Molecular identification and in vitro assessment of zoonotic-potential of a novel Orthobunyavirus isolated from broiler chicken in Malaysia.

We have previously isolated a novel avian Orthobunyavirus, Kedah Fatal Kidney Syndrome (KFKS) virus from a broiler farm in Kedah, Malaysia in 2020 with a severe kidney lesion in chickens. The virus was designated as KFKS2_CS virus. Sequence analysis of partial nucleocapsid (N) and nonstructural (NSs) sequence of this virus showed the highest sequence identity with previous KFKS1 from Malaysia (100%) and 97% with a zoonotic Umbre (UMB) virus, which was reported to cause encephalitis in immunocompromised humans in India. Phylogenetic analysis revealed that this virus was clustered together with previous KFKS1 virus from Malaysia, UMB and Cristoli viruses. This study aimed to assess the zoonotic potential of this KFKS2_CS virus in vitro by determining its ability to inhibit the production of interferon (IFN) in human glioblastoma multiforme (GBM) brain cells using reverse-transcriptase polymerase reaction (RT-PCR). This virus blocked the production of interferon-a in this human brain cells. In conclusion, this KFKS2_CS virus may have a zoonotic potential and become a public health concern in the future.

Constructing an ethical framework for priority allocation of pandemic vaccines.

BACKGROUND: Allocation of scarce resources during a pandemic extends to the allocation of vaccines when they eventually become available. We describe a framework for priority vaccine allocation that employed a cross-disciplinary approach, guided by ethical considerations and informed by local risk assessment. METHODS: Published and grey literature was reviewed, and augmented by consultation with key informants, to collate past experience, existing guidelines and emerging strategies for pandemic vaccine deployment. Identified ethical issues and decision-making processes were also included. Concurrently, simulation modelling studies estimated the likely impacts of alternative vaccine allocation approaches. Assembled evidence was presented to a workshop of national experts in pandemic preparedness, vaccine strategy, implementation and ethics. All of this evidence was then used to generate a proposed ethical framework for vaccine priorities best suited to the Australian context. FINDINGS: Published and emerging guidance for priority pandemic vaccine distribution differed widely with respect to strategic objectives, specification of target groups, and explicit discussion of ethical considerations and decision-making processes. Flexibility in response was universally emphasised, informed by real-time assessment of the pandemic impact level, and identification of disproportionately affected groups. Model outputs aided identification of vaccine approaches most likely to achieve overarching goals in pandemics of varying transmissibility and severity. Pandemic response aims deemed most relevant for an Australian framework were: creating and maintaining trust, promoting equity, and reducing harmful outcomes. INTERPRETATION: Defining clear and ethically-defendable objectives for pandemic response in context aids development of flexible and adaptive decision support frameworks and facilitates clear communication and engagement activities.

Priority allocation of pandemic influenza vaccines in Australia - Recommendations of 3 community juries.

BACKGROUND: Pandemic planning has historically been oriented to respond to an influenza virus, with vaccination strategy being a key focus. As the current COVID-19 pandemic plays out, the Australian government is closely monitoring progress towards development of SARS-CoV2 vaccines as a definitive intervention. However, as in any pandemic, initial supply will likely be exceeded by demand due to limited manufacturing output. METHODS: We convened community juries in three Australian locations in 2019 to assess public acceptability and perceived legitimacy of influenza pandemic vaccination distribution strategies. Preparatory work included literature reviews on pandemic vaccine allocation strategies and on vaccine allocation ethics, and simulation modelling studies. We assumed vaccine would be provided to predefined priority groups. Jurors were then asked to recommend one of two strategies for distributing remaining early doses of vaccine: directly vaccinate people at higher risk of adverse outcomes from influenza; or indirectly protect the general population by vaccinating primary school students, who are most likely to spread infection. RESULTS: Thirty-four participants of diverse backgrounds and ages were recruited through random digit dialling and topic-blinded social media advertising. Juries heard evidence and arguments supporting different vaccine distribution strategies, and questioned expert presenters. All three community juries supported prioritising school children for influenza vaccination (aiming for indirect protection), one by 10-2 majority and two by consensus. Justifications included that indirect protection benefits more people and is likely to be more publicly acceptable. CONCLUSIONS: In the context of an influenza pandemic, informed citizens were not opposed to prioritising groups at higher risks of adverse outcomes, but if resources and epidemiological conditions allow, achieving population benefits should be a strategic priority. These insights may inform future SARS-CoV-2 vaccination strategies.

Validation of the ultrasonographic assessment of the femoral trochlea epiphyseal cartilage in foals at osteochondrosis predilected sites with magnetic resonance imaging and histology.

BACKGROUND: Noninvasive imaging tools are needed to screen foal femoropatellar joints to detect subclinical osteochondrosis lesions due to focal failure of endochondral ossification to enhance early management to optimise intrinsic healing events. Recently investigations employing 3T susceptibility-weighted magnetic resonance imaging (3T SWI MRI) and CT have demonstrated their capacity for early osteochondrosis diagnosis, but these technologies are not practical for field screening. We postulate that ultrasonography is a valuable field tool for the detection of subclinical osteochondrosis lesions. OBJECTIVES: The goals were to 1) describe the ultrasonographic features of the femoral trochlea of healthy and osteochondrosis-predisposed neonatal foals, 2) validate the capacity of ultrasound to assess cartilage canal vascular archictecture and the ossification front and 3) evaluate field feasibility in a pilot study. STUDY DESIGN: Experimental study. METHODS: Ultrasonographic evaluation of osteochondrosis predisposed (n = 10) and control (n = 6) femoral trochleas was performed ex vivo and compared with site-matched histological sections and 3T SWI MRI. The articular and epiphyseal cartilage thickness, ossification front indentation and cartilage canal vascular archictecture were assessed at each ROI. Femoral trochleae of foals (n = 3) aged ≈ 1, 3 and 6 months were also evaluated with ultrasonography in field. RESULTS: Ultrasonographic measurements strongly correlated with the histological measurements. There was no difference in the cartilage thickness or ossification front indentation between control and osteochondrosis-predisposed specimens. The cartilage canal vascular archictecture on ultrasonograms corresponded with the vessel pattern observed on site matched histology and 3T SWI MRI. MAIN LIMITATIONS: The number of specimens for study was limited and no early osteochondrosis lesions were present within the predilected group, but a field study is now underway. CONCLUSION: Ultrasonographic examination of the femoral trochlea permitted accurate evaluation of cartilage thickness, cartilage canal vascular archictecture and ossification front indentation in young foals and is a promising, practical tool for screening subclinical osteochondrosis and monitoring and managing lesions at important clinical sites.

Cluster Effects in a National Dental PBRN restorative study.

Items in clusters, such as patients of the same clinician or teeth within the same patient, tend to be more similar than items from different groups. This within-group similarity, represented by the intraclass correlation coefficient (ICC), reduces precision, yielding less statistical power and wider confidence intervals, compared with non-clustered samples of the same size. This must be considered in the design of studies including clusters. We present ICC estimates from a study of 7,826 restorations placed in previously unrestored tooth surfaces of 4,672 patients by 222 clinicians in the National Dental Practice-Based Research Network, as a resource for sample size planning in restorative studies. Our findings suggest that magnitudes of ICCs in practice-based research can be substantial. These can have large effects on precision and the power to detect treatment effects. Generally, we found relatively large ICCs for characteristics that are influenced by clinician choice (e.g., 0.36 for rubber dam use). ICCs for outcomes within individual patients, such as tooth surfaces affected by a caries lesion, tended to be smaller (from 0.03 to 0.15), but were still sufficiently large to substantially affect statistical power. Clustering should be taken into account in the design of oral health studies and derivation of statistical power estimates for these studies (ClinicalTrials.gov, NCT00847470).

Differences between reported and actual restored caries lesion depths: results from The Dental PBRN.

OBJECTIVE: The objectives of this research were to (1) quantify the discordance between the caries lesion depth at which dentists restored initial lesions during a clinical study ("actual depth") and the lesion depth that they reported during a hypothetical clinical scenario ("reported depth"); (2) test the hypothesis that certain practitioner, practice, patient, and caries lesion characteristics are significantly associated with this discordance. METHODS: Practitioner-investigators who perform restorative dentistry in their practices completed an enrollment questionnaire and participated in two consecutive studies on caries diagnosis and treatment. The first study was a survey asking about caries treatment. The second study collected data on restorations placed in routine clinical practice due to caries in patients over 19 years of age on occlusal surfaces only or proximal surfaces only. We report results on 2691 restorations placed by 205 dentists in 1930 patients with complete data. RESULTS: Discordance between actual depth and reported depth occurred in only about 2% of the restorations done due to proximal caries, but about 49% of the restorations done due to occlusal caries. Practice type, restorative material used and the diagnostic methods used were significantly associated with discordance. CONCLUSION: Dentists frequently restored occlusal caries at a shallower depth as compared to their reported depth, but the discordance was very small for proximal lesions. Discordance for occlusal caries was more common when radiographs were not taken or if a resin restoration was placed.

Change in knowledge of women about cervix cancer, human papilloma virus (HPV) and HPV vaccination due to introduction of HPV vaccines.

OBJECTIVES: Test knowledge of HPV, cervix cancer awareness and acceptance of HPV vaccination of women now and a year ago. STUDY DESIGN: Questionnaires were filled out by 305 women visiting four gynaecologists of the Regional Hospital Heilig Hart, Tienen, Belgium during two subsequent weeks. Fisher T or Chi(2) were used as statistical methods to compare the data with the survey of 381 women exactly one year before. RESULTS: Knowledge about HPV as a cause of cervix cancer and the presence of a vaccine rose from roughly 50% in 2007 to over 80% in 2008 (p<0.0001). Level of education and having daughters, sons or no children no longer influenced the level of knowledge or willingness to accept the vaccine. Most parents favor the age group 12-16 years as an ideal time for vaccination. In contrast with the 2007 survey, women below 26 years had now acquired almost equivalent knowledge to older women about the virus, cervix cancer and the vaccine, but they were far less likely to accept the vaccine due to its cost, unless it would be reimbursed (OR 4.2 (1.6-11) p=0.0055). CONCLUSION: One year after introduction of the first two HPV vaccines, over 75% of women attending an ambulatory gynaecology clinic know HPV causes cervix cancer and that you can get vaccinated against it. Compared with a year earlier, young and lower educated women had dramatically improved their knowledge. However, women below 26 years are less prepared to pay the cost for vaccination if it is not reimbursed.

Predictors of change in satisfaction with chewing ability: a 24-month study of dentate adults.

People's satisfaction with chewing ability is not determined entirely by their mechanical chewing function. Instead, it is a complex measure that embraces broad physical, social and psychological components. Using data from the Florida Dental Care Study, a prospective longitudinal study of oral health and dental care, this current study aimed to identify the longitudinal relationships between changes in satisfaction with chewing ability and changes in other dimensions of oral health and oral health-related quality of life (OHRQoL). A multidimensional conceptual model of oral health and OHRQoL was applied to guide the analysis. Most dentate people were satisfied with their chewing ability. However, changes in satisfaction with chewing ability were common: nearly 11-22% of subjects experienced improved satisfaction, depending on the interval; while about 12-18% of subjects experienced deteriorated satisfaction by the end of the interval. Changes in satisfaction with chewing ability were significantly associated with changes in other aspects of oral health and OHRQoL. Onset of certain oral health problems/conditions or constantly having such problems was associated with a lower probability of reporting improvement in satisfaction and a higher probability of experiencing deterioration. In contrast, recovery from certain oral health problems/conditions or not having such problems was associated with a higher probability of improvement and a lower probability of deterioration.

Navigation and analysis of the energy landscape of small proteins using the activation-relaxation technique.

The resolution of the protein folding problem has been tied to the development of a detailed understanding of the configurational energy or of the free energy landscape associated with these molecules. Using the activation-relaxation technique and a simplified energy model, we present here a detailed analysis of the energy landscape of 16-residue peptide that folds into a beta-hairpin. Our results support the concept of an energy landscape with an effective topology consistent with a scale-free network.

Treat or test first? Decision analysis of empirical antiviral treatment of influenza virus infection versus treatment based on rapid test results.

BACKGROUND: neuraminidase (NA) inhibitors have recently become available for treatment of influenza. Rapid antigen detection assays at 'point-of-care' may improve the accuracy of clinical diagnosis, but the value of these techniques in assisting with the appropriate use of antivirals remains controversial. OBJECTIVE: to compare the diagnostic utilities of two management strategies for influenza, empirical antiviral therapy versus therapy based on a positive rapid test result in pre-epidemic and epidemic periods. STUDY DESIGN: a threshold decision analytic model was designed to compare these competing strategies and sensitivity analysis performed to examine the impact of diagnostic variables on the expected utility of the decision with a range of prior probabilities of infection between 1 and 50%. RESULTS: on the basis of the calculated sensitivity (77%) and specificity (95%) of a point-of-care test for influenza, pre-treatment testing was preferred and cost-effective in non-epidemic stage of the influenza cycle. The alternative strategy of empirical treatment produces a higher utility value during epidemics, but may result in overuse of antivirals for low-risk populations. The two strategies had equivalent efficacy when the probability of influenza was 42%. CONCLUSIONS: Patients with flu-like illness, who present outside the influenza outbreak and are considered to be at low risk for influenza-related complications, should be tested to confirm the diagnosis before starting antiviral treatment with a NA inhibitor. The most important variables in the model were the accuracy of the clinical diagnosis and the pre-test probability of influenza. A threshold probability of influenza of 42% would dictate changing from the rapid testing strategy to a 'treat regardless' strategy.

Risk indicators of edentulism, partial tooth loss and prosthetic status among black and white middle-aged and older adults.

OBJECTIVES: To describe the prevalence and risk indicators of edentulism; to describe the frequencies of wearing removable dentures; to describe the prevalence and risk indicators of fixed prosthetic restorations; to test the hypothesis that fixed prosthetic restorations are most likely to have been placed in persons at lower risk for dental and periodontal diseases, and to test the hypothesis that, with dental disease, dental behaviors, dental attitudes and ability to afford crowns taken into account, blacks are less likely than whites to have received crowns. METHODS: The Florida Dental Care Study is a cohort study of subjects 45 years old or older. A telephone screening interview was done as a first stage to identify 5254 subjects who met eligibility requirements and who self-reported whether they were edentulous. In a second stage, a subsample of dentate subjects was contacted after they completed their telephone screening interview. Of these, 873 subjects completed a baseline in-person interview and dental examination. RESULTS: A total of 19% of first-stage subjects were edentulous. In a single multiple logistic regression, having a poorer self-rated level of general health was significantly associated with edentulism, as were being poor, older and white. Among the second-stage participants (all of whom were dentate), several prosthetic patterns were observed. For example, a total of 64% of maxillary full denture wearers reported wearing their denture all the time. Participants had also received numerous fixed prosthodontic services. The proportion of subjects with at least one crown varied widely by subject characteristics. CONCLUSIONS: A substantial percentage of non-ideal frequencies of wearing removable prostheses was reported, as were prosthesis-related soreness and broken prostheses. Although we expected and observed an association between having a fixed prosthetic crown and periodontal status, dental fillings, dental attitudes and financial resources, a residual association with race suggests that blacks are much less likely to receive prosthetic crowns. The several possible reasons for this circumstance warrant further investigation.

Coping with tooth pain: a qualitative study of lay management strategies and professional consultation.

This research analyzes transcripts of semi-structured interviews with patients presenting with tooth pain at a rural dental clinic in North Florida. The primary objectives are to identify the strategies patients use to manage their pain and to elucidate the decision-making process leading to the clinic visit. Although respondents understood that their condition was not self-limiting, only about one-half contacted the clinic within several days of the onset of their pain. Most tried one or more lay management strategies.

Telemedicine: a new dimension in the practice of medicine.

Telemedicine has drawn increasing attention as one of the emerging service delivery vehicles running on the information highway. Until recently, the adoption of telemedicine has been discouraged by the cost of telecommunications and equipment and by the lack of infrastructure, standards, and evidence of cost-effectiveness and cultural acceptance. Although there have been attempts to reduce costs by making use of computer communication networks, they were technically limited by slow network speed and the lack of real-time audio/video compression technology. Ongoing technologic advances in telecommunications, imaging, multimedia computers, and information systems are making interactive telemedicine increasingly possible as high-speed video, voice, and data services are brought to large segments of the general population. The current synergy between health reform initiatives, which are redefining how health care services are accessed and delivered, and advances in technologies that support telemedicine has resulted in a proliferation of telemedicine projects. However, there is still no proof that telemedicine is necessarily cost-effective for a broad set of applications. Each prospective application requires its own business case analysis. Within the current environment, the development of a telemedicine strategy should be based on a sound knowledge of the current and future potential of telemedicine to improve health care access and quality while containing and possibly reducing health care costs.

Evaluation for an observation effect in a prospective cohort study of oral health outcomes.

OBJECTIVES: Evaluation for changes in behavior due to research participants' knowledge that behavior is being observed (also referred to as a Hawthorne effect or reactivity) has received little attention in the dental literature. The Florida Dental Care Study, a prospective, non-randomized, longitudinal study of oral health outcomes, provides some inferential power to evaluate for an effect on dental care use due to participants' knowledge that this behavior was being observed. The purpose of this paper is to document that an observation effect can occur in dental studies, and to estimate its magnitude in four groups that were defined by their typical approach to dental care as stated at baseline: consistent regular attenders (CRAs); inconsistent regular attenders (IRAs); consistent problem-oriented attenders (CPOAs); and inconsistent problem-oriented attenders (IPOAs). METHODS: At baseline, 873 respondents with at least one natural tooth and who were 45 years of age or older participated for an interview and clinical dental examination. Respondents were asked about their dental care use in general and check-up use in particular at 6-month intervals over a period of 24 months. RESULTS: Dental care use in general and check-up use in particular varied across time points and across the four groups of the sample. There was some stimulation in dental care use for the sample overall, but by the 18-to-24-month period, use had returned to baseline levels. In a direction opposite from that hypothesized, results from the CRAs suggested decreased use of dental care over the course of the 24 months of observation. No consistent pattern was evident for the IRAs, CPOAs, or IPOAs. CONCLUSIONS: An observation effect was evident, but was modest in magnitude and differed within and between sub-groups of the sample. While self-selection into dental care user groups is an expected and desirable feature of this design, the size of the user/non-user groups was affected for some subgroups. We conclude that dental care studies with the potential for an observation effect should evaluate for this effect by distinguishing sub-groups of the sample based on their propensity (as stated at baseline) to use dental care. These differential effects across sub-groups should be taken into account as inferences are made.

Taking dental self-care to the extreme: 24-month incidence of dental self-extractions in the Florida Dental Care Study.

OBJECTIVE: A common response to health-related symptoms is to treat oneself in lieu of or prior to seeking formal health care. Among the more extreme forms of dental self-care is dental self-extraction. To our knowledge, no study of the incidence of this behavior has been conducted. The objective of this study was to determine if one form of dental self-care, dental self-extraction, is a real phenomenon, and if so, to determine its incidence. METHODS: The Florida Dental Care Study is a longitudinal study of changes in oral health, whose subjects participated for an interview and clinical examination at baseline and 24 months after baseline. RESULTS: Of the 739 persons who participated through 24 months 176 lost one or more teeth. Of these 176 persons, 13 (7%) extracted one or more of their own teeth. The clinical status at baseline of the self-extracted teeth was consistent with the ability to self-extract. CONCLUSION: The phenomenon of dental self-extraction is real and is not limited to residents of developing nations or geographically isolated areas. Because of the potential for prolonged bleeding or bacterial endocarditis in certain population groups, community health clinicians and officials should be cognizant of this behavior.

Dietary implications of oral health decrements among African-American and white older adults.

OBJECTIVE: Older African-Americans are at disproportionate risk of chronic, nutritionally-related diseases. To begin to understand factors that may contribute to the disproportionate prevalence of life-threatening illnesses among African-Americans, this study investigates ethnic differences in the prevalence of oral health decrements. DESIGN: The Florida Dental Care Study (FDCS), a longitudinal study of changes in the oral health of 873 subjects age 45+, was used to explore a broad range of oral health status differences between African-Americans and White adults in the United States. The FDCS consists of clinical and self-reported measures of oral health, sociodemographic information, and other indicators of oral functional status. RESULTS: The prevalence of oral health decrements in this sample using a broad range of clinical and self-reported measures was substantial. African-American elders were at a heightened risk of poor oral health profiles, including having fewer teeth and being more likely to have a carious surface, fractured cusp or incisal edge, severely mobile teeth and severe periodontal levels than their White counterparts. Furthermore, the African-American respondents in our sample were significantly more likely to report a lower self-rated oral health and functioning than their White counterparts. These findings persist regardless of poverty status or educational level, two factors commonly thought to confound racial differences in health outcomes. CONCLUSION: Our study provides evidence that the widespread prevalence of oral health decrements and accompanying functional disability among this sample of dentate older adults impacts their daily lives. Of particular concern is the oral heath status of older African-Americans who may be nutritionally vulnerable due, in part, to these oral health decrements and disabilities. We suggest enhancing the access of health services in order to prevent those oral health decrements that presumably undermine adequate dietary intake.

Multidimensionality of oral health in dentate adults.

OBJECTIVES: An understanding of the validity and usefulness of self-reported measures (as distinct from clinically determined measures) of oral health is emerging. These self-reported measures include self-rated oral health (SROH). Three objectives were to: (1) describe self-rated oral health in dentate adults, (2) quantify associations between self-rated oral health and other measures of oral health (oral disease and tissue damage, pain and discomfort, functional limitation, and disadvantage), and (3) assess the construct validity of a model of oral health proposed herein. METHODS: The Florida Dental Care Study is a longitudinal study of oral health, which included at baseline 873 subjects who had at least one tooth, were 45 years or older, and who participated for an interview and clinical examination. RESULTS: The prevalence of self-rated oral health decrements was substantial; approximately one fourth of subjects reported their oral health as only fair or poor. Bivariate and multivariate results provided consistent evidence of the construct validity of the proposed model of oral health. Additionally, the salience of one measure of dental appearance suggests that persons may use esthetic cues when rating their oral health. CONCLUSIONS: The proposed multidimensional model of oral health has construct validity. Self-rated oral health is affected by oral disease and tissue damage, oral pain and discomfort, oral functional limitation, and oral disadvantage. These self-reported measures and the proposed model should provide useful information for dental care effectiveness research. General health status has been disaggregated into the "physical" and the "mental;" an additional separation into the "oral" aspects of health seems warranted.