Impact of hydrophobic and hydrophilic surface properties on Pseudomonas aeruginosa adhesion in materials used in mineral water wells.

Microbiologically contaminated water is a significant source of infections in humans and animals, with Pseudomonas aeruginosa (PSA) being particularly concerning due to its ability to thrive in water environments and its resistance to many disinfectants. Therefore, this study investigates the adhesion potential of PSA strains on various materials used in mineral water extraction wells, focusing on hydrophobic and hydrophilic properties. Mineral water samples were collected from three wells (P-01, P-07, and P-08) within the Guarani Aquifer System and Fractured Aquifer System (SAF) in Brazil. The physicochemical properties of the water, including concentrations of Sr (strontium), Fe (iron), Si (silicon), SO42- (sulfate ions), Cl- (chloride ions), and ORP (oxidation-reduction potential), were analyzed. Results indicated higher PSA adhesion on hydrophobic materials, particularly high-density polyethylene (HDPE) and geomechanically plasticized polyvinyl chloride (PVC). Multiple correlation analyses revealed positive correlations between PSA adhesion on hydrophilic materials and Sr, Fe, Si, SO42-, and Cl- concentrations. Conversely, ORP negatively correlated with bacterial adhesion on PVC surfaces, suggesting higher ORP values reduced PSA attachment. These findings highlight the importance of water composition and material properties in influencing bacterial adhesion and potential biofilm formation in mineral water extraction systems.

How multiple farming conditions correlate with the composition of the raw cow's milk lactic microbiome.

Questionnaires on farming conditions were retrieved from 2129 dairy farms and clustered, resulting in 106 representative raw cow's milk samples analysed in winter and summer. Substantiating the efficiency of our survey, some farming conditions affected the milk physicochemical composition. Culturing identified several species of lactic acid bacteria (LAB) per milk, whose number increased through 16S ribosomal RNA (rRNA) gene sequencing and shotgun metagenome analyses. Season, indoor versus outdoor housing, cow numbers, milk substitutes, ratio cattle/rest area, house care system during lactation, and urea and medium-chain fatty acids correlated with the overall microbiome composition and the LAB diversity within it. Shotgun metagenome detected variations in gene numbers and uniqueness per milk. LAB functional pathways differed among milk samples. Focusing on amino acid metabolisms and matching the retrieved annotated genes versus non-starter lactic acid bacteria (NSLAB) references from KEGG and corresponding to those identified, all samples had the same gene spectrum for each pathway. Conversely, gene redundancy varied among samples and agreed with NSLAB diversity. Milk samples with higher numbers of NSLAB species harboured higher number of copies per pathway, which would enable steady-state towards perturbations. Some farming conditions, which affected the microbiome richness, also correlated with the NSLAB composition and functionality.

Volatile organic compounds from Starmerella bacillaris to control gray mold on apples and modulate cider aroma profile.

Gray mold caused by Botrytis cinerea is a fungal disease that can determine significant economic losses of apple during the storage phase. An alternative to reduce the use of traditional synthetic fungicides is to employ the yeast Starmerella bacillaris as biological control agent (BCA), also with positive effect on apple juice fermentation for the production of cider. Thus, we aimed to evaluate the safety of 16 S. bacillaris strains and their ability to control B. cinerea. In addition, the fermentation performances in apple juice and the volatile organic compounds (VOCs) profile were assessed, both in single-strain and in sequential fermentations with Saccharomyces cerevisiae. The in vitro assays showed that all S. bacillaris strains can be considered safe from the analyzed virulence factors, and were able to significantly constrain the growth of B. cinerea, reducing mycelial growth of 50% in dual-culture and of 90% through VOCs. Moreover, in vivo antagonistic assays revealed a visible decrease of gray mold rot symptoms on apples confirming the potential of S. bacillaris as BCA. GC-MS analysis of the ciders obtained showed increased concentrations in the sequential fermentation of some higher alcohols and terpenes, positively correlated with the cider aromatic quality, and suggested the involvement of benzyl alcohol, known for its antimicrobial action, in the biocontrol efficacy.

Untangling Neolithic and Bronze Age mitochondrial lineages in South Asia.

Two key moments shaped the extant South Asian gene pool within the last 10 thousand years (ka): the Neolithic period, with the advent of agriculture and the rise of the Harappan/Indus Valley Civilisation; and Late Bronze Age events that witnessed the abrupt fall of the Harappan Civilisation and the arrival of Indo-European speakers. This study focuses on the phylogeographic patterns of mitochondrial haplogroups H2 and H13 in the Indian Subcontinent and incorporates evidence from recently released ancient genomes from Central and South Asia. It found signals of Neolithic arrivals from Iran and later movements in the Bronze Age from Central Asia that derived ultimately from the Steppe. This study shows how a detailed mtDNA phylogeographic approach, combining both modern and ancient variation, can provide evidence of population movements, even in a scenario of strong male bias such as in the case of the Bronze Age Steppe dispersals.

A K(ATP) channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila.

Humans sleep approximately a third of their lifetime. The observation that individuals with either long or short sleep duration show associations with metabolic syndrome and psychiatric disorders suggests that the length of sleep is adaptive. Although sleep duration can be influenced by photoperiod (season) and phase of entrainment (chronotype), human familial sleep disorders indicate that there is a strong genetic modulation of sleep. Therefore, we conducted high-density genome-wide association studies for sleep duration in seven European populations (N=4251). We identified an intronic variant (rs11046205; P=3.99 × 10(-8)) in the ABCC9 gene that explains ≈5% of the variation in sleep duration. An influence of season and chronotype on sleep duration was solely observed in the replication sample (N=5949). Meta-analysis of the associations found in a subgroup of the replication sample, chosen for season of entry and chronotype, together with the discovery results showed genome-wide significance. RNA interference knockdown experiments of the conserved ABCC9 homologue in Drosophila neurons renders flies sleepless during the first 3 h of the night. ABCC9 encodes an ATP-sensitive potassium channel subunit (SUR2), serving as a sensor of intracellular energy metabolism.

Population genetic structure of variable drug response.

Geographic patterns of genetic variation, including variation at drug metabolizing enzyme (DME) loci and drug targets, indicate that geographic structuring of inter-individual variation in drug response may occur frequently. This raises two questions: how to represent human population genetic structure in the evaluation of drug safety and efficacy, and how to relate this structure to drug response. We address these by (i) inferring the genetic structure present in a heterogeneous sample and (ii) comparing the distribution of DME variants across the inferred genetic clusters of individuals. We find that commonly used ethnic labels are both insufficient and inaccurate representations of the inferred genetic clusters, and that drug-metabolizing profiles, defined by the distribution of DME variants, differ significantly among the clusters. We note, however, that the complexity of human demographic history means that there is no obvious natural clustering scheme, nor an obvious appropriate degree of resolution. Our comparison of drug-metabolizing profiles across the inferred clusters establishes a framework for assessing the appropriate level of resolution in relating genetic structure to drug response.

A red wine intervention does not modify plasma trimethylamine N-oxide but is associated with broad shifts in the plasma metabolome and gut microbiota composition.

BACKGROUND: Gut microbiota profiles are closely related to cardiovascular diseases through mechanisms that include the reported deleterious effects of metabolites, such as trimethylamine N-oxide (TMAO), which have been studied as diagnostic and therapeutic targets. Moderate red wine (RW) consumption is reportedly cardioprotective, possibly by affecting the gut microbiota. OBJECTIVES: To investigate the effects of RW consumption on the gut microbiota, plasma TMAO, and the plasma metabolome in men with documented coronary artery disease (CAD) using a multiomics assessment in a crossover trial. METHODS: We conducted a randomized, crossover, controlled trial involving 42 men (average age, 60 y) with documented CAD comparing 3-wk RW consumption (250 mL/d, 5 d/wk) with an equal period of alcohol abstention, both preceded by a 2-wk washout period. The gut microbiota was analyzed via 16S rRNA high-throughput sequencing. Plasma TMAO was evaluated by LC-MS/MS. The plasma metabolome of 20 randomly selected participants was evaluated by ultra-high-performance LC-MS/MS. The effect of RW consumption was assessed by individual comparisons using paired tests during the abstention and RW periods. RESULTS: Plasma TMAO did not differ between RW intervention and alcohol abstention, and TMAO concentrations showed low intraindividual concordance over time, with an intraclass correlation coefficient of 0.049 during the control period. After RW consumption, there was significant remodeling of the gut microbiota, with a difference in ß diversity and predominance of Parasutterella, Ruminococcaceae, several Bacteroides species, and Prevotella. Plasma metabolomic analysis revealed significant changes in metabolites after RW consumption, consistent with improved redox homeostasis. CONCLUSIONS: Modulation of the gut microbiota may contribute to the putative cardiovascular benefits of moderate RW consumption. The low intraindividual concordance of TMAO presents challenges regarding its role as a cardiovascular risk biomarker at the individual level. This study was registered at clinical trials.gov as NCT03232099.

Role prediction of Gram-negative species in the resistome of raw cow's milk.

Extended use of antibiotics in dairy farming for therapeutic and prophylactic reasons, but also the higher prevalence of antibiotic resistant bacteria (ARB) in the farm environment raised the concern of consuming raw cow's milk and its derived products. The aim of this study was to predict by shotgun metagenomic analyses the presence of antibiotic resistance genes (ARGs) mainly correlated with Gram-negative bacteria in antibiotic residue free raw cow's milk derived exclusively from healthy animal from South Tyrol (Northern Italy), chosen as a model system. Assessment of shotgun metagenomic data of reconstructed scaffolds, revealed the existence of Pseudomonas spp. as the most abundant Gram-negative species in the raw cow's milk samples bearing ARGs. Besides, ARGs also linked to lactic acid bacteria such as Lactococcus sp. and Lactobacillus sp. ARGs correlated to microbiome found in milk samples conferred resistance towards aminoglycoside-streptothricin, beta-lactamase, macrolide, tetracycline, carbapenem, cephalosporin, penam, peptide, penem, fluoroquinolone, chloramphenicol and elfamycin antibiotics. Further bioinformatic processing included de-novo reassembly of all metagenomic sequences from all milk samples in one, to reconstruct metagenome assembled genomes (MAGs), which were further used to investigate mobile genetic elements (MGE). Analyses of the reconstructed MAGs showed that, MAG 9 (Pseudomonas sp1.) contained the oriT gene (origin of transfer gene) needed for transferring virulent factors. Although the presence of Pseudomonas is common in raw cow's milk, pasteurization treatment reduces their survivability. Nevertheless, attention should be paid on Pseudomonas spp. due to their intrinsic resistance to antibiotics and their capability of transferring virulent factors to other bacteria.

Potentially probiotic or postbiotic pre-converted nitrite from celery produced by an axenic culture system with probiotic lacticaseibacilli strain.

The present study evaluated the use of the probiotic Lacticaseibacillus paracasei DTA-83 as a nitrite-reducing agent to produce potentially probiotic or postbiotic pre-converted nitrite from celery. The results obtained were compared to those achieved by direct addition of sodium nitrite for the typical reddish color formation in cooked pork sausages and the inhibitory potential against the growth of target microorganisms, including the clostridia group. Regarding the sausages color, similar findings were observed when comparing the use of pre-converted nitrite from celery produced by L. paracasei DTA-83 and the direct addition of sodium nitrite. Additionally, it presented an inhibitory effect against Salmonella spp., which was not observed with the direct addition of nitrite, revealing a potential strategy to control salmonellosis in the matrix. However, a non-equivalent preservative effect against Clostridium perfringens (INCQS 215) was determined. The results highlight a promising alternative to produce probiotic or postbiotic meat ingredients; however, further studies should be conducted to investigate doses that achieve microbial control.

Contribution of non-Saccharomyces yeasts to wine volatile and sensory diversity: A study on Lachancea thermotolerans, Metschnikowia spp. and Starmerella bacillaris strains isolated in Italy.

Saccharomyces cerevisiae starter cultures are largely used in winemaking to repress the wild microorganisms and achieve more predictable and desired outcomes. Notwithstanding, alternative microbial resources received increasing attention for their potential to produce wines with more distinctive and typical features. Our previous survey revealed a great inter- and intra-species diversity in an extensive collection of non-Saccharomyces wine yeasts from multiple regions of Italy. This study aimed to explore the detected biodiversity evaluating the quality of wines obtained by sequential inoculation of specific selected strains of the collection (Lachancea thermotolerans or Metschnikowia spp. or Starmerella bacillaris), and S. cerevisiae EC 1118. Fermentations of natural grape must at laboratory scale were followed by microbiological, chemical and sensorial analysis of the wines. The results indicated that each yeast species and strain exerted a distinctive impact on the wine, giving final products clearly separated with Principal Component Analysis. In particular, L. thermotolerans contributed producing relevant amounts of lactic acid and had the highest potential to reduce ethanol content; the presence of S. bacillaris increased the level of glycerol, and, remarkably, reduced acetaldehyde and total SO2; Metschnikowia spp. promoted the formation of higher alcohols and esters, and reduced volatile phenols. The sensory analysis based on the orthonasal aroma confirmed the separation between the wines obtained with the sequential fermentations and the control with single inoculation of EC 1118, although the three non-Saccharomyces species used could not be clearly distinguishable by the panelists. This study indicates that the use of selected native non-Saccharomyces strains in conjunction with S. cerevisiae positively modulates some relevant chemical parameters, and improves the aromatic intensity of wine, therefore justifying investments in non-conventional yeasts as co-starter cultures.

New insights into the variability of lactic acid production in Lachancea thermotolerans at the phenotypic and genomic level.

Non-conventional yeasts are increasingly applied in fermented beverage industry to obtain distinctive products with improved quality. Among these yeasts, Lachancea thermotolerans has multiple features of industrial relevance, especially the production of l(+)-lactic acid (LA), useful for the biological acidification of wine and beer. Since few information is available on this peculiar activity, the current study aimed to explore the physiological and genetic variability among L. thermotolerans strains. From a strain collection, mostly isolated from wine, a huge phenotypic diversity was acknowledged and allowed the selection of a high (SOL13) and a low (COLC27) LA producer. Comparative whole-genome sequencing of these two selected strains and the type strain CBS 6340T showed a high similarity in terms of gene content and functional annotation. Notwithstanding, target gene-based analysis revealed variations between high and low producers in the key gene sequences related to LA accumulation. More in-depth investigation of the core promoters and expression analysis of the genes ldh, encoding lactate dehydrogenase, indicated the transcriptional regulation may be the principal cause behind phenotypic differences. These findings highlighted the usefulness of whole-genome sequencing coupled with expression analysis. They provided crucial genetic insights for a deeper investigation of the intraspecific variability in LA production pathway.

The effects of platinum complexes on seven enzymes.

The effects of K2PtCl4, cis-Pt(NH3)2Cl2, and trans-Pt(NH3)2Cl2 on the activities of glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phosphate dehydrogenase, dihydrofolate reductase, fructose-1,6-bisphosphate aldolase, catalase, tyrosinase, and peroxidase have been investigated. All of the enzymes which are thought to have essential sulfhydryl groups (glyceraldehyde-3-phosphate dehydrogenase, aldolase, and glucose-6-phosphate dehydrogenase) were significantly inhibited by K2PtCl4. The other four enzymes studied are not known to have essential sulfhydryl groups, and were not significantly affected by the Pt compounds under the conditions employed. Glyceraldehyde-3-phosphate dehydrogenase was the only enzyme inhibited by all three Pt compounds tested, with K2PtCl4 being the most effective and cis-Pt(NH3)2Cl2 the least effective inhibitor. Semilogarithmic plots of residual activity versus inhibition time indicated that the inhibition reactions were not simple first-order processes, except for the inhibition of glucose-6-phosphate dehydrogenase by K2PtCl4 which appeared to be first-order with respect to enzyme concentration.

Factors predicting the use of breast-conserving therapy in stage I and II breast carcinoma.

PURPOSE: To define patterns of care for the local therapy of stage I and II breast cancer and to identify factors used to select patients for breast-conserving therapy (BCT). PATIENTS AND METHODS: A convenience sample of 16,643 patients with stage I and II breast cancer treated in 1994 was obtained from hospital-based tumor registries. Histologic variables were determined from original pathology reports. RESULTS: BCT was performed in 42.6% of patients. Multivariate analysis demonstrated that living in the Northeast United States (odds ratio [OR], 2.48; 95% confidence interval [CI], 2.16 to 2.84), having a clinical T1 tumor (OR, 2.51; 95% CI, 2.27 to 2.78), and having a tumor without an extensive intraductal component (OR, 2.07; 95% CI, 1.81 to 2.37) were the strongest predictors of breast-conserving surgery. Radiation therapy was given to 86% of patients who had breast-conserving surgery. Age less than 70 years was the most significant predictor of receiving radiation (OR, 2.11; 95% CI, 1.77 to 2.25). Tumor variables did not correlate with the use of radiation, but favorable tumor characteristics were associated with the use of breast-conserving surgery. CONCLUSION: Despite strong evidence supporting the use of BCT, the majority of women continue to be treated with mastectomy. Predictors of the use of BCT do not correspond to those suggested in guidelines.

Large-cell lymphoma arising in the mediastinum in children and adolescents is associated with an excellent outcome: a Children's Cancer Group report.

PURPOSE: Large-cell lymphoma (LCL) arising in the mediastinum (LCL-M) is a heterogeneous group of non-Hodgkin's lymphoma (NHL) that includes B-cell lymphomas as well as T-cell lymphomas, including anaplastic LCL. LCL-M is well recognized in young adults but is less well characterized and infrequent in children and adolescents. METHODS: A retrospective review of Children's Cancer Group therapeutic studies for nonlymphoblastic lymphomas (CCG-551, CCG-503, CCG-552, and CCG-5911) identified 20 patients with LCL-M, representing 7.2% of all LCLs classified by central pathology review. RESULTS: The patients ranged in age from 4 to 19 years (median, 12.5 years; mean, 12 years); 55% of the patients were male. Although a variety of chemotherapy regimens were used, response was excellent, with all 20 patients (100%) achieving a complete response. Four patients (20%) experienced relapse locally or in distant sites including brain and kidney. One patient died of sepsis during therapy. For the 20 patients with LCL-M, the product-limit estimated 5-year event-free survival (EFS) and 5-year overall survival (OS) rates are 75% +/- 10% and 85% +/- 8%, respectively. For disseminated LCLs (192 cases), the EFS and OS rates were 50% +/- 4% and 63% +/- 4%, respectively, which differ significantly from the those of the LCL-M cases (EFS, P =.025; OS, P =.034). The 5-year EFS and OS rates for patients with localized LCL (67 cases) were 92 +/- 3% and 97 +/- 2%, respectively. CONCLUSION: LCL-M is a heterogeneous group of NHLs that makes up approximately 7.2% of LCL in children and adolescents. Response to therapy and OS in this young age group seems excellent and superior to that of disseminated LCLs but inferior to that of other localized LCL. Future studies of LCL-M will evaluate short intense chemotherapy administered without radiation therapy.

Central lymphatic irradiation for stage III nodular malignant lymphoma: long-term results.

PURPOSE: To report the long-term results of central lymphatic irradiation for stage III nodular malignant lymphoma. PATIENTS AND METHODS: Between 1969 and 1985, 34 patients (26 with nodular poorly differentiated lymphoma, four with nodular mixed lymphocytic/histiocytic lymphoma, and four with nodular histiocytic lymphoma) were treated with central lymphatic irradiation. Median age of the group was 51 years (range, 30 to 73). There were 15 men and 19 women. Staging work-up included a physical examination and bone marrow biopsy in all patients. Seventy-four percent had a lymphangiogram (LAG) and 44% a laparotomy (LAP). Eighty-two percent had either a LAP or a LAG. Thirty-two patients were Ann Arbor stage IIIA and two were stage IIIB. All patients received lymphatic irradiation that encompassed cervical, supraclavicular, axillary, mediastinal, paraaortic, mesenteric, pelvic, and femoral lymphatics to total doses ranging from 20 to 30 Gy in 1.0- to 1.8-Gy fractions. Waldeyer's ring was initially treated in 17 patients. Follow-up information is available on all 34 patients. Median follow-up is 9 years, 8 months (range, 15 to 244 months). RESULTS: Life-table actuarial overall, disease-free, and cause-specific survival rates at 15 years are 28%, 40%, and 46%, respectively. Only one relapse was observed after 9 years. Disease-free survival was significantly improved in patients with five or fewer sites of involvement (P = .02). Age, sex, B symptoms, histology, and technique of irradiation were not prognostically significant. Salvage therapy, including further irradiation and/or chemotherapy, was delivered to 20 patients. Ten percent of these patients remain alive without evidence of disease. Toxicity data were available for the patients treated at the Medical College of Wisconsin (MCW). Radiation Therapy Oncology Group (RTOG) acute hematologic, gastrointestinal, and salivary toxicity scores were < or = 2 in 83% of patients. Late toxicity scores were < or = 2 in 96%. Persistent xerostomia was noted in 23% of patients who received initial treatment to Waldeyer's ring. CONCLUSION: These results suggest that initial comprehensive central lymphatic irradiation may be the preferred approach to achieve a durable relapse-free interval for this group of patients.

Long-term follow-up of patients treated with COMP or LSA2L2 therapy for childhood non-Hodgkin's lymphoma: a report of CCG-551 from the Childrens Cancer Group.

PURPOSE: We analyzed the long-term results of a Childrens Cancer Group (CCG) randomized study comparing cyclophosphamide, vincristine, methotrexate, and prednisone (COMP) versus LSA2L2 as treatment for childhood non-Hodgkin's lymphoma. The initial results were previously reported (N Engl J Med 308:559, 1983). PATIENTS AND METHODS: A total of 429 patients are reported here, 68 with localized disease and 361 with disseminated disease. The distribution of disseminated-disease patients by histologic type was 164 lymphoblastic, 60 large-cell, and 137 undifferentiated lymphomas. Median follow-up duration of surviving patients is 8 years. RESULTS: Event-free survival (EFS) of patients with localized disease was 84% at 5 years. No differences were seen between the two treatment regimens. Results for patients with disseminated disease was dependent on histologic subtype: patients with lymphoblastic lymphoma did better when treated with LSA2L2 (5-year EFS of 64% v 35% for COMP); COMP produced better results for patients with undifferentiated lymphoma (5-year EFS of 50% v 29% for LSA2L2). Results for large-cell lymphoma patients were similar (5-year EFS of 52% for COMP v 43% for LSA2L2). Five percent of patients died of treatment-related complications while on therapy (primarily infections). Only four deaths without progression have been observed off-therapy (two from restrictive lung disease, one from an acute asthma attack, one from colon cancer). Patient survival rates after recurrence were poor. CONCLUSION: Treatment success can be expected in 84% of pediatric patients with localized non-Hodgkin's lymphoma. For patients with disseminated disease, treatment success can be expected in 64% of those with lymphoblastic and 50% of those with undifferentiated or large-cell disease. To date, late adverse events are rare.

Application of high-dimensional feature selection: evaluation for genomic prediction in man.

In this study, we investigated the effect of five feature selection approaches on the performance of a mixed model (G-BLUP) and a Bayesian (Bayes C) prediction method. We predicted height, high density lipoprotein cholesterol (HDL) and body mass index (BMI) within 2,186 Croatian and into 810 UK individuals using genome-wide SNP data. Using all SNP information Bayes C and G-BLUP had similar predictive performance across all traits within the Croatian data, and for the highly polygenic traits height and BMI when predicting into the UK data. Bayes C outperformed G-BLUP in the prediction of HDL, which is influenced by loci of moderate size, in the UK data. Supervised feature selection of a SNP subset in the G-BLUP framework provided a flexible, generalisable and computationally efficient alternative to Bayes C; but careful evaluation of predictive performance is required when supervised feature selection has been used.

Recombinant human interferon-beta (rHuIFN-beta) and radiation therapy for inoperable non-small cell lung cancer.

Fifteen patients with stage II, IIIA, and IIIB non-small cell lung cancer (NSCLC) received subcutaneous (s.c.) recombinant, glycosylated, human interferon-beta 1a (Rebif; rHuIFN-beta 1a) on each day of conventionally fractionated radiation therapy (RT) given in 2.0 Gy fractions to 60 Gy in 6 weeks. The rHuIFN-beta 1a was generated in CHO cells by recombinant DNA technology and is identical to natural IFN-beta produced by fibroblasts in primary sequence and glycosylation. Cohorts of three patients each were treated with escalating doses of rHuIFN-beta 1a: 1.5, 3, 6, 12, and 24 MIU/m2 per treatment day. Acute toxicity was assessed according to modified WHO criteria; late toxicity was graded using RTOG late toxicity criteria. The maximum tolerated dose (MTD) of rHuIFN-beta 1a was defined as the dose level immediately below that in which dose-limiting toxicity occurred in > or = two of six patients. Immunomodulatory effects and antigenicity of rHuIFN-beta 1a were assessed by 2-5A synthetase, beta 2-microglobulin, and neopterin levels and by measurement of anti-rHuIFN-beta antibodies, respectively. Fourteen of fifteen patients experienced grades 1-3 acute (early) toxicity (< or = 90 days), which was primarily gastrointestinal: dysphagia/esophagitis (14/15), nausea/vomiting (12/15), anorexia (7/15), and liver transaminasemia (6/15). One of three patients treated with 24 MIU/m2 per treatment day (total rHuIFN-beta 1a dose 672 MIU) died of complications secondary to pneumonia, sepsis, adult respiratory distress syndrome (ARDS), and radiation pneumonitis. Twelve patients were evaluable for late toxicity (> 90 days). Maximum toxicity was grade 0 in five patients, grade 1 in four patients, and grade 5 in one patient (radiation pneumonitis). Clinical responses from the combination were 1/15 CR, 6/15 PR, 6/15 stable disease, and 1/15 progressive disease. The MTD of rHuIFN-beta 1a has been estimated at 12 MIU/m2 per treatment day when given daily during conventional RT to 60 Gy in 6 weeks. Biologic response by rHuIFN-beta 1a alone was reflected by significant and dose-related increases in 2-5A synthetase, beta 2-microglobulin, and neopterin. Radiation therapy alone had no effect on these immune response parameters and did not diminish their augmentation by rHuIFN-beta 1a. There was no association of biologic modulation with clinical response or survival.

Channel-consistency following unilateral stroke: an examination of patient communications across verbal and nonverbal domains.

One way in which the dyadic communicative process can go awry is for one or both parties to send channel-inconsistent communications - communications in which the verbal and nonverbal elements are not matched in emotional valence (e.g., uttering positive words with a frown). We hypothesized that unilateral stroke patients would be likely to send such messages. Given the verbal impairments typically associated with left hemisphere damage (LHD), e.g., agrammatism, and the nonverbal impairments typically associated with right hemisphere damage (RHD), we expected LHD and RHD patients to send messages in which the impaired channel was perceived as inconsistent with the unimpaired channel. Ten LHD, 11 RHD and six normal control patients were videotaped while engaging in social interaction. Observers made judgments about the valence of the patients' (1) words (based on transcripts of the interactions), and (2) facial expressions (based on soundless videos of the interactions). Analysis of word-face difference scores revealed a significant linear trend, with messages of LHD patients judged more positive in facial expression than in verbal content, messages of RHD patients judged more positive in verbal content than in facial expression, and messages of control patients judged channel-consistent (similar in valence across facial and verbal channels).

Summary results of the ACR (American College of Radiology) experience with an in-training examination for residents in radiation oncology.

In 1984, the American College of Radiology administered its first in-training examination to residents in radiation oncology. This paper provides a summary of the overall results of the first 4 years of experience with this evaluatory instrument.