Developmental instability and phenotypic evolution in a small and isolated bear population.

We explored fluctuating asymmetry (FA) and morphological integration (MI) in the skull of the small, highly inbred and divergent Apennine bear (Ursus arctos marsicanus), to explore its uniqueness and investigate any potential effects of inbreeding depression. We used 3D geometric morphometrics contrasting Apennine bears with other two large outbred bear populations from Scandinavia and Kamchatka as controls. Shape divergence and variability were explored by a principal component analysis on aligned coordinates of 39 landmarks. Procrustes ANOVA, morphological disparity and the global integration index were used to explore FA, shape variance and MI. By remarking Apennine bears as a highly divergent phenotype, we recorded the highest FA and deviation from self-similarity compared with the other two control populations. We conclude that Apennine bears are likely facing developmental instability as a consequence of inbreeding depression, whereas the divergent trait covariance pattern may represent a potential source of evolutionary novelties. We discuss the implications for the conservation and management of this imperiled taxon.

Screening for Chlamydia is acceptable and feasible during Cervical Screening in General Practice.

The incidence of Chlamydia trachomatis (CT) & Neisseria gonorrhoeae (NG) are rising in Ireland. Both are often undiagnosed and may cause infertility amongst other complications. CT/NG screening is not routinely offered during cervical cancer screening. This study aimed to ascertain the feasibility and acceptability of screening for CT/NG at time of smear and to measure the diagnostic yield. Screening was offered to women aged 25-40 years attending four participating general practices as part of Cervical Check. A retrospective review of the three months preceding the study period, indicated that out of 138 smears, CT/NG testing was performed in 10 (7%) of cases. 236 (93%) patients consented to screening for CT/NG. The detection rate for Chlamydia was 6 (2.4%), with no positive results for NG. Feedback from patients was positive. Interestingly, 42 (18%) of participants who completed the questionnaire believed STI screening was already part of the routine smear.

Insights and Concerns of Patients and GPs Regarding Introduction of Universal Health Insurance in Ireland.

The implementation of a universal health insurance (UHI) model is a key political policy in Ireland. The objective here was to determine the understanding of general practitioners (GPs) and patients regarding UHI, its implementation and impact on both sets of stakeholders. Postal questionnaire to GPs, and opportunistic survey sampling of patients in two different GP practices were carried out. Response rates were 92.5% (patients) and 78% (GPs). 79.4% of patients (n = 418) and 96.7% of GPs (n = 149) have a 'poor' understanding of how UHI will be implemented. 89% (n = 493) of patients and 98.7% (n = 153) of GPs feel government communication about UHI has been 'poor'. 98.1% of GPs (n = 152) and 77.3% of patients (n = 383) are not confident that 'UHI will be ready for implementation by 2015'. Neither stakeholder group is confident in the government's ability to deliver UHI within the given timeframe. There is a lack of knowledge and consultation on proposals for its implementation.

Molecular systematics and evolutionary biogeography of the genus Talpa (Soricomorpha: Talpidae).

The range of the genus Talpa covers almost all Europe up to Western Asia. This genus has never been the object of comprehensive systematic studies using molecular and genetic techniques, such that the evolutionary relationships among species remain unclear. Talpa shows high levels of endemism, and the influence of past glaciation cycles on the distribution pattern of several species has been hypothesized. In this work, we assessed the molecular systematics of the genus using the mitochondrial gene cytochrome b from eight of the nine extant species of Talpa moles. Furthermore, molecular clock estimations were used to hypothesize a biogeographic scenario in concordance with fossil data. Results suggest a monophyletic origin of the genus and a common ancestor for the western European moles T. europaea, T. caeca, T. romana and T. occidentalis. The eastern species T. altaica and T. caucasica are basally divergent. The estimated ages of divergence among lineages are in accordance with a Miocene origin of the extant moles. The genus likely originated in Asia, spreading into Europe during the Pliocene. The evolution of moles appears to have been driven by changes in moisture levels that influenced extinction and speciation events during the Miocene and the Pliocene. Pleistocene climatic oscillations likely caused the range shrinkages and expansions that led to the current distribution pattern of most Talpa species.

Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene.

Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin sensitivity of the PTP-1B-/- mice was also evident in glucose and insulin tolerance tests. The PTP-1B-/- mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B+/+ mice. On a high-fat diet, the PTP-1B-/- and PTP-1B+/- mice were resistant to weight gain and remained insulin sensitive, whereas the PTP-1B+/+ mice rapidly gained weight and became insulin resistant. These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity.

Associations of the Oral Microbiota with Obesity and Menarche in Inner City Girls.

OBJECTIVE: Alterations of the oral microbiome have been associated with obesity, possibly based on inflammatory processes mediated by bacteria. Specific bacterial strains have been associated with obesity and periodontal disease. Little is known about the oral microbiome in children. Understanding the relationship between oral health and childhood growth could help identify preventable factors contributing to obesity and related conditions, including onset of menarche which is associated with obesity. METHODS: In this pilot study, we investigated the saliva microbiome among 25 girls 7-15 years old (mean 11.1) and their mothers in an inner city dental clinic in New York City. The main outcome measures were body size, presence or absence of menarche and dental practices. We examined associations of microbiome richness, diversity, and relative abundance with pubertal and demographic factors and oral health. RESULTS: Girls had good dental health and a typical rich oral microbiome, based on the Shannon Index of all species detected. Older girls flossed more often and younger girls had more frequent dental check-ups. Microbiome richness among girls was similar to their mothers', but diversity was greater among mothers than girls. Richness was reduced among mothers with gum bleeding, flossing and increased teeth brushing. Overweight girls had greater diversity and less richness than normal weight girls. Certain bacterial species differed in abundance with respect to whether girls had reached menarche (Flavobacteria, Actinobacteria), overweight (Megasphaera, Lactorbacillales, Lactobacillus) and gingivitis in the girls (Scardovia, Bifidobacteriales, Gemellaceae). CONCLUSIONS: Differences found in specific bacteria in the oral microbiome were related to body size and menarche. With increasing interest on studying microbiome variability related to the multifactorial etiology of obesity in children, saliva is capable of providing clinically informative markers of this and related conditions.

Methotrexate improves the health-related quality of life of children with juvenile idiopathic arthritis.

OBJECTIVES: To examine the change in health-related quality of life (HRQOL) and its determinants in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX). METHODS: Patients were extracted from the PRINTO clinical trial which aimed to evaluate the efficacy and safety profile of MTX administered in standard, intermediate or higher doses (10, 15 and 30 mg/m(2)/week respectively). Children with polyarticular-course JIA, who were less than 18 years and had a complete HRQOL assessment were included. RESULTS: A total of 521 children were included. At baseline, patients with JIA showed poorer HRQOL (p<0.01) than healthy children. In 207/412 (50%) and 63 (15%) children, HRQOL values were 2 standard deviations below the mean of healthy controls in the physical and psychosocial summary scale, respectively. After 6 months of treatment with standard dose MTX, there was a statistically significant improvement in all HRQOL health concepts, particularly the physical ones. Similar improvements were observed in those who did not respond to a standard dose of MTX and were subsequently randomised to a higher dose. The presence of marked disability at baseline was associated with a fivefold increased risk of retaining poor physical health after 6 months of active treatment with standard dose MTX. Other less important determinants of retaining poor physical well-being were the baseline level of systemic inflammation, pain intensity and an antinuclear-antibody-negative status. CONCLUSIONS: MTX treatment produces a significant improvement across a wide range of HRQOL components, particularly in the physical domains, in patients with JIA.

Systemic lupus erythematosus-like disease in a 6-year-old boy with prolidase deficiency.

This report describes the case of a boy with prolidase deficiency who presented with splenomegaly and leg ulcers. Laboratory examination revealed hypergammaglobulinaemia, hyperimmunoglobulinaemia E, increased erythrocyte sedimentation rate, elevated transaminases, positive antinuclear and anti-double-stranded DNA antibodies, and complement consumption. No haematological, renal or articular problems were detected; neutrophil count was normal. The skin lesions were thought to be of vasculitic origin, and a diagnosis of systemic lupus erythematosus was made although the requirements for diagnosis of systemic lupus erythematosus based on American Rheumatism Association criteria were not satisfied. The child was treated with immunosuppressive drugs with worsening of skin lesions before the diagnosis of prolidase deficiency. Prolidase deficiency and systemic lupus erythematosus share a number of common immunological features and at least three patients with prolidase deficiency and immunological and clinical findings fulfilling the diagnostic criteria for systemic lupus erythematosus of the American Rheumatism Association are reported in the literature. Here we review pathogenetic hypothesis linking the metabolic defect to the disturbance in immune function. In particular we discuss the role of highly increased rates of apoptosis and/or abnormal processing of apoptotic keratinocytes in prolidase deficiency and the role of C1q deficiency, which is associated with the failure of normal clearance of apoptotic cells bearing on their surfaces many of the autoantigens involved in systemic lupus erythematosus.

Diabetes and the myo-inositol paradox.

To test the general applicability of the hypothesis that diabetes mellitus causes increased polyol pathway activity, decreased tissue free myo-inositol, and resultant pathological changes in tissues susceptible to the ravages of diabetes, we measured glucose, sorbitol, and myo-inositol with quantitative histochemical techniques in layers of the cornea, the aortic myointima, the cardiac left ventricle and atrioventricular node (AVN), and retina and kidney after 19 days or 2 mo (mildly diabetic non-insulin-treated [MD] and severely diabetic insulin-treated [SD] groups) in the alloxan-induced diabetes model. In the aqueous humor, glucose rose linearly with increased serum glucose, sorbitol was markedly increased in the MD and SD groups, and myo-inositol did not change in any diabetic group. There was no change in glucose or sorbitol in aortic myointima in any group, but myoinositol was decreased in 19-day diabetic rabbits by 26%, unchanged in MD rabbits but paradoxically increased by 60% in SD rabbits. Glucose, sorbitol, and myo-inositol increased in all three corneal layers in SD rabbits but only in epithelium and stroma in 19-day and MD rabbits. AVN glucose and sorbitol did not change in 19-day diabetic, MD, or SD diabetic rabbits. AVN myo-inositol was three times higher than ventricular myo-inositol and did not appear to change in SD rabbits. Retinal pigmented epithelium myo-inositol was decreased 30% in SD rabbits. Glomerular myo-inositol was also decreased, but not significantly, in SD rabbits. We conclude that the paradoxical increase in corneal and aortal myo-inositol raises fundamental questions about the general applicability of the myo-inositol-depletion hypothesis.

Cyclooxygenase-2 expression in Warthin's tumour.

OBJECTIVES: To determine whether cyclooxygenase-2 (COX-2) is overexpressed in Warthin's tumours, and to characterize its pattern of expression. METHODS: Twenty-one paraffin-embedded Warthin's tumour specimens were analysed by immunohistochemical staining for expression of human COX-2. Semi-quantitative analysis of the staining was performed. RESULTS: In all of the specimens, we found that there was overexpression of COX-2 within the epithelial component of the tumours, with no expression in the lymphoid components. There was also overexpression of COX-2 in the salivary duct system of normal parotid tissue. CONCLUSIONS: Our results suggest that COX-2 is up-regulated in the epithelial component of Warthin's tumours. Our findings support the hypothesis that Warthin's tumours originate from heterotopic ductal epithelial cells of the parotid gland. The role of COX-2 expression in the pathogenesis of Warthin's tumours remains to be determined.

Clinically significant extra-cardiac findings in asymptomatic HIV-positive men undergoing cardiac magnetic resonance imaging.

Increased research-based imaging has led to an increase in clinically significant extra-cardiac findings. HIV patients are at increased risk of having polypathology at a younger age; therefore, it may be hypothesised that they would have more incidental findings on imaging. We reviewed the magnetic resonance imaging results of 169 HIV-positive and 40 HIV-negative, clinically well volunteers undergoing cardiac magnetic resonance imaging scanning to assess the prevalence of subclinical cardiac pathology. This sub-study assessed the prevalence of clinically significant extra-cardiac findings. Associated risk factors were assessed and clinical follow-up and outcome were ascertained. Of the HIV-positive study group, 12/169 (7.1%) vs. 1/40 (2.5%) control patients had a clinically significant extra-cardiac finding which warranted further radiological or clinical intervention (p = 0.28). A total of three out of 169 (1.1%) were highly clinically significant findings. On logistic regression analysis, age was the only significant contributing factor (p = 0.049); no HIV-associated factors were found to be significant. The prevalence of clinically significant extra-cardiac findings of 7.1% in this HIV-positive cohort is comparable to the prevalence found in previous studies carried out on an older, sicker general population. This highlights the need for planning for unexpected outcomes and also the high rate of clinically significant findings in a seemingly well HIV-positive population.

Measurement of extracellular space in the rabbit AV node.

We used quantitative histochemistry to measure the size of the extracellular space (ESC) in various regions of the rabbit heart. When inulin, sucrose, and sorbitol were used as ECS markers, the ECS of the AV-nodal tissue was found to be, respectively, 2.4, 2.2, and 2.5 times larger than that of left ventricular muscle. Glucose was also measured over a 50-fold serum concentration range as an extracellular marker for AV-nodal tissue, left ventricular muscle, and Purkinje fibers. Measurements with glucose also revealed that the ECS of the AV node was 2.5-2.8 times larger than that of ventricular muscle. In contrast, the ECS of the AV node was the same as that of Purkinje fibers when glucose was used as an extracellular marker. ATP content, measured as an intracellular marker, was similar in both AV-nodal and contractile tissue. Collectively, the data obtained with all extracellular markers indicate that the ECS of the AV-nodal region is approximately 2.5 times larger than that of adjacent contractile tissue. Differences in the size of the ECS in various regions of the heart probably have functional significance and should be considered appropriately during the interpretation of data obtained by biochemical and densitometric approaches.

Mother-to-child transmission of human immunodeficiency virus type 1: risk of infection and correlates of transmission.

One thousand eight hundred eighty-seven children born to human immunodeficiency virus type 1 (HIV-1) seropositive mothers, including 1045 infants prospectively followed up from birth, were studied. Intravenous drug use was the most frequent maternal risk factor, although the percentage of women infected by sexual contact increased from 5.8% in 1985 to 28.5% in 1990. Of the 551 first children followed up from birth and older than 15 months of age, 101 (18.3%) acquired infection and seroconverted to HIV-1. Another 31 (5.6%) asymptomatic seronegative children showed the presence of viral markers, for an apparent mother-to-offspring transmission rate of 23.9%. Overlapping results were seen in 22 second-born children followed up from birth. Of 59 sibships with definite infection status, when the first child was infected, 14 (40%) of 35 second children were infected, whereas when the first child was not infected, only 2 of 24 (8.3%) second children were infected. Discordance in HIV-1 transmission was found in 1 of 18 pairs of twins. Univariate and multivariate analyses of possible risk factors for HIV-1 transmission performed on the entire population of children and in the cohort of those followed up from birth were basically in agreement in indicating that the development of symptoms in the mother before delivery and breast-feeding (indeed adopted in only 22 infants in whom HIV-1 infection was identified at birth) were significantly and independently associated with a higher transmission rate. In addition, girls were more frequently infected than boys.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe lymphedema, intestinal lymphangiectasia, seizures and mild mental retardation: further case of Hennekam syndrome with a severe phenotype.

We report on an Italian patient affected by severe lymphedema of lower limbs, genitalia and face, intestinal lymphangiectasia, seizures, and moderate mental retardation. He has a flat face, flat nasal bridge, and hypertelorism. We propose that he presents with a severe form of Hennekam syndrome.

Isoelectricfocusing and reverse blotting as a diagnostic tool in pediatric HIV infection.

BACKGROUND: Early diagnosis of perinatally acquired HIV-infection is based on either direct HIV detection--by means of viral culture and/or PCR--or anti-HIV antibody detection. However, due to the passive, transplacental passage of maternal immunoglobulin G, antibody detection is nor reliable until 15-18 months of age. In this regard, clonotypic analysis of specific antibodies performed by isoelectricfocusing and reverse blotting (IEF-RB) can be very helpful, as it recognizes possibly different patterns between mother and infant. OBJECTIVES: We used IEF-RB in order to analyze the kinetics of development of anti-HIV antibodies in infants born to seropositive mothers. STUDY DESIGN: Sera from ten mother/infant pairs (all mothers were HIV-infected) were retrospectively analyzed in order to detect different patterns, between mother and infant, in anti-gp120 V3-loop clonotype. RESULTS: We diagnosed the real HIV status of the examined infants no later than month 6 and in one case as early as month 2. CONCLUSIONS: Considering the small size of sample number, these data are preliminary and should be confirmed by larger scale studies. However, they show IEF-RB, when applied to infants born to seropositive mothers, may be useful in evaluating the infants' dynamics of anti-HIV humoral immune response.

Immune response to rotavirus VP4 expressed in an attenuated strain of Shigella flexneri.

An attenuated strain of Shigella flexneri was utilised to express viral protein (VP) 4 of rotavirus and the immunogenicity of the recombinant constructs was studied in BALB/c mice. VP4 was expressed as a fusion with maltose binding protein (MBP) in both the cytoplasm and periplasm, with a much higher level of expression occurring in the former. While all constructs induced a Shigella-specific response in mice, only the construct expressing MBP-VP4 in the cytoplasm of Shigella stimulated an immune response specific to rotavirus. This study demonstrates that Shigella can be used to deliver rotavirus antigens and induces an immune response directed towards both rotavirus and Shigella.

Mineral oil lipoid pneumonia in a child with anoxic encephalopathy: treatment by whole lung lavage.

We describe a case of exogenous lipoid pneumonia in a child with anoxic encephalopathy who was taking mineral oil for constipation. Computed tomography produced images suggesting this condition, and the diagnosis was confirmed by demonstrating the presence of lipid-laden alveolar macrophages in the bronchoalveolar lavage fluid. Despite discontinuing the offending agent, the pulmonary infiltrates did not improve; however, successful resolution was obtained by whole lung lavage.

Shape changes and growth trajectories in the early stages of three species of the genus Diplodus (Perciformes, Sparidae).

The larvae of three species of the genus Diplodus (Diplodus vulgaris, D. sargus, and D. puntazzo) colonize shallow waters along the Mediterranean coasts and, after a short period spent in the water column, they settle. For all three species this habitat transition is characterized by important shape changes mostly related to swimming capacity and feeding behavior. In this study, geometric morphometrics are used to characterize shape changes during the early juvenile life of specimens collected in a single locality in order to compare growth curves and allometric relationships. Size-related shape changes proved to be similar for all three species and are consistent with the ecological transition. A nonparametric smoothing technique (Loess) was used to fit the scatter of shape on size. The graphical representation (of most size-related shape variability) of this fitting technique shows how major shape changes are rapid for small sizes and slow down successively. The approach allows for the visualization of allometry and the fitting technique might help in defining the allometric growth pattern, thus contributing to the study of the autoecology of the species and in establishing terms for comparison with other ecologically or phylogenetically related species.

Single-donor platelet concentrates stored in synthetic medium. In vitro and in vivo studies.

Single-donor platelet concentrates (PC) were prepared in 80-120 ml plasma and stored in two polyolefin bags after addition of 250 ml plasmalyte, a simple, glucose-free synthetic medium that was previously used for platelet storage; when compared to PC stored in plasma, PC stored in plasmalyte, showed similar platelet quality, morphology and function after 5 days of storage. In vivo increments observed after transfusion of PC stored for 5 days in plasmalyte were similar to those observed after transfusion of 1-2 day old PC stored in plasma. Moreover, transfusion of 5-day old PC stored in plasmalyte was associated with correction of prolonged bleeding times in all 3 of the 3 patients evaluated. It is concluded that plasmalyte seems to be promising as a medium for single-donor PC storage.

[Cefotiam, a new cephalosporin. Microbiological research, preliminary evaluation of its effect on phagocytosis and clinical multicenter research]. / Cefotiam, nuova cefalosporina. Ricerca microbiologica, valutazione preliminare dell'interferenza sulla fagocitosi e ricerca clinica policentrica.

After a brief review of the data on cefotiam in the literature the report presents the results of microbiological research, a preliminary study into the drug's possible actions on phagocytosis and a polycentric clinical study of 93 cases of broncho-pleuro-pulmonary pathology and one sinusitis of the jaw. In vitro cefotiam was found to have an excellent inhibitory effect on gram positive and gram negative bacteria with MICs50 and 90 respectively 0.2 and 0.8 mcg/ml V. Staph. aureus, Str. pyogenes. E. Coli, K. pneumoniae and Pr. mirabilis. A dose-dependent increase in phagocytosis was noted. The clinical response was excellent with 90.43% (88/94) of the cases achieving clinical and radiological cure or very much improved. Cefotiam was very well tolerated with the appearance of 2/94 skin rashes (2.12%). The liver and kidney parameters showed no change at the end of treatment. No increase in enzymuria was noted during treatment with cefotiam.