Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing

BACKGROUND: Improved hygiene has altered early microbial exposure by reducing childhood infections, which has been suggested as a cause for the continuously rising prevalence of atopic diseases. On the basis of both intensity and timing of stimulus, it has been hypothesized that exposure to commensal microflora may represent another key protective modulator of immunity against atopy and subsequent atopic diseases. OBJECTIVE: We sought to investigate whether differences in early gut microflora precede the later development of atopic sensitization. METHODS: Intestinal microflora from 76 infants at high risk of atopic diseases were analyzed at 3 weeks and 3 months of age by using conventional bacterial cultivation and 2 culture-independent methods, gas-liquid chromatography of bacterial cellular fatty acids and quantitative fluorescence in situ hybridization of bacterial cells. Infants evincing at least one positive skin prick reaction at 12 months were grouped as atopic subjects, and those without positive reactions were grouped as nonatopic subjects. RESULTS: Atopic sensitization was observed in 22 (29%) of 76 children. At 3 weeks, the bacterial cellular fatty acid profile in fecal samples differed significantly between infants in whom atopy was and was not developing (P =.005). By using fluorescence in situ hydridization, atopic subjects had more clostridia (geometric mean [95% confidence interval]: 9.3 x 10(7) [3.8-22.9 x 10(7)] vs 3.3 x 10(7) [1.8-6.1 x 10(7)], P =.04) and tended to have fewer bifidobacteria (1.8 x 10(9) [0.4-7.6 x 10(9)] vs 6.1 x 10(9) [2.5-14.6 x 10(9)], P =.11) in their stools than nonatopic subjects, resulting in a reduced ratio of bifidobacteria to clostridia (P =.03). The differences were not detected by bacterial cultivation. CONCLUSION: Differences in the neonatal gut microflora precede the development of atopy, suggesting a crucial role of the balance of indigenous intestinal bacteria for the maturation of human immunity to a nonatopic mode.     

Germline TP53 alterations in Finnish breast cancer families are rare and occur at conserved mutation-prone sites

We have screened for germline TP53 mutations in Finnish BRCA1 and BRCA2 mutation-negative families. This study represents the largest survey of the entire protein-encoding portion of TP53, and indicates that mutations are only found at conserved domains in breast cancer families also meeting the criteria for Li-Fraumeni/Li-Fraumeni-like syndrome, explaining only a very small additional fraction of the hereditary breast cancer cases.     

p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition

Germ-line mutations in the p53 gene predispose individuals to Li-Fraumeni syndrome (LFS). The cell cycle checkpoint kinases CHK1 and CHK2 act upstream of p53 in DNA damage responses, and recently rare germ-line mutations in CHK2 were reported in LFS families. We have analyzed CHK1, CHK2, and p53 genes for mutations in 44 Finnish families with LFS, Li-Fraumeni-like syndrome, or families phenotypically suggestive of LFS with conformation-sensitive gel electrophoresis. Five different disease-causing mutations were observed in 7 families (7 of 44 families; 15.9%): 4 in the p53 gene (5 of 44 families; 11.4%) and 1 in the CHK2 gene (2 of 44 families; 4.5%). Interestingly, the other CHK2-mutation carrier also has a mutation in the MSH6 gene. The cancer phenotype in the CHK2-families was not characteristic of LFS, and may indicate variable phenotypic expression in the rare families with CHK2 mutations. No mutations in the CHK1 gene were identified. Additional work is necessary to completely unravel the molecular background of LFS.     

A high tumor-associated macrophage content predicts favorable outcome in follicular lymphoma patients treated with rituximab and cyclophosphamide-doxorubicin-vincristine-prednisone.

PURPOSE: Tumor-associated macrophage (TAM) content predicts survival in follicular lymphoma (FL) patients treated with chemotherapy. The aim of this study was to determine how combination of rituximab with chemotherapy influences TAM-associated clinical outcome. EXPERIMENTAL DESIGN: Expression of a macrophage marker, CD68, was determined immunohistochemically from FL samples of 96 patients treated with rituximab and cyclophosphamide-Adriamycin-vincristine-prednisone regimen. Of them, 71 received therapy at diagnosis and 25 at relapse. Neutrophil and CD3+ lymphocyte counts were also measured. The median follow-up time for the cohort was 54 months. Fourty-five patients previously treated with chemotherapy served as a control group. RESULTS: Consistent with previous studies, high TAM amount was associated with adverse outcome in chemotherapy-treated patients (P = 0.026). In contrast, after rituximab and cyclophosphamide-doxorubicin-vincristine-prednisone regimen, high TAM content correlated with longer survival rates. According to Kaplan Meier estimates, the median progression free survival (PFS) was not reached for patients with high TAM content compared with 45 months for patients with low TAM scores (P = 0.006). A trend toward a better overall survival (OS) at 5 years was also observed for patients with high TAM content (OS, 97% versus 90%, P = 0.116). The positive prognostic value of TAMs was seen both for the patients treated at diagnosis and at relapse. In multivariate analyses, TAM content remained an independent prognostic factor for OS and PFS. Neutrophil and CD3+ lymphocyte counts did not correlate with outcome. CONCLUSIONS: The data suggest that high TAM score is associated with a favorable prognosis in FL patients treated with immunochemotherapy.     

Influence of cellular DNA content on survival in differentiated thyroid cancer

Cellular DNA content was measured using a novel flow cytometric method to analyze paraffin-embedded tissue blocks from 125 patients with differentiated thyroid cancer. DNA aneuploidy was found in 20 (24%) of the 82 papillary, 20 (56%) of the 36 follicular, and in four (57%) of the seven medullary carcinomas. Aneuploidy was found to be more common in the elderly (P less than 0.002), in moderately and poorly differentiated carcinomas (P less than 0.004), and in tumors infiltrating beyond the thyroid capsule (P less than 0.03). Patients with an aneuploid tumor had less favorable cumulative survival (P less than 0.0001) than patients with diploid cancer. However, in papillary and follicular carcinomas, multivariate analysis using stepwise Cox model showed age at diagnosis, follicular type, and tumor invasion beyond the thyroid capsule to be more important independent prognostic factors. Increasing probability of DNA aneuploidy with increasing age explains partially why prognosis of differentiated thyroid carcinoma is poor in older patients.     

Acute effects of tobacco on human brain stem evoked potentials

Reports of tobacco-induced electrocortical activation have frequently indicated that this effect is mediated via nicotine's action on sub-cortical structures. This study focused on human brain stem involvement by examining the acute effects of tobacco smoking on brain stem auditory potentials (BSAEPs). Twelve regular smokers were tested on two separate sessions involving sham or real smoking. On each session, BSAEPs were recorded during a baseline period and immediately after smoking. BSAEPs, recorded from Cz, were elicited by presentation of 1,000 monaural, rare fraction click stimuli. Latency and amplitudes of peak components I, III and V were assessed and analysed. No significant effects were observed for latency measures or for amplitudes of peaks I and III. A significant effect was observed for peak V with tobacco resulting in larger amplitudes relative to sham smoking. Peak V reflects activity from upper pontine-lower midbrain sites and this tobacco-peak V finding is discussed in relation to arousal and information processing theories of smoking.     

Hippocampal-dependent familiar area map supports corrective re-orientation following navigational error during pigeon homing: a GPS-tracking study

It is hypothesized that a central role of the vertebrate hippocampal formation (HF) in behavior is the learning and operation of a map-like representation of familiar landmarks and landscape features. One critical property of a map is that it should enable an individual to re-orient towards a goal location following a navigational error. To test this prediction on a spatial scale consistent with their naturally occurring behavior, control and HF-lesioned homing pigeons were trained from two locations and then subsequently released, while carrying portable GPS-tracking devices, following a phase-shift treatment. Analyses revealed that the HF-lesioned pigeons were less successful than control pigeons in re-orienting homewards following the phase-shift-induced error in their initial orientation. Furthermore, the observation that HF-lesioned pigeons were found to routinely ignore a land–sea landscape boundary when returning home from one of the release sites suggests that coarse landscape features may be an underappreciated source of navigational information for homing pigeons. The data demonstrate that, on a scale of tens of kilometers, homing pigeons are able to learn a hippocampal-dependent, map-like representation of familiar landmarks/landscape features that can support corrective re-orientation following a navigational error.     

Intraoperative Psoas Compartment Block vs Preoperative Fascia Iliaca Block for Pain Control After Direct Anterior Total Hip Arthroplasty: A Randomized Controlled Trial

Background

Modern joint arthroplasty protocols place an emphasis on minimizing patient-reported postoperative pain while minimizing opioid consumption. The use of multimodal pain management protocols has been reported to improve patient outcomes and satisfaction after total hip arthroplasty.

Impaired executive performance in healthy siblings of schizophrenia patients in a population-based study

There is increasing evidence that healthy siblings of schizophrenia patients have similar, although milder, neuropsychological deficits than their affected family members. However, the interpretation of these findings has been complicated by methodological differences, for example the selection of relatives studied and the sensitivity of tests used. We studied neuropsychological functioning in schizophrenia families in representative, population-based samples of schizophrenia patients (n=81) and healthy siblings (n=78) from 58 families, and control subjects (n=70). We found that the healthy sibling group was impaired in tests measuring performance speed and executive functions. The patients were significantly impaired in all neuropsychological variables studied when compared with the control subjects, and also when compared with the healthy siblings. The effects of age, sex and education were controlled for. In conclusion, in a study of representative, population-based sample the healthy siblings of schizophrenia patients demonstrated deficits in processing speed and executive functions.