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This study examined the ability of dental students and qualified dentists to visually assess the total occlusal convergence of clinical crowns. 10 working casts of maxillary molar crown preparations were installed in phantom heads in a clinical skills laboratory. 87 participants assessed the buccolingual and mesiodistal total occlusal convergence of the casts. 2nd-year students with no experience in fixed prosthodontics served as a control group with 3rd, 4th and 5th-year students and qualified dentists including specialists in restorative dentistry involved. Differences were calculated between the measured angles and the subject's estimate to assess accuracy. For 8 of the 20 surfaces measured there were significant differences. (p ⟨ 0.05). Differences were not standardized between the groups, with no clear patterns of difference in tooth type or aspect assessed. Differences were primarily between the control group and the more experienced groups. The remaining groups were of similar ability. A minority of participants in each group were highly divergent from their peers. This study found significant differences between participants with no experience of fixed prosthodontics and those with experience, however, the ability to assess total occlusal convergence does not appear to improve significantly with experience.

Chronic liver disease (CLD) is associated with tissue-destructive fibrosis. Considering that common mechanisms drive fibrosis across etiologies, and that steatosis is an important cofactor for pathology, we performed RNA sequencing on liver biopsies of patients with different fibrosis stages, resulting from infection with hepatitis C virus (HCV) (with or without steatosis) or fatty liver disease. In combination with enhanced liver fibrosis score correlation analysis, we reveal a common set of genes associated with advanced fibrosis, as exemplified by those encoding the transcription factor ETS-homologous factor (EHF) and the extracellular matrix protein versican (VCAN). We identified 17 fibrosis-associated genes as candidate EHF targets and demonstrated that EHF regulates multiple fibrosis-associated genes, including VCAN, in hepatic stellate cells. Serum VCAN levels were also elevated in advanced fibrosis patients. Comparing biopsies from patients with HCV with or without steatosis, we identified a steatosis-enriched gene set associated with advanced fibrosis, validating follistatin-like protein 1 (FSTL1) as an exemplar of this profile. In patients with advanced fibrosis, serum FSTL1 levels were elevated in those with steatosis (versus those without). Liver Fstl1 mRNA levels were also elevated in murine CLD models. We thus reveal a common gene signature for CLD-associated liver fibrosis and potential biomarkers and/or targets for steatosis-associated liver fibrosis.

Liver diseases in Australia are estimated to affect 6 million people with a societal cost of $51 billion annually. Information about utilisation of specialist hepatology care is critical in informing policy makers about the requirements for delivery of hepatology-related healthcare.This study examined the aetiology and severity of liver disease seen in a tertiary hospital hepatology clinic, as well as the resource utilisation patterns.A longitudinal cohort study included consecutive patients booked in hepatology outpatient clinics during a 3-month period. Subsequent outpatient appointments for these patients over the following 12 months were then recorded.During the initial 3-month period, 1471 appointments were scheduled with a hepatologist, 1136 of which were attended. Twenty-one per cent of patients were 'new cases'. Hepatitis B virus (HBV) was the most common disease aetiology for new cases (37%). Advanced disease at presentation varied between aetiology; only 5% of HBV cases had advanced liver disease at presentation, in contrast with HCV, NAFLD and ALD, in which advanced disease was identified at presentation in 31%, 46% and 72% of cases, respectively. Most patients (83%) attended multiple hepatology appointments, and a range of referral patterns for procedures, investigations and other specialty assessments were observed.There is a high prevalence of HBV in new case referrals. Patients with HCV infection, NAFLD and ALD have a high prevalence of advanced liver disease at referral, requiring ongoing surveillance for development of decompensated liver disease and liver cancer. These findings that describe the patterns of health service utilisation among patients with liver disease provide useful information for planning sustainable health service provision for this clinical population.

Although enormous amounts of time arid money have been invested in enhancing performance for college and professional athletes, their psychiatric needs have been minimally addressed. Given the virtual absence of controlled scientific literature, in this article the authors detail the diagnostic issues and delineate treatment principles, including: (1) making an accurate diagnosis; (2) setting realistic goals; (3) delivering psycho-education; (4) inducing the patient to undergo treatment, including involving the family and significant others; and (5) delivering appropriate treatment (the most difficult task). The objective is to improve performance and quality of life by treating the problem or psychiatric illness. A special concern is minimizing countertransference feelings and avoiding under-treatment, because by definition the athlete needs to perform.

The social stigma surrounding psychiatric illness may prevent athletes from seeking counseling, psychotherapy, medication, or other treatment when needed. Few controlled studies on athletes exist to guide the team physician, clinician, or psychiatrist who must deal with diagnostic issues. Management involves setting realistic goals, educating as well as inducing the patient into treatment, soliciting support from family or significant others, and delivering appropriate treatment (the most difficult task). The objective is to improve performance and quality of life. Confidentiality issues are paramount during diagnosis and treatment. Physicians who understand sports and team dynamics may have more success in helping patients follow through with treatment.

Background Liver macrophages are a heterogeneous cell population that produces factors involved in fibrogenesis and matrix turnover, including matrix metalloproteinase (MMP) -9. During liver injury, their close proximity to hepatic progenitor cells and the ductular reaction may enable them to regulate liver repair and fibrosis. Aims To enumerate and characterise liver macrophages in patients with chronic hepatitis C, to determine whether a distinct population of macrophages is associated with the ductular reaction and portal fibrosis. Methods Immunostaining for macrophage markers (CD68, CD163, CCR2), the ductular reaction (keratin-7) and MMP-9 was performed in liver biopsy sections from patients with chronic hepatitis C virus (HCV) (n=85). Results Portal tracts were more densely populated with macrophages (10.5 +/- 0.36 macrophages/HPF) than lobules (7.2 +/- 0.16 macrophages/HPF, P

Aim: To investigate the influence of macrophages on hepatocyte phenotype and function. Methods: Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophage-conditioned medium on HepG2 mRNA and protein expression determined. The in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus (HCV) infection. Results: Conditioned media from macrophages, but not monocytes, induced a transient morphological change in hepatocytes associated with upregulation of vimentin (7.8 +/- 2.5-fold, P = 0.045) and transforming growth factor (TGF)-beta 1 (2.6 +/- 0.2-fold, P < 0.001) and downregulation of epithelial cadherin (1.7 +/- 0.02-fold, P = 0.017) mRNA expression. Microarray analysis revealed significant upregulation of lipocalin-2 (17-fold, P < 0.001) and pathways associated with inflammation, and substantial downregulation of pathways related to hepatocyte function. In patients with chronic HCV, real-time polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA (F0 1.0 +/- 0.3, F1 2.2 +/- 0.2, F2 3.0 +/- 9.3, F3/4 4.0 +/- 0.8, P = 0.003) and protein expression (F1 1.0 +/- 0.5, F2 1.3 +/- 0.4, F3/4 3.6 +/- 0.4, P = 0.014) with increasing liver injury. High performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase (MMP)-9 in macrophage-conditioned medium, and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-beta 1 (2.9 +/- 0.2 vs 1.04 +/- 0.1, P < 0.001) in macrophage-conditioned media treated HepG2 cells. In patients with chronic HCV infection, hepatic mRNA expression of CD163 (F0 1.0 +/- 0.2, F1/2 2.8 +/- 0.3, F3/4 5.3 +/- 1.0, P = 0.001) and MMP-9 (F0 1.0 +/- 0.4, F1/2 2.8 +/- 0.3, F3/4 4.1 +/- 0.8, P = 0.011) was significantly associated with increasing stage of fibrosis. Conclusion: Secreted macrophage products alter the phenotype and function of hepatocytes, with increased expression of inflammatory mediators, suggesting that hepatocytes actively participate in liver injury Refereed/Peer-reviewed

SummaryThe capsular polysaccharide of type B. Friedlander bacillus inhibits the multiplication of mumps virus in the chick embryo and prevents adsorption of the virus by treated erythrocytes.

Currently the diagnosis and severity of hepatic steatosis can be established accurately only by liver biopsy. Previous small studies found that steatosis measured by magnetic resonance spectroscopy (MRS) and imaging (MRI) correlated with histological assessment of liver triglyceride content. However, the accuracy of MRS/MRI for grading the severity of steatosis has not been addressed. The aims of this study were (1) to determine whether MRS and MRI can discriminate grades of steatosis in a large cohort of consecutive patients with a wide spectrum of liver disease aetiology and severity (2) to evaluate the effect of hepatic fibrosis, inflammation and iron on quantitation of intrahepatocellular lipid (IHCL) by these techniques.Ninety-four sequential patients who underwent percutaneous liver biopsy or liver resection had MRS and MRI (Dixon in phase/out of phase (Dixon IP/OP) and with/without fat saturation (+/-FS) images) to determine IHCL. Histology was used as the reference standard.Close relationships were observed between the percentage of steatosis estimated by histology and MRS/MRI (r(s)=0.88 p0.001 for all techniques). However, separate equations were required for the percentage of steatosis to avoid underestimation by imaging for patients with moderate or advanced fibrosis. All techniques had good diagnostic accuracy for mild steatosis (AUROCor =0.87) as well as moderate/severe steatosis (AUROCor =0.89). Hepatic inflammation and mild iron deposition (Perls' grade 1 and 2) did not interfere with estimation of steatosis by imaging.MRS and MRI had good accuracy for grading the severity of steatosis in subjects with liver disease, provided that stage of fibrosis was considered.

Objectives. To determine the spectrum of disease among non-urgent referrals to a tertiary hospital hepatology outpatient clinic, assess the adequacy of referral information in terms of risk stratification and determine whether a specifically designed referral template altered urgency for specialist assessment. Methods. A snapshot of the waiting list of a hepatology clinic at a tertiary hospital was taken from the scheduling database. Information was retrieved from referrals and attached investigations. Updated information was requested from subjects and their current general practitioner. Results. Hepatitis C virus accounted for 68.7% of the 1223 reviewed referrals. Clinical information provided by referring clinicians was often incomplete. Provision of updated information identified the presence of comorbidities (obesity, ‘heavy’ alcohol consumption, mental health issues) and altered the need or urgency for specialist assessment in 22% of cases. Conclusions. Hepatitis C virus accounts for the majority of non-urgent referrals waiting to access hepatology outpatient consultations. Using a standardised assessment form as part of the referral process provides more information on comorbidities and risk factors and facilitates more accurate triaging of clinical urgency. Wider adoption of this strategy may increase appropriate access to hepatology services and reduce the future burden of cirrhosis and hepatocellular cancer. What is known about the topic? Little published data are available that describe the content and standard of hepatology referrals, or the urgency with which these patients need to be reviewed. Inadequate clinical information impairs the ability to accurately triage referrals and may lead to delays in access. What does the paper add? Almost 70% of reviewed referrals were for management of patients with hepatitis C virus infection, confirming this condition remains a major priority area in liver disease. Clinical information provided by referring clinicians was often incomplete, impairing the ability to accurately triage referrals. Only a minority of referrals provided information about relevant comorbidities (alcohol intake, injecting drug use, mental health issues and obesity) that negatively impact on the progression of liver disease or the response to antiviral treatment. What are the implications for practitioners? Hepatitis C virus remains a major health priority area in liver disease, increasing the future burden of cirrhosis and hepatocellular cancer. Many referred patients have comorbidities that increase their risk of progressive liver disease and related complications. Strategies to increase recognition and management of liver disease and its comorbidities in the community are required. The use of a standardised assessment form in referrals to hepatology outpatient services may assist with triaging of patients and improve access to appropriate care.

Background. Appropriate and uniform prioritisation (‘triaging’) of outpatient referrals is critical to good patient outcomes, equity of access to services and efficient use of resources. Objective. To determine whether there is uniformity in the allocation of triage categories for hepatology outpatient referrals at public hospitals in Queensland. Methods. A series of 10 recent hepatology referrals were de-identified for both patient and referring clinician details and sent to nine gastroenterology or hepatology centres throughout Queensland. Consultant gastroenterologists and hepatologists (n = 25) were asked to triage the referrals using the process in place in their centre. Responses were de-identified and analysed. Each case was reviewed and allocated an ‘agreed triage category’ based upon the majority view of respondents. Results. Nineteen responses were received. There was substantial variation amongst consultants in the allocation of triage categories. Although almost two-thirds of respondents agreed with the majority view in 60–80% of cases, none agreed with the majority for every case and some agreed in as few as 50% cases. Disagreement with the majority view of an appropriate triage category was not associated with geography or specialist experience. Conclusions. Variability in triage categorisation suggests that similar cases may be allocated different priorities by those responsible for determining the urgency of outpatient review. This has implications for equity of access to treatment. The development of triage guidelines and formal training in their implementation, along with periodic audits of triage practices in different centres, may reduce variability. What is known about the topic? Outpatient clinic appointments are allocated within categories according to ‘agreed’ clinical urgency. The process of triaging referrals seeks to prioritise referrals based on the severity of patients’ conditions and the potential for improving outcomes. At present there are no statewide guidelines or training for the triaging process in hepatology and no recommendations for who should take responsibility for prioritising referrals. What does the paper add? In Queensland, gastroenterologists (including hepatologists) triage hepatology cases differently and most likely interpret and weight clinical information provided in the referral differently. Disagreement with the majority view of an appropriate triage category is not associated with geography or specialist experience. What are the implications for practitioners? Variability in triage categorisation suggests that similar cases may be allocated different priorities by those responsible for determining the urgency of outpatient review. This has implications for equity of access to treatment. The development of triage guidelines and formal training in their implementation, along with periodic audits of triage practices in different centres, may reduce variability.

This article aims to raise nurses' awareness of the technique of gentle teaching, which has been used with considerable success in helping people who present challenging behaviours. Based on an appreciation of the essential worth of individuals, and in the need to manage people rather than behaviours, the authors claim that gentle teaching allows nurses to 'see people as they really are'.

Antigenic variants of influenza A virus strains emerge on serial passage in ovo in the presence of immune serum against different but related strains. An old laboratory strain (PR8) which had been through hundreds of animal passages was as readily modified by this procedure as recently recovered strains. Such variants apparently can be obtained at will and show antigenic patterns which are reproducible and appear to be predictable in terms of the immune serum used for their selection. Variant strains retain their new antigenic patterns on serial passage in ovo in the absence of immune serum. Limited serial passage in ovo of strains in the absence of immune serum did not result in the emergence of antigenic variants. Similarly, serial passages of strains in ovo in the presence of immune serum against widely different strains, which failed to show significant cross-neutralization, did not lead to the appearance of antigenic variants.

Combination between PVM and erythrocytes as well as between the influenza viruses and erythrocytes is inhibited at low electrolyte concentrations. Combination between PVM and lung particles as well as between the virus and erythrocytes can be dissociated in solutions of low electrolyte concentration. The rate of elution of influenza virus is decreased under similar conditions. PVM can combine with and be dissociated from erythrocytes repeatedly without affecting the combining capacity of the ceils and does not possess an enzyme-like activity similar to that of the influenza viruses. Because dissociation depends on electrolyte concentration and pH, it appears that the PVM-cell component complex may be in the nature of a weak salt.

Polysaccharides which cause inhibition of the multiplication of mumps virus in the allantoic sac may or may not cause inhibition of hemagglutination by the virus. Moreover, such substances may or may not prevent adsorption of the virus by erythrocytes. The available evidence indicates that polysaccharides active as inhibitors do not block adsorption of mumps virus by cells of the living allantoic membrane. With influenza A, influenza B, and Newcastle disease viruses, as well as with PVM, there also appears to be a lack of correlation between the in vitro and in vivo inhibiting activity of polysaccharides.

SummaryChick embryos killed by prolonged storage at room temperature or 4°C are capable of supporting the multiplication of influenza virus upon prolonged incubation at 35°C.

Tissue particles from a wide variety of animal tissues possess the capacity to combine with PVM. Various adsorbents also combine with the virus. Elution of PVM from combination with either tissue particles or adsorbents can be achieved by appropriately altering the ionic environment. Influenza viruses also are adsorbed on and eluted from adsorbents under similar conditions. Reasons are presented for thinking that combination of PVM with tissue particles results from the action of adsorptive forces between virus and tissue particles.

SummaryCross serological reactions indicated that egg strains of influenza B virus obtained in different years were dissimilar in antigenic composition. The extent of the differences in antigenic pattern was analyzed. All strains studied were antigenically different from the mouse adapted Lee strain. The implication of these findings on the problem of immunization in man was discussed.

Preexisting infection with PVM or mumps virus does not prevent multiplication of the virus of influenza A or B in the same tissue. Similarly, pre-existing infection with one or another of the influenza viruses does not prevent multiplication of either PVM or mumps virus in the same tissue. The failure of these two groups of viruses to interfere with the multiplication of each other is discussed in relation to the mechanism of inhibition of multiplication of mumps virus and PVM by the capsular polysaccharides of Friedländer bacilli, and the ability of influenza A and influenza B viruses to multiply in the presence of large quantities of these carbohydrates. It is suggested that differences in the requirements of the two groups of viruses for host cell metabolic systems may serve to explain both the lack of interference between them and the differing effect of polysaccharides upon their multiplication.

A mucoprotein isolated from human urine and possessing the capacity to react with a number of viruses is electrophoretically homogeneous at pH 6.8 and 8.6. After treatment with influenza virus and elimination of its biological activity, the substance remains homogeneous and its electrophoretic mobility is decreased by approximately 20 per cent.

The degree of inhibition of multiplication of influenza B virus, Lee strain, in membrane cultures in vitro appears to be directly related to the concentration of the inhibitory compounds used in this investigation. With each of the alkyl derivatives of benzimidazole, evidence for such a relationship was obtained in the range between 60 and 90 per cent inhibition of virus multiplication. Alteration of the structure of benzimidazole by substitution of alkyl radicals at various positions in either the benzene or the imidazole ring resulted in diverse differences in the capacity to inhibit influenza virus multiplication in vitro. Minor increases in inhibitory activity resulted when one to three methyl groups were introduced at certain positions in the molecule. Marked increases in inhibitory activity were achieved by more extensive substitution in either the benzene or the imidazole ring. The position and nature of substituent groups appeared to be of decisive importance. Among the more highly active compounds were 2,4,5,6,7-pentamethyl-benzimidazole, 5,6-diethylbenzimidazole, and 2-ethyl-5-methylbenzimidazole. Further extension of the alkyl chain at position 2 caused no significant change in the inhibitory activity of the derivative. The most active compounds studied caused 75 per cent inhibition of Lee virus multiplication in membrane cultures in vitro at concentrations of approximately 0.0002 M. Some of the implications of these findings are discussed.

Evidence is presented which shows that there is a component present in normal allantoic fluid, probably mucoprotein in nature, capable of combining with influenza A virus (PR8), and that following combination between this component and the virus only partial dissociation of the complex occurs. Evidence is also presented which strongly suggests that the component is present in virus-infected allantoic fluid in which it is in part combined with the virus and in part free although altered by viral action. The probability that the component is present as well in highly purified preparations of influenza virus, and its effect upon various reactions obtained with this agent are discussed.

The rates of elution from RBC of the Lee and PR8 strains of influenza virus were studied by means of a step-wise elution technique. By means of a single treatment with lanthanum acetate or irradiation with ultraviolet and subsequent passage in chick embryos, it was possible to alter the elution rate of the Lee strain so that it was similar to that of the PR8 strain. This alteration proved to be persistent on serial passage in the absence of the agent which caused it. As far as was determined, the elution rate of the virus appeared to be the only property which was altered. The phenomenon can be most readily understood on the assumption that the difference in elution rates of the two strains is due to a heterogeneous population of virus particles in the Lee strain with respect to elution rate.

Neutralization experiments with Newcastle disease, influenza A, or bacterial virus, T(3), reveal, under all conditions studied, a linear relationship between the logarithm of the serum dilution end point and that of the quantity of virus used. With Newcastle disease and influenza A, the slope of the neutralization line varies markedly with the host-cell system used and in the chick embryo is strikingly affected by the route of inoculation. The other variables examined have no definite effect upon the slope. Reactivation of neutralized influenza virus is demonstrable in the chick embryo on dilution of the mixture. There appears to be an inverse relationship between the degree of susceptibility of a host to infection with influenza A virus and the neutralizing titer of a serum as measured in that host. With the T(3)-serum system, comparable results are obtained when the number of unneutralized virus particles chosen as the end point is varied widely.

The type specific immunological properties of certain non-hemolytic streptococci, including Str. salivarius type I and type II, present in the respiratory tract of human beings appear to be dependent upon the presence of capsular polysaccharides. The levans formed from sucrose by Str. salivarius (encapsulated S cells or non-encapsulated R variants), or by cell-free enzymes derived from these microorganisms, are indistinguishable immunologically and show no evidence of type specificity. Such levans appear to be immunologically distinct from and unrelated to the capsular polysaccharides of the microorganisms which produce them.

1. The hemagglutinating capacity, enzymic activity, and infectivity of several influenza viruses were destroyed by repeated freezing and thawing of dialyzed allantoic fluids containing them. 2. Influenza virus degraded by freezing and thawing, by treatment with 5 M urea, or by heating at 65 degrees C. still combined with homologous antibody and was demonstrable by blocking of the hemagglutination-inhibition and virus neutralization reactions. 3. After 50 cycles of freezing and thawing, much of the blocking antigen activity was not sedimented by centrifugation at 120,000 g for 2 hours, and electron microscopy showed complete disruption of the virus particles. So called soluble blocking antigen was obtained from four strains of influenza A, the Lee strain of influenza B, mumps, and Newcastle disease viruses. 4. Soluble blocking antigens from influenza A viruses were highly strain-specific; gave little or no reaction in complement-fixation tests; stimulated but little antibody production in rabbits and did not induce immunity in mice; caused reactivation of infective virus in neutral mixtures of homologous virus and immune serum. 5. Repeatedly frozen and thawed influenza virus preparations did not interfere with the propagation of infective virus in the allantoic sac. The blocking antigen activity they contained was precipitated by half saturated ammonium sulfate, destroyed by trypsin, chymotrypsin, or heating at 56 degrees C. for 30 minutes, but was unaffected by desoxyribonuclease or ribonuclease. 6. These findings are in accord with the view that soluble blocking antigen obtained from influenza virus particles on disruption by repeated freezing and thawing is protein in nature and represents the essential antigenic material of the intact virus.

INFECTION of man with the virus of herpes simplex commonly occurs in infancy, when it is usually manifested as an acute stomatitis.1According to the widely accepted concept of Burnet and Williams,2the primary infantile infection is followed by the latent persistence of virus in the tissues. At times the latent virus may be activated and induce mild recurrent disease in the form of vesicular lesions ("fever blisters") of the lips or other sites invaded during the primary infection. Persons subject to recurrent herpes are found to have measurable concentrations of specific neutralizing antibody in the serum.3This seeming paradox has been attributed to the continuing antigenic stimulus arising from the presence of the latent virus. In the majority of adults (65 to 90%), serological evidence indicates previous infection with herpes simplex virus.4 Primary herpetic infection of the adult has been only rarely described. Essential to