Human mitochondrial disease exhibits large variation of clinical phenotypes, even in patients with the same causative gene defect. We illustrate this heterogeneity by confronting clinical and ...biochemical data of two patients with the uncommon pathogenic homoplasmic NC_012920.1(MT-ATP6):m.9035T>C variant in
. Patient 1 presented as a toddler with severe motor and speech delay and spastic ataxia without extra-neurologic involvement. Patient 2 presented in adolescence with ataxia and ophthalmoplegia without cognitive or motor impairment. Respiratory chain complex activities were normal in cultured skin fibroblasts from both patients when calculated as ratios over citrate synthase activity. Native gels found presence of subcomplexes of complex V in fibroblast and/or skeletal muscle. Bioenergetic measurements in fibroblasts from both patients detected reduced spare respiratory capacities and altered extracellular acidification rates, revealing a switch from mitochondrial respiration to glycolysis to uphold ATP production. Thus, in contrast to the differing disease presentation, biochemical evidence of mitochondrial deficiency turned out quite similar. We conclude that biochemical analysis remains a valuable tool to confirm the genetic diagnosis of mitochondrial disease, especially in patients with new gene variants or atypical clinical presentation.
This current case is the first report of severe unilateral (left-sided) post-traumatic trigeminal neuropathic pain involving all branches of the trigeminal nerve after custom-made total ...temporomandibular joint replacement (TMJR). After a bilateral TMJR procedure a, 43-year old female patient complained of left-sided lingual and mental nerve hypoesthesia. In the following months, the patient developed unsustainable neuropathic pain at the area of cutaneous distribution of the mental (V3) and infraorbital (V2) nerves combined with hypoesthesia in all trigeminal divisions. Neurosensory deficits in V1-3 were confirmed by quantitative sensory testing and electrophysiological studies. Treatments consisted of anti-depressants, anti-epileptics, opioids and eventually radiofrequent ablation of the peripheral branches without notable improvement in pain complaints or sensory deficits. The current case warrants temporomandibular joint surgeons for the possible risk of post-traumatic trigeminal neuropathic pain.
•Trigeminal neuropathic pain may follow temporomandibular joint replacement.•Symptoms may spread far beyond the affected dermatome on the basis of an inflammatory and/or excitotoxic response.•Quality of life deteriorates with persistent neuropathic pain.•Conservative treatment is disappointing.•A multidisciplinary approach with thorough investigation is advised.
OBJECTIVE:To determine the diagnostic performance and prognostic value of phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain (NfL) in CSF as possible biomarkers for ...amyotrophic lateral sclerosis (ALS) at the diagnostic phase.
METHODS:We measured CSF pNfH and NfL concentrations in 220 patients with ALS, 316 neurologic disease controls (DC), and 50 genuine disease mimics (DM) to determine and assess the accuracy of the diagnostic cutoff value for pNfH and NfL and to correlate with other clinical parameters.
RESULTS:pNfH was most specific for motor neuron disease (specificity 88.2% confidence interval (CI) 83.0%–92.3%). pNfH had the best performance to differentially diagnose patients with ALS from DM with a sensitivity of 90.7% (CI 84.9%–94.8%), a specificity of 88.0% (CI 75.7%–95.5%) and a likelihood ratio of 7.6 (CI 3.6–16.0) at a cutoff of 768 pg/mL. CSF pNfH and NfL levels were significantly lower in slow disease progressors, however, with a poor prognostic performance with respect to the disease progression rate. CSF pNfH and NfL levels increased significantly as function of the number of regions with both upper and lower motor involvement.
CONCLUSIONS:In particular, CSF pNfH concentrations show an added value as diagnostic biomarkers for ALS, whereas the prognostic value of pNfH and NfL warrants further investigation. Both pNfH and NfL correlated with the extent of motor neuron degeneration.
CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that elevated concentrations of CSF pNfH and NfL can accurately identify patients with ALS.
Posttraumatic pontomedullary rents have been described mainly as postmortem histopathological findings in patients who died immediately or within the first hours after trauma. To the best of our ...knowledge, no long-term survivors of this condition have been described, and those surviving initially were always severely impaired. We present the first patient with this condition and with corresponding lesions on imaging who survived longer than 3 months. Moreover, the patient regained almost complete independence 1 year after the trauma. We briefly discuss the proposed mechanisms of this injury. We conclude that this lesion, when incomplete, is not always lethal and can exceptionally have a good clinical outcome. Prevention of respiratory failure is of utmost importance in these patients.
Nanocomposites of Ni(OH)₂ or NiO have successfully been used in electrodes in the last five years, but they have been falsely presented as pseudocapacitive electrodes for electrochemical capacitors ...and hybrid devices. Indeed, these nickel oxide or hydroxide electrodes are pure battery-type electrodes which store charges through faradaic processes as can be shown by cyclic voltammograms or constant current galvanostatic charge/discharge plots. Despite this misunderstanding, such electrodes can be of interest as positive electrodes in hybrid supercapacitors operating under KOH electrolyte, together with an activated carbon-negative electrode. This study indicates the requirements for the implementation of Ni(OH)₂-based electrodes in hybrid designs and the improvements that are necessary in order to increase the energy and power densities of such devices. Mass loading is the key parameter which must be above 10 mg·cm
to correctly evaluate the performance of Ni(OH)₂ or NiO-based nanocomposite electrodes and provide gravimetric capacity values. With such loadings, rate capability, capacity, cycling ability, energy and power densities can be accurately evaluated. Among the 80 papers analyzed in this study, there are indications that such nanocomposite electrode can successfully improve the performance of standard Ni(OH)₂ (+)//6 M KOH//activated carbon (−) hybrid supercapacitor.
Glycerol/diol dehydratases catalyze the conversion of glycerol to 3-hydroxypropionaldehyde (3-HPA), the basis of a multi-component system called reuterin. Reuterin has antimicrobial properties and ...undergoes chemical conjugation with dietary heterocyclic amines (HCAs). In aqueous solution reuterin is in dynamic equilibrium with the toxicant acrolein. It was the aim of this study to investigate the extent of acrolein formation at various physiological conditions and to determine its role in biological and chemical activities. The application of a combined novel analytical approach including IC-PAD, LC-MS and NMR together with specific acrolein scavengers suggested for the first time that acrolein, and not 3-HPA, is the active compound responsible for HCA conjugation and antimicrobial activity attributed to reuterin. As formation of the HCA conjugate was observed in vivo, our results imply that acrolein is formed in the human gut with implications on detoxification of HCAs. We propose to re-define the term reuterin to include acrolein.
The traditional forcing–feedback framework has provided an indispensable basis for discussing global climate changes. However, as analysis of model behavior has become more detailed, shortcomings and ...ambiguities in the framework have become more evident, and physical effects unaccounted for by the traditional framework have become interesting. In particular, the new concept of adjustments, which are responses to forcings that are not mediated by the global-mean temperature, has emerged. This concept, related to the older ones of climate efficacy and stratospheric adjustment, is a more physical way of capturing unique responses to specific forcings. We present a pedagogical review of the adjustment concept, why it is important, and how it can be used. The concept is particularly useful for aerosols, where it helps to organize what has become a complex array of forcing mechanisms. It also helps clarify issues around cloud and hydrological response, transient versus equilibrium climate change, and geoengineering.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
