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There is a strong association between vitamin D levels and periodontal disease based on numerous epidemiological studies. We have previously shown that experimental deficiency of serum vitamin D in mice leads to gingival inflammation and alveolar bone loss. Treatment of cultured oral epithelial cells with the active form of vitamin D, 1,25(OH) 2 vitamin D 3 (1,25(OH) 2 D 3 ), inhibits the extracellular growth and intracellular invasion of bacteria associated with periodontal disease. Maintenance of periodontal health may be due in part to the anti-inflammatory activities of vitamin D. Furthermore, this hormone can induce the expression of an antimicrobial peptide in cultured oral epithelial cells. We have shown that oral epithelial cells are capable of converting inactive vitamin D to the active form, suggesting that topical treatment of the oral epithelium with inactive vitamin D could prevent the development of periodontitis. We subjected mice to ligature-induced periodontitis (LIP), followed by daily treatment with inactive vitamin D or 1,25(OH) 2 D 3 . Treatment with both forms led to a reduction in ligature-induced bone loss and inflammation. Gingival tissues obtained from vitamin D-treated LIP showed production of specialized proresolving mediators (SPM) of inflammation. To examine the mechanism, we demonstrated that apical treatment of 3-dimensional cultures of primary gingival epithelial cells with vitamin D prevented lipopolysaccharide-induced secretion of proinflammatory cytokines and led to a similar production of SPM. Analysis of the oral microbiome of the mice treated with vitamin D showed significant changes in resident bacteria, which reflects a shift toward health-associated species. Together, our results show that topical treatment of oral tissues with inactive vitamin D can lead to the maintenance of periodontal health through the regulation of a healthy microbiome and the stimulation of resolution of inflammation. This strongly supports the development of a safe and effective vitamin D-based topical treatment or preventive agent for periodontal inflammation and disease., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To assess pharmacy faculty members' perceptions of conditions associated with workload equity and factors that can improve workload equity., Methods: A 26-item survey instrument was developed and distributed via email to members of the American Association of Colleges of Pharmacy Council of Faculties. Questions pertained to the workload distribution, fairness in assignment, and perception of the conditions associated with workload equity (transparency, context, credit, clarity, norms, and accountability) as well as institutional and individual demographics., Results: A total of 662 responses were obtained (response rate 15.9%). Respondents' demographics were comparable to available national data. Approximately 41% of respondents reported their institutions did not have a written faculty workload policy. Most respondents reported their workload assignment was fair (highest with research/scholarship) but reported only moderate alignment between assigned and actual workloads. The rating level for what domains the primary decision maker uses to assign workload was highest for context, followed by credit, clarity, and transparency. Transparency was reported as the most needed condition to improve faculty perception of workload equity. Respondents also rated increasing trust between leadership and faculty and increasing productivity and accountability as the most important reasons to minimize workload inequities., Conclusion: This was the first national survey of pharmacy faculty perceptions around the conditions associated with workload equity. Though additional research is needed in this area, programs can work to implement strategies associated with all of the conditions, particularly transparency, to improve faculty perceptions of equity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Association of Colleges of Pharmacy. Published by Elsevier Inc. All rights reserved.)

Purpose: Despite potential benefits of intravenous (i.v.) administration of acetaminophen (APAP), consistent outcome data are lacking. This, combined with the higher acquisition cost of the drug, has led to variation in i.v. APAP management strategies. This project evaluated the contemporary formulary status and restrictions of i.v. APAP in the perioperative setting. Methods: A survey focusing on i.v. APAP formulary restriction in the perioperative setting was developed by the Vizient Pharmacy Research Committee and distributed to Vizient Pharmacy Program participant listservs for Pharmacy Directors or Drug Information Pharmacists. The four survey domains included hospital characteristics, perioperative i.v. APAP formulary status and prescribing restrictions, perioperative i.v. APAP use, and perioperative i.v. APAP medication use evaluation (MUE) results. Responses were collected and summarized, and primary outcomes were evaluated using Fisher's exact test. Results: A total of 1195 surveys were distributed with a response rate of 19%. Respondents were equally distributed between academic medical centers (AMC) and non-academic medical centers (non-AMC). Two cohorts were examined: those with i.v. APAP on formulary and those without. The non-AMCs showed a larger proportion of hospitals with the medication on formulary ( P  = .041). Regarding formulary decision-making, the AMCs were more considerate of value. Several different practices were employed to limit or restrict i.v. APAP. Conclusion: A survey of directors of pharmacy and drug information specialists revealed that the majority of hospitals have i.v. APAP on formulary for perioperative use, but use is restricted. Differences in i.v. APAP formulary practices between AMCs and non-AMCs warrant further consideration., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Competing Interests: JPB declares no competing interests. CK reports a patent Rv3 rotavirus vaccine issued (PCT/AU2013/000945).

The most mature aspect of applying artificial intelligence (AI)/machine learning (ML) to problems in the atmospheric sciences is likely post-processing of model output. This article provides some history and current state of the science of post-processing with AI for weather and climate models. Deriving from the discussion at the 2019 Oxford workshop on Machine Learning for Weather and Climate, this paper also presents thoughts on medium-term goals to advance such use of AI, which include assuring that algorithms are trustworthy and interpretable, adherence to FAIR data practices to promote usability, and development of techniques that leverage our physical knowledge of the atmosphere. The coauthors propose several actionable items and have initiated one of those: a repository for datasets from various real weather and climate problems that can be addressed using AI. Five such datasets are presented and permanently archived, together with Jupyter notebooks to process them and assess the results in comparison with a baseline technique. The coauthors invite the readers to test their own algorithms in comparison with the baseline and to archive their results. This article is part of the theme issue 'Machine learning for weather and climate modelling'.

Forecasting the weather is an increasingly data-intensive exercise. Numerical weather prediction (NWP) models are becoming more complex, with higher resolutions, and there are increasing numbers of different models in operation. While the forecasting skill of NWP models continues to improve, the number and complexity of these models poses a new challenge for the operational meteorologist: how should the information from all available models, each with their own unique biases and limitations, be combined in order to provide stakeholders with well-calibrated probabilistic forecasts to use in decision making? In this paper, we use a road surface temperature example to demonstrate a three-stage framework that uses machine learning to bridge the gap between sets of separate forecasts from NWP models and the 'ideal' forecast for decision support: probabilities of future weather outcomes. First, we use quantile regression forests to learn the error profile of each numerical model, and use these to apply empirically derived probability distributions to forecasts. Second, we combine these probabilistic forecasts using quantile averaging. Third, we interpolate between the aggregate quantiles in order to generate a full predictive distribution, which we demonstrate has properties suitable for decision support. Our results suggest that this approach provides an effective and operationally viable framework for the cohesive post-processing of weather forecasts across multiple models and lead times to produce a well-calibrated probabilistic output. This article is part of the theme issue 'Machine learning for weather and climate modelling'.

Background: Placental or breast milk maternal antibodies can potentially reduce oral rotavirus vaccine efficacy in developing countries. We aimed to examine the relationship between the level of rotavirus specific immunoglobulin A (IgA) and neutralising antibodies (NA) in colostrum and breast milk and cord IgG, with cumulative vaccine take following one and three doses of oral RV3-BB rotavirus vaccine within a Phase IIb trial in Indonesia., Methods: 196 infants received three doses of RV3-BB in a randomized, double-blinded trial, using a neonatal schedule (first dose at 0-5 days of age, n = 61), an infant schedule (first dose at ~ 8 weeks of age, n = 67) or placebo (n = 68). Rotavirus specific IgA and NA in colostrum and breast milk, rotavirus specific cord IgG, Serum IgA and stool excretion were measured., Results: There was little evidence of an association between IgA in colostrum or breast milk and cumulative vaccine take after three doses in the neonatal or infant groups. In the neonatal group, there was a negative association between IgG titre in cord blood and cumulative vaccine take (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.92-1.00; p = 0.03) and serum IgA response (OR 0.94; 95%CI 0.89-0.99; p = 0.02) after one dose of vaccine, which were not evident after three doses in the neonatal or infant groups., Conclusions: Amongst Indonesian infants we did not find an association between IgA in colostrum or breast milk and vaccine take after 3 doses of RV3-BB vaccine. Maternal rotavirus antibodies in breast milk appear to have minimal impact on RV3-BB vaccine take when administered with a short delay in breast-feeding in settings with a high rotavirus disease burden., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Rotavirus vaccines were introduced into the Australian National Immunisation Program in 2007. Despite this, Northern Territory Indigenous children continue to be hospitalised with rotavirus at a rate more than 20 times higher than non-Indigenous children in other Australian jurisdictions, with evidence of waning protection in the second year of life. We hypothesised that scheduling an additional (third) dose of oral human rotavirus vaccine (Rotarix, GlaxoSmithKline) for children aged 6 to <12 months would improve protection against clinically significant all-cause gastroenteritis., Methods and Analysis: This Bayesian adaptive clinical trial will investigate whether routinely scheduling an additional dose of Rotarix for Australian Indigenous children aged 6 to <12 months old confers significantly better protection against clinically important all-cause gastroenteritis than the current two-dose schedule at 2 and 4 months old. There are two coprimary endpoints: (1) seroconversion from baseline serum anti-rotavirus immunoglobulin A (IgA) titre <20 U/mL prior to an additional dose of Rotarix/placebo to serum anti-rotavirus IgA titre >20 U/mL following the administration of the additional dose of Rotarix/placebo and (2) time from randomisation to medical attendance (up to age 36 months old) for which the primary reason is acute gastroenteritis/diarrhoea. Secondary endpoints include the change in anti-rotavirus IgA log titre, time to hospitalisation for all-cause diarrhoea and for rotavirus-confirmed gastroenteritis/diarrhoea, and rotavirus notification. Analysis will be based on Bayesian inference with adaptive sample size., Ethics, Registration and Dissemination: Ethics approval has been granted by Central Australian Human Research Ethics Committee (HREC-16-426) and Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (HREC-2016-2658). Study investigators will ensure the trial is conducted in accordance with the principles of the Declaration of Helsinki and with the ICH Guidelines for Good Clinical Practice. Individual participant consent will be obtained. Results will be disseminated via peer-reviewed publication. The trial is registered with Clinicaltrials.gov (NCT02941107) and important modifications to this protocol will be updated., Trial Registration Number: NCT02941107; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rotavirus vaccines have been introduced into over 95 countries globally and demonstrate substantial impact in reducing diarrheal mortality and diarrheal hospitalizations in young children. The vaccines are also considered by WHO as "very cost effective" interventions for young children, particularly in countries with high diarrheal disease burden. Yet the full potential impact of rotavirus immunization is yet to be realized. Large countries with big birth cohorts and where disease burden is high in Africa and Asia have not yet implemented rotavirus vaccines at all or at scale. Significant advances have been made demonstrating the impact of the vaccines in low- and lower-middle income countries, yet the modest effectiveness of the vaccines in these settings is challenging. Current research highlights these challenges and considers alternative strategies to overcome them, including alternative immunization schedules and host factors that may inform us of new opportunities.

Background: Diarrheal disease is one of the leading causes of illness and death in young children in the world, especially the developing countries. Diarrheal disease results in about half a million childhood death per year, ranking second among all causes worldwide. Diarrheal disease due to rotavirus infection is currently the most common cause of severe diarrhea in infants and young children worldwide. Rotavirus immunization of infants is a safe and effective public health intervention for rotavirus infection control and expected to lead to a reduction of childhood morbidity and mortality., Methods: We conducted hospital-based surveillance at two representative hospitals in Mongolia to estimate the burden of hospitalizations for rotavirus diarrhea among children aged <5 years and to describe strain distribution patterns during 6-year study period. Fecal specimens were tested by rotavirus antigen detection enzyme immunoassay (EIA). Specimens that tested positive for rotavirus were further characterized to determine the genotype of strains by reverse-transcriptase polymerase chain reaction., Results: Between April 2009 and March 2016, among 7076 eligible children with diarrhea 6078 patients were enrolled nationally. Forty-six percent (2794/6078) of EIA a specimens were positive for rotavirus. Ninety-three percent (5649/6078) of hospitalizations for diarrhea involved children less than 2 years. No deaths were recorded due to rotavirus diarrhea. The most common genotype was G3P [8] (47.7%) followed by G9P [6] (14.4%), G2P [4] (12%), and G9P [8] (7.1%)., Conclusions: This study found a relatively high prevalence of severe rotavirus-associated diarrhea disease in Mongolia and infants were the most affected. It highlights the urgent need for introduction of rotavirus vaccine into the national immunization program. Continued surveillance is crucial and pre-vaccine introduction rotavirus genotype patterns in Mongolia are valuable and can be followed post-introduction to assess vaccine impact., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

With the availability of new and existing rotavirus vaccines, credible and reliable data on burden of rotavirus-associated disease are needed to enable evidence-based decision making regarding the introduction of rotavirus vaccines. The national rotavirus surveillance program in the Philippines, a sentinel-based surveillance, was established in 2012 to determine the proportion of laboratory-confirmed rotavirus cases among children under five years with acute gastroenteritis and to describe the geographic distribution and molecular epidemiology of rotavirus in the country. During 2013 to 2015, rotavirus infection was the cause of acute gastroenteritis among children under five years admitted to hospitals or evaluated in emergency rooms, constituting more than one-third of gastroenteritis hospitalizations at the sentinel site hospitals. The predominant genotype observed was G1P[8]. Although a rotavirus surveillance network has been established, findings suggest the need to strengthen the network in the country and to continue monitoring prevalent rotavirus strains to help identify the possible emergence of new strains., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Acute diarrhoeal disease caused by viral, bacterial and parasitic infections is a major global health problem; in low- and middle-income countries (LMICs) it is associated with substantial mortality and morbidity in children under 5. Some of these infections also impact large segments of populations in high-income countries (HICs), as well as individuals who travel overseas for work, business or pleasure., Aims: The aim of this review is to describe the current landscape of licensed enteric vaccines, potential new vaccines on the horizon, and the challenges of development and utilization of vaccines against enteric pathogens., Sources: Relevant data from the literature, as well as clinical trials described in European and US registries, were examined in the conduct of this review., Content: The review involves discussion of current licensed vaccines against rotavirus, cholera and typhoid, as well as potential second- and third-generation vaccines against these pathogens currently in the development pipeline. In addition, novel vaccines against enterotoxigenic Escherichia coli, shigellosis and norovirus in advanced development are described. Challenges to the development and utilization of global vaccines are discussed., Implications: Despite advances in population health, food security, improved sanitation and water quality, and the reduction in poverty, acute enteric infections continue to plague global populations. Advancing utilization of current enteric vaccines is of critical public health importance, as is the development of new vaccines, particularly for enteric pathogens where none currently exist., (Copyright © 2018. Published by Elsevier Ltd.)

Predictive mapping of indoor radon potential often requires the use of additional datasets. A range of geological, geochemical and geophysical data may be considered, either individually or in combination. The present work is an evaluation of how much of the indoor radon variation in south west England can be explained by four different datasets: a) the geology (G), b) the airborne gamma-ray spectroscopy (AGR), c) the geochemistry of topsoil (TSG) and d) the geochemistry of stream sediments (SSG). The study area was chosen since it provides a large (197,464) indoor radon dataset in association with the above information. Geology provides information on the distribution of the materials that may contribute to radon release while the latter three items provide more direct observations on the distributions of the radionuclide elements uranium (U), thorium (Th) and potassium (K). In addition, (c) and (d) provide multi-element assessments of geochemistry which are also included in this study. The effectiveness of datasets for predicting the existing indoor radon data is assessed through the level (the higher the better) of explained variation (% of variance or ANOVA) obtained from the tested models. A multiple linear regression using a compositional data (CODA) approach is carried out to obtain the required measure of determination for each analysis. Results show that, amongst the four tested datasets, the soil geochemistry (TSG, i.e. including all the available 41 elements, 10 major - Al, Ca, Fe, K, Mg, Mn, Na, P, Si, Ti - plus 31 trace) provides the highest explained variation of indoor radon (about 40%); more than double the value provided by U alone (ca. 15%), or the sub composition U, Th, K (ca. 16%) from the same TSG data. The remaining three datasets provide values ranging from about 27% to 32.5%. The enhanced prediction of the AGR model relative to the U, Th, K in soils suggests that the AGR signal captures more than just the U, Th and K content in the soil. The best result is obtained by including the soil geochemistry with geology and AGR (TSG + G + AGR, ca. 47%). However, adding G and AGR to the TSG model only slightly improves the prediction (ca. +7%), suggesting that the geochemistry of soils already contain most of the information given by geology and airborne datasets together, at least with regard to the explanation of indoor radon. From the present analysis performed in the SW of England, it may be concluded that each one of the four datasets is likely to be useful for radon mapping purposes, whether alone or in combination with others. The present work also suggest that the complete soil geochemistry dataset (TSG) is more effective for indoor radon modelling than using just the U (+Th, K) concentration in soil., (Copyright © 2016 Natural Environment Research Council. Published by Elsevier Ltd.. All rights reserved.)

Background: Infant morbidity and mortality rates remain high in Indonesia, with acute respiratory illnesses (ARI) and diarrhea the leading two health problems in children under 5 years. We aimed to describe the nutritional status, feeding practice and case management of ARI and diarrhea of infants from two regions of Indonesia during the first 6 months of life., Methods: This study was an observational study conducted in parallel to an immunogenicity and efficacy trial of an oral rotavirus vaccine (RV3-BB) in the Klaten and Yogyakarta regions, Indonesia. Mothers were interviewed at 3 time points: within the first 6 days of their infant's life, and at 8-10 and 22-24 weeks of age. Questions asked included pregnancy history, infant nutritional status, feeding status and health of infants within up to 2 weeks prior to the assessment., Results: Between February 2013 and January 2014, 233 mother-infant pairs were recruited. 60% (136/223) of infants were exclusively breastfed (EBF) until 6 months of age with the strongest support for EBF reported by mothers themselves 70% (101/223) and 25% (36/223) from their partners. At 6 months, 6% (14/223) of infants were underweight and severely underweight; 4% (8/ 223) wasted and severely wasted; and 12% (28/223) were stunted and severely stunted. Non-recommended medication use was high, with 54% (21/39) of infants with reported cough within 2 weeks of an assessment receiving cough medication, 70% (27 /39) an antihistamine, 26% (10/39) a mucolytic and 15% (6 /39) an oral bronchodilator. At age 22-24 week, infants with reported diarrhea within 2 weeks of an assessment had low use of oral rehydration solutions (ORS) (3/21;14%) and zinc therapy (2/ 21;10%)., Conclusion: In this unique observational study, breastfeeding rates of 60% at 6 months were below the Indonesian national target of >75%. Adherence to WHO guidelines for management of ARI and diarrhea was poor, with high use of non-recommended cough medications and oral bronchodilators in the first 6 months of life and low use of ORS and zinc therapy. Ongoing education of primary health care workers and parents regarding management of common illness is needed in Indonesia.

Pharmacists' specialized training and knowledge qualify them to lead and engage in research pertaining to optimal medication use. Performing research promotes pharmacy professionalism and fosters interdisciplinary collaboration. To conduct research appropriately, one must have thorough knowledge of when institutional review board (IRB) approval is required and how to successfully navigate IRB processes. The overarching mission of the IRB overseeing research at an organization per federal guidelines is to protect the rights and welfare of human subjects participating in research. This article discusses the following general pharmacy practice-based considerations relating to IRB processes: strategies for developing research projects, key distinctions between quality improvement and research, practical considerations for submitting IRB applications and documentation, different categories of IRB submission, informed consent and conditions for waivers or alterations of consent, and principal investigator obligations for approved research. Pharmacists should also account for organization-specific IRB processes when designing, submitting, and implementing research projects.

Seven commercial rotavirus antigen assays were compared with in-house PCR methods for detecting rotavirus in stool specimens. The assay sensitivities were 80% to 100%, while the specificities were 54.3% for one commercial immunochromatographic (ICT) method and 99.4% to 100% for other assays. Thus, except for one commercial ICT, all the assays were generally reliable for rotavirus detection., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Rotavirus is a ubiquitous double-stranded RNA virus responsible for most cases of infantile gastroenteritis. It infects pancreatic islets in vitro and is implicated as a trigger of autoimmune destruction of islet beta cells leading to type 1 diabetes, but pancreatic pathology secondary to rotavirus infection in vivo has not been documented. To address this issue, we inoculated 3 week-old C57Bl/6 mice at weaning with rhesus rotavirus, which is closely related to human rotaviruses and known to infect mouse islets in vitro. Virus was quantified in tissues by culture-isolation and enzyme-linked immunosorbent assay. A requirement for viral double stranded RNA was investigated in toll-like receptor 3 (TLR3)-deficient mice. Cell proliferation and apoptosis, and insulin expression, were analyzed by immunohistochemistry. Following rotavirus inoculation by gavage, two phases of mild, transient hyperglycemia were observed beginning after 2 and 8 days. In the first phase, widespread apoptosis of pancreatic cells was associated with a decrease in pancreas mass and insulin production, without detectable virus in the pancreas. These effects were mimicked by injection of the double-stranded RNA mimic, polyinosinic-polycytidylic acid, and were TLR3-dependent. By the second phase, the pancreas had regenerated but islets were smaller than normal and viral antigen was then detected in the pancreas for several days. These findings directly demonstrate pathogenic effects of rotavirus infection on the pancreas in vivo, mediated initially by the interaction of rotavirus double-stranded RNA with TLR3.

Introduction: RV3 is a human neonatal rotavirus strain (G3P[6]) that has been associated with asymptomatic neonatal infection and replicates well in the infant gut. RV3-BB rotavirus vaccine has been developed as a rotavirus vaccine candidate for administration at birth., Methods: A single-centre, double-blind, randomised placebo-controlled Phase I study evaluated the safety and tolerability of a single oral dose of the second generation RV3-BB rotavirus vaccine (8.3×10(6)FFU/mL) in 20 adults, 20 children and 20 infants (10 vaccine and 10 placebo per age cohort). Vaccine take was defined as seroconversion (a 3-fold increase in serum anti-rotavirus IgA or serum neutralising antibody (SNA) from baseline at day 28 post-dose) or evidence of RV3-BB viral replication in the faeces by RT-PCR analysis 3-6 days post-vaccination. RV3-BB presence was confirmed by sequence analysis., Results: The RV3-BB vaccine was well tolerated in all participants, with no pattern of adverse events shown to be associated with the study vaccine. In the infant cohort, vaccine take was demonstrated in 8/9 infants following a single dose of vaccine compared with 2/7 placebo recipients. In the infant vaccine group, 5/9 infants exhibited either IgA or SNA seroconversion and 7/9 infants had evidence of RV3-BB replication on days 3-6, compared with 2/7 infants who seroconverted and 0/10 infants with evidence of replication in the placebo group. Two infants in the placebo group had serological evidence of a rotavirus infection within the 28-day study period: one demonstrated an IgA and the other an SNA response, with wild-type virus replication detected in another infant., Conclusion: A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants. Most infants (8/9) who received RV3-BB demonstrated vaccine take following a single dose. These data support progression of RV3-BB to Phase II immunogenicity and efficacy trials., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

This paper reviews the literature on the history, efficacy, and putative mechanism of action of enteral nutrition for inflammatory bowel disease in both paediatric and adult patients. It also analyses the reasoning behind the low popularity of exclusive enteral nutrition in clinical practice despite the benefits and safety profile.

A large rotavirus gastroenteritis outbreak occurred in the Alice Springs region of the Northern Territory, Australia from the 12th of March until the 11th of July 2007. The outbreak occurred five months after the introduction of the Rotarix™ vaccine. Electropherotype and sequence analysis demonstrated that a single G9P[8] strain was responsible for the outbreak and that the strain remained highly conserved during the outbreak period. The outbreak strain contained amino acid changes in regions of the VP7 and NSP4 genes, with known biological function, when compared to previously characterised G9P[8] strains from Australia and other international locations. The recent vaccine introduction was unlikely to have influenced genotype selection in this setting. Importantly, Rotarix™ vaccine was highly effective against the G9P[8] outbreak strain., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The enteric bacterial flora play a key role in maintaining health. Inflammatory bowel disease is associated with quantitative and qualitative alterations in the microbiota. Early characterization of the microbiota involved culture-dependent techniques. The advent of metagenomic techniques, however, allows for structural and functional characterization using culture-independent methods. Changes in diversity, together with quantitative alterations in specific bacterial species, have been identified. The functional significance of these changes, and their pathogenic role, remain to be elucidated., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

Introduction: Past experience with live oral vaccines including licensed rotavirus vaccines demonstrates a trend towards reduced vaccine efficacy in developing countries compared with developed countries. The reasons behind this disparity are not well understood. Transplacental transfer of maternal antibodies and breast milk ingestion may attenuate vaccine responses in infants in developing countries where rotavirus infections are endemic, and maternal antibody levels are high. We examined the prevalence and level of rotavirus antibody in maternal and cord serum, colostrum and breast milk in a developing country setting., Methods: 100 mother-infant pairs were prospectively recruited from December 2008 to February 2009 at Dr. Sardjito Hospital, Yogyakarta, Indonesia. Maternal and cord sera were collected during delivery. Colostrum and transitional breast milk were collected between day 0-3 and day 7-10 postpartum respectively. Rotavirus-specific IgA and IgG were estimated for all specimens and virus neutralization assays were conducted on a subset of milk specimens., Results: All maternal and cord serum samples were positive for rotavirus-specific IgG antibodies with a strong correlation between levels of rotavirus-specific IgG in mothers and levels transferred to infants in cord blood (r=0.86; p=0.001). 78% of colostrum and 67% of transitional breast milk specimens were positive for rotavirus-specific IgA. There was a median 4-fold decrease in rotavirus-specific IgA from colostrum to transitional breast milk. Neutralizing antibodies were present in 56% of colostrum specimens assayed (19/34) and in 41% of transitional milk specimens assayed (14/34)., Conclusions: Maternal serum and breast milk antibodies to rotavirus are highly prevalent in a developing country setting. Evaluation of the impact of maternal anti-rotavirus serum and breast milk antibody upon vaccine immunogenicity would help to inform rotavirus vaccination strategies, especially in developing settings., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Unlabelled: The human rotavirus vaccine was evaluated during an outbreak of rotavirus G2P[4] infection in central Australia. No overall protective effect against hospitalization was demonstrated, raising concerns over the durability of vaccine protection against heterotypic strains., Background: Two and a half years after commencing routine vaccination with human rotavirus vaccine, an outbreak of rotavirus G2P[4] infection occurred in central Australia. Vaccine effectiveness against a P[8]-containing strain (G9P[8]) had been demonstrated previously in this setting. This subsequent outbreak provided the opportunity to evaluate vaccine effectiveness against hospitalizations for a non-vaccine-related genotype in the same population., Methods: A case-control study was nested within a cohort of vaccine-eligible children listed on a population-based immunization register. Children with rotavirus-confirmed gastroenteritis were individually matched by date of birth and Indigenous status with 4 control subjects., Results: Forty-one cases met the inclusion criteria, and 21 were severe cases among infants aged <12 months. Nineteen (46%) of 41 case patients had received 2 doses of human rotavirus vaccine, compared with 87 (53%) of 164 control subjects. Vaccine effectiveness against rotavirus-related hospitalization was 19% (odds ratio, .81; 95% confidence interval, .32-2.05) for 2 doses compared with none. On secondary analysis, there was evidence of a protective effect against disease complicated by acidosis in the subset of infants aged <12 months (odds ratio, .15; 95% confidence interval, .03-.84)., Conclusions: Evidence was not found for an overall protective effect of human rotavirus vaccine against hospitalization for rotavirus disease in this setting. Post hoc analyses suggested a protective effect against severe disease in young infants.

Background: A pattern of postural deformity was observed in a previous study that included an association between direction of spinal curvature and direction of windsweeping with more windswept deformities occurring to the right and lateral spinal curvatures occurring convex to the left. The direction of this pattern was found to be associated with preferred lying posture in early life. The aim of this study was to test the association between foetal position and both the preferred lying posture after birth, and the direction of subsequent postural deformity in non-ambulant children with cerebral palsy (CP)., Methods: A retrospective cohort study was carried out involving 60 participants at level five on the gross motor function classification for CP. Foetal position during the last month of pregnancy was taken from antenatal records and parents were interviewed to identify preferred lying posture in the first year of life. At the time of the physical assessment ages ranged from 1 year and 1 month to 19 years with a median age of 13 years and 1 month., Results: Foetal presentation was found to be associated with the preferred lying posture with participants carried in a left occipito-anterior/lateral position more likely to adopt a supine head right lying posture, and vice versa. An association was also observed between the foetal position and asymmetrical postural deformity occurring later in life with participants carried in a left occipito-anterior/lateral presentation more likely to have a convex left spinal curve, a lower left pelvic obliquity, and a windswept hip pattern to the right., Conclusions: Clinicians should be aware of the association between foetal presentation, asymmetrical lying posture, and the direction of subsequent postural deformity for severely disabled children. A hypothesis is described that might help to explain these findings.

Insomnia is a common sleep complaint in the elderly. The safety and efficacy of eszopiclone, a non-benzodiazepine hypnotic, in elderly patients with chronic insomnia has been established in two 2-week and one 12-week randomized, double-blind, placebo-controlled trials. Eszopiclone 1 mg was effective in reducing sleep latency. Eszopiclone 2 mg was effective in reducing latency to sleep and for increasing sleep maintenance. Eszopiclone doses of 1 mg and 2 mg reduced the number of daytime naps and decreased the duration of naps in elderly patients. Eszopiclone 2 mg improved the quality of life measures for mood, physical health, household activities, medication, leisure activities, and self-report of physical functioning and vitality in the 2-week trials, and vitality and general health in the 12-week trial. The most commonly reported side effects in the elderly included unpleasant taste, dry mouth, dizziness, and somnolence. The concurrent use of drugs that inhibit or induce the cytochrome P450 enzyme CYP3A4 can alter concentrations of eszopiclone and the dose may need to be adjusted. The recommended starting dose of eszopiclone for difficulty falling asleep is 1 mg at bedtime. For elders who complain of difficulty maintaining sleep, eszopiclone should be initiated at 2 mg at bedtime. Overall, eszopiclone is a safe and well-tolerated treatment option for elderly patients with insomnia.

A novel family of Burkholderiales bacteria was identified in ileal biopsy specimens from children presenting with symptoms of inflammatory bowel disease. A molecular subtyping approach based on sequencing of a variable region of the bacteria's 23S rRNA genes identified three variants. Pilot analysis identified one variant to be significantly associated with perianal Crohn's disease.

This study examined the temporal distribution of rotavirus genotypes in Malaysia. Rotaviruses from children with diarrhea admitted to hospitals in 1996 (n = 93) and 2007 (n = 12) in two different regions of Peninsular (West) Malaysia were analyzed for their G and P genotypes using a hemi-nested RT-PCR assay. In the 2007 samples, the dominant strain was G9P[8]. It was identified in 42% of the samples. Different strains all possessing the G1 genotype were identified in the rest of the samples. In contrast, 81% of the samples collected in 1996 were the G1P[8] strain. No strains with G9 genotype were detected in samples collected in 1996., (2010 Wiley-Liss, Inc.)

Bovine rotavirus (BRV) has been detected in both dairy and beef cattle herds worldwide. Stool samples collected from calves in the Gippsland region of Victoria, Australia were screened to determine the presence of BRV. A total of 100 faecal samples were collected from calves with and without diarrhoea across three farms during 2004 and 2005. Group A BRV was detected in 26% of faecal samples (22 from diarrheic calves and four from asymptomatic calves). Genotyping analysis of rotavirus positive samples indicated that G6P[5] was the most prevalent genotype (38.5%) followed by G6P[5+11] (15.4%). G10P[11] and G6+G10P[5] were each detected at a rate of 7.7%, and G6+G10P[11] was found in a single sample (3.8%). Seven samples (26.9%) could not be G and/or P typed. Thirty percent of the BRV positive samples were mixed infections, indicating that individual calves were co-infected with more than one strain of rotavirus. The G6P[5] strains exhibited high VP7 identity (>97% amino acid identity) with B-60, a G6 strain identified in Victorian calves during 1988. A G10P[11] isolate was closely related (>97% amino acid identity in VP7 and VP4 proteins) to a Victorian G10P[11] strain (B-11) also identified during 1988. This study demonstrates that BRV is a contributing pathogen to diarrhoeal disease in Victorian calves, with sequence analysis suggesting long-term conservation of the VP7 protein over a 16-year period.

Globally rotavirus is the most common cause of severe gastroenteritis in children. From March 2005 through February 2007, a prospective hospital-based surveillance study was conducted at a national hospital in Phnom Penh, Cambodia, to estimate the burden of rotavirus hospitalizations among children aged <5 years old and to determine strain patterns. Children with diarrhoea underwent standard clinical evaluations. Parents were interviewed for demographic and family information. Faecal specimens were tested for rotavirus by enzyme immunoassay (EIA) and positive specimens were further characterized. Of 2817 hospitalized children with diarrhoea, 56% (n=1278) were positive for rotavirus antigen. The G1P[8] strain was the most common genotype (53%) followed by G2P[4] (10%). The findings suggest a need for improved prevention and control programs for rotavirus diarrhoea in Cambodia.

Rotavirus is one of the most common causes of severe life-threatening diarrhoea in children leading to hospitalization especially in developing countries. At Mahosot Hospital in Vientiane, Lao PDR, children with diarrhoea underwent standard clinical evaluation and faecal specimen collection to estimate the burden of rotavirus hospitalizations and to determine rotavirus strain patterns among children aged less than 5 years old. From March 2005 to February 2007, a total of 1158 stool specimens were collected from children aged less than 5 years old hospitalized with acute diarrhoea. Rotavirus was identified in 624 (54%) of these patients. The G1P[8] strain was the most common genotype (35%), followed by G9P[8] (25%). These surveillance data suggest that improved prevention and control programs for rotavirus as well as other causes of diarrhoea are needed in Lao PDR.

Background: Rotavirus is the most common cause of severe gastroenteritis among children. We conducted hospital-based surveillance to estimate the burden of hospitalizations for rotavirus among children aged <5 years and to describe strain distribution patterns during the 2-year study period., Methods: Children aged <5 years with diarrhea were prospectively enrolled and evaluated by trained pediatricians at representative hospitals in Mongolia and Sri Lanka. Fecal specimens were tested by rotavirus antigen detection enzyme immunoassay. Specimens that tested positive for rotavirus were further characterized to determine the genotype of strains by reverse-transcriptase polymerase chain reaction., Results: From 1 March 2005 through 28 February 2007, a total of 1277 hospitalized children with diarrhea were enrolled in Mongolia, and 1916 were enrolled in Sri Lanka. Of the 1152 children in Mongolia who had samples tested, 458 (40%) had results positive for rotavirus, and in Sri Lanka, 428 (24%) of 1806 children with samples tested had positive results. G3P[8] was the most common genotype among rotavirus strains in Mongolia (68%) and Sri Lanka (15%)., Conclusions: Rotavirus causes 40% and 24% of hospitalizations for diarrhea among children in Mongolia and Sri Lanka, respectively. Each study site will continue surveillance of rotavirus, and additional laboratory testing will be performed to provide additional information on the distribution of rotavirus strains by G and P genotype.

This retrospective study examined the G/P type of rotavirus in RNA samples that have previously been e-typed by RNA-PAGE in 1996. The results were then compared to 2007 samples to ascertain the extent of changes that may have occurred in this 11-years time interval. The G and P genotypes were determined by hemi-nested PCR and further analysed by phylogenetic study. In 1996, the G/P combination G1P[8], G(UT)P[8] and G1P(UT) prevalence rate were 81%, 9% and 7%, respectively. As expected, the G9 genotype which has already emerged worldwide was identified in 42% of the 2007 samples with the remaining 33% G1P[8] and 25% G1P(UT) Analysis of the RNA pattern showed that majority of the isolates were long e-type in both series, nevertheless minor differences within electropherotypes were observed. Genetic diversity in some strains of the human group A rotaviruses was analysed by phylogenetic methods. These findings will help in the decision to introduce rotavirus vaccines within the next decade.

Background: It has been suggested that asymmetrical positioning of an infant with reduced mobility may lead to postural deformity becoming established over time. However, evidence to support or question this line of thinking is lacking. Therefore, the aim of this retrospective cohort study was to test the association between asymmetrical positioning in the first 12 months of life and the subsequent direction of postural deformity in non-ambulant people with cerebral palsy., Methods: The direction of scoliosis, pelvic obliquity and windswept hip pattern and also the side of unilateral hip subluxation/dislocation were determined for 246 young people ranging in age from 1 year and 2 months to 19 years (median age 10 years and 3 months). Parents/carers of the participants were interviewed to establish holding and feeding positions and preferred lying posture adopted in early life. Univariate analyses and multivariate logistic regression analyses were carried out., Results: The study provided evidence of an association between asymmetrical lying posture adopted in the first year of life and the direction of the subsequent pattern of postural deformity. If the child's head had been rotated to the right during supine lying, it was more likely that the scoliosis would be convex to the left, pelvic obliquity would be lower on the left, windswept hip pattern would be to the right and hip subluxation/dislocation would occur on the left. The likelihood of the deformities occurring in the same direction was also increased if consistent side lying on the right had been preferred., Conclusions: Clinicians should be aware of positioning for children with severe disabilities particularly those who prefer supine lying with their head rotated to the side and those who prefer consistent side lying.

Background: The use of molecular methods for rotavirus characterisation provides increased sensitivity for typing, and allows the identification of putative reassortant strains. However, due to the constant accumulation of point mutations through genetic drift; and to the emergence of novel genotypes; and possibly zoonotic transmission and subsequent reassortment, the reagents and methods used for genotyping require close monitoring and updating., Objectives: To design and evaluate a new VP4 consensus oligonucleotide primer pair that provides increased sensitivity and allows typing of strains that were untypeable using available methods., Study Design: A total of 489 rotavirus-positive faecal specimens from studies conducted between 1996 and 2006 were used for the evaluation of the new VP4 primers which was performed in the WHO Rotavirus Collaborating and Reference centres in the US, Australia, South Africa and the UK., Results: The new primer pair allowed P-typing of rotavirus strains and provided increased sensitivity, allowing typing of a significant number of strains that previously could not be P-typed., Conclusions: This study highlights the importance of a constant reconsideration of primer sequences employed for the molecular typing of rotaviruses.

Objective: To investigate: (a) associations between the direction of scoliosis, direction of pelvic obliquity, direction of windswept deformity and side of hip subluxation/ dislocation in non-ambulant people with cerebral palsy; and (b) the lateral distribution of these postural asymmetries., Design: Cross-sectional observational study., Setting: Posture management services in three centres in the UK., Subjects: Non-ambulant people at level five on the gross motor function classification system for cerebral palsy., Main Measures: Direction of pelvic obliquity and lateral spinal curvature determined from physical examination, direction of windswept hip deformity derived from range of hip abduction/adduction, and presence/side of unilateral hip subluxation defined by hip migration percentage., Results: A total of 747 participants were included in the study, aged 6-80 years (median 18 years 10 months). Associations between the direction of scoliosis and direction of pelvic obliquity, and between the direction of windswept hip deformity and side hip subluxation/dislocation were confirmed. A significant association was also seen between the direction of scoliosis and the direction of the windswept hip deformity (P<0.001) such that the convexity of the lateral spinal curve was more likely to be opposite to the direction of windsweeping. Furthermore, significantly more windswept deformities to the right (P=0.007), hips subluxed on the left (P=0.002) and lateral lumbar/lower thoracic spinal curves convex to the left (P=0.03) were observed., Conclusions: The individual asymmetrical postural deformities are not unrelated in terms of direction and not equally distributed to the left/right. A pattern of postural deformity was observed.

When herbal or other biologic therapies are used with conventional treatments, adverse drug-herb interactions can occur. Of course, benefits can also be derived that decrease the side effects of conventional medicine and/or support general recovery, a sense of well-being, and health. Even though people with cancer typically use complementary medicines along with conventional treatment, many of them do so without informing anyone on their health care team. This lack of discussion is of grave concern, especially for ingestible substances. This article considers some of the barriers to open communication about complementary treatments and provides support for why it is the health care professional's responsibility to bring up the topic for both medical and legal reasons. Strategies for initiating and guiding an informed dialogue are described and important resources are provided.

From 1 July 2007 two new rotavirus vaccines licensed for use in Australia (RotaTeq CSL Biotherapies/Merck and Rotarix Glaxo Smith Kline) will be funded for the National Immunisation Program. The vaccines differ with respect to their composition and the timing and mode of administration. Both have been evaluated in huge randomised trials and shown to be highly effective in preventing rotavirus gastroenteritis, including severe disease requiring hospital admission. Neither has been associated with an increased rate of intussusception; however, surveillance for adverse effects following vaccination will be important. As rotavirus infection is ubiquitous in young children, funding of this vaccine will significantly decrease the enormous morbidity and costs associated with this disease in our community.

Purpose of Review: Rotavirus is the most common cause of diarrhoea and dehydration in early childhood. The recent licensure in many nations of vaccines against rotavirus offers promise to significantly reduce this toll. The present review describes recent developments regarding rotavirus vaccines and the challenges they face., Recent Findings: Rotavirus causes significant morbidity and impact upon healthcare systems, at both inpatient and outpatient levels. An earlier rotavirus vaccine, since withdrawn, was temporally associated with intussusception causing small bowel obstruction, especially in infants receiving their first dose at an older age. Large-scale safety and efficacy studies of two new live, oral, attenuated vaccines have shown excellent efficacy against severe rotavirus gastroenteritis. Importantly, both studies detected no association with intussusception with these new vaccines when administered at the scheduled ages. Developed using different rotavirus vaccinology philosophies, questions remain regarding their coverage against new rotavirus serotypes. Ongoing intussusception surveillance following introduction should answer whether they may be safely administered beyond scheduled ages., Summary: Safe, efficacious rotavirus vaccines are available in many developed countries, offering significant promise to reduce the burden of gastroenteritis and dehydration. The impact of these vaccines upon not only morbidity, but also circulating rotavirus serotypes, will be monitored with interest.

Zolpidem modified-release (MR) is the first hypnotic agent to be marketed in an extended-release formulation. Zolpidem MR is a two-layered, biphasic release tablet indicated for the management of induction of sleep and sleep maintenance. The pharmacokinetics of the drug are similar to those of immediate-release zolpidem. Two double-blind, placebo-controlled, parallel-group trials demonstrated efficacy in adults and elderly patients treated with zolpidem MR for 3 weeks without significant impairment in next-day psychomotor functioning. The most common adverse effects with zolpidem MR were dizziness, somnolence, and headache. A starting dose of zolpidem MR 12.5 mg is recommended for adults and 6.25 mg for elderly patients.

An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology and dosing.

An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Twenty-one intussusception (IS)-associated and 59 temporally linked adenoviral isolates from clinical infections were compared. Species C (15/21 IS- and 32/59 non-IS-associated isolates) dominated. Of these, serotype 2 (AdV-2) (7/15 IS-associated isolates) and serotype 1 (AdV-1) (16/32 non-IS-associated isolates) were the most commonly identified serotypes. DNA restriction analysis of AdV-2 isolates identified six genomic types; of these, type D2 (3/7 IS- and 8/11 non-IS-associated isolates) was the dominant type after BamHI and SmaI digestion. IS-associated isolates are similar to circulating non-IS-associated strains.

During 2001, an outbreak of severe acute gastroenteritis swept through Central and northern Australia and caused serious disruption to health services. We tracked and characterized the rotavirus strain implicated in the outbreak. Comparison of the electropherotypes of outbreak samples suggested that one G9P[8] strain was likely responsible for the outbreak. Samples were obtained from geographically distinct regions of Australia where the epidemic had occurred. The outbreak strains showed identical nucleotide sequences in genes encoding three rotavirus proteins, VP7, VP8, and NSP4, but they were distinct from G9P[8] strains isolated in previous years. Several of the amino acid substitutions on the VP7 and NSP4 proteins were identified in regions known to influence function and may have contributed to the emergence and increased dominance of the outbreak strains. Rotavirus serotype surveillance should continue with methods capable of identifying new and emerging types.

The National Rotavirus Reference Centre together with collaborating laboratories Australia-wide has conducted rotavirus surveillance since June 1999. This report describes the serotypes of rotavirus strains responsible for the hospitalisation of children with acute gastroenteritis during the period 1 July 2003 to 30 June 2004. We examined 688 faecal samples using monoclonal antibody immunoassays, reverse transcription-polymerase chain reaction and polyacrylamide gel analysis. This revealed that serotype G1 has re-emerged as the major serotype nationally, representing 40 per cent of all strains, followed by serotype G3 (25.7%) serotype G2 (17.1%) and serotype G9 (11.7%). However, there is substantial geographic variation in the prevalence of rotavirus serotypes. These findings have implications for vaccine development strategies which have targeted prevention of disease due to serotypes G1-G4.

Rotavirus serotype G9 is recognized as the most widespread of the emerging serotypes, emerging since 1996 as a frequent cause of severe acute gastroenteritis in children from many countries covering all continents of the world. This study characterized serotype G9 strains collected in three widely separated Australian centers from 1997 to 2001. All G9 strains possessed the VP4 P[8] and VP6 subgroup II genes. The overall prevalence of the G9 strains increased in Australia, from 0.6% of the strains found in 1997 to 29% of the strains found in 2001. The prevalence of G9 relative to all other serotypes varied from year to year and with geographic location. In Melbourne (representing east coast urban centers), G9 made up 11 to 26% of all of the strains found from 1999 to 2001. In Perth (representing west coast urban centers), G9 made up less than 2% of the strains found in 1997 to 2000 but increased to 18.6% of the strains found in 2001. In Alice Springs (representing widely dispersed settlements in northern arid regions), G9 made up 0 to 5% of the strains found from 1997 to 2000 and was the dominant strain in 2001, making up 68.9% of all of the strains found. Three distinct antigenic groups based on reaction with neutralizing monoclonal antibodies (N-MAbs) were identified, including a dominant group (63%) that cross-reacted with the serotype G4 N-MAb. Phylogenetic analysis of the VP7-encoding gene from Australian strains, compared with a worldwide collection of G9 strains, showed that the Australian G9 strains made up a genetic group distinct from other serotype G9 strains identified in the United States and Africa. Future epidemiological studies of the occurrence of G9 strains should combine reverse transcription-PCR and typing with G1 to G4 and G9 N-MAbs to determine the extent of G9 and G4 cross-reactions among rotavirus strains, in order to assess the need to incorporate G9 strains into new candidate vaccines.

For many years, a sentinel laboratory system, the Laboratory Virology and Serology Reporting Scheme (LabVISE) has been collecting data on viral pathogens of public health importance in Australia. This report is one in a series of articles focussing on the epidemiology and public health aspects of viruses and viral groups under surveillance by LabVISE, which are of current public health interest.

In five separate fecal collections spanning three years, group A rotaviruses were detected by enzyme-linked immunosorbent assay in 35 (25%) of 142 specimens obtained from nondiarrheic, hospitalized neonates in Blantyre, Malawi. Molecular characterization of each strain identified, for the first time in neonates, a short electropherotype, genotype P[6], G8 strain type, similar to the dominant, cocirculating community strain detected in symptomatic infants in Blantyre. Partial sequence analysis of the VP4 and NSP4 genes of neonatal and community strains failed to identify changes which could explain the differences in clinical outcome. Neonatal serotype G8 rotaviruses should be considered as potential rotavirus vaccine candidates for use in Malawi.

Among 1316 rotavirus specimens collected during strain surveillance in the United States from 1996 to 1999, most strains (95%) belonged to the common types (G1 to G4 and G9), while 5% were mixed infections of common serotypes, rare strains, or not completely typeable. In this report, 2 rare (P[9],G3) and 2 partially typeable (P[6],G?; P[9],G?) strains from that study were further characterized. The P[6] strain was virtually indistinguishable by hybridization analysis in 10 of its 11 gene segments with recently isolated P2A[6],G9 strains (e.g., U.S.1205) from the United States, but had a distinct VP7 gene homologous (94.7% a.a. and 90.2% nt) to the cognate gene from P1B[4],G12 reference strain L26. Thus, this serotype P2A[6],G12 strain represents a previously unrecognized reassortant. Three P3[9] strains were homologous (97.8-98.2% aa) in the VP8 region of VP4 to the P3[9],G3 feline-like reference strain AU-1, but had a high level of genome homology to Italian bovine-like, P3[9],G3 and P3[9],G6 rotavirus strains. Two of the U.S. P3[9] strains were confirmed to be type G3 (97.2-98.2% VP7 aa homology with reference G3 strain AU-1), while the other was most similar to Italian bovine-like strain PA151 (P3[9],G6), sharing 99.0% a.a. homology in VP7. Cross-neutralization studies confirmed all serotype assignments and represented the first detection of these rotavirus serotypes in the United States. The NSP4 genes of all U.S. P3[9] strains and rotavirus PA151 were most closely related to the bovine and equine branch within the DS-1 lineage, consistent with an animal origin. These results demonstrate that rare strains with P and G serotypes distinct from those of experimental rotavirus vaccines circulate in the United States, making it important to understand whether current vaccine candidates protect against these strains.