Sheep condyle model evaluation of bone marrow cell concentrate combined with a scaffold for repair of large osteochondral defects

AIMS: Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone. METHODS: The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety. RESULTS: The results six months postoperatively showed that there were no significant differences in bone regrowth and mineral density between BMC-treated animals and controls. A significant upregulation of messenger RNA (mRNA) for types I and II collagens in the BMC group was observed, but there were no differences in the formation of hyaline-like cartilage between the groups. A trend towards reduced sulphated glycosaminoglycans (sGAG) breakdown was detected in the BMC group but this was not statistically significant. Functional weightbearing was not affected by the inclusion of BMC. CONCLUSION: Our results indicated that the addition of BMC to scaffold is safe and has some potentially beneficial effects on osteochondral-tissue regeneration, but not on the functional endpoint of orthopaedic interest. Cite this article: Bone Joint Res 2021;10(10):677-689

Vaccination against Foot-and-mouth disease : do initial conditions affect its benefit?

When facing incursion of a major livestock infectious disease, the decision to implement a vaccination programme is made at the national level. To make this decision, governments must consider whether the benefits of vaccination are sufficient to outweigh potential additional costs, including further trade restrictions that may be imposed due to the implementation of vaccination. However, little consensus exists on the factors triggering its implementation on the field. This work explores the effect of several triggers in the implementation of a reactive vaccination-to-live policy when facing epidemics of foot-and-mouth disease. In particular, we tested whether changes in the location of the incursion and the delay of implementation would affect the epidemiological benefit of such a policy in the context of Scotland. To reach this goal, we used a spatial, premises-based model that has been extensively used to investigate the effectiveness of mitigation procedures in Great Britain. The results show that the decision to vaccinate, or not, is not straightforward and strongly depends on the underlying local structure of the population-at-risk. With regards to disease incursion preparedness, simply identifying areas of highest population density may not capture all complexities that may influence the spread of disease as well as the benefit of implementing vaccination. However, if a decision to vaccinate is made, we show that delaying its implementation in the field may markedly reduce its benefit. This work provides guidelines to support policy makers in their decision to implement, or not, a vaccination-to-live policy when facing epidemics of infectious livestock disease

Rank-based poverty measures and poverty ordering with an application to Tunisia

Using the normative approach, we develop a class of poverty measures that is function of a weighting system. Each particular weighting function corresponds to a particular social judgment. This offers the decision-maker a large selection of social preferences functions, and he can choose the one that best represents his social judgment. We also develop new concepts of a-extended TIP curves. They are used to establish the conditions of the robust and unanimous poverty ranking of our measures. These conditions are in terms of second-and higher-degree TIP dominance. Finally, we provide an empirical illustration using Tunisian data on the 2005–2010 period.info:eu-repo/semantics/publishedVersio

Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders

How the genome activates or silences transcriptional programmes governs organ formation. Little is known in human embryos undermining our ability to benchmark the fidelity of stem cell differentiation or cell programming, or interpret the pathogenicity of noncoding variation. Here, we study histone modifications across thirteen tissues during human organogenesis. We integrate the data with transcription to build an overview of how the human genome differentially regulates alternative organ fates including by repression. Promoters from nearly 20,000 genes partition into discrete states. Key developmental gene sets are actively repressed outside of the appropriate organ without obvious bivalency. Candidate enhancers, functional in zebrafish, allow imputation of tissue-specific and shared patterns of transcription factor binding. Overlaying more than 700 noncoding mutations from patients with developmental disorders allows correlation to unanticipated target genes. Taken together, the data provide a comprehensive genomic framework for investigating normal and abnormal human development

The association of cold weather and all-cause and cause-specific mortality in the island of Ireland between 1984 and 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. Methods A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and cold period (October-March), using distributed lag models. Model stratification by age and gender assessed for modification of the cold weather-mortality relationship. Results In the ROI, the impact of cold weather in winter persisted up to 35 days, with a cumulative mortality increase for all-causes of 6.4% (95%CI=4.8%-7.9%) in relation to every 1oC drop in daily maximum temperature, similar increases for cardiovascular disease (CVD) and stroke, and twice as much for respiratory causes. In NI, these associations were less pronounced for CVD causes, and overall extended up to 28 days. Effects of cold weather on mortality increased with age in both jurisdictions, and some suggestive gender differences were observed. Conclusions The study findings indicated strong cold weather-mortality associations in the island of Ireland; these effects were less persistent, and for CVD mortality, smaller in NI than in the ROI. Together with suggestive differences in associations by age and gender between the two Irish jurisdictions, the findings suggest potential contribution of underlying societal differences, and require further exploration. The evidence provided here will hope to contribute to the current efforts to modify fuel policy and reduce winter mortality in Ireland

ruvA Mutants that resolve Holliday junctions but do not reverse replication forks

RuvAB and RuvABC complexes catalyze branch migration and resolution of Holliday junctions (HJs) respectively. In addition to their action in the last steps of homologous recombination, they process HJs made by replication fork reversal, a reaction which occurs at inactivated replication forks by the annealing of blocked leading and lagging strand ends. RuvAB was recently proposed to bind replication forks and directly catalyze their conversion into HJs. We report here the isolation and characterization of two separation-of-function ruvA mutants that resolve HJs, based on their capacity to promote conjugational recombination and recombinational repair of UV and mitomycin C lesions, but have lost the capacity to reverse forks. In vivo and in vitro evidence indicate that the ruvA mutations affect DNA binding and the stimulation of RuvB helicase activity. This work shows that RuvA's actions at forks and at HJs can be genetically separated, and that RuvA mutants compromised for fork reversal remain fully capable of homologous recombination

Treatment of head lice with dimeticone 4% lotion: comparison of two formulations in a randomised controlled trial in rural Turkey

<p>Abstract</p> <p>Background</p> <p>Dimeticone 4% lotion was shown to be an effective treatment for head louse infestation in two randomised controlled trials in England. It is not affected by insecticide resistance but efficacy obtained (70-75%) was lower than expected. This study was designed to evaluate efficacy of dimeticone 4% lotion in a geographically, socially, and culturally different setting, in rural Turkey and, in order to achieve blinding, it was compared with a potential alternative formulation.</p> <p>Methods</p> <p>Children from two village schools were screened for head lice by detection combing. All infested students and family members could participate, giving access to treatment for the whole community. Two investigator applied treatments were given 7 days apart. Outcome was assessed by detection combing three times between treatments and twice the week following second treatment.</p> <p>Results</p> <p>In the intention to treat group 35/36 treated using dimeticone 4% had no lice after the second treatment but there were two protocol violators giving 91.7% treatment success. The alternative product gave 30/36 (83.3%) treatment success, a difference of 8.4% (95% CI -9.8% to 26.2%). The cure rates per-protocol were 33/34 (97.1%) and 30/35 (85.7%) respectively. We were unable to find any newly emerged louse nymphs on 77.8% of dimeticone 4% treated participants or on 66.7% of those treated with the alternative formulation. No adverse events were identified.</p> <p>Conclusion</p> <p>Our results confirm the efficacy of dimeticone 4% lotion against lice and eggs and we found no detectable difference between this product and dimeticone 4% lotion with nerolidol 2% added. We believe that the high cure rate was related to the lower intensity of infestation in Turkey, together with the level of community engagement, compared with previous studies in the UK.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN10431107</p

Comparison of balance assessment modalities in emergency department elders: a pilot cross-sectional observational study

<p>Abstract</p> <p>Background</p> <p>More than one-third of US adults 65 and over fall every year. These falls may cause serious injury including substantial long-term morbidity (due declines in activities of daily living) and death. The emergency department (ED) visit represents an opportunity for identifying high risk elders and potentially instituting falls-related interventions. The unique characteristic of the ED environment and patient population necessitate that risk-assessment modalities be validated in this specific setting. In order to better identify elders at risk of falls, we examined the relationship between patient-provided history of falling and two testing modalities (a balance plate system and the timed up-and-go [TUG] test) in elder emergency department (ED) patients.</p> <p>Methods</p> <p>We conducted a cross-sectional observational study of patients ≥ 60 years old being discharged from the ED. Patient history of falls in the past week, month, 6 months, and year was obtained. Balance plate center of pressure excursion (COP) measurements and TUG testing times were recorded. COP was recorded under four conditions: normal stability eyes open (NSEO) and closed (NSEC), and perturbed stability eyes open and closed. Correlation between TUG and COP scores was measured. Univariate logistic regression was used to identify the relationship between patient-provided falls history and the two testing modalities. Proportions, likelihood ratios, and receiver-operating-characteristic (ROC) curves for prediction of previous falls were reported.</p> <p>Results</p> <p>Fifty-three subjects were enrolled, 11% had fallen in the previous week and 42% in the previous year. There was no correlation between TUG and any balance plate measurements. In logistic regression, neither testing modality was associated with prior history of falls (<it>p </it>> 0.05 for all time periods). Balance plate NSEO and NSEC testing cutoffs could be identified which were 83% sensitive and had a negative likelihood ratio (LR-) of 0.3 for falls in the past week. TUG testing was not useful for falls in the past week, but performed best for more distant falls in the past month, 6 months, or year. TUG cutoffs with sensitivity over 80% and LR(-) of 0.17-0.32 could be identified for these time periods.</p> <p>Conclusion</p> <p>Over 40% of community-dwelling elder ED patients report a fall within the past year. Balance plate and TUG testing were feasibly conducted in an ED setting. There is no relationship between scores on balance plate and TUG testing in these patients. In regression analysis, neither modality was significantly associated with patient provided history of falls. These modalities should not be adopted for screening purposes in elders in the ED setting without validation in future studies or as part of multi-factorial risk assessment.</p