Morphological changes and their associations with clinical parameters in children with nephropathic cystinosis and chronic kidney disease prior to kidney replacement therapy over 25 years.

BACKGROUND: Infantile nephropathic cystinosis (INC) is a rare lysosomal storage disorder, mostly and often firstly affecting the kidneys, together with impaired disharmonious growth and rickets, eventually resulting in progressive chronic kidney disease (CKD). With the introduction of cysteamine therapy, most pediatric patients reach adulthood with no need for kidney replacement therapy. Still, detailed changes in INC patients' clinical and morphological presentation over the past decades have not yet been thoroughly investigated. METHODS: Two groups with a respective total of 64 children with INC and 302 children with CKD, both treated conservatively and aged 2 to 18 years, were prospectively observed in the time span from 1998 to 2022 with 1186 combined annual clinical and morphological examinations clustered into two measurement periods (1998 to 2015 and ≥ 2016). RESULTS: In INC patients, thoracic proportion indices remained markedly increased, whereas body fat stores remained decreased over the past 25 years (+ 1 vs. below ± 0 z-score, respectively). Their CKD peers presented with overall improved growth, general harmonization of body proportions, and improved body fat stores, while INC patients only presented with an isolated significant increase in leg length over time (∆0.36 z-score). eGFR adjusted for age did not significantly change over the past 25 years in both groups. Alkaline phosphatase (ALP) showed a significant decrease in CKD patients over time, while remaining above normal levels in INC patients. CONCLUSIONS: Disproportionate thoracic shape and impaired body fat stores remain the most characteristic morphological traits in INC patients over the past 25 years, while causal mechanisms remain unclear.

Chest configuration in children and adolescents with infantile nephropathic cystinosis compared with other chronic kidney disease entities and its clinical determinants.

BACKGROUND: Infantile nephropathic cystinosis (INC) is a systemic lysosomal storage disease causing intracellular cystine accumulation, resulting in renal Fanconi syndrome, progressive kidney disease (CKD), rickets, malnutrition, and myopathy. An INC-specific disproportionately diminished trunk length compared to leg length poses questions regarding the functionality of the trunk. METHODS: Thus, we prospectively investigated thoracic dimensions and proportions, as well as their clinical determinants in 44 pediatric patients with INC with CKD stages 1-5 and 97 age-matched patients with CKD of other etiology between the ages of 2-17 years. A total of 92 and 221 annual measurements of patients with INC and CKD, respectively, were performed, and associations between anthropometric and clinical parameters were assessed using linear mixed-effects models. RESULTS: Patients with INC exhibited altered chest dimensions that were distinct from CKD controls, characterized by markedly increased chest depth to height and chest depth to chest width ratio z-scores (> 1.0), while those of patients with CKD were only mildly affected (z-score within ± 1.0). Ratio z-scores differed significantly between both patient groups from 2-6 years of age onward. The degree of chest disproportion in INC patients was significantly associated with both the degree of CKD and tubular dysfunction (e.g., low serum phosphate and bicarbonate) across three different age groups (2-6, 7-12, and 13-17 years). CONCLUSION: Our data show an INC-specific alteration in thoracic shape from early childhood onward, which is distinct from CKD of other etiologies, suggesting early childhood subclinical changes of the musculoskeletal unit of the thoracic cage, which are associated with kidney function. A higher resolution version of the Graphical abstract is available as Supplementary information.

Body growth, upper arm fat area, and clinical parameters in children with nephropathic cystinosis compared with other pediatric chronic kidney disease entities.

Children with infantile nephropathic cystinosis (INC), an inherited lysosomal storage disease resulting in cystine accumulation in all body cells, are prone to progressive chronic kidney disease (CKD), impaired growth and reduced weight gain; however, systematic anthropometric analyses are lacking. In this prospective multicenter study we investigated linear growth, body proportion, body mass index (BMI), upper arm fat area (UFA) and biochemical parameters in 43 pediatric INC patients with CKD stages 1 to 5 and 49 age-matched CKD controls, with 193 annual measurements. INC patients showed more impaired height than CKD controls (-1.8 vs -0.7 z-score; P < .001), despite adequate cysteamine therapy, treatment for Fanconi syndrome and more frequent use of growth hormone. Only the youngest INC patients shared the same body pattern with CKD controls characterized by preferential impairment of leg length and rather preserved trunk length. In late-prepuberty, body pattern changed only in INC patients due to improved leg growth and more impaired trunk length. Mean UFA z-score in INC patients was slightly reduced in early childhood and progressively decreased thereafter reaching -0.8 z-score in adolescence, while CKD controls showed a steady increase in standardized BMI and UFA especially during adolescent age. Menarche in female INC patients was significantly delayed compared to CKD controls. Our data indicate that with age and progression of disease, pediatric INC patients undergo unique changes of body growth and fat stores that are distinct from those with CKD stemming from other causes, suggesting other factors apart from CKD to contribute to this development. Pediatric patients with infantile nephropathic cystinosis display more severe impaired linear growth than other peer CKD patients, despite of cysteamine treatment, supplementation for Fanconi syndrome, and more frequent use of growth hormone, with a distinct change of body proportions and overall lower body fat.

Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer's disease.

INTRODUCTION: White matter hyperintensities (WMHs) increase the risk of Alzheimer's disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated. METHOD: Resting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts' projection areas within the default mode network (DMN). RESULTS: WMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas. CONCLUSIONS: High fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function.

The Effects of Virtual Reality in Targeting Transdiagnostic Factors for Mental Health: A Systematic Review of the Literature.

Virtual reality (VR) was found to be effective in the treatment of several specific psychopathologies. However, the effects of VR-based interventions beyond the disorder-specific approach and their ability to improve transdiagnostic factors of mental disorders are unknown. This PRISMA systematic review was conducted using databases PubMed and PsycINFO, searching articles published between 2010 and September 2022. Keywords "emotion regulation", "cognitive reappraisal", "avoidance", "impulsivity", "aggression", and "disinhibition" were combined with "virtual reality" to retrieve studies showing the effects of VR-based interventions on these transdiagnostic factors. 29 experimental studies and seven case-studies were selected. A total of 23 considered avoidance, eight dealt with emotion regulation, three concerned aggression, two addressed impulsivity, two dealt with cognitive reappraisal, and none examined disinhibition. Most of the studies included anxiety disorder patients (n = 15), especially with specific phobias (n = 8) and social anxiety disorder (n = 4). VR managed to improve all transdiagnostic factors, with results often maintained at follow-ups (n = 21 studies; range: 1-12 months) and similar to traditional interventions (e.g., cognitive-behavioral therapy). Exploring the transdiagnostic potential of VR may help to reduce costs and improve applicability in clinical psychology. While results were promising, further studies are needed for aggression, impulsivity and cognitive reappraisal, especially including follow-ups, comparisons with first-line treatments, and understudied clinical populations.

Dope Dyeing of Regenerated Cellulose Fibres with Leucoindigo as Base for Circularity of Denim.

Circularity of cellulose-based pre- and post-consumer wastes requires an integrated approach which has to consider the characteristics of the fibre polymer and the presence of dyes and additives from textile chemical processing as well. Fibre-to-fibre recycling is a condition to avoid downcycling of recycled material. For cellulose fibres regeneration via production of regenerated cellulose fibres is the most promising approach. Textile wastes contain dyes and additives, thus a recycling technique has to be robust enough to process such material. In an ideal case the reuse of colorants can be achieved as well. At present nearly 80% of the regenerated cellulose fibre production utilises the viscose process, therefore this technique was chosen to investigate the recycling of dyed material including the reuse of the colorant. In this work, for the first time, a compilation of all required process steps to a complete circular concept is presented and discussed as a model. Indigo-dyed viscose fibres were used as a model to study cellulose recycling via production of regenerated cellulose fibres to avoid downcycling. Indigo was found compatible to the alkalisation and xanthogenation steps in the viscose process and blue coloured cellulose regenerates were recovered from indigo-dyed cellulose. A supplemental addition of reduced indigo to the cellulose solution was also found feasible to adjust colour depth in the regenerated cellulose to the level required for use as warp material in denim production. By combination of fibre recycling and indigo dyeing the conventional yarn dyeing in denim production can be omitted. Model calculations for the savings in water and chemical consumption demonstrate the potential of the process. The proportion of the substitution will depend on the collection rate of denim wastes and on the efficiency of the fibre regeneration process. Estimates indicate that a substitution of more than 70% of the cotton fibres by regenerated cellulose fibres could be achieved when 80% of the pre- and post-consumer denim wastes are collected. Therefore, the introduction of fibre recycling via regenerated cellulose fibres will also make a substantial impact on the cotton consumption for jeans production.

Resistance to ampicillin, third-generation cephalosporins, ciprofloxacin, co-trimoxazole and azithromycin in clinical isolates of Salmonella enterica subsp. enterica from Germany: real problem or sporadic circumstance?

The objective of this study was to determine the in vitro activity of ampicillin, third-generation cephalosporins, ciprofloxacin, co-trimoxazole and azithromycin against Salmonella enterica isolates. None of the isolates tested showed resistance to third-generation cephalosporins or azithromycin. The rates of resistance to ampicillin, co-trimoxazole and ciprofloxacin were 16.8%, 3.2% and 0.8%, respectively. Moreover, 7.2% of the isolates showed reduced ciprofloxacin susceptibility, but none of them harboured qnr genes. To conclude, our data show that resistance to fluoroquinolones and third-generation cephalosporins in clinical isolates found in Germany still represents a rare circumstance.

High-Level Expression, Purification and Initial Characterization of Recombinant Arabidopsis Histidine Kinase AHK1.

Plants employ a number of phosphorylation cascades in response to a wide range of environmental stimuli. Previous studies in Arabidopsis and yeast indicate that histidine kinase AHK1 is a positive regulator of drought and osmotic stress responses. Based on these studies AHK1 was proposed a plant osmosensor, although the molecular basis of plant osmosensing still remains unknown. To understand the molecular role and signaling mechanism of AHK1 in osmotic stress, we have expressed and purified full-length AHK1 from Arabidopsis in a bacterial host to allow for studies on the isolated transmembrane receptor. Purification of the recombinant protein solubilized from the host membranes was achieved in a single step by metal-affinity chromatography. Analysis of the purified AHK1 by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting show a single band indicating that the preparation is highly pure and devoid of contaminants or degradation products. In addition, gel filtration experiments indicate that the preparation is homogenous and monodisperse. Finally, CD-spectroscopy, phosphorylation activity, dimerization studies, and protein-protein interaction with plant phosphorylation targeting AHP2 demonstrate that the purified protein is functionally folded and acts as phospho-His or phospho-Asp phosphatase. Hence, the expression and purification of recombinant AHK1 reported here provide a basis for further detailed functional and structural studies of the receptor, which might help to understand plant osmosensing and osmosignaling on the molecular level.

Current State and Future Prospects of EEG and fNIRS in Robot-Assisted Gait Rehabilitation: A Brief Review.

Gait and balance impairments are frequently considered as the most significant concerns among individuals suffering from neurological diseases. Robot-assisted gait training (RAGT) has shown to be a promising neurorehabilitation intervention to improve gait recovery in patients following stroke or brain injury by potentially initiating neuroplastic changes. However, the neurophysiological processes underlying gait recovery through RAGT remain poorly understood. As non-invasive, portable neuroimaging techniques, electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) provide new insights regarding the neurophysiological processes occurring during RAGT by measuring different perspectives of brain activity. Due to spatial information about changes in cortical activation patterns and the rapid temporal resolution of bioelectrical changes, more features correlated with brain activation and connectivity can be identified when using fused EEG-fNIRS, thus leading to a detailed understanding of neurophysiological mechanisms underlying motor behavior and impairments due to neurological diseases. Therefore, multi-modal integrations of EEG-fNIRS appear promising for the characterization of neurovascular coupling in brain network dynamics induced by RAGT. In this brief review, we surveyed neuroimaging studies focusing specifically on robotic gait rehabilitation. While previous studies have examined either EEG or fNIRS with respect to RAGT, a multi-modal integration of both approaches is lacking. Based on comparable studies using fused EEG-fNIRS integrations either for guiding non-invasive brain stimulation or as part of brain-machine interface paradigms, the potential of this methodologically combined approach in RAGT is discussed. Future research directions and perspectives for targeted, individualized gait recovery that optimize the outcome and efficiency of RAGT in neurorehabilitation were further derived.

Characterization of extended-spectrum beta-lactamases and qnr plasmid-mediated quinolone resistance in German isolates of Enterobacter species.

The objective of this study was to characterize the antimicrobial resistance patterns of 100 clinical isolates of Enterobacter spp. with special regard to the occurrence of extended-spectrum beta-lactamases (ESBLs) and plasmid-mediated quinolone resistance by qnr-determinants. The rate of ESBL- and qnr-positive isolates was 7% and 14%, respectively. Thirteen isolates harbored a qnrA1, and a further isolate harbored a qnrB4 gene. Moreover, qnr-determinants were significantly associated with ESBL-expression. No carbapeneme or tigecycline resistance was detected in the collective tested. To conclude, these data confirm the increase of multiple antimicrobial resistance mechanisms in Enterobacter spp.