Validation of a German version of the dementia screening questionnaire for individuals with intellectual disabilities (DSQIID-G) in Down's syndrome.

BACKGROUND: People with Down's syndrome (DS) are at high risk of developing Alzheimer dementia (DS-AD) due to a triplication of the amyloid precursor protein gene. While several tools to diagnose and screen for DS-AD, such as the dementia screening questionnaire for individuals with intellectual disabilities (DSQIID), are available in English, validated German versions of such instruments are scarce. METHODS: A German version of the DSQIID questionnaire (DSQIID-G) was completed by caregivers before attending our specialist outpatient department for DS-AD. All participants were assessed blind to DSQIID-G scoring using clinical and neuropsychological examinations, including the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). ICD-10 and amyloid/tau/neurodegeneration (A/T/N) criteria were applied to detect and categorise cognitive decline. RESULTS: Of 86 participants, 43 (50%) showed evidence of cognitive decline. A definite diagnosis of DS-AD was reached in 17 (19.8%) and mild cognitive impairment in seven (8.3%) participants. Secondary causes of cognitive decline were determined among 13 (15.1%) participants, and in six (7%) cases, the diagnosis remained unclassifiable due to co-morbidities. Compared with cognitively stable individuals, participants with cognitive decline (n = 43) displayed higher DSQIID-G total scores [median (range): 3 (0-21) vs. 19 (0-48), P < 0.001]. A total score of >7 provided a sensitivity of 0.94 against a specificity of 0.76, to discriminate DS-AD and participants without cognitive decline according to ROC analysis. The convergent validity against the CAMDEX-DS interview score was good (r = 0.74), and split-half reliability (r = 0.96), internal consistency (Cronbach's α r = 0.96), test-retest reliability (r = 0.88) (n = 25) and interrater reliability (r = 0.81) (n = 31) were excellent. CONCLUSIONS: The DSQIID-G showed excellent psychometric properties, including concurrent and internal validity and reliability. The cut-off value for screening was lower than in the original English validation study. For a screening instrument like DSQIID-G, a lower cut-off is preferable to increase case detection.

Axonal damage and astrocytosis are biological correlates of grey matter network integrity loss: a cohort study in autosomal dominant Alzheimer disease.

Brain development and maturation leads to grey matter networks that can be measured using magnetic resonance imaging. Network integrity is an indicator of information processing capacity which declines in neurodegenerative disorders such as Alzheimer disease (AD). The biological mechanisms causing this loss of network integrity remain unknown. Cerebrospinal fluid (CSF) protein biomarkers are available for studying diverse pathological mechanisms in humans and can provide insight into decline. We investigated the relationships between 10 CSF proteins and network integrity in mutation carriers (N=219) and noncarriers (N=136) of the Dominantly Inherited Alzheimer Network Observational study. Abnormalities in Aß, Tau, synaptic (SNAP-25, neurogranin) and neuronal calcium-sensor protein (VILIP-1) preceded grey matter network disruptions by several years, while inflammation related (YKL-40) and axonal injury (NfL) abnormalities co-occurred and correlated with network integrity. This suggests that axonal loss and inflammation play a role in structural grey matter network changes. Key points: Abnormal levels of fluid markers for neuronal damage and inflammatory processes in CSF are associated with grey matter network disruptions.The strongest association was with NfL, suggesting that axonal loss may contribute to disrupted network organization as observed in AD.Tracking biomarker trajectories over the disease course, changes in CSF biomarkers generally precede changes in brain networks by several years.

Efficacy of Mepliex® Ag Versus Xeroform® As A Split-Thickness Skin Graft Donor Site Dressing: Bad Habits Die Hard.

Autografting with split-thickness skin grafts (STSG) remains an essential procedure in burn and reconstructive surgery. The process of harvesting STSG, however, leaves behind a donor site, an exposed area of partial-thickness dermis left to heal by secondary intention. There has yet to be a consensus amongst surgeons regarding optimal management of the donor site. The ideal donor site dressing is one that allows for expeditious healing while minimizing pain and infection. Despite numerous studies demonstrating the superiority of moist wound healing, many surgeons continue to treat STSG donor sites dry, with petroleum-based gauze. In this study, two burn centers performed a retrospective review of burn patients whose STSG donor sites were treated with either Xeroform® or Mepilex® Ag dressings. Infections were documented and in a subgroup analysis of patients, postoperative pain scores were noted and total opiate usage during hospitalization was calculated. Analysis revealed an overall infection rate of 1.2% in the Mepilex® Ag group and 11.4% in the Xeroform® group (p<0.0001). Patients with Xeroform® donor site dressings had increased odds of donor site infection (OR=10.8, p=0.002). In subgroup analysis, there were no significant differences in maximum pain scores between Mepilex® Ag and Xeroform® groups, nor were there differences in opiate usage. STSG donor sites dressed with silver foam dressings have a lower rate of donor site infection relative to those dressed with petroleum-based gauze. Moist donor site dressings such as foam dressings (including Mepilex® Ag) should be the standard of care in STSG donor site wound care.

La greffes de peau mince (GPM) demeure une procédure essentielle dans la chirurgie de brûlure et de reconstruction. La zone donneuse de greffe (ZDG) représente une perte de substance cutanée superficielle, cicatrisant spontanément. Il n'y a pas de consensus concernant la prise en charge optimale de la ZDG. Le pansement idéal de la ZDG doit promouvoir la cicatrisation et réduire la douleur ainsi que le risque infectieux. Malgré les nombreuses publications montrant l'intérêt d'un environnement humide pour la cicatrisation, de nombreux chirurgiens réalisent des pansements secs vaselinés. Cette étude rétrospective effectuée dans 2 CTB compare les pansements de ZDG réalisés au Xéroform® ou au Mepilex Ag®. Les infections ont été documentées et, dans un sous-groupe, les scores de douleur et la consommation d'opiacés au long de l'hospitalisation ont été notés. Les taux d'infection sont de 1,2% dans le groupe Mepilex Ag® et 11,4% avec Xéroform® (p<0,0001). Le risque d'infection de la ZDG est augmenté (OR 10,8 ; p = 0,002) en cas d'utilisation de Xéroform®. Il n'y avait pas de différence de douleur et de consommation d'opiacés entre les 2 groupes. Les ZDG recouvertes d'un pansement hydrocellulaire imprégné d'argent s'infectent moins que celles traitées avec une gaze imprégnée de vaseline. L'utilisation sur les ZDG d'un pansement humide comme une mousse hydrocellulaire (par exemple Mepilex Ag®) devrait devenir la norme.

Lower oxygen saturation targets in preterm infants are not associated with increased rates of pulmonary hypertension.

BACKGROUND: The optimal oxygen saturation target in preterm infants is not known. In this study, we aimed to assess the effect of lower oxygen saturation targets on the rate of bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and pulmonary hypertension (PH) in preterm infants. METHODS: Retrospective cohort study comparing BPD, ROP, and PH incidence among two cohorts of infants born at≤32 weeks gestation with different oxygen saturation targets at≥34 weeks post-menstrual age (PMA): cohort 1, 94-98% (n = 126); cohort 2, 92-97% (n = 121). Groups compared by Chi-square test, t-test, and multivariable logistic regression. RESULTS: When comparing cohort 1 (average gestational age 29.8 weeks, average birth weight 1271g) with cohort 2 (average gestational age 29.6 weeks, average birth weight 1299g), there was no difference in rate of BPD (24% vs. 19%, p = 0.38), ROP (4% vs. 3%, p = 0.49), or PH (2% vs. 4%, p = 0.44). CONCLUSION: An oxygen saturation target of 92-97% at≥34 weeks PMA was not associated with a higher rate of PH or lower rate of BPD or ROP when compared with a higher target of 94-98%.

Substance use among HIV-infected adolescents in Uganda: rates and association with potential risks and outcome factors.

This article sets out to investigate alcohol and substance use (ASU) among adolescents living with HIV (ALWH) in the sub-Saharan African setting of Uganda. A cross-sectional analysis of the records of 479 adolescents (aged between 12and 17 years) attending the study, "Mental health among HIV infected CHildren and Adolescents in KAmpala and Masaka, Uganda (the CHAKA study)" was undertaken. ASU was assessed through both youth self-report and caregiver report using the Diagnostic and Statistical Manual of Mental Disorders-5 referenced instruments, the Youth Inventory-4R and the Child and Adolescent Symptom Inventory-5 (CASI-5). Rates and association with potential risk and outcome factors were investigated using logistic regression models. The rate of ASU was 29/484 (5.9%) with the most frequently reported ASU being alcohol 22/484 (4.3%) and marijuana 10/484 (2.1%). Functional impairment secondary to ASU was reported by 10/484 (2.1%) of the youth. ASU was significantly associated with urban residence, caregiver psychological distress and the psychiatric diagnosis of post-traumatic stress disorder. On associations with negative outcomes, ASU was significantly associated with only "ever had sex". Health care for ALWH in sub-Saharan Africa should include ASU prevention and management strategies.

[A German version of the Cambridge examination for mental disorders of older people with Down's syndrome and others with intellectual disabilities : A diagnostic procedure for detecting dementia in people with Down's syndrome]. / Eine deutsche Fassung der Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities : Ein Diagnoseverfahren zur Erfassung von Demenz bei Menschen mit einem Down-Syndrom.

BACKGROUND: Although people with Down's syndrome (DS) are at a high risk of developing an Alzheimer type dementia (AD) due to a triplication of the amyloid precursor gene, there are practically no internationally available test procedures to detect cognitive deficits in this at risk population in the German language. OBJECTIVE: The aim was to provide a German translation and intercultural adaptation of the Cambridge examination for mental disorders of older people with Down's syndrome and others with intellectual disabilities (CAMDEX-DS), which is available in English and Spanish. This instrument for diagnostics and monitoring consists of a psychological test examination (CAMCOG-DS) and a caregiver interview. METHODS: The translation and adaptation of the CAMDEX-DS were achieved through a multistep translation process, whereby two independent forward and back translations were provided by professional translators and a consensus version was finalized and tested. The final version of the caregiver interview was applied to 11 subjects and the CAMCOG-DS was conducted with 28 patients. RESULTS: The German version of the CAMDEX-DS proved to be easily administered. The CAMCOG-DS could be fully administered to 21 out of 28 patients (75%). The CAMCOG-DS values were much lower for older patients aged ≥45 years than for younger patients (46/109 vs. 73.5/109; p = 0.033). DISCUSSION: The German version of the CAMDEX-DS provides an internationally recognized tool for the diagnostics and monitoring of cognitive decline in Down's syndrome. Furthermore, the German version can standardize medical care of these patients. In particular it provides a means of participation in international research trials for this at risk population.

Blood product wastage reduction by utilising low-cost, low-impact multimodal physician-to-physician communication initiatives.

OBJECTIVES: To assess a multimodal physician-to-physician communication initiative that is low in cost and impact to daily workflow to reduce blood product wastage. BACKGROUND: Blood product stewardship is an important issue in all hospital systems. Previous studies have proposed low-cost interventions to reduce blood product wastage, but few have evaluated improvements in communication between the blood bank and providers. We undertook a prospective quality improvement project focusing on improving communication to reduce blood product wastage. METHODS: We conducted a prospective quality improvement project over the first quarter of 2017, identifying patients with issued but unused blood products. Each service overseeing the care of patients identified on the unit status report was contacted through two possible methods: (i) phone or (ii) proprietary Health Insurance Portability and Accountability Act of 1996 compliant digital messaging application. Collected variables included reserved blood product type and participant time spent. Outcomes included the rate of blood product release and changes in wastage compared with historical data tracked by the blood bank. RESULTS: Eight hundred and forty products were reserved during the study period, of which 436 (52%) were released. Average participant times ranged from 2 ± 1 min to 15 ± 4 min with no significant differences in time spent between participants (P = 0·194). Compared with the average product wastage 10 months prior to project initiation, there were significant reductions in the average wastage for platelets (5·3 ± 2·5 units vs 2·5 ± 1·5 units, P = 0·05), RBCs (6·1 ± 3·7 units vs 0 ± 0 units, P = 0·01) and overall wastage (58·3 ± 14·9 units vs 40 ± 15·7 units, P = 0·05). CONCLUSION: Efforts focusing on improving provider-to-provider communication can reduce blood product wastage.

Near-threshold photodissociation of cool OH+ to O + H+ and O+ + H.

We have measured the spectrum of laser photodissociation of OH+ molecular ions to O + H+ and O+ + H fragments for photon energies of 38 100-40 900 cm-1. The OH+ ions were stored as a fast beam (5.50 MeV) in the storage ring TSR for several seconds to achieve rovibrational cooling into the lowest rotations N'' = 0-11 of the vibrational ground state X3Σ-(v'' = 0), close to room temperature (≈300 K). The many resonances in the spectra reveal the energies, widths, and O/O+ branching ratios of 44 predissociating quasibound levels (Feshbach resonances) that lie between the fine-structure states of the O fragment and belong to the last, near-threshold vibrational states v' = 9 and 10 of the A3Π electronic state. For the A3Π0,1 substates, isolated levels with v' = 11 are observed and attributed to double-well distortions of these curves due to nonadiabatic interactions. Another five isolated levels are assigned to the v' = 0 and 1 states of the shallow 15Σ- electronic state, borrowing oscillator strength from nearby A3Π levels. Together, the near-threshold levels deliver a new value D0 = 40 253.8(1.1) cm-1 for the dissociation energy of OH+. Through a two-step photodissociation process, 72 levels from the lower bound states A3Π(v' = 7-8) appear as well and are rotationally analyzed. The level energies are used to construct improved A3Π and 15Σ- Born-Oppenheimer potentials. The totality of the spectral data (energies, widths, intensities, and branching ratios) can provide tight constraints for the potentials and nonadiabatic interactions assumed in future coupled-channel calculations of OH+ photodissociation or of the related charge-exchange reaction O + H+ → O+ + H.

Ictal autonomic activity recorded via wearable-sensors plus machine learning can discriminate epileptic and psychogenic nonepileptic seizures.

Differentiating epileptic seizures (ES) and psychogenic nonepileptic seizures (PNES) is commonly based on electroencephalogram and concurrent video recordings (vEEG). Here, we demonstrate that these two types of seizures can be discriminated based on signals related to autonomic nervous system activity recorded via wearable sensors. We used Empatica E4 Wristband sensors worn on both arms in vEEG confirmed seizures, and machine learning methods to train classifiers, specifically, extreme gradient boosting (XGBoost). Classification performance achieved a predictive accuracy of 78 ± 1.5% on previously unseen data for whether a seizure was epileptic or psychogenic, which is 6 standard deviations above the baseline of 68% accuracy. Our dataset contained altogether 35 seizures from 18 patients out of which 8 patients had 13 convulsive seizures. Prediction of seizure type was based on simple features derived from the segments of autonomic activity measurements (electrodermal activity, body temperature, blood volume pulse, and heart rate) and forearm acceleration. Features related to heart rate and electrodermal activity were ranked as the top predictors in XGBoost classifiers. We found that patients with PNES had a higher ictal heart rate and electrodermal activity than patients with ES. In contrast to existing published studies of mainly convulsive seizures, our classifier focuses on autonomic signals to differentiate convulsive or nonconvulsive semiology ES from PNES. Our results show that autonomic activity recorded via wearable sensors provides promising signals for detection and discrimination of psychogenic and epileptic seizures, but more work is necessary to improve the predictive power of the model.

The relationship between cognitive change and physical health and behavioural outcomes in a Ugandan cohort of adults living with HIV - a longitudinal study.

We investigated changes in cognitive function and physical health and behavioural outcomes (HIV disease progression, health-seeking behaviour, adherence to HIV medications and risky sexual behaviour) at baseline and 12 months later among 1126 Ugandan adults living with HIV. Overall, cognitive function improved from baseline to follow-up, except for gait speed, which was slower at follow-up compared to baseline. There were improvements in physical health and behavioural outcomes by follow-up, with greater improvements among individuals on ART compared to those not on ART. Change in gait speed over time significantly predicted risky sexual behaviours at follow-up. This is the first study to investigate the longitudinal relationships between cognitive function and health outcomes among Ugandan adults living with HIV and provide insights into the possible links between cognitive function and negative clinical and behavioural health outcomes in people living with HIV.

[Tauopathies : From molecule to therapy]. / Tauopathien : Vom Molekül zur Therapie.

BACKGROUND: The microtubule-associated tau protein is the defining denominator of a group of neurodegenerative diseases termed tauopathies. OBJECTIVE: Provide a timely state of the art review on recent scientific advances in the field of tauopathies. MATERIAL AND METHODS: Systematic review of the literature from the past 10 years. RESULTS: Tau proteins are increasingly being recognized as a highly variable protein, underlying and defining a spectrum of molecularly defined diseases, with a clinical spectrum ranging from dementia to hypokinetic movement disorders. Genetic variation at the tau locus can trigger disease or modify disease risk. Tau protein alterations can damage nerve cells and propagate pathologies through the brain. Thus, tau proteins may serve both as a serological and imaging biomarker. Tau proteins also provide a broad spectrum of rational therapeutic interventions to prevent disease progression. This knowledge has led to modern clinical trials. CONCLUSION: The field of tauopathies is in a state of dynamic and rapid progress, requiring close interdisciplinary collaboration.

Infant adiposity following a randomised controlled trial of a behavioural intervention in obese pregnancy.

OBJECTIVES: Randomised controlled trials are required to address causality in the reported associations between maternal influences and offspring adiposity. The aim of this study was to determine whether an antenatal lifestyle intervention, associated with improvements in maternal diet and reduced gestational weight gain (GWG) in obese pregnant women leads to a reduction in infant adiposity and sustained improvements in maternal lifestyle behaviours at 6 months postpartum. SUBJECTS AND METHODS: We conducted a planned postnatal follow-up of a randomised controlled trial (UK Pregnancies Better Eating and Activity Trial (UPBEAT)) of a complex behavioural intervention targeting maternal diet (glycaemic load (GL) and saturated fat intake) and physical activity in 1555 obese pregnant women. The main outcome measure was infant adiposity, assessed by subscapular and triceps skinfold thicknesses. Maternal diet and physical activity, indices of the familial lifestyle environment, were assessed by questionnaire. RESULTS: A total of 698 (45.9%) infants (342 intervention and 356 standard antenatal care) were followed up at a mean age of 5.92 months. There was no difference in triceps skinfold thickness z-scores between the intervention vs standard care arms (difference -0.14 s.d., 95% confidence interval -0.38 to 0.10, P=0.246), but subscapular skinfold thickness z-score was 0.26 s.d. (-0.49 to -0.02; P=0.03) lower in the intervention arm. Maternal dietary GL (-35.34; -48.0 to -22.67; P<0.001) and saturated fat intake (-1.93% energy; -2.64 to -1.22; P<0.001) were reduced in the intervention arm at 6 months postpartum. Causal mediation analysis suggested that lower infant subscapular skinfold thickness was partially mediated by changes in antenatal maternal diet and GWG rather than postnatal diet. CONCLUSIONS: This study provides evidence from follow-up of a randomised controlled trial that a maternal behavioural intervention in obese pregnant women has the potential to reduce infant adiposity and to produce a sustained improvement in maternal diet at 6 months postpartum.

A UHF RFID positioning system for use in warehouse navigation by employees with cognitive disability.

Unemployment among the almost 5 million working-age adults with cognitive disabilities in the USA is a costly problem in both tax dollars and quality of life. Job coaching is an effective tool to overcome this, but the cost of job coaching services sums with every new employee or change of employment roles. There is a need for a cost-effective, automated alternative to job coaching that incurs a one-time cost and can be reused for multiple employees or roles. An effective automated job coach must be aware of its location and the location of destinations within the job site. This project presents a design and prototype of a cart-mounted indoor positioning and navigation system with necessary original software using Ultra High Frequency Radio Frequency Identification (UHF RFID). The system presented in this project for use within a warehouse setting is one component of an automated job coach to assist in the job of order filler. The system demonstrated accuracy to within 0.3 m under the correct conditions with strong potential to serve as the basis for an effective indoor navigation system to assist warehouse workers with disabilities. Implications for rehabilitation An automated job coach could improve employability of and job retention for people with cognitive disabilities. An indoor navigation system using ultra high frequency radio frequency identification was proposed with an average positioning accuracy of 0.3 m. The proposed system, in combination with a non-linear context-aware prompting system, could be used as an automated job coach for warehouse order fillers with cognitive disabilities.

[Pathomechanisms and clinical aspects of frontotemporal lobar degeneration]. / Pathomechanismen und klinische Aspekte der frontotemporalen Lobärdegeneration.

BACKGROUND: Frontotemporal lobar degeneration (FTLD) includes a spectrum of heterogeneous clinical and neuropathological diseases. In a strict sense this includes the behavioral variant of frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA) and both variants can be associated with amyotrophic lateral sclerosis (FTD-ALS). In a broader sense FTLD also includes progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). In recent years the strong genetic component of FTLD has become increasingly clear. OBJECTIVE: The association between clinical presentation, neuropathology, genetics and pathophysiological mechanisms of FTLD are presented. RESULTS: The diagnostic criteria and tools for the clinical differential diagnosis of FTLD are presented. At autopsy patients show neuronal and glial inclusions of Tau, TDP-43 or FUS. While Tau pathology is often associated with extrapyramidal symptoms, patients with TDP-43 and FUS inclusions often also show signs of ALS. Pathogenic mutations directly increase the aggregation propensity of these proteins or impair protein degradation through autophagy or the proteasome. Pathogenic mutations in most FTLD genes trigger cytoplasmic missorting and aggregation of the RNA-binding protein TDP-43 and thus lead to a nuclear loss of TDP-43 function. Microgliosis and mutations in GRN and TREM2 suggest an important role of neuroinflammation in FTLD. CONCLUSION: There is still no causal therapy for FTLD but preclinical studies focusing on pathogenic mutations in C9orf72, GRN and Tau may lead to clinical trials soon; therefore, establishing large well characterized patient cohorts is crucial for trial readiness.

[Amyloid positron-emission-tomography with [18 F]-florbetaben in the diagnostic workup of dementia patients]. / Amyloid-Positronenemissionstomographie mit [18 F]-Florbetaben in der Demenzdiagnostik.

BACKGROUND: To this day the definite diagnosis of Alzheimer's disease still relies on post-mortem histopathological detection of neurofibrillary tangles and beta-amyloid deposits. Amyloid positron emission tomography (PET) is a new diagnostic tool that enables the in vivo quantification of pathological beta-amyloid deposits. The aim of the current study was to evaluate to what extent 18F-florbetaben-PET (FBB-PET) influences the diagnosis of patients with dementia. MATERIAL AND METHODS: Imaging with FBB-PET was performed on 33 patients from our outpatient department for cognitive neurology. Beforehand all patients underwent a comprehensive clinical, neuropsychiatric and laboratory examination as well as imaging by means of magnetic resonance imaging (MRI) and fluorodeoxyglucose-PET. The working diagnoses before and after FBB-PET imaging were compared. RESULTS: 17 out of 33 patients were scored as FBB-PET positive. In four cases the initial diagnosis had to be changed to Alzheimer's disease (three cases) and cerebral amyloid angiopathy (one case) due to the positive FBB-PET scan. 16 patients showed a negative FBB-PET scan. In three patients the initial diagnosis of Alzheimer's disease could be ruled out due to the negative FBB-PET scan. Overall, in 7 out of 33 examined patients the initial diagnosis had to be changed because of the findings of the FBB-PET scan. In 24 patients the initial diagnosis was confirmed by the results of the FBB-PET scan. CONCLUSION: Amyloid-PET is currently no standard procedure in the diagnosis of dementia; however, it can be a helpful additional diagnostic tool when used according to the "Appropriate Use Criteria" and the S3 guidelines on dementia in cases of unclear clinical presentation, atypically early age of onset as well as in patients with persistent or progressive unexplained mild cognitive impairment. By facilitating early diagnosis amyloid-PET imaging allows patient selection for therapeutic drug trials.

[A Pair of Siblings with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis and a Novel Thr462Lysfs Mutation in the TBK1 Gene]. / Ein Geschwisterpaar mit frontotemporaler Lobärdegeneration und amyotropher Lateralsklerose und einer neuen Mutation im TBK1-Gen (Thr462Lysfs).

We report on a pair of siblings with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) and a novel Thr462Lysfs mutation in the TANK-binding kinase 1 (TBK1) gene identified through the European Early-Onset Dementia Consortium. The patients presented at the age of 77 and 75 years and displayed dementia and bulbar symptoms as well as progressive paresis. After a progressive course, both of them died only a few months after diagnosis. Most recently, TBK1 mutations were identified in patients with FTD and ALS. A loss of expression of the mutant allele, leading to 50 % reduced TBK1 protein levels, seems to be causative. The occurrence of TBK1 mutations in FTD and ALS underlines the fact that FTD and ALS are part of the same disease spectrum. For future therapeutic trials, characterization of TBK1 mutation carriers in presymptomatic cohorts, such as the genetic frontotemporal dementia initiative (GENFI), is of great importance.

Flexible and capsule endoscopy for screening, diagnosis and treatment.

Endoscopy dates back to the 1860s, but many of the most significant advancements have been made within the past decade. With the integration of robotics, the ability to precisely steer and advance traditional flexible endoscopes has been realized, reducing patient pain and improving clinician ergonomics. Additionally, wireless capsule endoscopy, a revolutionary alternative to traditional scopes, enables inspection of the digestive system with minimal discomfort for the patient or the need for sedation, mitigating some of the risks of flexible endoscopy. This review presents a research update on robotic endoscopic systems, including both flexible scope and capsule technologies, detailing actuation methods and therapeutic capabilities. A future perspective on endoscopic potential for screening, diagnostic and therapeutic gastrointestinal procedures is also presented.

[Hereditary diffuse leukencephalopathy with spheroids: a microgliopathy due to CSF1 receptor impairment]. / Hereditäre diffuse Leukenzephalopathie mit Sphäroiden : Eine Mikrogliopathie durch Fehlfunktion des CSF1-Rezeptors.

Hereditary diffuse leukencephalopathy with spheroids (HDLS) is a rare progressive form of leukodystrophy with variable clinical presentation and little known pathophysiology. Characteristic pathological features at brain biopsy or postmortem can support the diagnosis. The genetic basis of HDLS was elusive until 2011 when mutations in the colony-stimulating factor 1 receptor (CSF1R) gene were identified as the cause. Mutations in the CSF1R gene had previously been associated with tumor development, including hematological malignancies. We report three patients with HDLS who carried missense mutations in the CSF1R gene, two of them novel (p.L582P and p.V383L). Particularly in younger patients with rapid cognitive decline and/or leukencephalopathy of unknown origin, HDLS appears to be more common than previously thought. Various compounds acting on the CSF1 receptor are available from the treatment of hemato-oncological malignancies, so novel therapeutic approaches could be developed for this devastating condition.

Wireless tissue palpation for intraoperative detection of lumps in the soft tissue.

In an open surgery, identification of precise margins for curative tissue resection is performed by manual palpation. This is not the case for minimally invasive and robotic procedures, where tactile feedback is either distorted or not available. In this paper, we introduce the concept of intraoperative wireless tissue palpation. The wireless palpation probe (WPP) is a cylindrical device (15 mm in diameter, 60 mm in length) that can be deployed through a trocar incision and directly controlled by the surgeon to create a volumetric stiffness distribution map of the region of interest. This map can then be used to guide the tissue resection to minimize healthy tissue loss. The wireless operation prevents the need for a dedicated port and reduces the chance of instrument clashing in the operating field. The WPP is able to measure in real time the indentation pressure with a sensitivity of 34 Pa, the indentation depth with an accuracy of 0.68 mm, and the probe position with a maximum error of 11.3 mm in a tridimensional workspace. The WPP was assessed on the benchtop in detecting the local stiffness of two different silicone tissue simulators (elastic modulus ranging from 45 to 220 kPa), showing a maximum relative error below 5%. Then, in vivo trials were aimed to identify an agar-gel lump injected into a porcine liver and to assess the device usability within the frame of a laparoscopic procedure. The stiffness map created intraoperatively by the WPP was compared with a map generated ex vivo by a standard uniaxial material tester, showing less than 8% local stiffness error at the site of the lump.