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Philosophical Transactions of the Royal... Nov 2022Influential theoretical models argue that an internal simulation mechanism (motor or sensorimotor simulation) supports the recognition of facial expressions. However,...
Influential theoretical models argue that an internal simulation mechanism (motor or sensorimotor simulation) supports the recognition of facial expressions. However, despite numerous converging sources of evidence, recent studies testing patients with congenital facial palsy (i.e. Moebius syndrome) seem to refute these theoretical models. However, these results do not consider the principles of neuroplasticity and degeneracy that could support the involvement of an alternative neural processing pathway in these patients. In the present study, we tested healthy participants and participants with Moebius syndrome in a highly sensitive facial expression discrimination task and concomitant high-density electroencephalographic recording. The results, both at the scalp and source levels, indicate the activation of two different pathways of facial expression processing in healthy participants and participants with Moebius syndrome, compatible, respectively, with a dorsal pathway that includes premotor areas and a ventral pathway. Therefore, these results support the reactivation of sensorimotor representations of facial expressions (i.e. simulation) in healthy subjects, in the place of an alternative processing pathway in subjects with congenital facial palsy. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.
Topics: Emotions; Facial Expression; Facial Paralysis; Humans; Mobius Syndrome; Recognition, Psychology
PubMed: 36126673
DOI: 10.1098/rstb.2021.0190 -
Journal of Anatomy Oct 2022The alteration in mechanical properties of posterior pelvis ligaments may cause a biased pelvis deformation which, in turn, may contribute to hip and spine instability...
The alteration in mechanical properties of posterior pelvis ligaments may cause a biased pelvis deformation which, in turn, may contribute to hip and spine instability and malfunction. Here, the effect of different mechanical properties of ligaments on lumbopelvic deformation is analyzed via the finite element method. First, the improved finite element model was validated using experimental data from previous studies and then used to calculate the sensitivity of lumbopelvic deformation to changes in ligament mechanical properties, load magnitude, and unilateral ligament resection. The deformation of the lumbopelvic complex relative to a given load was predominant in the medial plane. The effect of unilateral resection on deformation appeared to be counterintuitive, suggesting that ligaments have the ability to redistribute load and that they play an important role in the mechanics of the lumbopelvic complex.
Topics: Biomechanical Phenomena; Finite Element Analysis; Ligaments; Ligaments, Articular; Pelvis; Sacroiliac Joint
PubMed: 35986644
DOI: 10.1111/joa.13739 -
The Journal of Clinical Investigation Jun 2022Skeletal muscle fibers contain hundreds of nuclei, which increase the overall transcriptional activity of the tissue and perform specialized functions. Multinucleation...
Skeletal muscle fibers contain hundreds of nuclei, which increase the overall transcriptional activity of the tissue and perform specialized functions. Multinucleation occurs through myoblast fusion, mediated by the muscle fusogens Myomaker (MYMK) and Myomixer (MYMX). We describe a human pedigree harboring a recessive truncating variant of the MYMX gene that eliminates an evolutionarily conserved extracellular hydrophobic domain of MYMX, thereby impairing fusogenic activity. Homozygosity of this human variant resulted in a spectrum of abnormalities that mimicked the clinical presentation of Carey-Fineman-Ziter syndrome (CFZS), caused by hypomorphic MYMK variants. Myoblasts generated from patient-derived induced pluripotent stem cells displayed defective fusion, and mice bearing the human MYMX variant died perinatally due to muscle abnormalities. In vitro assays showed that the human MYMX variant conferred minimal cell-cell fusogenicity, which could be restored with CRISPR/Cas9-mediated base editing, thus providing therapeutic potential for this disorder. Our findings identify MYMX as a recessive, monogenic human disease gene involved in CFZS, and provide new insights into the contribution of myoblast fusion to neuromuscular diseases.
Topics: Animals; Humans; Membrane Proteins; Mice; Mobius Syndrome; Muscle Proteins; Muscular Diseases; Pierre Robin Syndrome
PubMed: 35642635
DOI: 10.1172/JCI159002 -
Laryngo- Rhino- Otologie May 2022Numerous studies confirm that the vagus nerve stimulation (VNS) is an efficient, indirect neuromodulatory therapy with electrically induced current for epilepsy that...
Numerous studies confirm that the vagus nerve stimulation (VNS) is an efficient, indirect neuromodulatory therapy with electrically induced current for epilepsy that cannot be treated by epilepsy surgery and is therapy-refractory and for drug therapy-refractory depression. VNS is an established, evidence-based and in the long-term cost-effective therapy in an interdisciplinary overall concept.Long-term data on the safety and tolerance of the method are available despite the heterogeneity of the patient populations. Stimulation-related side effects like hoarseness, paresthesia, cough or dyspnea depend on the stimulation strength and often decrease with continuing therapy duration in the following years. Stimulation-related side effects of VNS can be well influenced by modifying the stimulation parameters. Overall, the invasive vagus nerve stimulation may be considered as a safe and well-tolerated therapy option.For invasive and transcutaneous vagus nerve stimulation, antiepileptic and antidepressant as well as positive cognitive effects could be proven. In contrast to drugs, VNS has no negative effect on cognition. In many cases, an improvement of the quality of life is possible.iVNS therapy has a low probability of complete seizure-freedom in cases of focal and genetically generalized epilepsy. It must be considered as palliative therapy, which means that it does not lead to healing and requires the continuation of specific medication. The functional principle is a general reduction of the neuronal excitability. This effect is achieved by a slow increase of the effectiveness sometimes over several years. Responders are those patients who experience a 50% reduction of the seizure incidence. Some studies even reveal seizure-freedom in 20% of the cases. Currently, it is not possible to differentiate between potential responders and non-responders before therapy/implantation.The current technical developments of the iVNS generators of the new generation like closed-loop system (cardiac-based seizure detection, CBSD) reduce also the risk for SUDEP (sudden unexpected death in epilepsy patients), a very rare, lethal complication of epilepsies, beside the seizure severity.iVNS may deteriorate an existing sleep apnea syndrome and therefore requires possible therapy interruption during nighttime (day-night programming or magnet use) beside the close cooperation with sleep physicians.The evaluation of the numerous iVNS trials of the past two decades showed multiple positive effects on other immunological, cardiological, and gastroenterological diseases so that additional therapy indications may be expected depending on future study results. Currently, the vagus nerve stimulation is in the focus of research in the disciplines of psychology, immunology, cardiology as well as pain and plasticity research with the desired potential of future medical application.Beside invasive vagus nerve stimulation with implantation of an IPG and an electrode, also devices for transdermal and thus non-invasive vagus nerve stimulation have been developed during the last years. According to the data that are currently available, they are less effective with regard to the reduction of the seizure severity and duration in cases of therapy-refractory epilepsy and slightly less effective regarding the improvement of depression symptoms. In this context, studies are missing that confirm high evidence of effectiveness. The same is true for the other indications that have been mentioned like tinnitus, cephalgia, gastrointestinal complaints etc. Another disadvantage of transcutaneous vagus nerve stimulation is that the stimulators have to be applied actively by the patients and are not permanently active, in contrast to implanted iVNS therapy systems. So they are only intermittently active; furthermore, the therapy adherence is uncertain.
Topics: Conservative Treatment; Depression; Drug Resistant Epilepsy; Epilepsy; Humans; Quality of Life; Seizures; Treatment Outcome; Vagus Nerve; Vagus Nerve Stimulation
PubMed: 35605616
DOI: 10.1055/a-1660-5591 -
Critical Care (London, England) Mar 2022In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO...
BACKGROUND
In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional pathologies, such as endotheliitis, may further increase the risk of bleeding complications. To assess the frequency of bleeding events, we analyzed data from the German COVID-19 autopsy registry (DeRegCOVID).
METHODS
The electronic registry uses a web-based electronic case report form. In November 2021, the registry included N = 1129 confirmed COVID-19 autopsy cases, with data on 63 ECMO autopsy cases and 1066 non-ECMO autopsy cases, contributed from 29 German sites.
FINDINGS
The registry data showed that ECMO was used in younger male patients and bleeding events occurred much more frequently in ECMO cases compared to non-ECMO cases (56% and 9%, respectively). Similarly, intracranial bleeding (ICB) was documented in 21% of ECMO cases and 3% of non-ECMO cases and was classified as the immediate or underlying cause of death in 78% of ECMO cases and 37% of non-ECMO cases. In ECMO cases, the three most common immediate causes of death were multi-organ failure, ARDS and ICB, and in non-ECMO cases ARDS, multi-organ failure and pulmonary bacterial ± fungal superinfection, ordered by descending frequency.
INTERPRETATION
Our study suggests the potential value of autopsies and a joint interdisciplinary multicenter (national) approach in addressing fatal complications in COVID-19.
Topics: COVID-19; Extracorporeal Membrane Oxygenation; Humans; Intracranial Hemorrhages; Male; Respiratory Distress Syndrome; Respiratory Insufficiency; SARS-CoV-2
PubMed: 35346314
DOI: 10.1186/s13054-022-03945-x -
British Journal of Anaesthesia Jan 2023Patient-ventilator asynchrony during mechanical ventilation may exacerbate lung and diaphragm injury in spontaneously breathing subjects. We investigated whether...
BACKGROUND
Patient-ventilator asynchrony during mechanical ventilation may exacerbate lung and diaphragm injury in spontaneously breathing subjects. We investigated whether subject-ventilator asynchrony increases lung or diaphragmatic injury in a porcine model of acute respiratory distress syndrome (ARDS).
METHODS
ARDS was induced in adult female pigs by lung lavage and injurious ventilation before mechanical ventilation by pressure assist-control for 12 h. Mechanically ventilated pigs were randomised to breathe spontaneously with or without induced subject-ventilator asynchrony or neuromuscular block (n=7 per group). Subject-ventilator asynchrony was produced by ineffective, auto-, or double-triggering of spontaneous breaths. The primary outcome was mean alveolar septal thickness (where thickening of the alveolar wall indicates worse lung injury). Secondary outcomes included distribution of ventilation (electrical impedance tomography), lung morphometric analysis, inflammatory biomarkers (gene expression), lung wet-to-dry weight ratio, and diaphragmatic muscle fibre thickness.
RESULTS
Subject-ventilator asynchrony (median [interquartile range] 28.8% [10.4] asynchronous breaths of total breaths; n=7) did not increase mean alveolar septal thickness compared with synchronous spontaneous breathing (asynchronous breaths 1.0% [1.6] of total breaths; n=7). There was no difference in mean alveolar septal thickness throughout upper and lower lung lobes between pigs randomised to subject-ventilator asynchrony vs synchronous spontaneous breathing (87.3-92.2 μm after subject-ventilator asynchrony, compared with 84.1-95.0 μm in synchronised spontaneous breathing;). There were also no differences between groups in wet-to-dry weight ratio, diaphragmatic muscle fibre thickness, atelectasis, lung aeration, or mRNA expression levels for inflammatory cytokines pivotal in ARDS pathogenesis.
CONCLUSIONS
Subject-ventilator asynchrony during spontaneous breathing did not exacerbate lung injury and dysfunction in experimental porcine ARDS.
Topics: Animals; Female; Lung Injury; Pulmonary Alveoli; Respiration, Artificial; Respiratory Distress Syndrome; Swine; Thoracic Injuries; Ventilators, Mechanical
PubMed: 34895719
DOI: 10.1016/j.bja.2021.10.037 -
Cirugia Pediatrica : Organo Oficial de... Oct 2021Splenogonadal fusion is a rare congenital anomaly of unknown etiology caused by an abnormal fusion of the splenic tissue and the gonadal tissue.
INTRODUCTION
Splenogonadal fusion is a rare congenital anomaly of unknown etiology caused by an abnormal fusion of the splenic tissue and the gonadal tissue.
CASE REPORT
2-year-old patient with paralysis of the 6th, 7th, and 9th cranial nerves, tent-shaped mouth, cleft palate, right pectoralis major hypoplasia, disruptive defect of the right upper limb, and a mass located at the left inguinal region. At inguinal hernia repair surgery, a processus vaginalis with non-reducible content was observed. When opening the hernia sac, a descending segment of splenic tissue merging with the upper pole of the left testis was found. The patient was diagnosed with splenogonadal fusion. The splenic tissue merging with the testis upper pole was resected, and the remaining splenic tissue was reduced towards the abdominal cavity.
DISCUSSION
Splenogonadal fusion is difficult to diagnose. Being familiar with it allows unnecessary orchiectomies to be prevented.
Topics: Child, Preschool; Humans; Male; Scrotum; Spleen; Testis; Poland Syndrome; Mobius Syndrome
PubMed: 34606704
DOI: No ID Found -
Scientific Reports Sep 2021Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with significant mortality....
Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with significant mortality. Accurate information on the specific circumstances of death and whether patients died from or with SARS-CoV-2 is scarce. To distinguish COVID-19 from non-COVID-19 deaths, we performed a systematic review of 735 SARS-CoV-2-associated deaths in Hamburg, Germany, from March to December 2020, using conventional autopsy, ultrasound-guided minimally invasive autopsy, postmortem computed tomography and medical records. Statistical analyses including multiple logistic regression were used to compare both cohorts. 84.1% (n = 618) were classified as COVID-19 deaths, 6.4% (n = 47) as non-COVID-19 deaths, 9.5% (n = 70) remained unclear. Median age of COVID-19 deaths was 83.0 years, 54.4% were male. In the autopsy group (n = 283), the majority died of pneumonia and/or diffuse alveolar damage (73.6%; n = 187). Thromboses were found in 39.2% (n = 62/158 cases), pulmonary embolism in 22.1% (n = 56/253 cases). In 2020, annual mortality in Hamburg was about 5.5% higher than in the previous 20 years, of which 3.4% (n = 618) represented COVID-19 deaths. Our study highlights the need for mortality surveillance and postmortem examinations. The vast majority of individuals who died directly from SARS-CoV-2 infection were of advanced age and had multiple comorbidities.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Alveolar Epithelial Cells; Autopsy; COVID-19; Comorbidity; Female; Germany; Humans; Lung; Male; Middle Aged; Mortality; Pneumonia; Prospective Studies; Pulmonary Embolism; SARS-CoV-2; Thrombosis
PubMed: 34588486
DOI: 10.1038/s41598-021-98499-3 -
Brain & Development Jan 2022Moebius syndrome (MBS) is a congenital disorder characterized by facial and abducens palsy, sometimes accompanied with other cranial nerve palsies and comorbid...
Moebius syndrome (MBS) is a congenital disorder characterized by facial and abducens palsy, sometimes accompanied with other cranial nerve palsies and comorbid conditions. Anatomical anomalies of the brainstem are assumed to be major etiologies of MBS. Its phenotypic presentation can be variable. We report a female patient with MBS who presented with neurogenic bladder (NB). She was born via normal vaginal delivery. At birth, she showed bilateral abducens palsy and right facial palsy. We diagnosed MBS by cranial computed tomography scan and magnetic resonance imaging. She had recurrent urinary tract infection. Hydronephrosis was noted on ultrasonography and bilateral vesicoureteral reflux (grade 5) on voiding cystourethrography. Urodynamic investigation showed detrusor overactivity and detrusor-sphincter dyssynergia, which follow the pattern of NB resulting from infrapontine-suprasacral lesions. Patients with MBS have lower brainstem dysfunction, and accordingly we should be aware of NB.
Topics: Child, Preschool; Female; Humans; Male; Mobius Syndrome; Pons; Urinary Bladder, Neurogenic; Urodynamics
PubMed: 34400011
DOI: 10.1016/j.braindev.2021.07.006 -
American Journal of Physiology. Cell... Sep 2021
Topics: Animals; Cell Differentiation; Cell Fusion; Disease Models, Animal; Humans; Membrane Fusion; Membrane Proteins; Mice; Mice, Knockout; Mobius Syndrome; Muscle Proteins; Muscular Diseases; Mutation, Missense; Myoblasts, Skeletal; Pierre Robin Syndrome; Protein Isoforms; Zebrafish
PubMed: 34288723
DOI: 10.1152/ajpcell.00187.2021