Review of literature and clinical practice experience for the therapeutic management of Morgellons disease.

Morgellons disease (MD) is a rare and contentious health condition characterized by dermatological symptoms including slow-healing skin lesions 'attributed' to fibres emerging from or under the skin. Patients also report sensations of crawling, biting and infestation with inanimate objects. This review examines the aetiology, patient characteristics, epidemiology, historical context, correlation with Lyme disease, role of internet, impact on quality of life and treatment approaches for MD. Despite ongoing debate, MD is not officially recognized in medical classifications, with differing views on its aetiology. Some link MD to Lyme disease, while others view it as a variant of delusional infestation. The literature suggests both psychiatric and environmental factors may contribute. The manuscript explores the association with substance abuse, psychiatric comorbidities, infectious agents and the role of internet communities in shaping perceptions. MD's impact on quality of life is significant, yet often overlooked. Treatment approaches are varied due to limited evidence, with low-dose antipsychotics being considered effective, but patient beliefs may influence adherence. A patient-centred, multidisciplinary approach is emphasized, considering both the physical and psychological dimensions of MD. Addressing the controversies surrounding MD while focusing on patient well-being remains a critical challenge for healthcare professionals.

Exploring the directionality in the relationship between descriptive and injunctive parental and peer norms and snacking behavior in a three-year-cross-lagged study.

BACKGROUND: People's eating behavior is assumed to be influenced by what other people do (perceived descriptive norms) and what others approve of (perceived injunctive norms). It has been suggested that adolescents are more susceptible to peer norms than parental norms, because they experience a strong need for group acceptance that leads to conforming to peer group norms. The current study examined changes in snacking behavior and four types of social norms (i.e., parental and peer descriptive and injunctive norms) that promoted fruit and vegetable intake among adolescents. This study was the first to examine whether snacking behavior also influenced norm perceptions by testing the directionality of these associations. METHODS: The study consisted of 819 participants (M [SD] age = 11.19 [1.36]; 46.1% boys), collected at three time points (T1 = 2016, T2 = 2017 and T3 = 2018) during the MyMovez project. Self-reported frequency of snack consumption, perceived parental and peer descriptive and injunctive norms were assessed. The primary analysis consisted of a series of cross-lagged autoregressive models specified in a structural equation modeling framework. RESULTS: Model comparisons testing the descriptive and injunctive norms in separate models and in an additional combined model revealed evidence for bi-directional associations between norms and snacking behavior. Descriptive peer and parent norms were not found to have an effect on subsequent snacking behaviors. Perceived injunctive parental norms were positively associated with healthy snack food intake and negatively associated with unhealthy snack intake (forward direction). Injunctive peer norms were negatively associated with healthy snack food intake. In addition, higher unhealthy snack food intake was negatively associated with the perception of descriptive and injunctive parental norms 1 year later (reversed direction). We did not find peer norms to be more closely associated with changes in snacking behaviors compared to parental norms. CONCLUSIONS: Parents expecting their children to snack healthy had a positive influence on healthy snacking behavior whereas only acting as a healthy role model did not. Future research should address the possible interaction between descriptive and injunctive norms. Research should also take into account the bi-directional relations between eating behaviors and normative perceptions.

Experienced sitting-related problems and association with personal, lesion and wheelchair characteristics in persons with long-standing paraplegia and tetraplegia.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To describe experienced sitting-related health and stability problems among persons with paraplegia (PP) or tetraplegia (TP) and to investigate associations with personal, lesion and wheelchair characteristics as well as satisfaction with sitting posture. SETTING: Dutch community. METHODS: A self-report questionnaire on seating was developed and completed by wheelchair-users living with Spinal Cord Injury (SCI) for ≥10 years (N = 264). Sitting-related problems and satisfaction with sitting posture were compared between participants with PP and TP using Chi-square and t-tests. Logistic regression analyses were performed to investigate associated characteristics. RESULTS: Reported sitting-related problems comprised: sitting to be tiring (regularly to always) (33%), sitting to be painful (28%), pressure ulcers in the last three months (29%), instability while sitting (8%) and instability during reaching (33%). Except for instability during reaching, no differences in occurrence of sitting-problems were found between lesion-group. Persons with TP were more dissatisfied with their sitting posture than persons with PP: 51% vs 36% (p = 0.022) and 51% and 47% respectively thought their sitting posture could be improved (p = 0.670). 'Experienced lack of support in the wheelchair' was associated with most sitting-problems. Pain and instability were associated with dissatisfaction with sitting posture. CONCLUSION: Sitting-related problems and dissatisfaction with sitting posture were frequently reported by persons with long-standing SCI. Sitting problems appeared to associate with lacking support in the wheelchair/seating. A comprehensive feedback from the wheelchair user and a stability check (reach task), as part of the wheelchair/seating-user fitting, may contribute to prevention of sitting-related problems.

Correction: Experienced sitting-related problems and association with personal, lesion and wheelchair characteristics in persons with long-standing paraplegia and tetraplegia.

A correction to this paper has been published and can be accessed via a link at the top of the paper.

Management of drug interactions with direct-acting antivirals in Dutch HIV/hepatitis C virus-coinfected patients: adequate but not perfect.

OBJECTIVES: Direct-acting antivirals (DAAs) for treatment of chronic hepatitis C virus (HCV) infection can cause drug-drug interactions (DDIs) with combination antiretroviral therapy (cART) and non-cART co-medication. We mapped how physicians manage DDIs between DAAs and co-medication and analysed treatment outcomes. METHODS: Data were prospectively collected as part of the ATHENA HIV observational cohort and retrospectively analysed. Dutch patients with HIV/HCV coinfection who initiated treatment with DAAs between January 2015 and May 2016 were included. Co-medication 3 months prior to and during DAA therapy was identified. Potential DDIs with the DAAs were checked using http://hep-druginteractions.org. DDIs were categorized as: (1) no interaction expected; (2) potential interaction; (3) contra-indication; (4) no recommendation. These categories were used to determine which patients switched or had a DDI during DAA therapy with co-medication. RESULTS: A total of 423 patients were treated with DAAs, of whom 418 (99%) used cART and 251 (59%) used non-cART co-medication. Before commencing DAA treatment, in 17 of 84 (20%) patients the non-cART co-medication which could result in a category 2/3 DDI was discontinued before DAA initiation, including two of six (33%) prescriptions of category 3 drugs. A total of 196 of 418 (47%) patients had a category 2/3 DDI between their DAA regimen and cART. Category 2/3 DDIs were prevented by switching cART in 78 of 147 (53%) and 47 of 49 (98%) patients. Overall, 367 of 423 (87%) patients have achieved a sustained virological response (33 in follow-up). CONCLUSIONS: Prescription patterns suggest that physicians are aware of potential DDIs between co-medication and DAAs, in particular potential DDIs with cART. Greater awareness is needed concerning category 3 interactions between non-cART co-medication and DAAs.

Impact of health problems secondary to SCI one and five years after first inpatient rehabilitation.

STUDY DESIGN: This is a multicenter prospective cohort study. OBJECTIVES: The objective of this study was to describe and compare the impact of health problems secondary to spinal cord injury (SCI) on functioning at home and on social activities at 1 and 5 years after discharge from first inpatient rehabilitation. SETTING: The study was conducted in a Dutch community. METHODS: Participants with SCI who use a wheelchair for everyday mobility (N=110) completed a self-report questionnaire as part of a larger cohort study including four items on extra time needed (body care, bladder and bowel regulation, 'organization' and transportation) and impact of 10 health problems on functioning at home and on social activities. The 10 health problems include secondary health conditions (bladder regulation, bowel regulation, decubitus, pain, spasticity, gain in body weight and edema), psychosocial problems (sexuality, having difficulty with being dependent on help from others) and handicap management. RESULTS: Median extra time needed for self-management and transportation was not significantly higher 1 year after discharge (16 (IQR 13.5) h per week) compared with 5 years after discharge (13 (IQR 17) h per week) (P=0.925). Participants reported slightly less impact, comparing the severity sum-score (range 10-50) of the 10 health problems on functioning at home and in social activities, 5 years post discharge (20 and 17, respectively) than 1 year post discharge (21 and 18, respectively; P<0.05). Most frequently mentioned health problems were handicap management, being dependent on help from others, bladder regulation, bowel regulation, pain and sexuality. CONCLUSIONS: The impact of health problems after SCI is considerable and hardly diminishes over time. These results emphasize the need for structured long-term care for people with SCI.

Virological and Social Outcomes of HIV-Infected Adolescents and Young Adults in The Netherlands Before and After Transition to Adult Care.

BACKGROUND: As a result of effective combination antiretroviral therapy (cART) and advanced supportive healthcare, a growing number of human immunodeficiency virus (HIV)-infected children survive into adulthood. The period of transition to adult care is often associated with impaired adherence to treatment and discontinuity of care. We aimed to evaluate virological and social outcomes of HIV-infected adolescents and young adults (AYAs) before and after transition, and explore which factors are associated with virological failure. METHODS: We included 59 HIV-infected AYAs from the Netherlands who had entered into pediatric care and transitioned from pediatric to adult healthcare. We used HIV RNA load and cART data from the Dutch Stichting HIV Monitoring database (1996-2014), and collected social and treatment data from patients' medical records from all Dutch pediatric HIV treatment centers and 14 Dutch adult treatment centers involved. We evaluated risk factors for virological failure (VF) in a logistic regression model adjusted for repeated measurements. RESULTS: HIV VF occurred frequently during the study period (14%-36%). During the transition period (from 18 to 19 years of age) there was a significant increase in VF compared with the reference group of children aged 12-13 years (odds ratio, 4.26 [95% confidence interval, 1.12-16.28]; P = .03). Characteristics significantly associated with VF were low educational attainment and lack of autonomy regarding medication adherence at transition. CONCLUSIONS: HIV-infected AYAs are vulnerable to VF, especially during the transition period. Identification of HIV-infected adolescents at high risk for VF might help to improve treatment success in this group.

Evidence for and cost-effectiveness of physiotherapy in haemophilia: a Dutch perspective.

INTRODUCTION: Musculoskeletal impact of haemophilia justifies physiotherapy throughout life. Recently the Dutch Health Care Institute constrained their 'list of chronic conditions', and withdrew financial coverage of physiotherapy for elderly persons with haemophilia (PWH). This decision was based on lack of scientific evidence and not being in accordance with 'state of science and practice'. METHODS: In general, evidence regarding physiotherapy is limited, and especially in rare diseases like haemophilia. 'Evidence based medicine' classifies and recommends evidence based on meta-analyses, systematic reviews and randomized controlled trials, but also means integrating evidence with individual clinical expertise. For the evaluation of physiotherapy - usually individualized treatment - case studies, observational studies and Case Based Reasoning may be more beneficial. RESULTS: Overall annual treatment costs for haemophilia care in the Netherlands are estimated over 100 million Euros, of which 95% is covered by clotting factor concentrates. The cost for physiotherapy assessments in all seven Dutch HTCs (seven centres for adult PWH and seven centres for children) is limited at approximately 500 000 Euros annually. Costs of the actual physiotherapy sessions, carried out in our Dutch first-line care system, will also not exceed 500 000 Euros. Thus, implementation of physiotherapy in haemophilia care the Netherlands in a most optimal way would cost less than 1% of the total budget. AIM: The present paper describes the role of physiotherapy in haemophilia care including available evidence and providing suggestions regarding generation of evidence. Establishing the effectiveness and cost-effectiveness of physiotherapy in haemophilia care is a major topic for the next decennium.

Electromechanical abdominal massage and colonic function in individuals with a spinal cord injury and chronic bowel problems.

STUDY DESIGN: A prospective intervention of noninvasive abdominal massage using an electromechanical apparatus on bowel function in individuals with spinal cord injury (SCI). OBJECTIVES: To evaluate the effects of noninvasive abdominal massage using an electromechanical apparatus on bowel function in individuals with SCI and chronic bowel problems. This easy-to-use apparatus can be applied by the patients at home without the help of a therapist. SETTING: Homes of community-living individuals. METHODS: Twenty-one subjects with SCI were instructed to use the massage apparatus daily for 20 min during a 10-week period. Compliance, effects, side effects and user satisfaction were assessed using questionnaires. RESULTS: Fifteen subjects completed the 10-week period. Although some characteristics of defecation changed positively for some of the subjects (time to result, amount, consistency), none felt better or more confident after using the massage device. In addition, some individuals experienced negative side effects (predominantly pain or discomfort). The overall satisfaction with the device is ambiguous, with half of the group judging the device as insufficient and the other half as at least adequate. CONCLUSION: The use of an electromechanical massage device does not improve bowel function in most individuals with SCI who have chronic bowel problems. Why some subjects benefit and others do not should be investigated in future studies.

Identification of 2 Distinct Boundaries Distinguishes Critical From Noncritical Isthmuses in Ablating Atypical Atrial Flutter.

BACKGROUND: Atypical atrial flutters often involve complex circuits. Classic methods of identifying ablation targets, including detailed electroanatomical mapping and entrainment within a well-defined isthmus, may not always be sufficient to allow the critical isthmus to be delineated and ablated, with flutter termination and prevention of reinduction. OBJECTIVES: This study sought a systematic method to classify conduction barriers and isthmuses as critical or noncritical that would improve understanding and ablation success. We also sought a construct unifying single- and dual-loop re-entry. Re-entrant circuits are bounded on 2 sides, although these are not consistently identified. We hypothesized 2 distinct critical boundaries, and a critical isthmus could be consistently defined without requiring entrainment, and ablation connecting these 2 boundaries would terminate tachycardia. METHODS: Activation maps were created electroanatomically. Conduction barriers were classified as noncritical barriers or critical boundaries. Critical boundaries showed sequential activation around the barrier, spanning ≥90% of the cycle length. Noncritical barriers showed nonsequential, parallel, or colliding activation or <90% of the cycle length. Only tissue separating the 2 critical boundaries defined a critical isthmus (CI); all others were considered noncritical. The effect of ablation across a CI was assessed. RESULTS: Complete maps were obtained in 128 cases in 121 patients (28 atypical right atrial, 100 left atrial). In all cases, 2 distinct critical boundaries were identified. Ablation across a CI connecting these critical boundaries terminated tachycardia in 123 of 128 cases (96.1%). Failures were due to inability to achieve block across the isthmus. CONCLUSIONS: Activation mapping of atypical atrial flutter allows consistent identification of 2 critical boundaries. Successful ablation connecting the 2 critical boundaries reliably results in termination of atypical atrial flutter.

Gluteal blood flow and oxygenation during electrical stimulation-induced muscle activation versus pressure relief movements in wheelchair users with a spinal cord injury.

BACKGROUND: Prolonged high ischial tuberosities pressure (IT pressure), decreased regional blood flow (BF) and oxygenation (%SO2) are risk factors for developing pressure ulcers (PUs) in patients with spinal cord injury (SCI). Electrical stimulation (ES)-induced gluteal and hamstring muscle activation may improve pressure distribution by changing the shape of the buttocks while sitting and also increase BF and %SO2. OBJECTIVE: To compare acute effects of ES-induced gluteal and hamstring muscle activation with pressure relief movements (PRMs) on IT pressure, BF and %SO2. PARTICIPANTS AND METHODS: Twelve men with SCI performed PRMs - push-ups, bending forward and leaning sideward - and received surface ES (87±19 mA) to the gluteal and hamstring muscles while sitting in their wheelchair. Ischial tuberosities pressure was measured using a pressure mapping system; (sub)cutaneous BF and %SO2 were measured using reflection spectroscopy and laser Doppler, respectively. RESULTS: Compared with rest (156±26 mm Hg), IT pressure was significantly lower during all other conditions (push-ups 19±44; bending forward 56±33; leaning sideward 44±38; ES 67±45 mm Hg). For the whole group, all PRMs significantly augmented BF (+39 to -96%) and %SO2 (+6.0 to -7.9%-point), whereas ES-induced muscle activation did only for peak BF. In all, 63% of the participants showed an increased BF (average 52%) with ES. CONCLUSION: PRMs acutely reduced IT pressure and improved oxygenation and BF in SCI. The currently used ES method cannot replace PRMs, but it may be used additionally. ES-induced muscle activation is not as effective for acute pressure relief, but the frequency of stimulation is much higher than the performance of PRMs and can therefore be more effective in the long term.

Acceptance and timeliness of post-exposure vaccination against mpox in high-risk contacts, Amsterdam, the Netherlands, May-July 2022.

BACKGROUND: May 2022, several countries reported mpox outbreaks among men-who-have-sex-with-men. In the Netherlands, high-risk contacts were offered the third-generation smallpox vaccine as post-exposure-prophylaxis (PEP) within 4 but maximum 14 days after exposure. We investigated their PEP acceptance, timeliness of uptake and development of mpox for the region of the Public Health Service (PHS) Amsterdam. METHODS: High-risk contacts identified during 20 May-22 July 2022 were included. Contacts were followed-up 21 days after exposure and classified as: no patient (no mpox symptoms or orthopoxvirus PCR-negative) or mpox patient (clinically suspected mpox or orthopoxvirus PCR-positive). We calculated time intervals between date of last exposure and first PHS consultation, PEP administration, and symptom onset. RESULTS: Two-hundred-ninety contacts were at high-risk of mpox predominantly due to sexual and/or direct skin-skin contact (212/290, 73 %). First PHS consultation was a median of 5 (IQR 3, 7) days after exposure, at which point 26/290 (9 %) contacts were ineligible for PEP. 84 % (223/264) of contacts eligible for PEP, received PEP within a median of 6 (IQR 3, 8) days after exposure. Of 282 contacts (missing outcome n = 8) 38 (14 %) developed mpox a median of 7 (IQR 5, 12) days after exposure, of whom 50 % (19/38) developed mpox before their first PHS consultation. Among contacts eligible for PEP, 2/38 (5 %) unvaccinated and 16/218 (7 %) vaccinated contact developed mpox. CONCLUSIONS: PEP acceptance among contacts of mpox patients was high. However, PEP timeliness was inadequate. Half of contacts received PEP 6 or more days after exposure, and half of contacts who developed mpox had an onset prior to their first PHS consultation. Estimating PEP vaccine effectiveness is problematic due to the timeliness of PEP and the time it takes to generate vaccine-induced immunity. It is important to assess how PEP timeliness may improve and to promote pre-exposure vaccination to control mpox outbreaks.

Steps towards implementation of protocolized dose reduction of adalimumab, etanercept and ustekinumab for psoriasis in daily practice.

BACKGROUND: Dose reduction (DR) of adalimumab, etanercept and ustekinumab has proven to be (cost-)effective in psoriasis patients with low disease activity. Further implementation is needed to establish application of DR for eligible patients. OBJECTIVES: To evaluate the implementation of protocolized biologic DR in daily practice. METHODS: A pilot implementation study was performed in 3 hospitals during 6 months. By combining education and protocol development, involved healthcare providers (HCPs) were directed toward the adoption of protocolized DR. DR of adalimumab, etanercept, and ustekinumab was achieved by stepwise injection interval prolongation. Implementation outcomes (fidelity, feasibility) were assessed. Factors for optimizing implementation were explored in interviews with HCPs. Uptake was measured in patients by chart review. RESULTS: The implementation strategy was executed as planned. Implementation fidelity was less than 100% as not all provided tools were used across study sites. HCPs indicated the feasibility of implementing protocolized DR, although time investment was needed. Identified additional factors for successful implementation included support for patients, uptake of DR into guidelines, and supportive electronic health record systems. During the 6 months intervention period, 52 patients were eligible for DR of whom 26 (50%) started DR. The proposed DR protocol was followed in 22/26 patients (85%) on DR. CONCLUSION: Additional staff for support, extra time during consultations, education on DR for HCPs and patients, and effective tools such as a feasible protocol can lead to more patients on biologic DR.

Effects of electrical stimulation-induced gluteal versus gluteal and hamstring muscles activation on sitting pressure distribution in persons with a spinal cord injury.

STUDY DESIGN: Ten participants underwent two electrical stimulation (ES) protocols applied using a custom-made electrode garment with built-in electrodes. Interface pressure was measured using a force-sensitive area. In one protocol, both the gluteal and hamstring (g+h) muscles were activated, in the other gluteal (g) muscles only. OBJECTIVES: To study and compare the effects of electrically induced activation of g+h muscles versus g muscles only on sitting pressure distribution in individuals with a spinal cord injury (SCI). SETTING: Ischial tuberosities interface pressure (ITs pressure) and pressure gradient. RESULTS: In all participants, both protocols of g and g+h ES-induced activation caused a significant decrease in IT pressure. IT pressure after g+h muscles activation was reduced significantly by 34.5% compared with rest pressure, whereas a significant reduction of 10.2% after activation of g muscles only was found. Pressure gradient reduced significantly only after stimulation of g+h muscles (49.3%). g+h muscles activation showed a decrease in pressure relief (Δ IT) over time compared with g muscles only. CONCLUSION: Both protocols of surface ES-induced of g and g+h activation gave pressure relief from the ITs. Activation of both g+h muscles in SCI resulted in better IT pressure reduction in sitting individuals with a SCI than activation of g muscles only. ES might be a promising method in preventing pressure ulcers (PUs) on the ITs in people with SCI. Further research needs to show which pressure reduction is sufficient in preventing PUs.

A new OECD test guideline for the predatory soil mite Hypoaspis aculeifer: results of an international ring test.

Predatory mites are considered important biological indicators to assess potential effects of plant protection products. Toxicity testing of terrestrial mite species is required for authorisation of plant protection products in the European Union in cases where testing of leaf dwelling mites is not relevant, i.e. for defoliating herbicides, or when persistence of the chemical in soil is a concern. Since a standardised guideline for soil mites was not available in the past, an international working group developed a soil ecotoxicity test with the gamasid mite Hypoaspis aculeifer. This paper outlines the guideline development process and the principles of the protocol, and presents the results of an international ring test from which the validity criteria for the final guideline were derived. The protocol, which was published as OECD guideline 226 in 2008, is suitable for routine regulatory testing and can be used to generate data for risk assessment of soil inhabiting arthropods.

Recreation reduces tick density through fine-scale risk effects on deer space-use.

Altered interactions between pathogens, their hosts and vectors have potential consequences for human disease risk. Notably, tick-borne pathogens, many of which are associated with growing deer abundance, show global increasing prevalence and pose increasing challenges for disease prevention. Human activities can largely affect the patterns of deer space-use and can therefore be potential management tools to alleviate human-wildlife conflicts. Here, we tested how deer space-use patterns are influenced by human recreational activities, and how this in turn affects the spatial distribution of the sheep tick (Ixodes ricinus), a relevant disease vector of zoonoses such as Lyme borrelioses. We compared deer dropping and questing tick density on transects near (20 m) and further away from (100 m) forest trails that were either frequently used (open for recreation) or infrequently used (closed for recreation, but used by park managers). In contrast to infrequently used trails, deer dropping density was 31% lower near (20 m) than further away from (100 m) frequently used trails. Similarly, ticks were 62% less abundant near (20 m) frequently used trails compared to further away from (100 m) these trails, while this decline in tick numbers was only 14% near infrequently used trails. The avoidance by deer of areas close to human-used trails was thus associated with a similar reduction in questing tick density near these trails. As tick abundance generally correlates to pathogen prevalence, the use of trails for recreation may reduce tick-borne disease risk for humans on and near these trails. Our study reveals an unexplored effect of human activities on ecosystems and how this knowledge could be potentially used to mitigate zoonotic disease risk.

Reduction of fibrogenesis by selective delivery of a Rho kinase inhibitor to hepatic stellate cells in mice.

One of the pathways activated during liver fibrosis is the Rho kinase pathway, which regulates activation, migration, and contraction of hepatic stellate cells (HSC). Inhibition of this kinase by the Rho kinase inhibitor Y27632 [(+)-(R)-trans- 4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride] has been shown to reduce fibrosis in animal models. However, kinase expression is ubiquitous, so any inhibitor may affect many cell types. We hypothesize that cell-specific delivery of a kinase inhibitor will be beneficial. Therefore, we conjugated Y27632 to the carrier mannose-6-phosphate (M6P) human serum albumin (HSA), which is taken up specifically in activated HSC through the M6P/insulin-like growth factor II receptor. This conjugate decreased protein expression of phosphorylated myosin light chain 2 (pMLC2) and vinculin, downstream of Rho kinase, in activated primary HSC and decreased the migration and contraction of HSC. In an ex vivo model, free Y27632 decreased contractility of rat aortas, whereas the Y27-conjugate did not, showing that the Y27-conjugate does not affect nontarget tissue. In chronic CCl(4)-induced liver fibrosis, both free drug and conjugate reduced HSC activation; however, only the Y27-conjugate significantly reduced collagen deposition. Treatment with the Y27-conjugate, but not with free drug, reduced pMLC2 expression in livers 24 h after injection, demonstrating prolonged inhibition of the Rho kinase pathway. The Rho kinase inhibitor Y27632 can be specifically targeted to HSC using M6PHSA, decreasing its effects in nontarget tissues. The targeted drug effectively reduced fibrotic parameters in vivo via the inhibition of the Rho kinase pathway.

Cervical microleakage in Class II open-sandwich restorations: an in vitro study.

INTRODUCTION: The open-sandwich technique was proposed to solve the problem of cervical micro-leakage of deep Class II composite restorations by making use of the self-adhesive nature of the glass-ionomers. Recent advances in the properties of this family of materials may continue to make the technique relevant today. AIMS AND OBJECTIVES: The aim of this in vitro study was to determine the effect of thermocycling, cervical position and the use of different materials on the cervical microleakage of Class II open-sandwich restorations. METHODS: Two hundred standardised Class II cavities with the cervical margins placed in either enamel (100) or dentine (100) were prepared in 100 extracted human molars. Ketac Molar, set with ultrasound (US), Ketac Molar, Ketac Nano and Vitremer were used in equal groups to restore the cervical boxes, while Filtek Z250 was used to complete the restorations and also provided a control group in which the sandwich technique was not used. One half of each group was subjected to thermocycling. Microleakage was assessed by measuring the distance of penetration of basic fuchsin dye along the cervical step. RESULTS: The open-sandwich technique significantly (p<0.001) reduced the microleakage otherwise seen in Filtek Z250 when margins were placed in dentine and thermocycled. CONCLUSIONS: The use of an ultrasonically cured glass-ionomer in the open-sandwich resulted in the least microleakage (after thermocycling) when the cervical margins of Class II restorations were placed in dentine.

Management and outcome of middle ear adenomatous neuroendocrine tumours: A systematic review.

Middle ear adenomatous neuroendocrine tumours (MEANTs) are rare, unpredictable tumours. Although most MEANTs are characterized by a benign biological behaviour and indolent growth pattern, some studies have reported locally invasive and metastastic disease. Currently, the optimal management strategy for MEANTs remains subject of debate. The aim of this study is to review the literature on MEANTs with focus on its clinical characteristics, treatment strategies and outcome. A systematic review was conducted using PubMed, Embase and Cochrane databases. A total of 111 studies comprising 198 patients with MEANT were included. Treatment modalities comprised surgery (90%), surgery with adjuvant radiotherapy (9%) and palliative (chemo)radiotherapy in (1%). Local recurrence was observed in 25% of the patients and 7% of the patients developed metastasis, over a median period of 5.7 years (range 7 months - 32 years). Twelve of 13 patients (92%) who developed metastases had a local recurrence. Four patients (2%) died of MEANT: three due to distant metastases and one due to extensive local recurrence. Reliable histopathologic predictors of outcome could not be identified. These findings indicate that the clinical presentations of MEANT vary substantially, the overall recurrence rate is considerable and initial local tumour control is paramount. Because of the unpredictable clinical course, prolonged follow-up is warranted.

Evaluation of the physical activity scale for individuals with physical disabilities in people with spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To evaluate the physical activity scale for individuals with physical disabilities (PASIPD) in people with spinal cord injury (SCI). SETTING: Eight Dutch rehabilitation centers with a specialized SCI unit. METHODS: The PASIPD was examined by comparing group scores of people with different personal (age, gender and body mass index) and lesion characteristics (level (paraplegia/tetraplegia), completeness, time since injury (TSI)) in 139 persons with SCI 1 year after discharge from in-patient rehabilitation. Relationships between PASIPD scores and measures of activities (wheelchair skills, Utrecht Activity List, mobility range and social behavior subscales of the SIP68) and fitness (peak oxygen uptake, peak power output and muscular strength) were determined. RESULTS: Persons with tetraplegia had significantly lower PASIPD scores than those with paraplegia (P<0.02). Persons with longer TSI had lower PASIPD scores than persons with shorter TSI (P<0.03). PASIPD scores showed moderate correlations with activities (0.36-0.51, P<0.01) and weak-to-moderate correlations with fitness parameters (0.25-0.36, P<0.05). CONCLUSION: In a fairly homogeneous group of persons with SCI, 1 year after in-patient rehabilitation, the PASIPD showed weak-to-moderate relationships with activity and fitness parameters. There seems to be a limited association between self-reported activity level and fitness in people with SCI.