A CL50 (543,5 µg Kg-1) demonstrou ser tóxica frente à A. salina. Conclui-se que sob condições agudas de exposição, o extrato do Pithecellobium cochliocarpum é um agente tóxico, devendo ser considerado como tal, dependendo da dose administrada ou absorvida, do etempo e frequência de exposição e das vias de administração.

The popular use, and even the traditional one, is not enough to validate medicinal plants as effective and safe medicines. For a better understanding, it is necessary to assess the risk / benefit ratio of their use through toxicological studies. The aim of this work was to evaluate the acute toxicity of Pithecellobium cochliocarpum (Gomez) Macbr dried bark ethanolic extract through its lethal dose (LD50), in mice, and lethal concentration (LC50) in relation to Artemia salina Leach. Experiments were performed by oral and intraperitoneal route using female Swiss albino mice (Mus musculus) (n = 6). The first three doses were given orally (1,000, 3,000 and 5,000 mg kg-1) and the last five doses were given intraperitoneally (155, 160, 176, 345.6 and 414.72 Kg-1). The behavioral signs were evaluated one hour after administration of the extract, being observed up to 48 hours. The number of deaths was quantified for subsequent calculation of LD50. The intraperitoneal administration was carried out at an interval of 5 minutes for each animal. For the oral toxicity test, the solution was introduced in the digestive system of the animals through a metal cannula coupled to a syringe (gavage) at the same time interval used for the intraperitoneal route. The animals from the oral group presented some reactions, but they were not lethal up to the dose of 5.000 mg kg-1. The LD50 for the intraperitoneal group was 257.49 mg kg-1 (very toxic, grade 4) (Schuartsman, 1980). The LC50 (543.5 mg kg-1) was toxic to A. salina. We can conclude that, under acute conditions of exposure, the Pithecellobium cochliocarpum extract is a poisonous agent and should be considered as such depending on the administered or absorbed dose, the time and frequency of exposure, and the administration routes.

Parasite prolyl oligopeptidases and the challenge of designing chemotherapeuticals for Chagas disease, leishmaniasis and African trypanosomiasis.

The trypanosomatids Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp. cause Chagas disease, leishmaniasis and human African trypanosomiasis, respectively. It is estimated that over 10 million people worldwide suffer from these neglected diseases, posing enormous social and economic problems in endemic areas. There are no vaccines to prevent these infections and chemotherapies are not adequate. This picture indicates that new chemotherapeutic agents must be developed to treat these illnesses. For this purpose, understanding the biology of the pathogenic trypanosomatid- host cell interface is fundamental for molecular and functional characterization of virulence factors that may be used as targets for the development of inhibitors to be used for effective chemotherapy. In this context, it is well known that proteases have crucial functions for both metabolism and infectivity of pathogens and are thus potential drug targets. In this regard, prolyl oligopeptidase and oligopeptidase B, both members of the S9 serine protease family, have been shown to play important roles in the interactions of pathogenic protozoa with their mammalian hosts and may thus be considered targets for drug design. This review aims to discuss structural and functional properties of these intriguing enzymes and their potential as targets for the development of drugs against Chagas disease, leishmaniasis and African trypanosomiasis.

Complex dynamics during metal dissolution: from intrinsic to faceted anomalous scaling.

The kinetic roughening of dissolving polycrystalline pure iron has been studied. A depth analysis of surface images has shown two consecutive growth regimes characterized by different scaling anomalous properties: an initial intrinsic anomalous scaling evolving in the thick film limit towards the theoretically conjectured faceted anomalous scaling. This represents the first experimental evidence of such scaling as well as of such transition. The dynamics presented here may account for the striped surface pattern observed during the evolution of metals or alloys in a large number of processes.

Anomalous kinetic roughening during anodic dissolution of polycrystalline Fe.

Dynamics of surface roughness during polycrystalline pure iron electrodissolution is investigated at constant current density by means of ex situ atomic force microscopy. The scaling of the local surface width reveals that surface kinetic roughening is anomalous with both the exponents of local roughness, alpha(loc) , and growth, beta , close to 1 pointing out that interface evolution is unstable. We show that this anomalous unstable behavior results from the development of a faceted surface structure exposing different crystal orientations. The presence of smooth faceted walls is consistent with the value alpha(local) approximately 1 , whereas the difference in the dissolution rates on the different crystallographic planes account for the nonlocal effects causing the unstable growth. Results are discussed in the context of a recently reported anomalous scaling which accounts for dynamics of self-organized depinning models displaying faceted interfaces. The influence of the electrode potential on the dissolution rates of the different crystallographic planes, along with its effect on the mobility of metal adatoms, are discussed to be behind the complex behavior of local roughness when the current density is varied.

Chronic suppurative otitis media in Tanzanian school children and its effects on hearing.

OBJECTIVES: To compare different treatment regimens of chronic suppurative otitis media (CSOM) in school children, in regard to their consequence in hearing and discharge from the ear drum perforation. DESIGN: Randomised controlled trial. SETTING: Randomly selected primary schools within Dar es Salaam. SUBJECTS: Three hundred and twenty eight children between 5-17 years of age with CSOM in one or both ears. RESULTS: Three to four months after the onset of treatment 31% of group 1, 54% of group 2, and 56% of group 3, had dry ears. Treatment with dry mopping and boric acid in alcohol ear drops was significantly better than dry mopping alone. Adding amoxicillin to the treatment did not improve the end results. Hearing test performed before and after treatment showed that the hearing thresholds were the same or better after the treatment. The possible risk that boric acid in alcohol ear drops should lead to sensorineural hearing loss has not been confirmed. CONCLUSION: Based on the above results, the treatment of choice for CSOM in children in Dar es Salaam should be dry mopping and boric acid in spirit ear drops.

Trypanosoma cruzi prolyl oligopeptidase Tc80 is involved in nonphagocytic mammalian cell invasion by trypomastigotes.

Trypanosoma cruzi is an intracellular protozoan parasite able to invade a wide variety of mammalian cells. To have access to the target organs/cells, the parasite must cross the basal laminae and the extracellular matrix (ECM). We previously characterized an 80-kDa proteinase (Tc80) secreted by the infective trypomastigotes that hydrolyzes native collagens and might be involved in infection by degrading ECM components. Here, we present evidence indicating a role for Tc80 in the invasion of nonphagocytic cells. Tc80 was classified as a member of the prolyl oligopeptidase (POP) family of serine proteases and was also found to hydrolyze fibronectin. Selective inhibitors for POP Tc80 were synthesized that blocked parasite entry into cells. Blockage occurred when trypomastigotes were preincubated with irreversible inhibitors but not after host cell preincubation, and the blockage correlated with inhibition of POP Tc80 activity in treated parasites. These data and the enzyme location inside a vesicular compartment close to the flagellar pocket, a specialized domain in endocytosis/exocytosis, strongly suggest a role for POP Tc80 in the maturation of parasite protein(s) and/or, after secretion, in a local action on parasite or host cell/ECM components required for invasion.

An unusual foreign body in the rectum.

This is the report of an unusual foreign body in the rectum which was a complication of the migration of an esophageal Celestin's prosthesis.

Middle ear disease and hearing impairment in northern Tanzania. A prevalence study of schoolchildren in the Moshi and Monduli districts.

A total of 854 schoolchildren from one urban and one rural district in northern Tanzania were examined for the presence of middle ear pathology and hearing loss by means of pneumotoscopy and screening audiometry (air conduction). The prevalence of chronic otitis media (COM) was 1.6%, with no difference between urban and rural children. Scarred and sclerotic tympanic membranes were found in 10.9% of urban children and in 15.1% of rural children, the difference being significant. Hearing loss within the speech frequency range in all the children studied was found in 37% of the urban children and in 18% of the rural children. However, the prevalence of hearing loss above 30 dB HL was 3% in both districts. High frequency loss was significantly more common among urban than among rural children. Undetected severe hearing impairment/deafness was found in three children in the rural district, while none was found in the urban district.

Otitis media and hearing loss in children attending an ENT clinic in Luanda, Angola.

At the ENT clinic in Luanda, Angola, 110 consecutive cases of children with chronic otitis media (COM) were studied to find out some clinical characteristics regarding age of onset and duration of otorrhea as well as the general state of health of the children. Eighty-five percent of the children had had longstanding otorrhea. In 75% of all the cases ear discharge had started during early childhood. It was possible to institute a simple conservative treatment of COM. Fifty percent returned to the clinic for a follow-up. The majority of the children came from families who lived under fairly good social conditions. One-hundred and five children with sensorineural hearing loss consulted the clinic. Many of them had had their hearing loss for several years before coming to the clinic. The etiology was in 39 cases infectious disease, meningitis being the most common one. Seventy-two percent had severe to profound hearing loss. Children with slight to moderate hearing loss rarely appeared at the clinic. Some of the hearing-handicapped children could be sent to a special school for rehabilitation.

Highly acidic glycans from sea cucumbers. Isolation and fractionation of fucose-rich sulfated polysaccharides from the body wall of Ludwigothurea grisea.

The body wall of the sea cucumber contains high amounts of sulfated glycans, which differ in structure from glycosaminoglycans of animal tissues and also from the fucose-rich sulfated polysaccharides isolated from marine algae and from the jelly coat of sea urchin eggs. In Ludwigothurea grisea, glycans can be separated into three fractions which differ in molecular mass and chemical composition. The fraction containing a high-molecular-mass component has a high proportion of fucose and small amounts of amino sugars, whereas another fraction contains primarily a sulfated fucan. The third fraction, which represents the major portion of the sea cucumber polysaccharides, contains besides fucose, approximately equimolar proportions of glucuronic acid and amino sugars, and has a sulfate content higher than that in the other two fractions. Both D and L-isomers of fucose are found in these polysaccharides, and the sulfate is linked to the O-3 position of the fucose residues. The attachment position of the sulfate groups to the glucuronic acid units and amino sugars is still undetermined. It is possible that these compounds are involved in maintaining the integrity of the sea cucumber's body wall, in analogy with the role of other macromolecules in the vertebrate connective tissue.

A proposito de dois casos de polineuropatia amiloidotica familiar (doenca de Corino Andrade). / Apropos of 2 cases of familial amyloidotic polyneuropathy (Corino Andrade disease)

Sao estudados dois casos de polineuropatia amiloidotica familiar confirmados por biopsia, e apesar de nao haver duvidas quanto ao diagnostico, foi ressaltado o comportamento diferente de uma mesma doencao. Destacam-se as investigacoes realizadas por Corino Andrade, que relatou o primeiro caso portugues da doenca, chamando atencao para a incidencia familiar. Procurou-se, tambem, definir polineuropatia amiloidotica familiar, baseando-se em relatos publicados por varios autores

Comprometimento neurologico na esquistossomose mansonica. / Neurological involvement in schistosomiasis mansoni

Os autores chamam atencao para o problema do comprometimento neurologico da esquistossomose mansonica em nosso meio, com areas endemicas, onde milhoes de individuos sao acometidos por esta parasitose. Assinalam a subestimacao destas complicacoes que sao pouco diagnosticadas, apesar das multiplas manifestacoes medulares e encefalicas que surgem nestes casos, embora as lesoes medulares sejam bem mais frequentes e mais sugestivas. Ressaltam a importancia do diagnostico etiologico diante da existencia de possibilidades terapeuticas satisfatorias