Gestational weight gain and visceral adiposity in adult offspring: Is there a link with the fecal abundance of Acidaminococcus genus?

Intrauterine environment can influence the offspring's body adiposity whose distribution affect the cardiometabolic risk. Underlying mechanisms may involve the gut microbiome. We investigated associations of gestational weight gain with the adult offspring's gut microbiota, body adiposity and related parameters in participants of the Nutritionists' Health Study. METHODS: This cross-sectional analysis included 114 women who had early life and clinical data, body composition, and biological samples collected. The structure of fecal microbiota was analyzed targeting the V4 region of the 16 S rRNA gene. Beta diversity was calculated by PCoA and PERMANOVA used to test the impact of categorical variables into the diversity. Bacterial clusters were identified based on the Jensen-Shannon divergence matrix and Calinski-Harabasz index. Correlations were tested by Spearman coefficient. RESULTS: Median age was 28 (IQR 24-31) years and BMI 24.5 (IQR 21.4-28.0) kg/m2. Fifty-eight participants were assigned to a profile driven by Prevotella and 56 to another driven by Blautia. Visceral adipose tissue was correlated to abundance of Acidaminococcus genus considering the entire sample (r = 0.37; p < 0.001) and the profiles (Blautia: r = 0.35, p = 0.009, and Prevotella: r = 0.38, p = 0.006). In Blautia-driven profile, the same genus was also correlated to maternal gestational weight gain (r = 0.38, p = 0.006). CONCLUSIONS: Association of Acidaminococcus with gestational weight gain could reinforce the relevance with mothers' nutritional status for gut colonization at the beginning of life. Whether Acidaminococcus abundance could be a marker for central distribution of adiposity in young women requires further investigation.

Traumatic Ulcerative Granuloma with Stromal Eosinophilia: CD30 analysis and clonality for T cell receptor gene re-arrangement.

INTRODUCTION: Traumatic Ulcerative Granuloma with Stromal Eosinophilia (TUGSE) is a rare oral ulcerated lesion of uncertain etiology, showing eosinophil-rich granulation tissue, with occasional large atypical CD30 positive mononuclear cells. It had been suggested that it may represent an oral counterpart of cutaneous lymphomatoid papulosis, with a potential to evolve into CD30 + T cell lymphoma OBJECTIVES: To compare TUGSE and non-specific oral ulcers (NSU) clinically, histopathologically and by clonality analysis for T-cell receptor re-arrangement, aiming to determine whether TGUSE with atypical cells is a lymphomatous premalignant condition, and whether therapeutic approach should be radical or conservative. MATERIALS AND METHODS: Retrospective archival analysis included 17 TUGSE and 8 NSU cases. Histopathological parameters included mean eosinophil number per high power field (HPF), presence of infiltration of deep soft tissues and presence of atypical cells. Immuno-morphometry comprised of the mean number of CD30+ atypical cells per HPF. T-cell receptor (TCR) gene rearrangement by polymerase chain reaction (PCR) was performed in all cases showing atypical cells. Clinical and follow up data were retrieved from files. RESULTS: TUGSE showed a significantly higher mean eosinophil number/HPF in comparison to NSU (7.0 + 4.2 cells and 2.3 + 1.72, respectively; p < 0.001). Atypical cells were found in 9 (53%) cases of TUGSE and in only 1 (11%) case of NSU. CD30+ atypical cells were found in 7 (41%) cases of TUGSE and only in 1 (11%) case of NSU. Mean number of CD30+ cells/HPF was 0.23 + 0.19 (range 0 - 0.54 cells/HPF) for TUGSE. In the only NSU case with CD30+ cells, their density was 0.52/HPF. All lesions with atypical cells were polyclonal for TCR. All cases were self-limiting, with no recurrences, after 3-9 years (mean 4.6 years) follow up. CONCLUSIONS: Analysis found no support to the suggestion that TUGSE with atypical cells represents the oral counterpart of lymphomatoid papulosis or predisposes the lesions for a hematolymphoid malignancy. Suggestions for radical therapeutic approach and long-term follow-up are probably unjustified, with no recurrences or malignancy recorded following conservative treatment alone for a period of up to 9 years of follow-up. Staining for CD30 and PCR for TCR gene rearrangement should be reserved only for rare cases with abundant large atypical cells and/or unusual clinical behavior.

Genetic features of Lynch syndrome in the Israeli population.

Diagnosis of Lynch syndrome (LS) may be complex. Knowledge of mutation spectrum and founder mutations in specific populations facilitates the diagnostic process. Aim of the study is to describe genetic features of LS in the Israeli population and report novel and founder mutations. Patients were studied at high-risk clinics. Diagnostics followed a multi-step process, including tumor testing, gene analysis and testing for founder mutations. LS was defined by positive mutation testing. We diagnosed LS in 242 subjects from 113 families coming from different ethnicities. We identified 54 different mutations; 13 of them are novel. Sixty-seven (59%) families had mutations in MSH2, 20 (18%) in MSH6, 19 (17%) in MLH1 and 7 (6%) in PMS2; 27% of the MSH2 mutations were large deletions. Seven founder mutations were detected in 61/113 (54%) families. Constitutional mismatch repair deficiency (CMMR-D) was identified in five families. Gene distribution in the Israeli population is unique, with relatively high incidence of mutations in MSH2 and MSH6. The mutation spectrum is wide; however, 54% of cases are caused by one of seven founder mutations. CMMR-D occurs in the context of founder mutations and consanguinity. These features should guide the diagnostic process, risk estimation, and genetic counseling.

Percutaneous bone-anchored hearing aids at a pediatric institution.

OBJECTIVES: The goals were to evaluate hearing, complications, and patient satisfaction with the percutaneous bone-anchored hearing aid (BAHA) and to monitor long-term successful use achieved by careful patient selection. METHODS: This prospective longitudinal study included participants with inoperable congenital bilateral aural atresia, pure-tone average (PTA) bone conduction less than 45 dB HL, prior use of a conventional bone-conduction hearing aid (CBCA), and adequate intelligence, integration, and personal hygiene. Surgery for BAHA implantation was performed in two stages. Evaluation consisted of skin reactions, audiologic results with CBCA and BAHA, and patient satisfaction. Follow-up was at least 24 months. RESULTS: In 11 participants aged 5 to 17 years, the PTA free-field air conduction improved 37%, and free-field speech discrimination improved 23%. Successful integration and implant use were achieved in 10 cases but were lost in 1 case as a result of head trauma. All patients preferred the BAHA as opposed to the CBCA. CONCLUSIONS: The BAHA is a valuable device that can improve hearing and provide significant parent and patient satisfaction. Careful selection appears to correlate with successful long-term use.

Pediatric vocal fold paralysis: a long-term retrospective study.

OBJECTIVE: To review our experience of pediatric vocal fold paralysis (VFP), with particular emphasis on etiological factors, associated airway pathologic conditions, and treatment and prognostic outcomes. DESIGN: Retrospective case review of a cohort of patients presenting with VFP. SETTING: Tertiary referral center. PATIENTS: A consecutive sample of 102 patients presenting with VFP to Great Ormond Street Hospital for Children, London, England, over a 14-year period from 1980 to 1994. RESULTS: There was an almost equal distribution of unilateral (52% [n = 53]) and bilateral (48% [n = 49]) VFP. Iatrogenic causes (43% [n = 44]) formed the largest group, followed by idiopathic VFP (35% [n = 36]), neurological causes (16% [n = 16]), and finally birth trauma (5% [n = 5]). Associated upper airway pathologic conditions were noted in 66% (n = 23) of patients who underwent tracheotomy. Tracheotomy was necessary in only 57% (n = 28) of children with bilateral VFP. Prognosis was variable depending upon the cause, with neurological VFP having the highest rate of recovery (71% [5/7]) and iatrogenic VFP the lowest rate (46% [12/26]). CONCLUSION: Recovery after an interval of up to 11 years was seen in idiopathic bilateral VFP; this has significant implications when considering lateralization procedures in these patients.

Linker modification introduces useful molecular instability in a single chain antibody.

SCA 4-4-20/212, is a recombinant single chain antibody directed against fluorescein (Fl) composed of the variable light (VL) and variable heavy (VH) domains of the monoclonal antibody 4-4-20, tethered by a 14 amino acid linker. Binding of SCA 4-4-20/212 to Fl quenches its fluorescence, thus enabling the distinction between bound and free Fl. This was used to follow antibody denaturation which followed a two-step process: rapid selected and restricted denaturation followed by slow and progressive denaturation. This two-phase phenomenon might reflect selective susceptibility of the CDR loops to denaturation. Furthermore, a new SCA, SCA 4-4-20/9, was constructed by site-directed mutagenesis of SCA 4-4-20/212 using PCR methodology. SCA 4-4-20/9 was similar to SCA 4-4-20/212, but for a nine residue linker. The two SCAs were compared for Fl binding, heat stability, the effect of denaturing agents and susceptibility to proteolysis. The modification of the linker caused a general conformational rearrangement in the SCA molecule, rendering it more sensitive to denaturation and proteolysis. This molecular instability may find utility in the application of SCAs in analytical systems or as the recognition component in biosensors.

Association of erythrocyte glycophorin with protoporphyrin-IX derivatives: a fluorimetric study.

Based on demonstrations that protoporphyrin-IX and its metabolic derivatives bilirubin and hemin bind to the red cell membrane, their association with glycophorin A, the main transmembrane sialoglycoprotein, was assessed. No interaction between bilirubin and glycophorin could be demonstrated but both protoporphyrin-IX and hemin were found to bind to the protein. Interaction of protoporphyrin-IX and glycophorin was demonstrated by changes in both ligand and protein fluorescence characteristics in the presence of the other reactant. Binding of hemin, (Fe+3-protoporphyrin-IX) with glycophorin was revealed by quenching of the proteins' intrinsic fluorescence intensity by hemin and a shifted Soret absorption of hemin in the presence of glycophorin. The association constants of protoporphyrin-IX and hemin with glycophorin at 25 degrees C were calculated as 2.5 +/- 0.5 x 10(6)M-1 and 1.4 +/- 0.4 x 10(6)M-1 respectively.

Long-term intercalation of residual hemin in erythrocyte membranes distorts the cell.

The effect of long-term incubation of residual globin-free hemin on whole red blood cell and isolated cytoskeletal proteins was studied. Hemin at concentrations found in pathological red cells was inserted to fresh erythrocytes. Increased hemolysis developed in the hemin-containing cells after a few days at 37 degrees C and after about four weeks at 4 degrees C. Since lipid and hemoglobin peroxidation did not depend on the presence of hemin, time-dependent effects on the cytoskeleton proteins were studied. Observations were: (1) spectrin and protein 4.1 exhibited a time-dependent increasing tendency to undergo hemin-induced peroxidative crosslinking. (2) The ability of the serum proteins, albumin and hemopexin, to draw hemin from spectrin, actin and protein 4.1 decreased with time of incubation with hemin. These results were attributed to time-dependent hemin-induced denaturation of the cytoskeletal proteins. Albumin taken as a control for physiological hemin trap was unaffected by hemin. Small amounts of hemo-spectrin (2-5%) were analyzed in circulating normal cells, and this in vivo hemo-spectrin also failed to release hemin. It was concluded that slow accumulation of hemin, a phenomenon increased in pathological cells, is a toxic event causing erythrocyte destruction.

Hemin-promoted peroxidation of red cell cytoskeletal proteins.

Hemin-induced crosslinking of the erythrocyte membrane proteins was analyzed at three levels: (i) whole membranes, (ii) integrated or dissociated cytoskeletons, and (iii) isolated forms of the three main cytoskeletal proteins, spectrin, actin, and protein 4.1. Addition of H2O2 and hemoglobin to resealed membranes from without did not affect any of the membrane proteins. Hemin that can transport across the membrane induced, in the presence of H2O2, crosslinking of protein 4.1 and spectrin. Both free hemin and hemoglobin added with H2O2 induced crosslinking of integer cytoskeletons and mixtures of isolated cytoskeletal proteins, but hemin was always more active. Of the three major cytoskeletal proteins, spectrin and protein 4.1 were most active while the participation of actin was only minor. The yield of crosslinked products was increased in all reaction mixtures with pH, with an apparent pK above 9.0. Replacement of H2O2 by phenylhydrazine and tert-butyl hydroperoxide resulted in crosslinking of the same proteins, but with lower activity than H2O2. Bityrosines, which were identified by their specific fluorescence emission characteristics, were formed in reaction mixtures containing hemin and hydrogen peroxide and either spectrin or protein 4.1, but not actin. On the basis of fact that bityrosines were revealed only in reaction mixtures that produced protein adducts, formation of intermolecular bityrosines was analyzed to be involved in crosslinking of the cytoskeletal proteins. Since the levels of membrane-intercalated hemin are correlated with aggregation of membrane proteins, it is suggested that the peroxidative properties of hemin are responsible for its toxicity.

Serum proteins as mediators of hemin efflux from red cell membranes: specificity of hemopexin.

The involvement of the serum heme-binding proteins hemopexin and albumin in the clearance of erythrocyte membranes from toxic hemin was compared. In the presence of hemopexin initial rates of hemin efflux from resealed ghosts were faster and the amount of extracted hemin larger. When hemin-containing ghosts were treated with a protein mixture of 1:45 hemopexin to albumin, as present in serum, most of the hemin was extracted in the form of heme-hemopexin. It was concluded that hemopexin is the serum protein responsible for heme extraction from cell membranes.

Association of hemin with protein 4.1 as compared to spectrin and actin.

The interaction of hemin with protein 4.1 isolated from red cell membrane cytoskeleton has been studied. Spectrophotometric titration has shown one strong binding site and additional lower affinity sites for hemin. From fluorescence quenching data an association binding constant of 1.3 . 10(7) M-1 has been calculated for the primary site. The conformation of cytoskeletal proteins after hemin binding was followed by the use of far UV circular dichroism and compared to that of the serum hemin trap, albumin. The secondary structure of albumin was unchanged in the presence of high hemin concentrations. Both spectrin and actin lost their conformation upon hemin binding in a ligand-concentration and time-dependent manner. Unlike spectrin and actin, the secondary structure of protein 4.1 appeared. The findings of this study suggest that protein 4.1 may serve as the cytoskeletal temporary sink for small amounts of membrane-intercalated hemin similarly to the function of albumin in the serum. However, an increased release of hemin under pathological conditions may cause hemin association with the cytoskeletal proteins and as a result the cell membrane is expected to be distorted.

The growth and reproductive endocrinology of adult triploid Pacific salmonids.

This paper describes the effect of triploidy on growth and reproductive endocrinology in the months leading up to and including spawning in rainbow trout,Salmo gairdneri, and pink salmon,Oncorhynchus gorbuscha. Growth rates were the same for diploid and triploid rainbow trout, but triploid female pink salmon were smaller than maturing diploid females and diploid and triploid males of the same age. Triploid males of both species developed typical secondary sexual characteristics and had normal endocrine profiles, although their cycle appeared to be delayed by about one month. Triploid females remained silvery in appearance and showed no endocrine signs of maturation, even at the level of the pituitary. Thus, although triploids of both sexes are genetically sterile, only the females do not undergo physiological maturation.

[Supplementation of swine feed rations with zeolite during cage rearing]. / Obohatenie krmnej dávky prasiat zeolitom pri klietkovom odchove.

The effect of the addition of zeolite to pig feed ration was studied in the cage rearing system under production conditions. Zeolite was mixed in the COS I and COS II feed mixtures directly in the feed plant, the mixing ratio being 100 kg feed mixture + 5 kg zeolite. The feed mixture was administered in granular form ad libitum. The test group had 648 weanlings and the control group 674 weanlings; the piglets, kept in two-story cages in four sections, were arranged so that the test group could be a mirror-like reflection of the control group. The trial lasted 45 days. The piglets given the fortified feed ration had daily weight gains higher by 0.017 kg and feed consumption lower by 0.234 kg per 1 kg of gain, as compared with the control animals. The costs of the feed ration required for producing a kilogram of gain were 8.55 Cz. crowns in the zeolite group and 9.422 crowns in the control group.