Inhibition of CaMKK2 Enhances Fracture Healing by Stimulating Indian Hedgehog Signaling and Accelerating Endochondral Ossification

Approximately 10% of all bone fractures do not heal, resulting in patient morbidity and healthcare costs. However, no pharmacological treatments are currently available to promote efficient bone healing. Inhibition of Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) reverses age-associated loss of trabecular and cortical bone volume and strength in mice. In the current study, we investigated the role of CaMKK2 in bone fracture healing and show that its pharmacological inhibition using STO-609 accelerates early cellular and molecular events associated with endochondral ossification, resulting in a more rapid and efficient healing of the fracture. Within 7 days postfracture, treatment with STO-609 resulted in enhanced Indian hedgehog signaling, paired-related homeobox (PRX1)-positive mesenchymal stem cell (MSC) recruitment, and chondrocyte differentiation and hypertrophy, along with elevated expression of osterix, vascular endothelial growth factor, and type 1 collagen at the fracture callus. Early deposition of primary bone by osteoblasts resulted in STO-609–treated mice possessing significantly higher callus bone volume by 14 days following fracture. Subsequent rapid maturation of the bone matrix bestowed fractured bones in STO-609–treated animals with significantly higher torsional strength and stiffness by 28 days postinjury, indicating accelerated healing of the fracture. Previous studies indicate that fixed and closed femoral fractures in the mice take 35 days to fully heal without treatment. Therefore, our data suggest that STO-609 potentiates a 20% acceleration of the bone healing process. Moreover, inhibiting CaMKK2 also imparted higher mechanical strength and stiffness at the contralateral cortical bone within 4 weeks of treatment. Taken together, the data presented here underscore the therapeutic potential of targeting CaMKK2 to promote efficacious and rapid healing of bone fractures and as a mechanism to strengthen normal bones

Evaluation of the psychometric properties of the SF-36 health survey for use among Turkish and Moroccan ethnic minority populations in the Netherlands

Purpose: To evaluate the psychometrics of the SF-36 Health Survey among Turkish and Moroccan ethnic minority populations in the Netherlands and to compare the results to those based on the indigenous Dutch population. Methods: Data were derived from the Second Dutch National Survey of General Practice. In total, SF-36 data were available for 409 Turkish, 377 Moroccan, and 9,628 Dutch respondents. Language subgroup analyses were performed for the Turkish (n = 162) and Moroccan-Arabic (n = 52) versions of the SF-36. Psychometric properties were evaluated by descriptive statistics, factor analysis, internal consistency estimates, known-group comparisons, and differential item function (DIF) analysis. Results Low levels of missing SF-36 data were observed across all groups. Confirmatory factor analysis supported the hypothesized SF-36 scale structure for the Dutch and Turkish group, but high correlations between the MH and VT factors were observed in the Moroccan group. All Cronbach’s alpha coefficients were above 0.70, except for the Vitality scale in the Moroccan group and the Vitality and Social Functioning scales in the Moroccan-Arabic language subgroup. Known-groups validity was found across samples using age, sex, education, and comorbidity as grouping variables, but not marital status. Some evidence for DIF was found in both ethnic group samples. Conclusions: The results generally support the use of the SF-36 for general population research among Turkish and Moroccan ethnic minorities in the Netherlands. Additional studies are needed to confirm the psychometrics of the questionnaire when used among these populations in other Western European countries. (aut. ref.

The relationship between Europeanisation and policy styles: a study of agricultural and public health policymaking in three EU Member States

© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDer-ivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distri-bution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.The role of policy styles in policymaking has attracted renewed scholarly interestin recent years. One of the central debates in this literature revolves around thequestion of how to reconcile archetype national policy styles with considerabledifferences in modus operandi across policy sectors. A sector-specific featurethat is considered a key determinant of the manifestation of archetypenational policy styles in the European Union is the degree of Europeanisationof policy sectors. This paper picks up this suggestion by addressing thequestion of whether and how Europeanisation affects the degree to whichfeatures of an archetype national policy style are manifest within a sector. Weaddress this question by exploring sectoral policy styles in agricultural andfood-related public health policymaking across three EU Member States: TheNetherlands, the United Kingdom (England), and France. Our findings suggestthat the degree of Europeanisation of a policy sector does prove an importantcondition that helps to understand the relationship between national andsectoral policy styles. More specifically, Europeanisation has the strongesteffect when sectors face a higher adaptation pressure, i.e., when there is alarger misfit between sectoral regimes and EU-induced institutional demands.We suggest various promising avenues of future research on this relationship.Peer reviewe

Clinical practice guidelines for the foot and ankle in rheumatoid arthritis: a critical appraisal

Background: Clinical practice guidelines are recommendations systematically developed to assist clinical decision-making and inform healthcare. In current rheumatoid arthritis (RA) guidelines, management of the foot and ankle is under-represented and the quality of recommendation is uncertain. This study aimed to identify and critically appraise clinical practice guidelines for foot and ankle management in RA. Methods: Guidelines were identified electronically and through hand searching. Search terms 'rheumatoid arthritis', 'clinical practice guidelines' and related synonyms were used. Critical appraisal and quality rating were conducted using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Results: Twenty-four guidelines were included. Five guidelines were high quality and recommended for use. Five high quality and seven low quality guidelines were recommended for use with modifications. Seven guidelines were low quality and not recommended for use. Five early and twelve established RA guidelines were recommended for use. Only two guidelines were foot and ankle specific. Five recommendation domains were identified in both early and established RA guidelines. These were multidisciplinary team care, foot healthcare access, foot health assessment/review, orthoses/insoles/splints, and therapeutic footwear. Established RA guidelines also had an 'other foot care treatments' domain. Conclusions: Foot and ankle management for RA features in many clinical practice guidelines recommended for use. Unfortunately, supporting evidence in the guidelines is low quality. Agreement levels are predominantly 'expert opinion' or 'good clinical practice'. More research investigating foot and ankle management for RA is needed prior to inclusion in clinical practice guidelines

An outbreak of ST307 extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae in a rehabilitation center: An unusual source and route of transmission

Objective: Nosocomial outbreaks due to multidrug-resistant microorganisms in rehabilitation centers have rarely been reported. We report an outbreak of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (ESBL-K. pneumoniae) on a single ward in a rehabilitation center in Rotterdam, The Netherlands.Design: Outbreak description.Setting: A 40-bed ward of a rehabilitation center in the Netherlands.Methods: In October 2016, 2 patients were found to be colonized by genetically indistinguishable ESBL-K. pneumoniae isolates. Therefore, an outbreak management team was installed, by whom a contact tracing plan was made. In addition to general outbreak measures, specific measures were formulated to allow continuation of the rehabilitation process. Also, environmental cultures were taken. Multiple-locus variable-number tandem-repeat analysis and amplification fragment-length polymorphism were used to determine strain relatedness. Selected isolates were subjected to whole-genome multilocus sequence typing.Results: The outbreak lasted 8 weeks. In total, 14 patients were colonized with an ESBL-K. pneumoniae, of whom 11 patients had an isolate belonging to

Hepatitis B virus infected health care workers in the Netherlands, 2000-2008

In response to the confirmed transmission of hepatitis B virus (HBV) from a surgeon to several patients in the Netherlands, a ‘Committee for Prevention of Iatrogenic Hepatitis B’ was established in 2000. During the years 2000–2008, the committee reviewed 99 cases of HBV-infected health care workers. Fifty of them were found to perform exposure prone procedures (EPPs). Because of high levels of HBV DNA (>100,000 copies/ml), a ban on performing EPPs was applied in 11/50 cases; 25/50 low-viremic health care workers were allowed to continue EPPs while their HBV load was being monitored; and 14/50 cases had stopped working or changed profession. In five restricted workers who started oral antiviral treatment, HBV replication was persistently suppressed, enabling the ban on EPPs to be lifted. Throughout the European Union different levels of HBV viremia have been chosen, above which health care workers are not allowed to perform EPPs. It remains unknown how this affects the safety of patients. Application in the Netherlands of a European or a British guideline would have, respectively, doubled or tripled the number of restricted health care workers

The cost-effectiveness of a new disease management model for frail elderly living in homes for the elderly, design of a cluster randomized controlled clinical trial

<p>Abstract</p> <p>Background</p> <p>The objective of this article is to describe the design of a study to evaluate the clinical and economic effects of a Disease Management model on functional health, quality of care and quality of life of persons living in homes for the elderly.</p> <p>Methods</p> <p>This study concerns a cluster randomized controlled clinical trial among five intervention homes and five usual care homes in the North-West of the Netherlands with a total of over 500 residents. All persons who are not terminally ill, are able to be interviewed and sign informed consent are included. For cognitively impaired persons family proxies will be approached to provide outcome information. The Disease Management Model consists of several elements: (1) Trained staff carries out a multidimensional assessment of the patients functional health and care needs with the interRAI Long Term Care Facilities instrument (LTCF). Computerization of the LTCF produces immediate identification of problem areas and thereby guides individualized care planning. (2) The assessment outcomes are discussed in a Multidisciplinary Meeting (MM) with the nurse, primary care physician, nursing home physician and Psychotherapist and if necessary other members of the care team. The MM presents individualized care plans to manage or treat modifiable disabilities and risk factors. (3) Consultation by an nursing home physician and psychotherapist is offered to the frailest residents at risk for nursing home admission (according to the interRAI LTCF). Outcome measures are Quality of Care indicators (LTCF based), Quality Adjusted Life Years (Euroqol), Functional health (SF12, COOP-WONCA), Disability (GARS), Patients care satisfaction (QUOTE), hospital and nursing home days and mortality, health care utilization and costs.</p> <p>Discussion</p> <p>This design is unique because no earlier studies were performed to evaluate the effects and costs of this Disease Management Model for disabled persons in homes for the elderly on functional health and quality of care.</p> <p>Trail registration number</p> <p>ISRCTN11076857</p

Grammar disruption in a patient with Neuro-Sweet syndrome

This paper for the first time reports detailed neurolinguistic findings in a patient with Neuro-Sweet syndrome. In this patient the presenting symptoms of central nervous system (CNS) involvement primarily consisted of a selective grammar deficit restricted to spontaneous speech. On MRI a left prefrontal ischemic stroke (superior part BA 6) and two small subcortical left parietal infarctions were found. Neurolinguistic analyses, however, did not reveal a profile consistent with any observations of agrammatism caused by structural damage to the language areas critically involved in grammatical processing. It is hypothesized that selectively distorted grammar might reflect disruption of the frontosubcortical network involved in language processing. Prefrontal neurobehavioral abnormalities associated with functional disruption of the inferior medial frontal regions as demonstrated by SPECT, additionally suggest that agrammatic symptoms may be linked to a higher-level cognitive disorder following encephalopathic CNS involvement