Here we study links between aminoglycoside-induced mistranslation, protein misfolding and neuropathy. We demonstrate that aminoglycosides induce misreading in mammalian cells and assess endoplasmic ...reticulum (ER) stress and unfolded protein response (UPR) pathways. Genome-wide transcriptome and proteome analyses revealed upregulation of genes related to protein folding and degradation. Quantitative PCR confirmed induction of UPR markers including C/EBP homologous protein, glucose-regulated protein 94, binding immunoglobulin protein and X-box binding protein-1 (XBP1) mRNA splicing, which is crucial for UPR activation. We studied the effect of a compromised UPR on aminoglycoside ototoxicity in haploinsufficient XBP1 (XBP1(+/-)) mice. Intra-tympanic aminoglycoside treatment caused high-frequency hearing loss in XBP1(+/-) mice but not in wild-type littermates. Densities of spiral ganglion cells and synaptic ribbons were decreased in gentamicin-treated XBP1(+/-) mice, while sensory cells were preserved. Co-injection of the chemical chaperone tauroursodeoxycholic acid attenuated hearing loss. These results suggest that aminoglycoside-induced ER stress and cell death in spiral ganglion neurons is mitigated by XBP1, masking aminoglycoside neurotoxicity at the organismal level.
The healthcare practice of dentistry, as well as medicine, is framed within a legal environment. Patients have the right to know all the information related to any action performed on them and dental ...or medical doctors are obliged to obtain their patient's prior written informed consent (IC) before undertaking any healthcare procedures.
Here we reviewed the legality and jurisprudence in Spain regarding IC. We also used INFLESZ text readability analysis software to analyse a sample of official Spanish informed consent documents (ICDs) from different surgical and interventional procedures related to dentistry and oral cavity interventions.
It is a mistake to confound IC with ICDs. This error prevents physicians from considering the former as a care process in which the patient's authorisation signature is the last link in a chain formed, almost in its entirety, by the informative process and deliberation alongside the patient. Multiple factors can influence communication between practitioners and their patients. Importantly, treatment adherence is greater when patients feel involved and autonomous in shared decision-making and when the circumstances of their lives are adequately considered. We concluded that although the ICDs we analysed conformed to the requirements set out in international law, they were somewhat difficult to read according to the reading habits of the general Spanish population.
Knowledge about the legality of IC helps professionals to understand the problems that may arise from their non-compliance. This is because the omission or defective fulfilment of IC obligations is the origin of legal responsibility for medical practitioners. In this sense, to date, there have been more convictions for defective ICs than for malpractice. The information provided in ICs should include the risks, benefits, and treatment alternatives and must be tailored to the needs and capabilities of the patient to enable autonomous decision-making.
Diffuse axonal injury (DAI) is one of the most common pathological features of traumatic brain injury (TBI). Diffusion tensor imaging (DTI) indices can be used to identify and quantify white matter ...microstructural changes following DAI. Recently, many studies have used DTI with various machine learning approaches to predict white matter microstructural changes following TBI. The current study sought to examine whether our classification approach using multiple DTI indices in conjunction with machine learning is a useful tool for diagnosing/classifying TBI patients and healthy controls.
Participants were adult patients with chronic TBI (n = 26) with DAI pathology, and age- and sex-matched healthy controls (n = 26). DTI images were obtained from all participants. Tract-based spatial statistics analyses were applied to DTI images. Classification models were built using principal component analysis and support vector machines. Receiver operator characteristic curve analysis and area under the curve were used to assess the classification performance of the different classifiers.
Tract-based spatial statistics revealed significantly decreased fractional anisotropy, as well as increased mean diffusivity, axial diffusivity, and radial diffusivity in patients with TBI compared with healthy controls (all p-values < 0.01). The principal component analysis and support vector machine-based machine learning classification using combined DTI indices classified patients with TBI and healthy controls with an accuracy of 90.5% with an area under the curve of 93 ± 0.09.
These results highlight the potential of our approach combining multiple DTI measures to identify patients with TBI.
Abdelrahman HAF, Ubukata S, Ueda K, et al. Neuropsychiatr Dis Treat. 2022;18:1801-1814. On page 1801, Abstract, Results, last sentence, the text "area under the curve of 93 ± 0.09" should read "area ...under the curve of 0.93 ± 0.09". On page 1803, Imaging Acquisition section, line four, the text "64 non-collinear axis motion-probing gradients" should read "81 non-collinear axis motion-probing gradients". On page 1803, Image Processing section, second paragraph, line seven, the text "was then thresholder at an FA value of 0.2" should read "was then thresholded at an FA value of 0.2". On page 1803, Image Processing section, second paragraph, line two from the bottom, the text "Voxel-wise maps were thresholder at p < 0.05" should read "Voxel-wise maps were thresholded at p < 0.05". The authors apologize for any inconvenience caused by these errors and for any confusion that may have arisen as a result. The authors would also like to assure the readers that these corrections do not affect the results or conclusions of the paper and are intended only to improve the accuracy of the methodology and data presentation.
To determine whether preservation of blood supply to the index metacarpophalangeal joint decreases the rate of physeal arrest.
A retrospective review of 41 pollicized digits in 35 patients with ...2-year minimum radiographic follow-up was conducted at a single institution. Other complications evaluated included nonunion at the pollicized digit base and clinical instability at the new carpometacarpal joint. Findings were compared to historical controls, which were performed by our group prior to routine identification and sparing of the metacarpophalangeal joint blood supply. No other modifications to surgical technique were made between the previous and current patient cohorts.
Two pollicized digits in two different patients had radiographic evidence of physeal arrest, one of which was partial and the other complete, for an arrest rate of 4.9%. This was significantly less than the arrest rate in our historical cohort of 24.7% (21 of 85 patients). Five patients did not have radiographic bony union at the base of the index metacarpal, but only one patient had clinical instability at the new carpometacarpal joint.
Significantly fewer patients who underwent index finger pollicization with preservation of the metacarpophalangeal joint blood supply went on to develop physeal arrest when compared to patients who underwent pollicization prior to adoption of this technique. This finding suggests that sparing of the physeal blood supply is preventative against proximal phalanx physeal arrest.
Therapeutic IV.
Patients with Parkinson disease (PD) often experience visual hallucinations (VH) with retained insight (nonpsychotic) but the precise mechanism remains unclear.
To clarify which neural substrates ...participate in nonpsychotic VH in PD, the authors evaluated regional cerebral blood flow (rCBF) changes in patients with PD and VH.
The authors compared 24 patients with PD who had nonpsychotic VH (hallucinators) and 41 patients with PD who had never experienced VH (non-hallucinators) using SPECT images with N-isopropyl-p-(123)Iiodoamphetamine. There were no significant differences in age, sex, duration of disease, doses of PD medications, Hoehn and Yahr scale, or Mini-Mental State Examination (MMSE) scores between the two groups. The rCBF data were analyzed using statistical parametric mapping (SPM).
The rCBF in the right fusiform gyrus was lower in the hallucinators than in the non-hallucinators (corrected p < 0.05 at cluster levels). The hallucinators revealed higher rCBF in the right superior and middle temporal gyri than the non-hallucinators (uncorrected p < 0.001). These significant differences were demonstrated after MMSE scores and duration of disease, which are the relevant factors associated with VH, were covariated out.
Nonpsychotic visual hallucinations in Parkinson disease (PD) may be associated with hypoperfusion in the right fusiform gyrus and hyperperfusion in the right superior and middle temporal gyri. These temporal regions are important for visual object recognition and these regional cerebral blood flow changes are associated with inappropriate visual processing and are responsible for nonpsychotic visual hallucinations in PD.
Purpose To investigate the distinguishing morphological characteristics of children with radial longitudinal deficiency (RLD) in Holt-Oram syndrome (HOS). Methods One hundred fourteen involved ...extremities in 62 patients with a diagnosis of HOS were identified at 3 institutions. Medical records and radiographs were evaluated. Radial longitudinal deficiency and thumb hypoplasia were classified according to the modified Bayne and Klug classification and Blauth classifications, respectively, when possible. Other unusual or distinguishing characteristics were catalogued. Results There was bilateral involvement in 84% of patients. The forearm was involved in 81% of the extremities and a shortened distal radius (Bayne and Klug type I RLD) was the most commonly identified forearm anomaly (40%). Radioulnar synostosis was present in 15% of the extremities, all in the proximal forearms with reduced radial heads. Thumb aplasia (Blauth type V hypoplastic thumb) was the most common type of classifiable thumb abnormality and occurred in 35% of involved thumbs. Twenty-seven percent of abnormal thumbs affected were not classifiable according to the Blauth classification, and 19% of involved thumbs (hypoplastic or absent) had first-web syndactyly. Conclusions The upper extremity in HOS differs from the typical presentation of RLD. The forearm is more often involved and may demonstrate radioulnar synostosis. The thumb is frequently unclassifiable by the Blauth classification and has first-web syndactyly. The presence of radioulnar synostosis and syndactyly of the radial 2 digits in RLD should prompt the hand surgeon to obtain a cardiac evaluation and consider genetic testing for HOS. Type of study/level of evidence Diagnostic III.
Correction of a rigid forearm deformity in children is often desired in congenital radioulnar synostosis, brachial plexus palsy, cerebral palsy, or posttraumatic torsional deformity. Osteotomies at ...the diaphyseal level present difficulties with maintenance of reduction, whether or not internal or pin fixation is used. The stabilizing and healing potential of the periosteum in these cases can be used to advantage in the correction of these deformities.
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