The impact of face coverings on audio-visual contributions to communication with conversational speech.

The use of face coverings can make communication more difficult by removing access to visual cues as well as affecting the physical transmission of speech sounds. This study aimed to assess the independent and combined contributions of visual and auditory cues to impaired communication when using face coverings. In an online task, 150 participants rated videos of natural conversation along three dimensions: (1) how much they could follow, (2) how much effort was required, and (3) the clarity of the speech. Visual and audio variables were independently manipulated in each video, so that the same video could be presented with or without a superimposed surgical-style mask, accompanied by one of four audio conditions (either unfiltered audio, or audio-filtered to simulate the attenuation associated with a surgical mask, an FFP3 mask, or a visor). Hypotheses and analyses were pre-registered. Both the audio and visual variables had a statistically significant negative impact across all three dimensions. Whether or not talkers' faces were visible made the largest contribution to participants' ratings. The study identifies a degree of attenuation whose negative effects can be overcome by the restoration of visual cues. The significant effects observed in this nominally low-demand task (speech in quiet) highlight the importance of the visual and audio cues in everyday life and that their consideration should be included in future face mask designs.

Genetic mosaicism in normal tissues of Wilms' tumour patients.

We describe the partial loss of heterozygosity (LOH) at chromosome 11p loci in normal tissues (normal kidney and/or blood) from four of 67 Wilms' tumour patients. Autologous tumour DNA showed complete loss of the same, maternally derived, alleles. These observations indicate that the normal tissues were mosaic for cells heterozygous and homozygous for 11p markers and that tumours subsequently developed from the homozygous cells that had undergone an 11p somatic recombination event. We suggest that LOH for 11p alleles is compatible with normal growth and differentiation and is significant pathologically only when accompanied by other genetic alterations.

Accelerated re-epithelialization in beta3-integrin-deficient- mice is associated with enhanced TGF-beta1 signaling.

The upregulation of TGF-beta1 and integrin expression during wound healing has implicated these molecules in this process, but their precise regulation and roles remain unclear. Here we report that, notably, mice lacking beta(3)-integrins show enhanced wound healing with re-epithelialization complete several days earlier than in wild-type mice. We show that this effect is the result of an increase in TGF-beta1 and enhanced dermal fibroblast infiltration into wounds of beta(3)-null mice. Specifically, beta(3)-integrin deficiency is associated with elevated TGF-beta receptor I and receptor II expression, reduced Smad3 levels, sustained Smad2 and Smad4 nuclear localization and enhanced TGF-beta1-mediated dermal fibroblast migration. These data indicate that alpha(v)beta(3)-integrin can suppress TGF-beta1-mediated signaling, thereby controlling the rate of wound healing, and highlight a new mechanism for TGF-beta1 regulation by beta(3)-integrins.

Transmission of classical scrapie to wild-type mice: the influence of the ovine PrP sequence on lesion profiles.

Susceptibility of sheep to classical scrapie is determined by polymorphisms in the coding region of the prion protein gene (PRNP), mainly at codons 136, 154 and 171. It has recently been shown that lesion profiles from classical field scrapie isolates that transmitted to RIII mice can be classified into different groups. There was also strong, but not absolute, association between the different groups and codon 136. Here, we examine the hypothesis that additional polymorphisms in the open reading frame sequence of the ovine PRNP may account for the different groups of lesion profiles observed following transmission to mice.

Maturation of hemolysin-producing cell clones. I. The kinetics of the induction period of an in vitro hemolysin response to erythrocyte antigen.

INVESTIGATIONS OF THE INDUCTION PERIOD OF AN IN VITRO HEMOLYSIN RESPONSE TO SHEEP ERYTHROCYTE ANTIGEN REVEALED THE FOLLOWING: 1. After antigen stimulation precursors of plaque-forming cells rapidly maturate to the point of hemolysin production. 2. Initial maturation probably occurs in the absence of cell division. 3. After initial maturation, a latent period of about 12 hr occurs before the first doubling of PFC. 4. At least the first three cell doublings are synchronous, with a generation time of 7-8 hr. 5. Synchronous cell division implies that all precursor cells are at the same point in the cell cyde when they are initially stimulated.

Maturation of hemolysin-producing cell clones. II. The appearance and localization of precursor units in lymphoid tissues of neonatal mice.

Cells capable of reacting with sheep erythrocyte (SRBC) antigen to maturate and produce hemolysin appear simultaneously in the bone marrow and spleen of 1-day old Swiss-Webster mice. However, hemolysin-producing cell clones (HPCC) do not result. Complete functional precursor units generally appear in the spleens of mice older than 3 days. In vivo and in vitro data correlate well in this regard. Complete precursor units are not seen in the bone marrow and only very rarely in the thymus. The efficiency of precursor units of neonatal mice when they become functional approximates that of the mature animal when based on the doubling time of plaque-forming cells (PFC). Possible explanations of the initial appearance of incomplete precursor units have been discussed.

Canine sterile nodular panniculitis: a retrospective study of 14 cases.

BACKGROUND: Sterile nodular panniculitis (SNP) is an uncommon inflammatory condition of subcutaneous fat that can be idiopathic, but has also been associated with underlying conditions such as pancreatic disease or systemic lupus erythematosus (SLE). The pathogenesis and clinical course of the condition are not well understood. OBJECTIVES: To retrospectively review cases of SNP associated with systemic signs, concurrent disease, or both and characterize the clinical, laboratory, imaging, and histopathologic findings, treatment, and response to treatment. ANIMALS: Fourteen dogs with histologically confirmed SNP diagnosed between 1996 and 2008. METHODS: Retrospective study. RESULTS: Skin lesions were ulcerated or draining nodules in 9 dogs and nonulcerative subcutaneous nodules in 5. Most dogs had systemic signs, such as fever, inappetence, lethargy, and multiple lesions. Common clinicopathologic findings included neutrophilia with or without left shift, increased alkaline phosphatase activity, mild hypoglycemia, hypoalbuminemia, and proteinuria. Concurrent diseases included pancreatic disease, SLE, rheumatoid arthritis, polyarthritis, lymphoplasmacytic colitis, and hepatic disease. Dogs responded to immunosuppressive doses of corticosteroids when administered. Prognosis for recovery was related to the underlying disease process. CONCLUSIONS AND CLINICAL IMPORTANCE: SNP is not a single disease. Rather, it is a cutaneous marker of systemic disease in many cases. After thorough evaluation for concurrent disease and infectious causes, immunosuppressive treatment is often effective.

Effects of silymarin on gossypol toxicosis in divergent lines of chickens.

Gossypol, a pigment of cotton, is a hepatic toxin for chickens. Thus, despite its high protein content, inclusion of cottonseed meal in poultry diets is problematic. Silymarin, an extract from milk thistle, has hepatoprotective qualities and could potentially serve as a feed additive to offset the toxicity of gossypol. The objective of this study was to determine if silymarin could counteract gossypol toxicosis. Cockerels (n = 144) from lines divergently selected for humoral immunity were used. Three individuals from each line were randomly assigned to a cage and fed a corn-soybean meal (control) diet for 14 d. Six cages per line were then randomly assigned 1 of 4 dietary treatments (1,000 mg/kg of gossypol, 1,000 mg/kg of silymarin, 1,000 mg/kg of both gossypol and silymarin, or a control diet). Body weight and feed intake data were collected for 21 d, with chickens bled weekly to collect plasma and determine hematocrits. Chickens were then killed, and livers were collected for subsequent histology and enzymatic activity analyses. Endpoints measured weekly were analyzed with repeated measures and regression methodologies. Plasma and liver enzyme activities, and histological measures, were analyzed using ANOVA. No significant interactions between diets and lines were observed. Chickens assigned to the gossypol and gossypol-silymarin diets stopped gaining weight at d 14 (P < 0.001) and lost weight by d 21 (P < 0.001). Gamma glutamyltransferase was also elevated in these chickens at d 14; activities increased further by d 21 (P < 0.001). Histological examination of liver slices indicated substantial lipidosis (P < 0.001). Furthermore, quinone reductase activity was higher in gossypol- and gossypol-silymarin-treated chickens than in control and silymarin-treated chickens (P < 0.001). Silymarin did not alleviate any clinical effects of gossypol toxicosis.

Protective effect of the T112 PrP variant in sheep challenged with bovine spongiform encephalopathy.

Sheep with an ARQ/ARQ PRNP genotype at codon positions 136/154/171 are highly susceptible to experimental infection with bovine spongiform encephalopathy (BSE). However, a number of sheep challenged orally or intracerebrally with BSE were clinically asymptomatic and found to survive or were diagnosed as BSE-negative when culled. Sequencing of the full PRNP gene open reading frame of BSE-susceptible and -resistant sheep indicated that, in the majority of Suffolk sheep, resistance was associated with an M112T PRNP variant (TARQ allele). A high proportion (47 of 49; 96%) of BSE-challenged wild-type (MARQ/MARQ) Suffolk sheep were BSE-infected, whereas none of the 20 sheep with at least one TARQ allele succumbed to BSE. Thirteen TARQ-carrying sheep challenged with BSE are still alive and some have survival periods equivalent to, or greater than, reported incubation periods of BSE in ARR/ARR and VRQ/VRQ sheep.

Antibody synthesis initiated in vitro by paired explants of spleen and thymus.

Primary in vitro synthesis of antibody has been achieved with a mouse spleen-thymus organ culture system 54 hours after it was incubated for 18 hours with coliphage R17.

Cell-free modulation of proinsulin synthesis.

In vivo, glucose preferentially stimulates proinsulin biosynthesis; at least part of this process is independent of new RNA synthesis and is accompanied by increases in the overall rate of polypeptide chain initiation. The cell-free translation of proinsulin messenger RNA is very sensitive to changes in the protein-synthesizing system. Proinsulin synthesis is preferentially inhibited by the addition of increasing quantities of polyadenylate-containing RNA from the fetal bovine pancreas or by the addition of the drug, aurintricarboxylic acid, which blocks polypeptide chain initiation. These results suggest that proinsulin messenger RNA completes less efficiently for rate controlling initiation factors. We propose that glucose stimulates proinsulin biosynthesis by allowing the less competitive proinsulin messenger RNA to be translated more efficiently.

Phagocytosis: flow cytometric quantitation with fluorescent microspheres.

The phagocytosis of uniform fluorescent latex particles by pulmonary macrophages in the rat was analyzed by flow cytometric methods. The percentage of phagocytic macrophages and the number of particles per cell were determined from cell-size and fluorescence histograms. A comparison of in vivo and in vitro phagocytosis data showed that the percentage of phagocytic lavaged macrophages reflected the availability of instilled particles. With sodium azide used to model phagocytosis inhibition, it was shown that the percentage of phagocytic cells and the number of particles per cell can be determined simultaneously.

Idiopathic eosinophilic masses of the gastrointestinal tract in dogs.

BACKGROUND: Eosinophilic inflammation of the gastrointestinal tract of dogs occurs in numerous disorders, typically resulting in diffuse intestinal thickening. Rarely, eosinophilic masses have been reported. OBJECTIVE: Describe a series of dogs with 1 or more idiopathic eosinophilic gastrointestinal masses (IEGM) to better characterize the clinical features, treatment, and prognosis. ANIMALS: Seven dogs with 1 or more gastrointestinal masses composed primarily of eosinophilic infiltrates for which no underlying cause was found. METHODS: Retrospective case series. RESULTS: Rottweilers and purebred, large breed dogs predominated. Dogs were middle-aged and typically had chronic signs of upper or lower gastrointestinal disease. Decreased appetite, vomiting, and evidence of gastrointestinal hemorrhage were present in the majority of cases. An abdominal or rectal mass was frequently noted on physical examination. Common laboratory abnormalities included peripheral eosinophilia, mature neutrophilia, hypoproteinemia, and hypocholesterolemia. The masses were histologically composed of moderate to severe eosinophilic infiltrates, which were often transmural and accompanied by fibrosis. All dogs treated with surgery alone died of complications of their disease. Treatment with corticosteroids and ivermectin improved clinical signs, caused resolution of eosinophilic infiltrates, and prolonged survival in most dogs treated medically. CONCLUSIONS AND CLINICAL IMPORTANCE: These findings suggest that the prognosis for dogs with IEGM may be good when recognized and managed appropriately. When surgery is performed, medical treatment should also be added.

The human placental lactogen genes: structure, function, evolution and transcriptional regulation.

hPL is a member of an evolutionarily related gene family including hGH and hPRL. Expression of hPL is limited to the placenta but its physiological actions are far reaching. hPL has a direct somatotropic effect on fetal tissues, it alters maternal carbohydrate and lipid metabolism to provide for fetal nutrient requirements, and aids in stimulation of mammary cell proliferation. Two hPL genes (hPL3 and hPL4) encoding identical proteins are responsible for the production of up to 1-3 g PL hormone/day. Recent studies have characterized the regulatory controls of hPL expression. At the post transcriptional level, RNA stability may contribute to variable levels of hPL3 vs. hPL4 production. In addition, non-tissue-specific protein-promoter interactions involving the Sp1 transcription factor are necessary for hPL transcription initiation. A transcriptional enhancer located 3' to the hPL3 gene is responsible for the placenta-specific expression of this gene, while an additional enhancer may be located 3' to the hPl4 gene. The hPL enhancer is bound by multiple proteins including at least one placental specific protein that interacts with a TEF-1 motif. Therefore, enhancer-protein interactions most likely play a large part in the high levels of placenta-specific hPL expression.

Identification of a proteinase K resistant protein for use as an internal positive control marker in PrP Western blotting.

The routine use of an internal positive control (IPC) marker could prove useful in the diagnosis of transmissible spongiform encephalopathy (TSE) diseases, particularly in surveillance programmes where large numbers of negative results are reported. Detection of an endogenous IPC protein in a negative sample adds confidence to the correct sample processing throughout the analytical procedure and could avoid the reporting of false negative diagnoses. Proteinase K (PK) resistance is one of the key diagnostic determinants of the disease-associated form of PrP (PrP(Sc)), the only disease-specific macromolecule currently associated with TSE disease. Additional PK resistant proteins, endogenous to TSE-suspect diagnostic tissue samples, were therefore assessed for use as IPC markers in the Western blot diagnosis of BSE and scrapie. Results indicated that, whilst essentially maintaining a standard PrP extraction and detection protocol, a ferritin heavy chain sub-unit of approximately 22kDa, was consistently detected in all PK treated TSE positive and negative tissue samples tested. Its presence in a range of sample types, any of which could be submitted under BSE and scrapie surveillance programmes, confirmed it as a suitable protein for an IPC marker in PrP(Sc) Western blotting.

Activation of the human PAX6 gene through the exon 1 enhancer by transcription factors SEF and Sp1.

PAX6 is a transcription factor that plays a major role in ocular morphogenesis. PAX6 is expressed in the eye, central nervous system and pancreas. Two alternative promoters, P0 and P1, which are differentially regulated during development, drive PAX6 transcription. We identified a 57 bp cis-regulatory element in exon 1 of the human PAX6 gene exon 1 enhancer (EIE). EIE enhances P1-driven PAX6 expression. Three regions in E1E (E1E-1, E1E-2 and E1E-3) have sequence similarities with binding sites of transcription factors ARP-1, Isl-1 and SEF, respectively. As shown by electrophoretic mobility shift assays, E1E-3, but not E1E-1 or E1E-2, bound to proteins in nuclear extracts of human glioma cells and transcription factor SEF bound to E1E-3. As shown by transient transfection experiments, deletion or site-specific mutations in E1E-3 dramatically decreased P1 promoter activity. Mutations in E1E-2, however, did not affect function of the P1 promoter. Co-transfection of SEF and PAX6 promoter-reporter constructs showed that SEF up-regulates PAX6 gene expression through the P1 promoter. Two Sp1 sites in the E1E region were also shown to be important by transient co-transfection assays. Data from immunoprecipitation and transient transfection assays demonstrated that SEF and Sp1 interacted in vitro and may act together in vivo to regulate PAX6 expression.

RNA expression of the WT1 gene in Wilms' tumors in relation to histology.

BACKGROUND: On the basis of accumulating data, the recently isolated WT1 gene is a Wilms' tumor gene and a putative tumor suppressor gene. These findings include expression in developing fetal kidney, intragenic deletions in tumors, and germline mutations in predisposed individuals. Wilms' tumors, which exhibit a broad range of differentiation, are composed of three cell types: blastema, epithelium, and stroma. PURPOSE: The purpose of this study was to investigate the relationship between WT1 gene expression and histologic composition in Wilms' tumors in an effort to elucidate how the WT1 gene functions in proliferation of these histologic components. METHODS: We used Northern blot hybridization to study WT1 gene expression by messenger RNA (mRNA) accumulation in 20 tumors of varying histology and in adjacent uninvolved kidney tissue. In two patients, tumors were also compared before and after therapy. RESULTS: Tumors that were predominantly blastemal expressed high amounts of WT1 mRNA, whereas predominantly stromal tumors expressed either low or undetectable amounts. Blastemal tumors that were predominantly poorly differentiated expressed WT1 mRNA at higher levels than those that were more well differentiated. Although we expected that a putative tumor suppressor gene like WT1 would generally be expressed at lower levels in tumor than in normal kidney, this was true only in predominantly stromal cells. One of the two patients studied before and after therapy had a dramatic response to therapy accompanied by a decline in WT1 gene expression and disappearance of blastemal and epithelial elements. CONCLUSIONS: A correlation was observed between WT1 gene expression and histology of the tumors. Level of expression was inversely related to the degree of differentiation in blastemal tumors and in the patient with a dramatic response to therapy. These results, in conjunction with the observation that WT1 mRNA is abundant in normal fetal kidney, suggest that WT1 gene expression is related to kidney development, especially in differentiation of blastemal components. IMPLICATIONS: Further studies to search for alterations of the WT1 gene in tumors and to identify regulatory factors in gene expression will increase understanding of the role of this gene in normal development and tumorigenesis.

Resistance in clinical isolates of Enterococcusfaecalis encountered at the University Hospital of the West Indies, Jamaica.

Enterococcus faecalis isolates were examined by an automated identification and susceptibility system. Almost all of the 97 isolates were ampicillin susceptible (n = 86) and tetracycline resistant (n = 89). All were nitrofurantoin susceptible. About a third of isolates showed high level resistance to the aminoglycosides streptomicin and gentamicin and this was usually associated with ciprofloxacin resistance (n = 34). Seven isolates were vancomycin resistant, including one that was ampicillin resistant. Most forms of resistance described elsewhere were found

Effect of bleomycin on the synthesis and function of RNA.

Bleomycin inhibits cellular RNA synthesis and the inhibition is nonspecific. The ratio of polyadenylate- [poly(A)] containing RNA to non-poly(A)-containing RNA in the drug-treated human lymphocytic cells, line Wil2, was the same as that in untreated cells. Poly(A) RNA isolated from untreated cells was used as a template for reverse transcriptase to synthesize complementary DNA, which was then used as a probe to assay the sequence diversity of poly(A)RNA's from treated and untreated cells. It was found that essentially all of the poly(A) RNA's in the untreated cells were also present in the treated cells. The effect of bleomycin on the biological activity of messenger RNA (mRNA) was tested with globin mRNA in a wheat germ embryo translation system. Although bleomycin inhibited protein synthesis at high concentrations, the inhibition was not due to a modification of mRNA. This was evidenced by the fact that no decrease in the ability of mRNA to function in the test system was found when globin mRNA was pretreated with high concentrations of bleomycin followed by removal of the drug.