How people with persistent pain experience in-person physiotherapy blended with biopsychosocial digital health - A qualitative study on participants' experiences with Back2Action.

Background: A blended intervention consisting of in-person physiotherapy and psychologically-informed digital health, called Back2Action, was developed to optimise the management of people with persistent spinal pain who also have psychosocial risk factors associated with the development or maintenance of persistent pain. This study aimed to gain insights in how participants experienced this blended intervention. Methods: A qualitative study using semi-structured interviews was conducted. Eleven people with persistent non-specific spinal pain who received the blended intervention within a randomised clinical trial were included. All interviews were recorded, transcribed verbatim and analysed independently by two researchers. Data were analysed using a thematic analysis. Results: The analysis identified four themes: (1) Experiencing a better understanding of the relationship between own physical and mental health; (2) Importance of the physiotherapist's active involvement in biopsychosocial blended care, which describes the crucial role of physiotherapists in supporting participants in this; (3) Appreciation of digital health, to better understand persistent pain and make meaningful lifestyle changes; and (4) Trials and triumphs, revealing gains such as better coping, but also challenges with implementation of changes into long-term routines. Conclusion: Participants of the blended intervention experienced positive changes in thoughts and behaviours, which highlights the feasibility and acceptability of the blended intervention as a more holistic treatment within pain management. The differences in personal preferences for receiving psychologically-informed digital health poses challenges for implementation of blended biopsychosocial care in evidence-based practice.

Illusory Essences: A Bias Holding Back Theorizing in Psychological Science.

The reliance in psychology on verbal definitions means that psychological research is unusually moored to how humans think and communicate about categories. Psychological concepts (e.g., intelligence, attention) are easily assumed to represent objective, definable categories with an underlying essence. Like the "vital forces" previously thought to animate life, these assumed essences can create an illusion of understanding. By synthesizing a wide range of research lines from cognitive, clinical, and biological psychology and neuroscience, we describe a pervasive tendency across psychological science to assume that essences explain phenomena. Labeling a complex phenomenon can appear as theoretical progress before there is sufficient evidence that the described category has a definable essence or known boundary conditions. Category labels can further undermine progress by masking contingent and contextual relationships and obscuring the need to specify mechanisms. Finally, we highlight examples of promising methods that circumvent the lure of essences and suggest four concrete strategies for identifying and avoiding essentialist intuitions in theory development.

[Drug of abuse screening in urine in emergency situations; useful or not?] / Toxicologische screening van urine in acute situaties.

Drug of abuse (DOA) screening in urine is often performed in the clinical emergency setting. However, there is considerable evidence that questions the usefulness of this screening in the acute management of patients with suspected intoxications. The used method is an immunoassay, in which cross reactivity with false positive results may occur. A positive result does not always indicate current toxicity, a negative result does not exclude drug use or a current intoxication. Therefore, DOA screening has limited value in the acute clinical management of patients with intoxications.

Effect of maternal diabetes on fetal heart function on echocardiography: systematic review and meta-analysis.

OBJECTIVE: Maternal diabetes in pregnancy is associated with structural anomalies of the fetal heart, as well as hypertrophy and functional impairment. This systematic review and meta-analysis aimed to estimate the effect of maternal diabetes on fetal cardiac function as measured by prenatal echocardiography. METHODS: We performed a search of the EMBASE, PubMed and The Cochrane Library databases, from inception to 4 July 2019, for studies evaluating fetal cardiac function using echocardiography in pregnancies affected by diabetes compared with uncomplicated pregnancies. Outcome measures were cardiac hypertrophy and diastolic, systolic and overall cardiac function as assessed by various ultrasound parameters. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Data on interventricular septal (IVS) thickness, myocardial performance index (MPI) and E/A ratio were pooled for the meta-analysis using random-effects models. For pregnancies with diabetes, results were reported overall and according to whether diabetes was pregestational (PDM) or gestational (GDM). Results were also stratified according to the trimester in which fetal cardiac assessment was performed. RESULTS: Thirty-nine studies were included, comprising data for 2276 controls and 1925 women with pregnancy affected by diabetes mellitus (DM). Of these, 1120 had GDM, 671 had PDM and in 134 cases diabetes type was not specified. Fetal cardiac hypertrophy was more prevalent in diabetic pregnancies than in non-diabetic controls in 21/26 studies, and impaired diastolic function was observed in diabetic pregnancies in 22/28 studies. The association between DM and systolic function was inconsistent, with 10/25 studies reporting no difference between cases and controls, although more recent studies measuring cardiac deformation, i.e. strain, did show decreased systolic function in diabetic pregnancies. Of the studies measuring overall fetal cardiac function, the majority (14/21) found significant impairment in diabetic pregnancies. Results were similar when stratified according to GDM or PDM. These effects were already present in the first trimester, but were most profound in the third trimester. Meta-analysis of studies performed in the third trimester showed, compared with controls, increased IVS thickness in both PDM (mean difference, 0.75 mm (95% CI, 0.56-0.94 mm)) and GDM (mean difference, 0.65 mm (95% CI, 0.39-0.91 mm)) pregnancies, decreased E/A ratio in PDM pregnancies (mean difference, -0.09 (95% CI, -0.15 to -0.03)), no difference in E/A ratio in GDM pregnancies (mean difference, -0.01 (95% CI, -0.02 to 0.01)) and no difference in MPI in either PDM (mean difference, 0.04 (95% CI, -0.01 to 0.09)) or GDM (mean difference, 0.03 (95% CI, -0.01 to 0.06)) pregnancies. CONCLUSIONS: The findings of this review show that maternal diabetes is associated with fetal cardiac hypertrophy, diastolic dysfunction and overall impaired myocardial performance on prenatal ultrasound, irrespective of whether diabetes is pregestational or gestational. Further studies are needed to demonstrate the relationship with long-term outcomes. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Repeated oral glucose tolerance tests in women at risk for gestational diabetes mellitus.

OBJECTIVE: Pregnant women with a negative oral glucose tolerance test (OGTT) between 24-28 weeks as part of risk-based screening for gestational diabetes mellitus (GDM) may develop clinical signs or symptoms suggestive for GDM in the third trimester. We aimed to determine the additional yield of repeating an OGTT to detect missed GDM in this group and assess patient characteristics and indications associated with a positive second OGTT. STUDY DESIGN: We conducted a retrospective cohort study of women with a negative OGTT between 24-28 weeks of pregnancy in two hospitals in the Netherlands. Patient characteristics, pregnancy outcomes, OGTT results and indications were compared between women with normal (non-GDM) and abnormal (GDM) results of the second OGTT, using the WHO 1999 criteria (fasting glucose ≥7.0 mmol/L or 2 -h post load ≥7.8 mmol/L). We used receiver operating characteristic (ROC) curve analysis to determine cut-offs for fasting and 2 -h glucose values of the index OGTT that were associated with a positive OGTT in the third trimester. RESULTS: Of 3147 women at risk for GDM, 183 underwent a second OGTT in the third trimester following their regular OGTT at 24-28 weeks. In 43 women (23.5%) GDM was diagnosed based on the second OGTT. A history of GDM was associated with subsequent GDM diagnosis, with an odds ratio of 2.6 (95% CI 1.0-6.3). Both fasting and 2 -h post load glucose values of the index OGTT were significantly higher in women with abnormal OGTT results later in pregnancy. Index OGTT glucose value cut-offs of 4.8 mmol/L (fasting) and 6.5 mmol/L (2 -h) had positive predictive values of 0.32 and 0.47 for a positive OGTT in the third trimester, and negative predictive values of 0.83 and 0.90, respectively. Fetal growth as a clinical symptom for GDM was the most frequent indication for repeating the OGTT, resulting in the diagnosis of GDM in 22.7% of women tested for this indication. CONCLUSION: Repeating an OGTT after initial negative screening results in additional GDM diagnoses. In case of clinical signs, especially in women with additional risk factors such as a history of GDM or higher index OGTT glucose values, repeating an OGTT could be considered.

Workshop on the validation and regulatory acceptance of innovative 3R approaches in regulatory toxicology - Evolution versus revolution.

At a joint workshop organized by RIVM and BfR, international experts from governmental institutes, regulatory agencies, industry, academia and animal welfare organizations discussed and provided recommendations for the development, validation and implementation of innovative 3R approaches in regulatory toxicology. In particular, an evolutionary improvement of our current approach of test method validation in the context of defined approaches or integrated testing strategies was discussed together with a revolutionary approach based on a comprehensive description of the physiological responses of the human body to chemical exposure and the subsequent definition of relevant and predictive in vitro, in chemico or in silico methods. A more comprehensive evaluation of biological relevance, scientific validity and regulatory purpose of new test methods and assessment strategies together with case studies that provide practical experience with new approaches were discussed as essential steps to build up the necessary confidence to facilitate regulatory acceptance.

Adoption and implementation of a web-based self-management application "Oncokompas" in routine cancer care: a national pilot study.

PURPOSE: A web-based self-management application "Oncokompas" was developed to monitor health-related quality of life and to support cancer survivors in finding and obtaining optimal supportive care. Access to this application is provided via a healthcare professional (HCP). The aim of this study was to explore the adoption and implementation of Oncokompas in routine clinical practice and to obtain insights in potentially relevant determinants of implementation. METHODS: A pilot study was carried out among 65 hospitals throughout The Netherlands. HCPs filled out a questionnaire on the implementation of Oncokompas in their organization, consisting of study specific items and items based on the Measurement Instrument for Determinants of Innovations (MIDI). The MIDI comprises 29 determinants in four domains that predict the use of innovations: the innovation itself (Oncokompas), the user (HCP), the organization (hospital), and socio-political context. RESULTS: In total, 20/65 eligible hospitals agreed to implement Oncokompas (adoption rate 31%). In these 20 adopting hospitals, the majority of the responding HCPs (72/205) in this study (44/61) indicated their patients were offered access to Oncokompas (implementation rate 72%). Comparing those HCPs who did and did not implement Oncokompas, the groups differed significantly on innovation-related (procedural clarity, complexity) and user-related determinants (importance of outcome expectations, professional obligation, social support, and self-efficacy). CONCLUSIONS: During this 1-year study, nationwide adoption rate of Oncokompas was at 31%, and subsequent implementation rate was at 72%. The results of this study contribute to further optimize interventions and strategies to adopt and implement (online) self-management applications in cancer care.

Variations in DNA methylation of interferon gamma and programmed death 1 in allograft rejection after kidney transplantation.

BACKGROUND: The role of DNA methylation in the regulation of the anti-donor-directed immune response after organ transplantation is unknown. Here, we studied the methylation of two mediators of the immune response: the pro-inflammatory cytokine interferon γ (IFNγ) and the inhibitory receptor programmed death 1 (PD1) in naïve and memory CD8+ T cell subsets in kidney transplant recipients receiving immunosuppressive medication. Both recipients experiencing an episode of acute allograft rejection (rejectors) as well as recipients without rejection (non-rejectors) were included. RESULTS: CpGs in the promoter regions of both IFNγ and PD1 were significantly (p < 0.001) higher methylated in the naïve CD8+ T cells compared to the memory T cell subsets. The methylation status of both IFNγ and PD1 inversely correlated with the percentage of IFNγ or PD1-producing cells. Before transplantation, the methylation status of both IFNγ and PD1 was not significantly different from healthy donors. At 3 months after transplantation, irrespective of rejection and subsequent anti-rejection therapy, the IFNy methylation was significantly higher in the differentiated effector memory CD45RA+ (EMRA) CD8+ T cells (p = 0.01) whereas the PD1 methylation was significantly higher in all memory CD8+ T cell subsets (CD27+ memory; p = 0.02: CD27- memory; p = 0.02: EMRA; p = 0.002). Comparing the increase in methylation in the first 3 months after transplantation between rejectors and non-rejectors demonstrated a significantly more prominent increase in the PD1 methylation in the CD27- memory CD8+ T cells in rejectors (increase in rejectors 14%, increase in non-rejectors 1.9%, p = 0.04). The increase in DNA methylation in the other memory CD8+ T cells was not significantly different between rejectors and non-rejectors. At 12 months after transplantation, the methylation of both IFNγ and PD1 returned to baseline levels. CONCLUSIONS: The DNA methylation of both IFNγ and PD1 increases the first 3 months after transplantation in memory CD8+ T cells in kidney transplant recipients. This increase was irrespective of a rejection episode indicating that general factors of the kidney transplantation procedure, including the use of immunosuppressive medication, contribute to these variations in DNA methylation.

Predicting sickness impact profile at six months after stroke: further results from the European multi-center CERISE study.

PURPOSE: To develop prognostic models and equations for predicting participation at six months after stroke. METHODS: This European prospective cohort study recruited 532 consecutive patients from four rehabilitation centers. Participation was assessed at six months after stroke with the Sickness Impact Profile (SIP), which consists of a physical, psychosocial and independent dimension. Twenty-six independent variables on admission to the rehabilitation center and 13 additional variables measured at two months post stroke were included in the analysis. A multiple logistic regression analysis was conducted predicting good participation (SIP < 20%). Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: The prognostic models for the three dimensions provided independent predictors containing demographics, complications, diagnostic, and disability measures. Sensitivity ranged from 64-84%, specificity 66-85%, positive predictive value 70-78%, and negative predictive value 76-87%. Barthel Index on admission, Euroqol Health State at two months and Caregiver Strain Index at two months were retained in all prediction models. CONCLUSIONS: A combination of variables was found in the prognostic models of the three dimensions of the SIP at six months after stroke. Already from the early beginning of stroke rehabilitation it seems important to focus on personal activities of daily living as well as caregivers' strain. IMPLICATIONS FOR REHABILITATION: Prognostic factors predicting participation, measured by the three dimensions of the Sickness Impact Profile at six months post stroke include demographic variables, post-stroke complications, diagnostic parameters and disability measures. Significant prognostic variables for all three dimensions of the Sickness Impact Profile were a higher Barthel Index score on admission to the rehabilitation center, a higher Euroqol Health State score at two months post stroke and a lower Caregiver Strain Index score at two months post stroke. Early stroke therapy should therefore further emphasize rehabilitation of personal activities of daily living such as mobility, walking, feeding, dressing, and toilet use, as well as considering strategies to reduce caregiver strain such as giving support, providing information and training carers.

Anxiety and depression after stroke: a 5 year follow-up.

PURPOSE: The aim was to document the prevalence and predictors of anxiety and depression 5 years after stroke, across four European centres. METHOD: A cohort of 220 stroke patients was assessed at 2, 4 and 6 months and 5 years after stroke. Patients were assessed on the Hospital Anxiety and Depression Scale and measures of motor function and independence in activities of daily living. RESULTS: At 5 years, the prevalence of anxiety was 29% and depression 33%, with no significant differences between centres. The severity of anxiety and depression increased significantly between 6 months and 5 years. Higher anxiety at 6 months and centre were significantly associated with anxiety at 5 years, but not measures of functional recovery. Higher depression scores at 6 months, older age and centre, but not measures of functional recovery, were associated with depression at 5 years. CONCLUSIONS: Anxiety and depression were more frequent at 5 years after stroke than at 6 months. There were significant differences between four European centres in the severity of anxiety and depression. Although the main determinant of anxiety or depression scores at 5 years was the level of anxiety or depression at 6 months, this accounted for little of the variance. Centre was also a significant predictor of mood at 5 years. There needs to be greater recognition of the development of mood disorders late after stroke and evaluation of variation in management policies across centres.

Current application of selective decontamination of the digestive tract, perioperative antibiotics and mechanical bowel preparation in surgical departments in the Netherlands.

OBJECTIVE: To study the current application of selective decontamination of the digestive tract (SDD), the use of preoperative antibiotics and mechanical bowel preparation (MBP) in elective gastrointestinal (GI) surgery in surgical departments in the Netherlands. METHODS: A point prevalence survey was carried out and an online questionnaire was sent to GI surgeons of 86 different hospitals. RESULTS: The response rate was 74%. Only 4/64 (6.3%) of the Dutch surgical wards are currently using perioperative SDD as a prophylactic strategy to prevent postoperative infectious complications. The 4 hospitals using SDD on their surgical wards also use it on their ICUs. All hospitals make use of perioperative intravenous antibiotic prophylaxis in elective GI surgery. In most hospitals, a cephalosporin and metronidazole are applied (81.3 and 76.6%). MBP was used in 58 hospitals (90.6%) mainly in left colonic surgery. CONCLUSIONS: Perioperative SDD is rarely used in elective GI surgery in the Netherlands. Perioperative intravenous antibiotic prophylaxis is given in all Dutch hospitals, conforming to guidelines. Although the recent literature does not recommend MBP before surgery, it is still selectively used in 90.6% of the Dutch surgical departments, mainly in open or laparoscopic left colonic surgery (including sigmoid resections).

Randomized clinical trial of perioperative selective decontamination of the digestive tract versus placebo in elective gastrointestinal surgery.

BACKGROUND: This randomized clinical trial analysed the effect of perioperative selective decontamination of the digestive tract (SDD) in elective gastrointestinal surgery on postoperative infectious complications and leakage. METHODS: All patients undergoing elective gastrointestinal surgery during a 5-year period were evaluated for inclusion. Randomized patients received either SDD (polymyxin B sulphate, tobramycin and amphotericin) or placebo in addition to standard antibiotic prophylaxis. The primary endpoint was postoperative infectious complications and anastomotic leakage during the hospital stay or 30 days after surgery. RESULTS: A total of 289 patients were randomized to either SDD (143) or placebo (146). Most patients (190, 65·7 per cent) underwent colonic surgery. There were 28 patients (19·6 per cent) with infectious complications in the SDD group compared with 45 (30·8 per cent) in the placebo group (P = 0·028). The incidence of anastomotic leakage in the SDD group was 6·3 per cent versus 15·1 per cent in the placebo group (P = 0·016). Hospital stay and mortality did not differ between groups. CONCLUSION: Perioperative SDD in elective gastrointestinal surgery combined with standard intravenous antibiotics reduced the rate of postoperative infectious complications and anastomotic leakage compared with standard intravenous antibiotics alone. Perioperative SD.D should be considered for patients undergoing gastrointestinal surgery. REGISTRATION NUMBER: P02.1187L (Dutch Central Committee on Research Involving Human Subjects).

European micronutrient recommendations aligned: a general framework developed by EURRECA.

BACKGROUND: In Europe, micronutrient recommendations have been established by (inter)national committees of experts and are used by public health-policy decision makers to monitor and assess the adequacy of the diets of population groups. Current micronutrient recommendations are, however, heterogeneous, whereas the scientific basis for this is not obvious. Alignment of setting micronutrient recommendations is necessary to improve the transparency of the process, the objectivity and reliability of recommendations that are derived by diverse regional and (inter)national bodies. OBJECTIVE: This call for alignment of micronutrient recommendations is a direct result of the current sociopolitical climate in Europe and uncovers the need for an institutional architecture. There is a need for evidence-based policy making, transparent decision making, stakeholder involvement and alignment of policies across Europe. RESULTS: In this paper, we propose a General Framework that describes the process leading from assessing nutritional requirements to policy applications, based on evidence from science, stakeholder interests and the sociopolitical context. The framework envisions the derivation of nutrient recommendations as scientific methodology, embedded in a policy-making process that also includes consumer issues, and acknowledges the influences of the wider sociopolitical context by distinguishing the principal components of the framework: (a) defining the nutrient requirements for health, (b) setting nutrient recommendations, (c) policy options and (d) policy applications. CONCLUSION: The General Framework can serve as a basis for a systematic and transparent approach to the development and review of micronutrient requirements in Europe, as well as the decision making of scientific advisory bodies, policy makers and stakeholders involved in this process of assessing, developing and translating these recommendations into public health nutrition policy.

Patients with Leber hereditary optic neuropathy fail to compensate impaired oxidative phosphorylation.

Ninety-five percent of Leber hereditary optic neuropathy (LHON) patients carry a mutation in one out of three mtDNA-encoded ND subunits of complex I. Penetrance is reduced and more male than female carriers are affected. To assess if a consistent biochemical phenotype is associated with LHON expression, complex I- and complex II-dependent adenosine triphosphate synthesis rates (CI-ATP, CII-ATP) were determined in digitonin-permeabilized peripheral blood mononuclear cells (PBMCs) of thirteen healthy controls and for each primary mutation of a minimum of three unrelated patients and of three unrelated carriers with normal vision and were normalized per mitochondrion (citrate synthase activity) or per cell (protein content). We found that in mitochondria, CI-ATP and CII-ATP were impaired irrespective of the primary LHON mutation and clinical expression. An increase in mitochondrial density per cell compensated for the dysfunctional mitochondria in LHON carriers but was insufficient to result in a normal biochemical phenotype in early-onset LHON patients.

Defective complex I assembly due to C20orf7 mutations as a new cause of Leigh syndrome.

BACKGROUND: Leigh syndrome is an early onset, progressive, neurodegenerative disorder with developmental and motor skills regression. Characteristic magnetic resonance imaging abnormalities consist of focal bilateral lesions in the basal ganglia and/or the brainstem. The main cause is a deficiency in oxidative phosphorylation due to mutations in an mtDNA or nuclear oxidative phosphorylation gene. METHODS AND RESULTS: A consanguineous Moroccan family with Leigh syndrome comprise 11 children, three of which are affected. Marker analysis revealed a homozygous region of 11.5 Mb on chromosome 20, containing 111 genes. Eight possible mitochondrial candidate genes were sequenced. Patients were homozygous for an unclassified variant (p.P193L) in the cardiolipin synthase gene (CRLS1). As this variant was present in 20% of a Moroccan control population and enzyme activity was only reduced to 50%, this could not explain the rare clinical phenotype in our family. Patients were also homozygous for an amino acid substitution (p.L159F) in C20orf7, a new complex I assembly factor. Parents were heterozygous and unaffected sibs heterozygous or homozygous wild type. The mutation affects the predicted S-adenosylmethionine (SAM) dependent methyltransferase domain of C20orf7, possibly involved in methylation of NDUFB3 during the assembly process. Blue native gel electrophoresis showed an altered complex I assembly with only 30-40% of mature complex I present in patients and 70-90% in carriers. CONCLUSIONS: A new cause of Leigh syndrome can be a defect in early complex I assembly due to C20orf7 mutations.

[Abdominal pain and rectal blood loss]. / Buikpijn en rectaal bloedverlies.

The medical history of a 46-year-old man recorded osteomas in the maxillary bone 18 years before, haemorrhoids, and kidney stones. He presented with pain in the right lower abdomen and rectal blood loss. His complaints were diagnosed as familial adenomatous polyposis, culminating in sigmoid carcinoma. Due to the extent of the polyps and, consequently, the great cancer relapse risk, a surgical treatment was indicated. A symptom ofa familial adenomatous polyposis variant, Gardner's syndrome, is osteomas in the orofacial region. Dentists and oral surgeons should be aware of this rare syndrome in a patient with orofacial osteomas, especially if the patient has a familial risk of adenomatous polyposis.

Chapter 9 Reliable assay for measuring complex I activity in human blood lymphocytes and skin fibroblasts.

Complex I deficiency is probably the most common enzyme defect among the group of OXPHOS disorders. To evaluate a deficiency of complex I activity, biochemical measurements based on estimation of the mitochondrial rotenone-sensitive NADH: ubiquinone oxidoreductase activity are an important tool. Skeletal muscle is the most widely used tissue to examine complex I deficiency. However, obtaining a muscle biopsy requires an invasive surgical operation. It is much easier to obtain blood lymphocytes or skin fibroblasts, and, moreover, these cells can be expanded in number by standard techniques for extensive research on complex I. On the other hand, each of these cell types has disadvantages that hinder its measurement, such as the apparent low enzyme activity of lymphocytes and the highly contaminating nonmitochondrial NADH-quinone oxidoreductase activity of fibroblasts. This chapter describes a method to assay complex I activity reliably in a minute amount of either cell type.

Termination of damaged protein repair defines the occurrence of symptoms in carriers of the m.3243A > G tRNA(Leu) mutation.

BACKGROUND: The m.3243A>G mutation in the mitochondrial tRNA(Leu(UUR)) gene is an example of a mutation causing a very heterogeneous phenotype. It is the most frequent cause (80%) of the MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), but it can also lead in addition or separately to type 2 diabetes, deafness, renal tubulopathy and/or cardiomyopathy. METHODS: To identify pathogenic processes induced by this mutation, we compared global gene expression levels of muscle biopsies from affected and unaffected mutation carriers with controls. RESULTS AND CONCLUSIONS: Gene expression changes were relatively subtle. In the asymptomatic group 200 transcripts were upregulated and 12 were downregulated, whereas in the symptomatic group 15 transcripts were upregulated and 52 were downregulated. In the asymptomatic group, oxidative phosphorylation (OXPHOS) complex I and IV genes were induced. Protein turnover and apoptosis were elevated, most likely due to the formation of dysfunctional and reactive oxygen species (ROS) damaged proteins. These processes returned to normal in symptomatic patients. Components of the complement system were upregulated in both groups, but the strongest in the symptomatic group, which might indicate muscle regeneration--most likely, protein damage and OXPHOS dysfunction stimulate repair (protein regeneration) and metabolic adaptation (OXPHOS). In asymptomatic individuals these processes suffice to prevent the occurrence of symptoms. However, in affected individuals the repair process terminates, presumably because of excessive damage, and switches to muscle regeneration, as indicated by a stronger complement activation. This switch leaves increasingly damaged tissue in place and muscle pathology becomes manifest. Therefore, the expression of complement components might be a marker for the severity and progression of MELAS clinical course.

Laparoscopic ventral rectopexy for obstructed defecation syndrome.

INTRODUCTION: Obstructed defecation remains a serious syndrome. Several procedures have been applied to treat it. A concomitant enterocele excludes some of these procedures, because of potential threat of damaging the bowel. The aim of this study was to assess the outcome of patients who underwent laparoscopic nerve sparing ventral rectopexy for obstructed defecation syndrome with concomitant enterocele. METHODS: Seventeen patients were included. Data about clinical history, physical examination and a defecogram were collected. All patients underwent a laparoscopic ventral rectopexy. Complications, hospital stay, postoperative morbidity and long-term outcome were documented. RESULTS: All patients underwent laparoscopic ventral rectopexy. The median operating time was 199 min (range 186-239 min). One conversion laparotomy was required. Six patients had postoperative complications (ileus n = 2, posttraumatic leg dystrophy n = 1, wound infection n = 1, incisional hernia n = 2). The median hospital stay was 6 days (range 3-24 days). Fifteen patients had improvement of their defecation problem, although six patients still had minor constipation symptoms. In one patient the mesh was rejected and finally removed. CONCLUSION: Obstructed defecation syndrome is a combined functional and mechanical problem. In selected patients, especially when an enterocele is present, laparoscopic ventral rectopexy is a feasible technique, with an acceptable number of complications.