Globular glial tauopathy (GGT) is a progressive neurodegenerative disease involving the grey matter and white matter (WM) and characterized by neuronal deposition of hyper-phosphorylated, abnormally conformed, truncated, oligomeric 4Rtau in neurons and in glial cells forming typical globular astrocyte and oligodendrocyte inclusions (GAIs and GOIs, respectively) and coiled bodies. Present studies centre on four genetic GGT cases from two unrelated families bearing the P301T mutation in MAPT and one case of sporadic GGT (sGGT) and one case of GGT linked to MAPT K317M mutation, for comparative purposes. Clinical and neuropathological manifestations and biochemical profiles of phospho-tau are subjected to individual variations in patients carrying the same mutation, even in carriers of the same family, independently of the age of onset, gender, and duration of the disease. Immunohistochemistry, western blotting, transcriptomic, proteomics and phosphoproteomics, and intra-cerebral inoculation of brain homogenates to wild-type (WT) mice were the methods employed. In GGT cases linked to MAPT P301T mutation, astrocyte markers GFAP, ALDH1L1, YKL40 mRNA and protein, GJA1 mRNA, and AQ4 protein are significantly increased; glutamate transporter GLT1 (EAAT2) and glucose transporter (SLC2A1) decreased; mitochondrial pyruvate carrier 1 (MPC1) increased, and mitochondrial uncoupling protein 5 (UCP5) almost absent in GAIs in frontal cortex (FC). Expression of oligodendrocyte markers OLIG1 and OLIG2 mRNA, and myelin-related genes MBP, PLP1, CNP, MAG, MAL, MOG, and MOBP are significantly decreased in WM; CNPase, PLP1, and MBP antibodies reveal reduction and disruption of myelinated fibres; and SMI31 antibodies mark axonal damage in the WM. Altered expression of AQ4, GLUC-t, and GLT-1 is also observed in sGGT and in GGT linked to MAPT K317M mutation. These alterations point to primary astrogliopathy and oligodendrogliopathy in GGT. In addition, GGT linked to MAPT P301T mutation proteotypes unveil a proteostatic imbalance due to widespread (phospho)proteomic dearrangement in the FC and WM, triggering a disruption of neuron projection morphogenesis and synaptic transmission. Identification of hyper-phosphorylation of variegated proteins calls into question the concept of phospho-tau-only alteration in the pathogenesis of GGT. Finally, unilateral inoculation of sarkosyl-insoluble fractions of GGT homogenates from GGT linked to MAPT P301T, sGGT, and GGT linked to MAPT K317M mutation in the hippocampus, corpus callosum, or caudate/putamen in wild-type mice produces seeding, and time-and region-dependent spreading of phosphorylated, non-oligomeric, and non-truncated 4Rtau and 3Rtau, without GAIs and GOIs but only of coiled bodies. These experiments prove that host tau strains are important in the modulation of cellular vulnerability and phenotypes of phospho-tau aggregates. Keywords Globular glial tauopathy • Tau • Astrogliopathy • Oligodendrogliopathy • Phosphoproteome • Seeding and spreading alien hand, myoclonus, and dystonic movements...
Objective We report the findings from the Spanish Society of Neurology's NeuroCOVID-19 Registry. Methods We performed a multicentre study of patients with neurological manifestations of COVID-19. Participating physicians reported demographic, clinical, and paraclinical data and judged the involvement of COVID-19 in causing neurological symptoms. Results A total of 233 cases were submitted, including 74 different combinations of manifestations. The most frequently reported were stroke (27%), neuromuscular symptoms (23.6%), altered mental status (23.6%), anosmia (17.6%), headache (12.9%), and seizures (11.6%). The mean age of patients was 61.1 years, with 42.1% being women; a higher proportion of women was recorded among patients with altered mental status, anosmia, and headache. The onset of symptoms differed within categories. Onset of anosmia occurred a mean (standard deviation) of 2.9 (2.5) days after the first general symptom, whereas neuromuscular symptoms appeared after 13.9 (10.1) days. Neurological symptoms were persistent in 33% of patients. General symptoms were present in 97.7% of patients, and results from general laboratory studies were abnormal in 99.4% of patients. Cerebrospinal fluid analysis findings were abnormal in 62.7% of the cases in which this test was performed ( n = 51), but positive results for SARS-CoV-2 were only found in one case. Conclusions The neurological manifestations of COVID-19 are diverse. Anosmia, myalgia, and headache occur earlier in the course of the disease. Altered mental status, neuromuscular symptoms, and stroke are associated with greater severity. COVID-19 must be incorporated into most clinical and radiological differential diagnoses. COVID-19 may cause persistent and disabling neurological symptoms.
The broiler industry is currently experiencing a muscle anomaly referred to as "woody breast," and the effect of different cooking methods on the marination properties of severe woody breast (SWB) has not yet been reported. This study compared the texture attributes of marinated (injected) normal (NOR) and SWB using a convection oven and a flat-top grill. The objectives were 1) to develop and validate a descriptive texture attribute panel with 6 trained panelists using a 16-point scale and 2) to evaluate the instrumental texture profile analysis (TPA) using a texture analyzer. Sixty-four NOR and SWB were obtained from a commercial facility. Fillet color (L*, a*, b*) and pH were measured before marination. In each of 2 trials, the breast muscles were injected in bulk with 15% brine (0.48 STPP, 0.55% NaCl, final concentration), and marinade retention was determined after 20 minutes. The meat was vacuum packaged, stored at -20°C (7 d sensory; 29 d TPA) and then thawed (4°C, 24 h). Fillets were cooked to 73°C on a flat-top grill (176°C) or in an oven (176°C), and cook loss % was determined. Panelist samples (2 × 2 cm) and TPA samples (4 × 2 cm) were cut into 3 pieces. Color and pH were higher for SWB than NOR fillets (P < 0.05). Marinade retention was 83.21% for NOR meat and 59.23% for SWB meat. The flat-top grill method resulted in higher cook loss than oven (P < 0.05). SWB had higher cook loss when compared to NOR (P < 0.05). Sensory texture descriptors springiness, hardness, denseness, cohesiveness, fracturability, fibrousness, crunchiness, and chewiness were higher for SWB than NOR fillets (P < 0.05). TPA attributes also showed higher values for SWB compared to NOR (P < 0.05). No differences in texture were found between the grill and oven for sensory and TPA attributes. In summary, marinated SWB has significant texture differences when compared to NOR, regardless of cooking method.
Objectives Since the beginning of the COVID-19 pandemic, the Spanish Society of Neurology has run a registry of patients with neurological involvement for the purpose of informing clinical neurologists. Encephalopathy and encephalitis were among the most frequently reported complications. In this study, we analyse the characteristics of these complications. Patients and methods We conducted a retrospective, descriptive, observational, multicentre study of patients with symptoms compatible with encephalitis or encephalopathy, entered in the Spanish Society of Neurology's COVID-19 Registry from 17 March to 6 June 2020. Results A total of 232 patients with neurological symptoms were registered, including 51 cases of encephalopathy or encephalitis (21.9%). None of these patients were healthcare professionals. The most frequent syndromes were mild or moderate confusion (33%) and severe encephalopathy or coma (9.8%). The mean time between onset of infection and onset of neurological symptoms was 8.02 days. Lumbar puncture was performed in 60.8% of patients, with positive PCR results for SARS-CoV-2 in only one case. Brain MRI studies were performed in 47% of patients, with alterations detected in 7.8% of these. EEG studies were performed in 41.3% of cases, detecting alterations in 61.9%. Conclusions Encephalopathy and encephalitis are among the complications most frequently reported in the registry. More than one-third of patients presented mild or moderate confusional syndrome. The mean time from onset of infection to onset of neurological symptoms was 8 days (up to 24 hours earlier in women than in men). EEG was the most sensitive test in these patients, with very few cases presenting alterations in neuroimaging studies. All patients treated with boluses of corticosteroids or immunoglobulins progressed favourably.
We have developed a reproducible renovascular model of hypertension via a controllable, suprarenal aortic coarctation in the pig. This model has many potential applications, including investigation of the effects of acute hypertension in the conscious animal; identification of cardiac and vascular adaptations to chronic hypertension and their reversal; determining the effect of pharmacologic agents or other interventions on hypertension; and furthering our understanding of the implications of chronic hypertension on neurologic function. A totally implantable system was devised by attaching a reinforced silicone vascular occluder to a vascular access port. The occluder was placed around the suprarenal aorta proximal to the diaphragm. Ten pigs were made hypertensive by sequentially inflating the occluder. In six pigs, telemetric monitoring of blood pressure was used to determine when the pigs had reached target pressures (mean arterial blood pressure >150 mm Hg). Four pigs did not have telemetry units placed and blood pressure and heart rate were monitored for 4 weeks by periodically restraining the pigs in a sling. Two pigs reversed their occlusion due to presumed technical errors; the remaining pigs were studied for 4 (n = 5) or 8 (n = 3) weeks and then euthanized. Advantages of this model of aortic coarctation are that the occlusions are performed in awake animals and excessive occlusion of the aorta resulting in neurologic dysfunction or other distress to the animal can be easily corrected by simply withdrawing a small amount of the fluid used for inflation of the occluder. Additionally, removal of the constriction does not require a second surgical procedure.
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