Het klieven van de buigpees bij ulcera van de tenen

Meer dan 25% van alle diabetische voetproblemen wordt veroorzaakt door ulcera. De genezingskans met een conservatief beleid is laag, waarbij ruim tweederde van de ulcera na twintig weken nog niet genezen is. Ondanks dat de recidiefkans en de amputatiekans afnemen bij een multidisciplinaire aanpak van diabetische voetulcera, worden voor beiden nog percentages van boven de 80% gerapporteerd. Meer dan 50% van alle diabetische voetulcera bevindt zich ter hoogte van de tenen. Bij een groot deel hiervan ligt een anatomische standsafwijking (klauw- of hamerteen) aan ten grondsla

Impact of upper blepharoplasty, with or without orbicularis oculi muscle removal, on tear film dynamics and dry eye symptoms:A randomized controlled trial

PURPOSE: Upper blepharoplasty may be related to dry eye symptoms since the function of the orbicularis oculi muscle may affect the tear film. We aimed to assess the effect of blepharoplasty with or without the removal of a strip of orbicularis oculi muscle on tear film dynamics and dry eye symptoms. METHODS: A double-blind, randomized, controlled trial comparing upper blepharoplasty without (group A) or with (group B) orbicularis oculi muscle excision was performed on 54 healthy Caucasian patients. Tear film dynamics and dry eye symptoms were evaluated using multiple dry eye parameters, i.e. tear osmolarity, Schirmer test I, corneal/conjunctival staining, tear break-up time (TBUT), Oxford Scheme, Sicca Ocular Staining Score and Ocular Surface Disease Index questionnaire. All the parameters were assessed preoperatively and 6 and 12 months after upper blepharoplasty. All the groups' outcomes were compared. RESULTS: The differences were not significant between the two upper blepharoplasty techniques regarding most of the above-mentioned outcomes. Subjective symptoms of ocular irritation, consistent with dry eye disease and vision-related impairment, were reduced after upper blepharoplasty independent of the type of the technique applied, while the pre and postoperative outcomes of the objective tear dynamics did not differ 12 months after surgery. However, group B demonstrated a significant increase in tear osmolarity and TBUT at the 6-month follow-up visit. CONCLUSION: An upper blepharoplasty alleviates subjective dry eye complaints in the long term, while not changing the tear dynamics. The improvement was independent of the blepharoplasty technique used

STAT5-mediated self-renewal of normal hematopoietic and leukemic stem cells

The level of transcription factor activity critically regulates cell fate decisions such as hematopoietic stem cell self-renewal and differentiation. The balance between hematopoietic stem cell self-renewal and differentiation needs to be tightly controlled, as a shift toward differentiation might exhaust the stem cell pool, while a shift toward self-renewal might mark the onset of leukemic transformation. A number of transcription factors have been proposed to be critically involved in governing stem cell fate and lineage commitment, such as Hox transcription factors, c-Myc, Notch1, β-catenin, C/ebpα, Pu.1 and STAT5. It is therefore no surprise that dysregulation of these transcription factors can also contribute to the development of leukemias. This review will discuss the role of STAT5 in both normal and leukemic hematopoietic stem cells as well as mechanisms by which STAT5 might contribute to the development of human leukemias

Disease Combinations Associated with Physical Activity Identified: The SMILE Cohort Study

In the search of predictors of inadequate physical activity, an investigation was conducted into the association between multimorbidity and physical activity (PA). So far the sum of diseases used as a measure of multimorbidity reveals an inverse association. How specific combinations of chronic diseases are associated with PA remains unclear. The objective of this study is to identify clusters of multimorbidity that are associated with PA. Cross-sectional data of 3,386 patients from the 2003 wave of the Dutch cohort study SMILE were used. Ward's agglomerative hierarchical clustering was executed to establish multimorbidity clusters. Chi-square statistics were used to assess the association between clusters of chronic diseases and PA, measured in compliance with the Dutch PA guideline. The highest rate of PA guideline compliance was found in patients the majority of whom suffer from liver disease, back problems, rheumatoid arthritis, osteoarthritis, and inflammatory joint disease (62.4%). The lowest rate of PA guideline compliance was reported in patients with heart disease, respiratory disease, and diabetes mellitus (55.8%). Within the group of people with multimorbidity, those suffering from heart disease, respiratory disease, and/or diabetes mellitus may constitute a priority population as PA has proven to be effective in the prevention and cure of all three disorders

Synergistic Effects of Six Chronic Disease Pairs on Decreased Physical Activity: The SMILE Cohort Study

Little is known about whether and how two chronic diseases interact with each other in modifying the risk of physical inactivity. The aim of the present study is to identify chronic disease pairs that are associated with compliance or noncompliance with the Dutch PA guideline recommendation and to study whether specific chronic disease pairs indicate an extra effect on top of the effects of the diseases individually. Cross-sectional data from 3,386 participants of cohort study SMILE were used and logistic regression analysis was performed to study the joint effect of the two diseases of each chronic disease pair for compliance with the Dutch PA guideline. For six chronic disease pairs, patients suffering from both diseases belonging to these disease pairs in question show a higher probability of noncompliance to the Dutch PA guideline, compared to what one would expect based on the effects of each of the two diseases alone. These six chronic disease pairs were chronic respiratory disease and severe back problems; migraine and inflammatory joint disease; chronic respiratory disease and severe kidney disease; chronic respiratory disease and inflammatory joint disease; inflammatory joint disease and rheumatoid arthritis; and rheumatoid arthritis and osteoarthritis of the knees, hips, and hands

Optimisation of three-dimensional lower jaw resection margin planning using a novel Black Bone magnetic resonance imaging protocol

Background MRI is the optimal method for sensitive detection of tumour tissue and pre-operative staging in oral cancer. When jawbone resections are necessary, the current standard of care for oral tumour surgery in our hospital is 3D virtual planning from CT data. 3D printed jawbone cutting guides are designed from the CT data. The tumour margins are difficult to visualise on CT, whereas they are clearly visible on MRI scans. The aim of this study was to change the conventional CT-based workflow by developing a method for 3D MRI-based lower jaw models. The MRI-based visualisation of the tumour aids in planning bone resection margins. Materials and findings A workflow for MRI-based 3D surgical planning with bone cutting guides was developed using a four-step approach. Key MRI parameters were defined (phase 1), followed by an application of selected Black Bone MRI sequences on healthy volunteers (phase 2). Three Black Bone MRI sequences were chosen for phase 3: standard, fat saturated, and an out of phase sequence. These protocols were validated by applying them on patients (n = 10) and comparison to corresponding CT data. The mean deviation values between the MRI-and the CT-based models were 0.63, 0.59 and 0.80 mm for the three evaluated Black Bone MRI sequences. Phase 4 entailed examination of the clinical value during surgery, using excellently fitting printed bone cutting guides designed from MRI-based lower jaw models, in two patients with oral cancer. The mean deviation of the resection planes was 2.3 mm, 3.8 mm for the fibula segments, and the mean axis deviation was the fibula segments of 1.9 E. Conclusions This study offers a method for 3D virtual resection planning and surgery using cutting guides based solely on MRI imaging. Therefore, no additional CT data are required for 3D virtual planning in oral cancer surgery

Coenzyme A precursors flow from mother to zygote and from microbiome to host

Coenzyme A (CoA) is essential for metabolism and protein acetylation. Current knowledge holds that each cell obtains CoA exclusively through biosynthesis via the canonical five-step pathway, starting with pantothenate uptake. However, recent studies have suggested the presence of additional CoA-generating mechanisms, indicating a more complex system for CoA homeostasis. Here, we uncovered pathways for CoA generation through inter-organismal flows of CoA precursors. Using traceable compounds and fruit flies with a genetic block in CoA biosynthesis, we demonstrate that progeny survive embryonal and early larval development by obtaining CoA precursors from maternal sources. Later in life, the microbiome can provide the essential CoA building blocks to the host, enabling continuation of normal development. A flow of stable, long-lasting CoA precursors between living organisms is revealed. This indicates the presence of complex strategies to maintain CoA homeostasis

Compound heterozygous SCN5A mutations in severe sodium channelopathy with Brugada syndrome : a case report

Aims:Brugada syndrome (BrS) is an inherited cardiac arrhythmia with an increased risk for sudden cardiac death (SCD). About 20% of BrS cases are explained by mutations in theSCN5Agene, encoding the main cardiac sodium Na(v)1.5 channel. Here we present a severe case of cardiac sodium channelopathy with BrS caused bySCN5Acompound heterozygous mutations. We performed a genetic analysis ofSCN5Ain a male proband who collapsed during cycling at the age of 2 years. Because of atrial standstill, he received a pacemaker, and at the age of 3 years, he experienced a collapse anew with left-sided brain stroke. A later ECG taken during a fever unmasked a characteristic BrS type-1 pattern. The functional effect of the detected genetic variants was investigated. Methods and Results:Next-generation sequencing allowed the detection of twoSCN5Avariants intrans: c.4813+3_4813+6dupGGGT-a Belgian founder mutation-and c.4711 T>C, p.Phe1571Leu. A familial segregation analysis showed the presence of the founder mutation in the proband's affected father and paternal aunt and thede novooccurrence of the p.Phe1571Leu. The functional effect of the founder mutation was previously described as a loss-of-function. We performed a functional analysis of the p.Phe571Leu variant in HEK293 cells alone or co-expressed with the beta(1)-subunit. Compared to theSCN5Awild type, p.Phe1571Leu displayed a hyperpolarizing shift in the voltage dependence of inactivation (loss-of-function), while the activation parameters were unaffected. Using the peptide toxin nemertide alpha-1, the variant's loss-of-function effect could be restored due to a toxin-dependent reduction of channel inactivation. Conclusion:This is the first report providing support for the pathogenicity of the p.Phe1571LeuSCN5Avariant which, together with the c.4813+3_4813+6dupGGGT founder mutation, explains the severity of the phenotype of cardiac sodium channelopathy with BrS in the presented case