Patients suffering from dystrophic epidermolysis bullosa are prone to developing autoantibodies against skin proteins: A longitudinal confirmational study.

Epidermolysis bullosa (EB) is a heritable skin blistering disease caused by variants in genes coding for proteins that secure cell-cell adhesion and attachment of the epidermis to the dermis. Interestingly, several proteins involved in inherited EB are also associated with autoimmune blistering diseases (AIBD). In this study, we present a long-term follow-up of 15 patients suffering from recessive dystrophic or junctional EB. From these patients, 62 sera were analysed for the presence of autoantibodies associated with AIBD. We show that patients suffering from recessive dystrophic EB (RDEB) are more susceptible to developing autoantibodies against skin proteins than patients suffering from junctional EB (70% vs. 20%, respectively). Interestingly, no correlation with age was observed. Most patients showed reactivity to Type XVII collagen/linear IgA bullous dermatosis autoantigen (n = 5; 33%), followed by BP230 (n = 4; 27%), Type VII collagen (n = 4; 27%) and laminin-332 (n = 1; 7%). The pathogenicity of these autoantibodies remains a subject for future experiments.

ICARUS at the Fermilab Short-Baseline Neutrino program: initial operation.

The ICARUS collaboration employed the 760-ton T600 detector in a successful 3-year physics run at the underground LNGS laboratory, performing a sensitive search for LSND-like anomalous νe appearance in the CERN Neutrino to Gran Sasso beam, which contributed to the constraints on the allowed neutrino oscillation parameters to a narrow region around 1 eV2. After a significant overhaul at CERN, the T600 detector has been installed at Fermilab. In 2020 the cryogenic commissioning began with detector cool down, liquid argon filling and recirculation. ICARUS then started its operations collecting the first neutrino events from the booster neutrino beam (BNB) and the Neutrinos at the Main Injector (NuMI) beam off-axis, which were used to test the ICARUS event selection, reconstruction and analysis algorithms. ICARUS successfully completed its commissioning phase in June 2022. The first goal of the ICARUS data taking will be a study to either confirm or refute the claim by Neutrino-4 short-baseline reactor experiment. ICARUS will also perform measurement of neutrino cross sections with the NuMI beam and several Beyond Standard Model searches. After the first year of operations, ICARUS will search for evidence of sterile neutrinos jointly with the Short-Baseline Near Detector, within the Short-Baseline Neutrino program. In this paper, the main activities carried out during the overhauling and installation phases are highlighted. Preliminary technical results from the ICARUS commissioning data with the BNB and NuMI beams are presented both in terms of performance of all ICARUS subsystems and of capability to select and reconstruct neutrino events.

Cluster-randomized crossover trial of chlorhexidine-alcohol versus iodine-alcohol for prevention of surgical-site infection (SKINFECT trial).

Background: Surgical-site infection (SSI) is a serious surgical complication that can be prevented by preoperative skin disinfection. In Western European countries, preoperative disinfection is commonly performed with either chlorhexidine or iodine in an alcohol-based solution. This study aimed to investigate whether there is superiority of chlorhexidine-alcohol over iodine-alcohol for preventing SSI. Methods: This prospective cluster-randomized crossover trial was conducted in five teaching hospitals. All patients who underwent breast, vascular, colorectal, gallbladder or orthopaedic surgery between July 2013 and June 2015 were included. SSI data were reported routinely to the Dutch National Nosocomial Surveillance Network (PREZIES). Participating hospitals were assigned randomly to perform preoperative skin disinfection using either chlorhexidine-alcohol (0·5 per cent/70 per cent) or iodine-alcohol (1 per cent/70 per cent) for the first 3 months of the study; every 3 months thereafter, they switched to using the other antiseptic agent, for a total of 2 years. The primary endpoint was the development of SSI. Results: A total of 3665 patients were included; 1835 and 1830 of these patients received preoperative skin disinfection with chlorhexidine-alcohol or iodine-alcohol respectively. The overall incidence of SSI was 3·8 per cent among patients in the chlorhexidine-alcohol group and 4·0 per cent among those in the iodine-alcohol group (odds ratio 0·96, 95 per cent c.i. 0·69 to 1·35). Conclusion: Preoperative skin disinfection with chlorhexidine-alcohol is similar to that for iodine-alcohol with respect to reducing the risk of developing an SSI.

Antecedentes: La infección del sitio quirúrgico (surgical site infection, SSI) es una complicación quirúrgica grave que se puede prevenir mediante una desinfección cutánea preoperatoria. En los países de Europa occidental, la desinfección preoperatoria se realiza habitualmente usando clorhexidina o yodo en una solución a base de alcohol. Nuestro objetivo fue investigar si la clorhexidina alcohólica es superior al yodo con alcohol para prevenir la SSI. Métodos: Este ensayo prospectivo aleatorizado por conglomerados y de grupos cruzados se realizó en cinco hospitales docentes. Se incluyeron todos los pacientes que se sometieron a cirugía mamaria, vascular, colorrectal, biliar y ortopédica entre julio de 2013 y junio de 2015. Los datos de SSI se presentaron de manera rutinaria a la Red Nacional Holandesa de Vigilancia Nosocomial (PREZIES). Los hospitales participantes fueron asignados al azar para realizar una desinfección cutánea preoperatoria con clorhexidina alcohólica (0,5%/70%) o yodo con alcohol (1%/70%) durante los primeros tres meses del estudio; cada 3 meses a partir de entonces, cambiaron a usar el otro agente antiséptico, durante un total de 2 años. El criterio de valoración principal fue el desarrollo de SSI. Resultados: Se incluyeron un total de 3.665 pacientes; 1.835 y 1.830 de estos pacientes recibieron desinfección cutánea preoperatoria con clorhexidina alcohólica o yodo con alcohol, respectivamente. La incidencia global de SSI fue del 3,8% entre los pacientes en el grupo de clorhexidina alcohólica y del 4,0% entre los pacientes en el grupo de yodo con alcohol (razón de oportunidades, odds ratio, OR 0,96; i.c. del 95%: 0,69­1,35). Conclusión: La desinfección cutánea preoperatoria con clorhexidina alcohólica es similar al yodo con alcohol con respecto a la reducción del riesgo de desarrollar una SSI.

Outcome and clinical course of EHEC O104 infection in hospitalized patients: A prospective single center study.

OBJECTIVES: Shiga-toxin producing O157:H7 Entero Haemorrhagic E. coli [STEC/EHEC] are the most common cause of Haemolytic Uraemic Syndrome [HUS] related to infectious haemorrhagic colitis. Nearly all recommendations on long term treatment of EHEC infections refer to this strain. The 2011 outbreak in Northern Europe was the first of this dimension to be caused by the serotype O104:H4. We report on the 3.5 year follow up of 61 patients diagnosed with symptomatic EHEC O104:H4 infection in spring 2011. METHODS: Patients with EHEC O104 infection were followed in a monocentric, prospective observational study at four time points: 4, 12, 24 and 36 months. These data include the patients' histories, clinical findings, and complications. RESULTS: Sixty-one patients suffering from EHEC O104:H4 associated enterocolitis participated in the study at the time of hospital discharge. The mean age of patients was 43 ± 2 years, 37 females and 24 males. 48 patients participated in follow up 1 [FU 1], 34 patients in follow up 2 [FU 2], 23 patients in follow up 3 [FU 3] and 18 patients in follow up 4 [FU 4]. Out of 61 patients discharged from the hospital and included in the study, 54 [84%] were examined at least at one additional follow up. Serum creatinine decreased significantly between discharge and FU 1 from 1.3 ± 0.1 mg/dl to 0.7 ± 0.1 mg/dl [p = 0.0045]. From FU 1 until FU 4, no further change in creatinine levels could be observed. The patients need of antihypertensive medications decreased significantly [p = 0.0005] between discharge and FU 1 after four months. From FU 1 until FU 3, 24 months later, no further significant change in antihypertensive treatment was observed. CONCLUSIONS: Our findings suggest that patients free of pathological findings at time of discharge do not need a specific follow up. Patients with persistent health problems at hospital discharge should be clinically monitored over four months to evaluate chronic organ damage. Progressive or new emerging renal damage could not be observed over time in any patient.

[Medical quality standards for selected urological aids and devices : Consensus for patients with neurogenic urinary bladder dysfunction]. / Medizinische Qualitätsstandards ausgewählter urologischer Hilfsmittel : Konsens für Patienten mit neurogenen Harnblasenfunktionsstörungen.

BACKGROUND: Using the CE mark of therapeutic appliances is, on its own, not sufficient enough for their appropriate and effective application. In order to treat the patient successfully, not jeopardizing the success of the treatment, medical quality criteria for therapeutic appliances care are necessary to acceptably compensate for a patient's disabilities. OBJECTIVES: Medical quality criteria are formulated for the most frequently used urological aids and devices, considering hygienic requirements, international literature and the practical experience of physicians and nurses with regard to the care of patients with neurogenic urinary bladder dysfunction. METHODS: An expert group of urologists, surgeons, rehabilitation physicians and nurses has developed medical quality criteria via a structured consensus procedure. Developing these criteria, the group has taken into account current jurisprudence, the current resource directory of neurourological relevant aids, data from international literature and hygiene requirements. RESULTS: Medical quality requirements are discussed and defined for selected groups of urological devices (single use catheters, indwelling catheters, external catheters, urine bags, templates and diapers as well as devices for the electrostimulation of nerves). CONCLUSION: The presented quality requirements offer the possibility to stabilize quality of care with neurourological relevant therapeutic appliances. The catalogue of therapeutic appliances must be urgently updated. Urinal catheters for single use must be classified as an individual product group. Devices for anterior root stimulation and neuromodulation must be included in the resource directory. The incontinence severity classification needs to be reviewed.

[Neuro-urological diagnosis and therapy of lower urinary tract dysfunction in patients with spinal cord injury : S2k Guideline of the German-Speaking Medical Society of Paraplegia (DMGP), AWMF register no. 179/001]. / Neuro-urologische Diagnostik und Therapie bei Funktionsstörungen des unteren Harntrakts nach einer Rückenmarkschädigung : S2k-Leitlinie der Deutschsprachigen Medizinischen Gesellschaft für Paraplegie (DMGP), AWMF-Register Nr: 179/001.

BACKGROUND: Most patients with spinal cord injury (SCI) suffer from neurogenic lower urinary tract dysfunction (NLUTD), bowel dysfunction and sexual dysfunction. If these remain untreated, severe medical complications and serious limitations (restrictions) in quality of life are imminent. OBJECTIVES: In the long term, there are considerable differences in the treatment results of highly specialized centers versus other treatment facilities. MATERIALS AND METHODS: Against this background, a consensus-based guideline, according to the AWMF (Association of the Scientific Medical Societies in Germany) criteria (S2k), was developed by the neuro-urology working group of the DMPG (German-Speaking Medical Society of Paraplegia). RESULTS: The guideline defines the principles and objectives of the neuro-urological care of patients with SCI and discusses in detail the principles of diagnosis and therapy of NLUTD. The need for video-urodynamic studies as a basis for the classification of the NLUTD and as a foundation for the development of a treatment strategy is emphasized. Both conservative and surgical therapy options and their indications are explained in detail. Possible complications and their prevention in the long-term course of SCI are presented with a particular consideration of the specific features of urinary tract infections and autonomic dysreflexia. Finally, the principles of the provision of urological appliances are discussed. CONCLUSIONS: The presented S2k guideline provides the current standards in the neuro-urological care of patients with NLUTD due to SCI. Their consistent implementation both in the acute and chronic phase as well as in the context of lifelong surveillance of SCI patients should prevent the impending complications of NLUTD.

Genetic identification of istiophorid larvae from the Gulf of Mexico based on the analysis of mitochondrial DNA control region sequences.

Assigning relative importance of spawning and nursery habitats for threatened and endangered teleosts, such as those seen in the Gulf of Mexico (GoM), relies on the proper identification of the early life-history stages of the species of concern. Here, sequencing a portion of the mitochondrial DNA (mtDNA) control region (CR) I as barcodes is recommended to identify istiophorid (billfish) larvae in the Atlantic Ocean because of its high resolution and the intrinsic value of the levels of genetic variation that can be extracted from these data. The universality of the primers employed here demonstrates their utility for not only the positive identification of istiophorids in the GoM, but for any larval teleost occurring in areas recognized as larval hotspots worldwide.

[Objective and subjective requirement of aids and appliances in patients with neurogenic lower urinary tract dysfunction : Multicenter study to determinate the daily necessity of urological aids and appliances]. / Objektiver und subjektiver Hilfsmittelbedarf bei Patienten mit neurogenen Harnblasenfunktionsstörungen : Multicenterstudie zur Ermittlung des täglichen Bedarfs an urologischen Hilfsmitteln.

BACKGROUND: The provision of urological appliances for patients with neurogenic lower urinary tract dysfunction (NLUTD) is essential. Hitherto existing standard guidelines for the estimation of monthly material requirements are based solely on estimates. OBJECTIVE: The goal of this work was to define the objective and subsequently subjective requirements for urological appliances on a scientifically validated basis. MATERIALS AND METHODS: Data concerning bladder management and daily consumption of urological appliances for patients with NLUTD were collected through a standardized survey at six different centers in Germany during the period of October to December 2014 and statistically evaluated. RESULTS: In all, 767 patient records were analyzed: 543 men and 221 woman (N/A = 3). The daily disposable catheter consumption of 577 patients who exclusively used intermittent catheterization was 5.13. Patients who used other means of bladder emptying (n = 31) in addition to catheterization consumed on average 3.17 catheters. The margin of deviation was larger for children. Of the 608 patients with intermittent catheterization, 94 (15.5 %) required additional paddings as absorbent aids (on average 2.29 paddings per day), 34 patients (5.6 %) additionally used pants (2.55 per day) and 46 patients (7.6 %) utilized condom catheters (3.81 per day) between catheterization. Among all surveyed patients, 126 (16.4 %) used paddings (5.03 per day) and 51 patients (6.6 %) pants (3.03 per day). Of all male respondents 82 (15.1 %) used condom catheters (2.80 urinary sheaths per day). CONCLUSION: Applying twice the standard deviation of the mean as a measure of assessing the objective requirement of urological appliances and aids for adult patients with NLUTD allows the following daily thresholds to be defined: 1-9 disposable catheters, 0-7 urinary sheaths, 1-9 paddings and 0-7 pants. These thresholds can serve as a basis for estimating the subjective need. They allow for a scientifically validated benchmark for an economically feasible and patient-tailored supply with urological aids and appliances. Individually required appliances and aids have to be recognized. Verifiable quality standards need to be developed.

Amelioration of junctional epidermolysis bullosa due to exon skipping.

Mutations in the COL17A1 gene lead to the genetic blistering disorder junctional epidermolysis bullosa generalized intermediate type (JEB-gen-intermed). Antisense oligonucleotide-mediated exon skipping is a strategy that aims to skip the mutation-containing exon and thereby produce a smaller but functional protein. COL17A1 is an interesting candidate, as 53 of the 55 exons (96%) can be skipped without disturbing the reading frame. Information on the functionality of the shortened protein product is important in order to obtain support for this therapeutic strategy. Here we report a patient with JEB-gen-intermed with amelioration of the phenotype due to exon 49 skipping by two distinct mechanisms - premature termination codon-induced exon skipping and revertant mosaicism - both of which induced skipping of the same exon. The patient was compound heterozygous for two inherited COL17A1 mutations, a frameshift mutation in exon 18 (c.1490_1491delinsT, p.Ala497Valfs*23) and a nonsense mutation in exon 49 (c.3487G>T, p.Glu1163Ter). Upon clinical examination, skin patches were found that were resistant to blister formation. In these patches, naturally corrected cells were present that harboured an additional splice-site mutation, c.3419-1G>T, resulting in skipping of the mutation-containing exon 49. This natural gene therapy phenomenon shows that type XVII collagen with residues 1140-1169 deleted is largely functional. In addition, in affected skin cells a low level of exon 49 skipping was observed. Our results support the notion that skipping of a mutated in-frame exon in COL17A1 ameliorates the phenotype.

A moiré deflectometer for antimatter.

The precise measurement of forces is one way to obtain deep insight into the fundamental interactions present in nature. In the context of neutral antimatter, the gravitational interaction is of high interest, potentially revealing new forces that violate the weak equivalence principle. Here we report on a successful extension of a tool from atom optics--the moiré deflectometer--for a measurement of the acceleration of slow antiprotons. The setup consists of two identical transmission gratings and a spatially resolving emulsion detector for antiproton annihilations. Absolute referencing of the observed antimatter pattern with a photon pattern experiencing no deflection allows the direct inference of forces present. The concept is also straightforwardly applicable to antihydrogen measurements as pursued by the AEgIS collaboration. The combination of these very different techniques from high energy and atomic physics opens a very promising route to the direct detection of the gravitational acceleration of neutral antimatter.

[Botulinum neurotoxin type A in neurogenic detrusor overactivity: consensus paper of the Working Group Neuro-Urology of the DMGP]. / Botulinumneurotoxin Typ A bei neurogener Detrusorüberaktivität: Konsensus des Arbeitskreises Neuro-Urologie der DMGP.

The use of botulinum neurotoxin (BoNT-A) for suppression of neurogenic detrusor overactivity was first reported in 2000. Since that time, this method has gained widespread use. A number of recommendations and consensus statements have already been published. The current practice-oriented consensus paper takes into account recent developments and the over 10-year experience of most members of the Working Group Neuro-Urology of the German-speaking Medical Society for Paraplegia (DMGP) with a focus on the use of BoNT-A in paraplegic patients and in patients with multiple sclerosis.

Shake and stew: a non-destructive PCR-ready DNA isolation method from a single preserved fish larva.

A rapid non-destructive alternative to isolate DNA from an individual fish larva is presented, based on the suspension of epithelial cells through vortex forces, and the release of DNA in a heated alkaline solution. DNA from >6056 fish larvae isolated using this protocol has yielded a high PCR amplification success rate (>93%), suggesting its applicability to other taxonomic groups or sources when tissue amount is the limiting factor.

Erythropoietin receptor expression in normal and neoplastic choroid plexus.

BACKGROUND: The erythropoietin receptor (EpoR) is expressed widely throughout the human CNS, including the choroid plexus. Recent studies have shown that EpoR is also expressed in various human tumors, including carcinomas, meningiomas and gliomas. Thereby, the Epo-EpoR pathway plays a role in inhibition of apoptosis and tumor growth, infiltration, angiogenesis and metastasis as well as treatment resistance and is a potential target in oncological treatment. Lower levels of EpoR have been associated with shorter survival in high grade gliomas and higher risk of tumor recurrence in meningiomas. METHODS: Since the EpoR status in human choroid plexus tumors (CPT) is not known, we investigated 57 CPT from 43 cases including 14 recurrent tumors and compared them with 23 samples of normal choroid plexus (CP). CPT samples consisted of choroid plexus papillomas/CPP (n = 41), atypical CPP (n = 15) and choroid plexus carcinoma/CPC (n = 1). EpoR expression was determined by immunohistochemistry using semi-quantitative scoring for staining intensity and was validated in exemplary cases using western blot and RT-PCR. RESULTS: EpoR expression was observed in all samples of normal and neoplastic CP with significantly lower expression levels in CPT (p < 0.001). CONCLUSION: No significant correlation was found between EpoR expression and age, gender, WHO grade, number of mitosis or tumor recurrence. EpoR expression in CPT is in line with its expression in normal CP and with previous reports on EpoR expression in other glial neoplasms. Association of EpoR levels in CPT with survival, as known in astrocytic gliomas, remains to be determined.

High-resolution melting analysis (HRMA): a highly sensitive inexpensive genotyping alternative for population studies.

High-resolution melting analysis (HRMA) is a highly sensitive closed-tube genotyping method used primarily in clinical studies. As the method is rapid, inexpensive and amenable to high throughput, we decided to investigate its applicability to population studies. Small amplicons and unlabelled probes were used to genotype the nuclear genes, lactate dehydrogenase-A (ldh-A), myosin light chain-2 (mlc-2), acidic ribosomal phosphoprotein P0 (ARP) and calmodulin (CaM) in populations of swordfish, Xiphias gladius. Results indicate that HRMA is a powerful genotyping tool to study wild populations.

Implementation of endovenous laser ablation for varicose veins in a large community hospital: the first 400 procedures.

UNLABELLED: Endovenous laser ablation (ELA) has become a standard treatment of the incompetent great saphenous vein (GSV). Our prospective audit examines the implementation of this new method in a large community hospital with special attention to obstacles, technical results, pain scores, failures and our learning curve. METHODS: Three hundred and twenty-three patients (403 limbs) with incompetence of the GSV underwent ELA. Patients were assessed by clinical examination and venous duplex ultrasound was performed 6 weeks after operation. Visual analog scale (VAS) pain scores of the first postoperative week were recorded. Operative time and success rate were analysed. RESULTS: After 6 weeks, 301 (74.7%) treated legs were examined by duplex ultrasound imaging. Successful complete occlusion was present in 282 (93.7%) GSVs. Partial occlusion was present in 12 (4.0%) GSVs. In seven (2.3%) limbs the GSV was not occluded. The maximum mean VAS pain score was noted on the 5th postoperative day. From the start of this series, the operation time decreased rapidly for each surgeon, stabilising after 15 limbs. CONCLUSION: ELA of the incompetent GSV is effective and safe. ELA is simple to perform, well accepted by patients and relatively atraumatic. In our opinion, ELA can be easily implemented in surgical practice.