Innovative biochemisurgical treatment for stabilisation of an end-stage chronic wound in a complex vascular compromized patient.

INTRODUCTION: Treating advanced peripheral arterial occlusive disease (e.g. PAOD IV) poses a significant challenge, as conventional treatments quite often fall short at this stage. However, a range of interventions can be considered to postpone amputation. This study presents an example of advanced stage of Peripheral Artery Occlusive Disease (PAOD) stage IV, encompassing a history of a high thigh amputation on the left side, coupled with pronounced wound healing disorders. PRESENTATION OF CASE: Our patient, 55 years old, smoker and ASA Class III is in a left sided above-the knee-amputation situation. He presented to our outpatient clinic with blistering in the stump area, caused by non-proportinate pressure from the prosthesis. With an emerging septic course and advanced peripheral arterial occlusive disease (PAOD) at Fontaine class IV, revascularization was unfeasible in the left iliac artery axis and groin arteries. Additionally, a stage PAOD IV presents itself with poorly healing wounds on the right side which our patient still uses to support his transfers in and out bed and his wheelchair. Multiple surgical stump revisions and femur shortenings and diverse wound treatments were performed all were unsatisfying for patient and practitioners. We introduced a novel biochemisurgical treatment in our teaching hospital. DISCUSSION: Desiccating-agent-A is an innovative dehydrating agent with potent desiccating characteristics upon application to organic substances. Its formulation involves blending 83% methane sulfonic acid with proton acceptors and dimethyl sulfoxide, as outlined in patent application. The case description results in an illustrated follow up period of 16 months and is presented in line with the recommendations of the consensus-based surgical case reporting guideline development. CONCLUSION: The goal of achieving a secondary healing trend is to establish stability within the wound area or achieve complete healing. This endeavor becomes particularly intricate when severe blood circulation compromise exists. Nonetheless, progress in wound treatment measures has made it feasible to achieve this aim by fostering the formation of dry and clean necrotic tissue. This dry and clean wound is now manageable in a patient's home situation, allowing for effective care and a better chance at preventing further severe complications.

Comparison of aerosol generation between electrocautery and cold dissection tonsillectomy.

OBJECTIVE: Coronavirus disease 2019 can spread through aerosols produced by surgical procedures, but knowledge of the extent of aerosol production and the risk posed by many common procedures does not exist. This study analysed aerosol generation during tonsillectomy and how it differs between distinct surgical techniques and instruments. The results can be used in risk assessment during current and future pandemics and epidemics. METHOD: An optical particle sizer was used to measure particle concentrations generated during tonsillectomy from the perspectives of the surgeon and other staff. Coughing is commonly used as a reference for high-risk aerosol generation; therefore, coughing and the operating theatre's background concentration were chosen as reference values. Different instruments were also compared to find the safest way to perform the tonsillectomy from the perspective of airborne transmission. RESULTS: Eighteen tonsillectomies were evaluated; all techniques mostly generated less than 1 µm particles. For the surgeon, bipolar electrocautery significantly exceeded the particle generation of coughing in both total and less than 1 µm particles and was found to produce significantly higher total and less than 1 µm aerosol concentrations than cold dissection and BiZact. No technique exposed other staff to a greater aerosol concentration than is generated by a cough. CONCLUSION: Bipolar electrocautery generated high aerosol concentrations during tonsillectomy; cold dissection generated significantly less. The results support cold dissection as the primary tonsillectomy technique, particularly during the epidemics of airborne diseases.

Burden of hospital-acquired SARS-CoV-2 infections in Germany: occurrence and outcomes of different variants.

BACKGROUND: Avoiding in-hospital transmissions has been crucial in the COVID-19 pandemic. Little is known on the extent to which hospital-acquired SARS-CoV-2 variants have caused infections in Germany. AIM: To analyse the occurrence and the outcomes of HAI with regard to different SARS-CoV-2 variants. METHODS: Patients with SARS-CoV-2 infections hospitalized between March 1st, 2020 and May 17th, 2022 in 79 hospitals of the Helios Group were included. Information on patients' characteristics and outcomes were retrieved from claims data. In accordance with the Robert Koch Institute, infections were classified as hospital-acquired when tested positive >6 days after admission and if no information hinted at a different source. FINDINGS: In all, 62,875 SARS-CoV-2 patients were analysed, of whom 10.6% had HAI. HAIs represented 14.7% of SARS-CoV-2 inpatients during the Wildtype period, 3.5% during Alpha (odds ratio: 0.21; 95% confidence interval: 0.19-0.24), 8.8% during Delta (2.70; 2.35-3.09) and 10.1% during Omicron (1.10; 1.03-1.19). When age and comorbidities were accounted for, HAI had lower odds for death than community-acquired infections (0.802; 0.740-0.866). Compared to the Wildtype period, HAIs during Omicron were associated with lower odds for ICU (0.78; 0.69-0.88), ventilation (0.47; 0.39-0.56), and death (0.33; 0.28-0.40). CONCLUSION: Hospital-acquired SARS-CoV-2 infections occurred throughout the pandemic, affecting highly vulnerable patients. Although transmissibility increased with newer variants, the proportion of HAIs decreased, indicating improved infection prevention and/or the effect of immunization. Furthermore, the Omicron period was associated with improved outcomes. However, the burden of hospital-acquired SARS-CoV-2 infections remains high.

Clinical and genetic spectrum of SCN2A-associated episodic ataxia.

BACKGROUND: Pathogenic variants in SCN2A are associated with various neurological disorders including epilepsy, autism spectrum disorder and intellectual disability. Few reports have recently described SCN2A-associated episodic ataxia (EA). Our study identifies its broader clinical and genetic spectrum, and describes pharmacological approaches. RESULTS: We report 21 patients with SCN2A-associated EA, of which 9 are unpublished cases. The large majority of patients present with epileptic seizures (18/21, 86%), often starting within the first three months of life (12/18, 67%). In contrast, onset of episodic ataxia ranged from 10 months to 14 years of age. The frequency of EA episodes ranged from brief, daily events up to 1-2 episodes per year each lasting several weeks. Potential triggers include minor head traumas and sleep deprivation. Cognitive outcome is favorable in most patients with normal or mildly impaired cognitive development in 17/21 patients (81%). No clear genotype-phenotype correlations were identified in this cohort. However, two mutational hotspots were identified, i.e. 7/21 patients (33%) harbor the identical pathogenic variant p.A263V, whereas 5/21 (24%) carry pathogenic variants that affect the S4 segment and its cytoplasmic loop within the domain IV. In addition, we identified six novel pathogenic variants in SCN2A. While acetazolamide was previously reported as beneficial in SCN2A-associated EA in one case, our data show a conflicting response in 8 additional patients treated with acetazolamide: three of them profited from acetazolamide treatment, while 5/8 did not. CONCLUSIONS: Our study describes the heterogeneous clinical spectrum of SCN2A-associated EA, identifies two mutational hotspots and shows positive effects of acetazolamide in about 50%.

Clinician's guide to genes associated with Rett-like phenotypes-Investigation of a Danish cohort and review of the literature.

The differential diagnostics in Rett syndrome has evolved with the development of next generation sequencing-based techniques and many patients have been diagnosed with other syndromes or variants in newly described genes where the associated phenotype(s) is yet to be fully explored. The term Rett-like refers to phenotypes with distinct overlapping features of Rett syndrome where the clinical criteria are not completely fulfilled. In this study we have combined a review of Rett-like disorders with data from a Danish cohort of 35 patients with Rett-like phenotypes emphasizing the diagnostic overlap with Pitt-Hopkins syndrome, Cornelia de Lange syndrome with SMC1A variants, and epileptic encephalopathies, for example, due to STXBP1 variants. We also found a patient with a pathogenic variant in KCNB1, which has not been previously linked to a Rett-like phenotype. This study underlines the clinical and genetic heterogeneity of a Rett syndrome spectrum, and provides an overview of the Rett syndrome-related genes described to date, and hence serves as a guide for diagnosing patients with Rett-like phenotypes.

Electron-induced photon emission above the quantum cutoff due to time-energy uncertainty.

The light emission from a tunneling junction induced by tunneling electrons has been studied around the cutoff at hν=eVt. The emitted photons are found to exceed the excitation energy provided by the energy of the tunneling electrons. The experiments have been performed by a low- temperature scanning tunneling microscope at 80 K for an Ag(111) surface and an Ag-covered PtIr tip. A detailed analysis of the emission spectra reveals that the findings cannot be explained by the thermal broadening of the electron Fermi distribution alone. However, a correct description is found if a finite lifetime of the excited states in the range of 30-80 fs is included.

Epilepsy in patients with GRIN2A alterations: Genetics, neurodevelopment, epileptic phenotype and response to anticonvulsive drugs.

OBJECTIVE: To delineate the genetic, neurodevelopmental and epileptic spectrum associated with GRIN2A alterations with emphasis on epilepsy treatment. METHODS: Retrospective study of 19 patients (7 females; age: 1-38 years; mean 10.1 years) with epilepsy and GRIN2A alteration. Genetic variants were classified according to the guidelines and recommendations of the American College of Medical Genetics (ACMG). Clinical findings including epilepsy classification, treatment, EEG findings, early childhood development and neurodevelopmental outcome were collected with an electronic questionnaire. RESULTS: 7 out of 19 patients fulfilled the ACMG-criteria of carrying "pathogenic" or "likely pathogenic variants", in twelve patients the alterations were classified as variants of unknown significance. The spectrum of pathogenic/likely pathogenic mutations was as follows: nonsense n = 3, missense n = 2, duplications/deletions n = 1 and splice site n = 1. First seizures occurred at a mean age of 2.4 years with heterogeneous seizure types. Patients were treated with a mean of 5.6 AED. 4/5 patients with VPA had an improved seizure frequency (n = 3 with a truncation: n = 1 missense). 3/5 patients with STM reported an improvement of seizures (n = 2 truncation, n = 1 splicing). 3/5 CLB patients showed an improvement (n = 2: truncation; n = 1 splicing). Steroids were reported to have a positive effect on seizure frequency in 3/5 patients (n = 1 each truncation, splicing or deletion). CONCLUSIONS: Our data indicate that children with epilepsy due to pathogenic GRIN2A mutations present with different clinical phenotypes and a spectrum of seizure types in the context of a pharmacoresistant epilepsy providing information for clinicians treating children with this form of genetically determined epileptic syndrome.

Reversible 2D Phase Transition Driven By an Electric Field: Visualization and Control on the Atomic Scale.

We report on a reversible structural phase transition of a two-dimensional system that can be locally induced by an external electric field. Two different structural configurations may coexist within a CO monolayer on Cu(111). The balance between the two phases can be shifted by an external electric field, causing the domain boundaries to move, increasing the area of the favored phase controllable both in location and size. If the field is further enhanced new domains nucleate. The arrangement of the CO molecules on the Cu surface is observed in real time and real space with atomic resolution while the electric field driving the phase transition is easily varied over a broad range. Together with the well-known molecular manipulation of CO adlayers, our findings open exciting prospects for combining spontaneous long-range order with man-made CO structures such as "molecule cascades" or "molecular graphene". Our new manipulation mode permits us to bridge the gap between fundamental concepts and the fabrication of arbitrary atomic patterns in large scale, by providing unprecedented insight into the physics of structural phase transitions on the atomic scale.

X-linked congenital ptosis and associated intellectual disability, short stature, microcephaly, cleft palate, digital and genital abnormalities define novel Xq25q26 duplication syndrome.

Submicroscopic duplications along the long arm of the X-chromosome with known phenotypic consequences are relatively rare events. The clinical features resulting from such duplications are various, though they often include intellectual disability, microcephaly, short stature, hypotonia, hypogonadism and feeding difficulties. Female carriers are often phenotypically normal or show a similar but milder phenotype, as in most cases the X-chromosome harbouring the duplication is subject to inactivation. Xq28, which includes MECP2 is the major locus for submicroscopic X-chromosome duplications, whereas duplications in Xq25 and Xq26 have been reported in only a few cases. Using genome-wide array platforms we identified overlapping interstitial Xq25q26 duplications ranging from 0.2 to 4.76 Mb in eight unrelated families with in total five affected males and seven affected females. All affected males shared a common phenotype with intrauterine- and postnatal growth retardation and feeding difficulties in childhood. Three had microcephaly and two out of five suffered from epilepsy. In addition, three males had a distinct facial appearance with congenital bilateral ptosis and large protruding ears and two of them showed a cleft palate. The affected females had various clinical symptoms similar to that of the males with congenital bilateral ptosis in three families as most remarkable feature. Comparison of the gene content of the individual duplications with the respective phenotypes suggested three critical regions with candidate genes (AIFM1, RAB33A, GPC3 and IGSF1) for the common phenotypes, including candidate loci for congenital bilateral ptosis, small head circumference, short stature, genital and digital defects.

Communication: Substrate induced dehydrogenation: transformation of octa-ethyl-porphyrin into tetra-benzo-porphyrin.

Individual molecules of octa-ethyl-porhphyrin-iron(III)-chloride adsorbed on a Cu(111) surface are studied by scanning tunneling microscopy. Upon moderate heating the molecules are found to transform into Fe-tetra-benzo-porphyrin at a surprisingly low temperature of 380 K. If the annealing is interrupted, the different steps of the transformation can be imaged. By evaluating the ratio of transformed molecules as function of annealing temperature, an approximate activation energy of 1.2 eV ± 0.1 eV could be determined.

Scanning noise microscopy.

The paper describes a simple scheme enabling the real-time characterization of fluctuations, e.g., of the conductance in scanning tunneling microscopy. The technique can be used in parallel to other data acquisition, evaluating the rate, the amplitude, and the duty cycle of telegraphic noise in the tunneling current. This kind of scanning probe microscopy allows to evaluate the noise parameters as a function of the average tunneling current, the electron energy, and the lateral position. Images of the noise with Ångstrom spatial resolution are acquired simultaneously to the topographic information providing a direct correlation between the structural information and the noise. The method can be applied to a large variety of systems to monitor dynamics on the nanoscale, e.g., the localization of tunneling current induced switching within a single molecule. Noise spectroscopy may reveal the involved molecular orbitals, even if they cannot be resolved in standard scanning tunneling spectroscopy. As an example we present experimental data of the organic molecule copper phthalocyanine on a Cu(111) surface [J. Schaffert, M. C. Cottin, A. Sonntag, H. Karacuban, C. A. Bobisch, N. Lorente, J.-P. Gauyacq, and R. Möller, Nature Mater. 12, 223-227 (2013)].

Genetic studies in congenital anterior midline cervical cleft.

Congenital anterior midline cervical cleft (CAMCC) is a rare anomaly, with less than 100 cases reported. The cause of CAMCC is unknown, but genetic factors must be considered as part of the etiology. Three cases of CAMCC are presented. This is the first genetic study of isolated CAMCC. Conventional cytogenetics, array-comparative genomic hybridization (CGH) and whole exome sequencing were performed, including a search of relevant syndromes in the Online Mendelian Inheritance in Man (OMIM) database. Array CGH indicated a loss of the PAPPA gene in one of the patients, while exome sequencing showed a mutation in SIX5 in another patient. Both aberrations were inherited from unaffected parents. These results most likely imply that the identified mutations are not disease-causing, although they may be contributing factors if CAMCC has a polygenic inheritance.

Current induced surface diffusion on a single-crystalline silver nanowire.

Scanning tunnelling microscopy was used to study the morphological changes of the surface of a single-crystalline silver nanowire caused by a lateral electron current. At current densities of about 1.5 × 10(7) A cm(-2), surface atoms are extracted from step edges, resulting in the motion of surface steps, islands and holes with a thickness or depth of one monolayer. Upon current reversal the direction of the material transport can be altered. The findings are interpreted in terms of the wind force.

Reduced urinary glutamate levels are associated with the frequency of migraine attacks in females.

BACKGROUND AND PURPOSE: Recent evidences indicate that glutamatergic homeostasis disorders are implicated in the pathogenesis of migraine. In particular, plasma and cerebrospinal fluid glutamate levels seem to be altered in migraine patients. However, the impacts of glutamate on migraine and especially on aura symptoms, alterations in the frequency of migraine attacks as well as investigations on glutamate on migraine-related metabolic dysfunctions, like hyperinsulinaemia, and an atherogenic lipid profile remain elusive to date. The aim of the present study was to investigate the impact of glutamate on migraine and related metabolic dysfunctions. METHODS: We investigated the urinary glutamate levels of female migraineurs (n = 48) in the interictal phase and healthy controls (n = 48). Parameters of the insulin- and lipid metabolism, inflammatory parameters and anthropometric parameters were additionally determined. RESULTS: Urinary glutamate levels of female migraineurs were significantly decreased with respect to the control group. Logistic regression revealed an odds ratio of 4.04 for migraine. We found a significant correlation with the time-period of patients' last attack and a significant inverse correlation with the annual frequency of migraine attacks. Other parameters of the insulin- and lipid metabolism, anthropometric and inflammatory parameters showed no significant correlation with glutamate levels. CONCLUSION: We show here that female migraineurs exhibit decreased urinary glutamate levels which are associated with a 4.04-fold higher risk for migraine and correlated with patients' frequency of migraine attacks.

PTCDA on Cu(111) partially covered with NaCl.

The organic molecule 3,4,9,10-perylene-tetracarboxylic dianhydride (PTCDA) was studied by means of scanning tunneling microscopy (STM) on thin insulating NaCl films grown on a Cu(111) single crystal. The deposition of approximately two monolayers (ML) of sodium chloride onto a Cu(111) substrate at a sample temperature of about 350 K causes a rather rough growth of (100)-oriented NaCl islands up to a local height of 4 ML. For submonolayer coverages (0.1 and 0.4 ML) of PTCDA on a Cu(111) surface partly covered with NaCl, two different rod structures of PTCDA were found on the copper surface, which are in contrast to previously published data for PTCDA on Cu(111) showing a herringbone-like arrangement. These findings can be explained by the formation of a Na(x)-PTCDA complex. On NaCl covered areas, single PTCDA molecules adsorb at vacancies of [010] and [001] oriented steps of the NaCl(100) islands. In this case, the electrostatic forces between the polar step edges and the PTCDA molecules are dominant. The terraces of the alkali halide surface are free of PTCDA molecules.

NIPA1 mutation in complex hereditary spastic paraplegia with epilepsy.

BACKGROUND AND PURPOSE: Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterized in the 'pure' phenotype by progressive spasticity and weakness of the lower limbs. In the 'complex' phenotype, additional neurologic symptoms or signs are found. Mutations in the NIPA1 gene have been reported to cause spastic paraplegia type 6 (SPG6) in 10 families. SPG6 is a rare form of autosomal dominantly inherited HSP associated with a pure phenotype; however, in one complex SPG6 family, idiopathic generalized epilepsy (IGE) has been described and in addition, recurrent microdeletions at 15q11.2 including NIPA1 have been identified in patients with IGE. The purpose was to identify NIPA1 mutations in patients with pure and complex HSP. METHODS: Fifty-two patients with HSP were screened for mutations in NIPA1. RESULTS: One previously reported missense mutation c.316G>A, p.Gly106Arg, was identified in a complex HSP patient with spastic dysarthria, facial dystonia, atrophy of the small hand muscles, upper limb spasticity, and presumably IGE. The epilepsy co-segregated with HSP in the family. CONCLUSION: NIPA1 mutations were rare in our population of patients with HSP, but can be found in patients with complex HSP. Epilepsy might be more common in SPG6 than in other forms of HSP because of a genetic risk factor closely linked to NIPA1.

Oxidative stress is associated with migraine and migraine-related metabolic risk in females.

BACKGROUND AND PURPOSE: Oxidative stress is discussed to be implicated in the pathophysiology of migraine. However, data are in part controversial and the possible underlying mechanisms remain elusive to date. The aim of this study was to investigate the oxidative stress status of female patients with migraine and its implications on migraine-related metabolic alterations. METHODS: Oxidative stress markers malondialdehyde (MDA), 4-hydroxy-2-nonenal (HNE), carbonylated proteins, parameters of associated nitric oxide stress, inflammation, lipid- and glucose-metabolism were determined in the interictal phase in female patients with migraine and controls. RESULTS: We found significantly increased HNE levels in female migraineurs compared with controls. Logistic regression analyses of HNE revealed an odds ratio for migraine of 4.55. HNE showed significant correlations with the nitric oxide pathway, the insulin- and the lipid-metabolism. CONCLUSIONS: We show here that increased oxidative stress is associated with migraine and contributes to migraine-related metabolic risk like nitrosative stress, an atherogenic lipid profile and hyperinsulinemia. Our data suggest that oxidative stress may represent a key event in the pathophysiology of migraine and a suitable therapeutic target.

Increased matrix metalloproteinase activity is associated with migraine and migraine-related metabolic dysfunctions.

OBJECTIVE: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are discussed to be involved in the pathophysiology of migraine. Moreover, MMPs may also be involved in migraine-related metabolic alterations like an atherogenic lipid profile and hyperinsulinemia. The aim of this study was to investigate the impact of MMPs and TIMPs on migraine with and without aura and related metabolic dysfunctions. METHODS: MMP activity, six MMPs and three TIMPs, parameters of the insulin and lipid metabolism as well as anthropometric parameters were determined in 124 non-obese subjects. RESULTS: We found highly significant increased MMP activity in migraine patients independent of aura symptoms, which was associated with migraine with an odds ratio of 7.57. Interestingly, none of the determined MMPs and TIMPs showed significant different serum levels between migraine patients and healthy controls. We found significant correlations between MMP activity and parameters of the insulin and lipid metabolism, like Homeostasis Model Assessment index (HOMA index), cholesterol, triglycerides, and oxidized LDL. CONCLUSION: We show here that increased MMP activity is tightly associated with migraine and migraine-related hyperinsulinemia and atherogenic lipid alterations. Our findings represent a new pathophysiological mechanism, which may be of clinical relevance, especially in regard to therapeutic approaches using MMP inhibitors.