IgG functionalized polymeric nanoparticles for oral insulin administration.

The oral route is the best way to administer a drug; however, fitting peptide drugs in this route is a major challenge. In insulin cases, less than 0.5% of the administered dose achieves systemic circulation. Oral delivery by nanoparticles can increase insulin permeability across the intestinal epithelium while maintaining its structure and activity until release in the gut. This system can be improved to increase permeability across intestinal cells through active delivery. This study aimed to improve a nanoparticle formulation by promoting functionalization of its surface with immunoglobulin G to increase its absorption by intestinal epithelium. The characterization of formulations showed an adequate size and a good entrapment efficiency. Functionalized nanoparticles led to a desirable increase in insulin release time. Differential scanning calorimetry, infrared spectroscopy and paper chromatography proved the interactions of nanoparticle components. With immunoglobulin G, the nanoparticle size was slightly increased, which did not show aggregate formation. The developed functionalized nanoparticle formulation proved to be adequate to carry insulin and potentially increase its internalization by epithelial gut cells, being a promising alternative to the existing formulations for orally administered low-absorption peptides.

[Infective endocarditis: Clinical features and prognosis between 2004 and 2014 in a non-teaching hospital]. / Endocardite infectieuse : caractéristiques cliniques et pronostic entre 2004 et 2014 dans un hôpital non universitaire.

AIMS: Despite diagnostic and therapeutic advances, infective endocarditis (IE) remains a severe disease. The aim of the study was to describe clinical features and prognosis of patients with IE in a non-teaching hospital and compare them with current data and a similar study conducted 10 years earlier in the same center. METHODS: We performed a single institution retrospective study including all patients with Duke-Li definite IE between 2004 and 2014. RESULTS: Ninety-four patients were included. Results are consistent with current French and international data, including in-hospital death rate of 16%. In accordance with literature, we report on an increase in Staphylococcus and health care-associated IE and endocarditis on pacemaker leads, but without significant difference compared to our previous study. In univariate analyses, renal failure, age over 77 years and Staphylococcus aureus IE were associated with in-hospital mortality. In multivariate analyses, predictors of in-hospital death were renal failure and lack of surgery. There was a non-significant trend of excess mortality in Staphylococcus endocarditis and in patients with heart failure. CONCLUSION: IE remains a severe disease and S. aureus is more often involved. IE seems to be safely managed in a peripheral hospital provided that there is a partnership with a reference hospital.

Molecular and genetic studies on the region of translocation and duplication in the neuroblastoma cell line NGP at the 1p36.13-p36.32 chromosomal site.

Cytogenetic and molecular studies suggest that chromosome 1p might contain oncosuppressor genes involved in the pathogenesis of neuroblastoma and other adult tumors. The isolation of these genes by the 'positional cloning' approach will be facilitated by the characterization of cell lines with well defined chromosomal aberrations. In the present report we provide molecular data on the NGP neuroblastoma cell line which contains a reciprocal t(1;15) translocation. Two regions, possibly hosting oncosuppressor genes, have been identified: one is distal to the ENO1 locus, the other one is comprised between PND and A12M2 and corresponds to that of a constitutional t(1;17) translocation described in a neuroblastoma patient. Genetic data also suggest that the NGP cell line, despite the presence of two chromosomes 1, might be hemizygous for the subtelomeric 1p region.

Risks associated with obesity in pregnancy, for the mother and baby: a systematic review of reviews.

Maternal obesity is linked with adverse outcomes for mothers and babies. To get an overview of risks related to obesity in pregnant women, a systematic review of reviews was conducted. For inclusion, reviews had to compare pregnant women of healthy weight with women with obesity, and measure a health outcome for mother and/or baby. Authors conducted full-text screening, quality assurance using the AMSTAR tool and data extraction steps in pairs. Narrative analysis of the 22 reviews included show gestational diabetes, pre-eclampsia, gestational hypertension, depression, instrumental and caesarean birth, and surgical site infection to be more likely to occur in pregnant women with obesity compared with women with a healthy weight. Maternal obesity is also linked to greater risk of preterm birth, large-for-gestational-age babies, foetal defects, congenital anomalies and perinatal death. Furthermore, breastfeeding initiation rates are lower and there is greater risk of early breastfeeding cessation in women with obesity compared with healthy weight women. These adverse outcomes may result in longer duration of hospital stay, with concomitant resource implications. It is crucial to reduce the burden of adverse maternal and foetal/child outcomes caused by maternal obesity. Women with obesity need support to lose weight before they conceive, and to minimize their weight gain in pregnancy.

Validation of a nomogram predicting sentinel lymph node status in melanoma in an Irish population.

BACKGROUND: Sentinel lymph node (SLN) positivity is an important prognostic factor in cutaneous melanoma. A nomogram has been developed at Memorial Sloan-Kettering Cancer Centre (MSKCC) to predict SLN positivity and this may be useful to select patients for SLN biopsy. AIMS: We aimed to determine whether this nomogram would be of clinical use in an Irish population. METHODS: Age, Breslow thickness, Clark's level, presence of ulceration and tumour location indices were used to calculate the probability of SLN positivity with the MSKCC nomogram in 124 patients who underwent SLN biopsy in Beaumont Hospital between 2006 and 2012. Discrimination and calibration of the nomogram were evaluated. Negative predictive value (NPV) of the nomogram was calculated, using a cut-off of nomogram predicted probability of <9%. RESULTS: SLN biopsy was positive in 25 patients (20.16%). Overall predictive accuracy of the nomogram was found to be significant with an area under the curve of 0.805 (95% confidence interval 0.710-0.899). The mean predicted probability correlated well with observed risk (r = 0.887). The NPV was 92.86% with an error rate of 3.23%. This would lead to a reduction in SLN biopsy rate of 45.16%. CONCLUSIONS: This nomogram is valid and accurate at predicting SLN positivity in an Irish population. This may facilitate the clinical decision to perform a SLN biopsy in malignant melanoma.

Further linkage evidence for localization of mutational sites for nonsyndromic types of X-linked mental retardation at the pericentromeric region.

We used several microsatellite markers scattered along the X chromosome to search for linkage relationships in a large Sardinian pedigree segregating for nonspecific X-linked mental retardation (MRX). Markers DXS573 and AR, located at chromosomal subregions Xp11.4-p11.22 and Xq11.2-q12, respectively, were found to segregate in full concordance with the disease, leading to a LOD score of 4.21 at zero recombination value. Recombination with the disease was found with markers MAOB and DXS454 located at Xp11.4-p11.3 and Xq21.1-q22, respectively; accordingly, markers distal to Xp11.4 and Xq22 also segregated independently of the disease. These findings provide strong linkage evidence in favor of the localization of one MRX mutational site in the pericentromeric region of the human X chromosome, justifying the assignment of a new symbol (MRX26) to our pedigree. Finally, on the basis of the recombinational events observed in the Xq21-q22 region, we have been able to refine the assignment of marker DXS456 to Xq21.33-q22.

Management of chronic fatigue syndrome: case study.

1. Chronic fatigue syndrome (CFS) is a complex disorder marked by incapacitating fatigue of uncertain etiology which has resulted in a least a 50% reduction in activity and is of at least 6 months' duration. 2. Definitive diagnosis can be very challenging. Because no markers objectively identify the presence of CFS, diagnosis depends heavily on the presence of subjective complaints. 3. The current philosophy of CFS management is to use a multidisciplinary approach incorporating these rehabilitation goals: restore a sense of self efficacy and control; gradually increase physical activity; and decrease the restrictions imposed by CFS.

PCB and organochlorine pesticides in home-produced eggs in Belgium.

The level of polychlorinated biphenyls (PCB) and persistent organochlorinated pesticides (OC) in home-produced eggs was investigated in Belgium. The concentration of dichlorodiphenytrichloroethane (DDT) is above the norm for 17% of the eggs collected during the spring on 58 different locations. For PCB, aldrin, dieldrin, and chlordane, 3-5% of the samples are above the norm too. These levels are surprisingly high for compounds banned for about 30 years. Higher concentrations in home-produced eggs are expected compared to battery eggs because of contact with the environment and especially the soil. For ten selected locations, the concentration in soils, excreta and feed was measured, but no simple correlation between egg and feed or soil level could be established. Hexachlorohexane, endosulfan, endrin, methoxychlor and nitrofen were not detected in any sample.

A refined restriction map of YAC clones spanning the entire human dystrophin gene.

The enormous size of the human dystrophin gene (2300 kb) has so far hindered the analysis of its organization and the characterization at the genomic level of the deletion and duplication mutations causing Duchenne or Becker muscular dystrophy. A detailed physical map of the gene locus would considerably simplify these studies. We constructed a refined, long-range restriction map of the entire human dystrophin gene, using 12 overlapping YAC clones as DNA sources. The sites for six rare cutting enzymes (SfiI, NruI, EagI, BssHII, SacII, and NotI) were mapped by partial digest analysis of YACs over a region of 2600 kb, within a level of resolution of about 10 kb. Such a map provides the first detailed representation of the physical structure of the dystrophin gene. It will be useful for mapping unlocalized exons and, eventually, for the characterization of deletions and duplications leading to disease.

Search for neuroblastoma loci: characterization of tumor cell lines that could facilitate their positional cloning.

Specific chromosomal aberrations might indicate the position of genes responsible for a particular disease. Neuroblastoma is characterized by frequent deletions and/or rearrangements of the subtelomeric 1p region which, accordingly, is believed to host one or more oncosuppressor gene(s) directly or indirectly involved in the development of this and other tumors. Identification of these genes could be facilitated if cell lines with well characterized interstitial deletions or reciprocal translocations could be available for application of positional cloning strategies. In the present report we present additional and novel molecular data on three well established neuroblastoma cell lines (NLF, NMB and NGP). In one of these we have identified two sites that might be good candidates for hosting oncosuppressor genes; one of these is flanked by the D1S47 and ENO1 loci while the other is distal to the A12M2 locus.

Genomic organization of the human dystrophin gene across the major deletion hot spot and the 3' region.

The genomic organization of most of the human dystrophin gene has not been defined at single-exon level, owing to its enormous size (2300 kb). By taking advantage of a YAC-based restriction map of the gene previously constructed, we have localized individual dystrophin exons from 42 to 79 along the central and 3' regions of the gene. These data elucidate the general organization of this large portion of the gene (1250 kb) and, in particular, characterize the genomic region most frequently involved in deletion mutations responsible for Duchenne and Becker muscular dystrophies.

Exon-intron organization of the human dystrophin gene.

Analysis of the exon-intron organization of the human dystrophin gene has been hampered by its enormous size. By using a YAC-based exon mapping approach and long PCR, we have succeeded in defining the size of the gene and its organization. Our results, compared with data on the distribution of deletion breakpoints by intron, elucidate the topography of the intragenic deletion-prone regions. Within the central high-frequency deletion region, the small, 6.6-kb, intron 49 shows a much higher density of deletion breakpoints than intron 44, which was previously believed to coincide with the most mutable zone of the gene. On the other hand, in the proximal part of the gene, deletion breakpoints do not preferentially occur in a few introns, but are spread over a large DNA segment containing introns 2 to 42.

Sindrome da diarreia aguda e protraida em criancas internadas no Hospital das Clinicas da Faculdade de Medicina de Botucatu. / Acute and protracted diarrhea syndrome in children hospitalized at Hospital das Clinicas da Faculdade de Medicina de Botucatu

Foi feito estudo prospectivo de 39 casos de diarreia internados na Enfermaria de Pediatria da FMB, 74,4% dos quais ja previamente manipulados. Detectou-se dois fatores predisponentes para o desenvolvimento da diarreia grave: peso baixo ao nascer e curta duracao do aleitamento materno; no entanto, raramente a diarreia ocorreu no mes que se seguiu a retirada de leite materno. Foi alta a frequencia com que foram isolados enteropatogenos das fezes, principalmente dos casos com evolucao protraida. A conduta adotada levou a cura relativamente rapida em 89,7% dos casos, e houve evidencias de que a ma-absorcao de hidratos de carbono inclusive monossacarideos e talvez a intolerancia a proteina do leite de vaca foram importantes fatores de perpetuacao das diarreias. Raramente a melhora da diarreia ocorreu apos antibioticoterapia, embora esta fosse necessaria para grande parte dos casos devido as intercorrencias infecciosas. Isto nos leva a supor que esquemas terapeuticos como o empregado, encurtando o tempo de duracao da diarreia e, portanto, diminuindo o numero de intercorrencias, seja importante fator na diminuicao de mortalidade pela diarreia, pois os obitos que ocorreram foram consequentes a intercorrencias graves, tais como a septicemia. A partir das observacoes feitas foram sugeridas algumas modificacoes no esquema terapeutico proposto