Background and Aim: Long post-COVID vaccination syndrome (LPCVS) is an increasingly recognized disease that occurs after SARS-CoV-2 vaccinations and lasts >4 weeks. However, little is known about the clinical presentation, underlying pathophysiology, treatment, and outcome of LPCVS. This study aims to present a series of patients with LPCVS, their treatment, and outcomes. Methods: This was a retrospective analysis of three patients with LPCVS. Results: In an observation period of 2 months (January and February 2022), three patients were collected in whom side effects after vaccination against COVID-19 lasted >4 weeks and in whom instrumental examinations were largely unremarkable. All three patients received only symptomatic therapy and only partially recovered within 6–8 months after vaccination. LPCVS significantly impaired the quality of life of the included patients. Conclusions: SARS-CoV-2 vaccinations may cause not only short-term but also long-term side effects that include not only known diseases but also non-specific symptoms with normal or slightly abnormal clinical and instrumental findings. Although LPCVS leads to long-term disability, it is not widely recognized and not always accepted by manufacturers, health authorities, and even scientists. LPCVS should not be dismissed as a functional disorder and patients with LPCVS should be taken seriously. Relevance for Patients: The possible causal relation between some long side effects and SARS-CoV-2 vaccines cannot be ignored. The pathophysiology of LPCVS should be further studied to lay a foundation for further improvement of the vaccines.
The Effects of L-Cysteine on Alzheimer’s Disease Pathology in APOE2, APOE3, and APOE4 Homozygous Mice Stephen Gerard Cieslak Jr. Department of Physiology and Developmental Biology, BYU Master of Science The APOE gene is of profound importance regarding the onset of Alzheimer’s disease (AD). From the small physical differences among the protein products of the isoforms of this gene arises a profound difference in their physiologies. For example, the APOE2 isoform confers resistance to AD, the APOE3 isoform confers neutral susceptibility to AD, and the APOE4 isoform confers proneness to AD. L-cysteine is an amino acid that has several anti-AD properties, among which are its ability to sequester iron and form glutathione – a powerful antioxidant – and therefore may be a promising potential dietary supplement for ameliorating AD pathology. In our experiment, we fed Mus musculus (mice) homozygous for APOE2, APOE3, and APOE4 either a control diet or a diet high in L-cysteine. Using Western blotting analysis, we quantified Amyloid β (Aβ), hyper-phosphorylated Tau (HP-Tau), and the three APOE proteins that we extracted from post-mortem brains of APOE2, APOE3, and APOE4 homozygous mice of 3-, 6-, 9-, and 12-month ages. We calculated a three-way ANOVA on a sample of 86 mice to examine the effect of age, genotype, and diet on protein quantities. We found that administration of L-cysteine trends towards lowering levels of Aβ in each cohort, but this effect is statistically insignificant. On the other hand, L-cysteine caused a significant decrease in APOE production with regard to diet [F(1,62) = 6.17, p=0.02], indicating that less APOE is produced due to the decrease in Aβ burden. Furthermore, administration of L-cysteine revealed no significant impact on or trends regarding HP-Tau deposition between diet types for each cohort. However, we observed that L-cysteine appeared to nullify the increasing trend in HP-Tau deposition between APOE2 and APOE4 cohorts. Thus, L-cysteine may be weakly affecting HP-Tau deposition via its ability to somewhat reduce Aβ burden and consequently prevent the shutdown of the proteosomes responsible for the degradation and clearance of HPTau. Taken together, these data suggest that L-cysteine should be considered as an intervention for AD pathology.
Cyclopia syndrome typically coexists with holoprosencephaly. This ocular lesion may present as complete ocular fusion in a single orbit or as two eyes in a single orbit. Eye defects linked with cyclopia syndrome include colobomas (gaps) in the iris, retina, and optic nerve; inconstant optic nerve numbers (either one or two is possible), and an absent or abnormal optic chiasm. Cyclopia syndrome is caused by mutations in the PAX2 and PAX6 genes. Cyclopia syndrome occurs when the rostral (anterior) portion of the notochord and adjacent mesoderm are deficient in mass. This shortage leads to the aberrant induction of the forebrain tissues followed by severe derangement of midline facial development.
Introduction: To discuss the thought-provoking and difficult clinical management of a case of spontaneous intracerebral haemorrhage and immune thrombocytopenic purpura (ITP). Case presentation: A 6-year-old female, known ITP, presented with a one-day history of traumatic dislodged tooth, with associated neurological symptoms. However, her neurological status was alert and oriented, with absence of focal deficits. The complete blood count showed a platelet count of 26 x 10 9 /L and was in keeping with her known baseline platelet level. Computed tomography of the brain demonstrated three sites of cerebral contusions with no associated midline shift. Hours after admission, there was progressive decline in the patient’s clinical status. Additionally, repeat blood investigations showed a downward trend in platelet counts. Aggressive medical management was implemented with the aid of neurosurgery, haematology, paediatrics, and the intensive care unit. Despite various therapeutic modalities, the patient succumbed to her underlying disorder. Conclusion: On retrospective review, this patient had a severe phenotype of ITP. This was demonstrated by repeated oral mucosa bleeds, gastrointestinal bleeds and episodes of haematuria preceding this last admission. Despite multimodal therapies and the combined efforts of a multi-disciplinary team, the clinical management remained arduous.
Megalencephaly (MEG) and macrocephaly are defined as a head circumference measurements two standard deviations above the age-related mean. A distinction between megalencephaly and macrocephaly has been proposed despite the fact that these terms encompass individuals with a large head and, in some cases, with similar neurologic manifestations including intellective disability of various degree, epileptic seizures, and motor impairment. Nevertheless they differ widely in causal events, cerebral structural anomalies, approach in the work-up, treatment and prognosis for which a clinical distinction is justified. From July 2013 through July 2019, 10 children with non-syndromic MEG were selected (7 male, 3 female), and followed up at the Pediatric Unity of the University Hospital Policlinic-Vittorio Emanuele , Catania, Italy for pediatric and neuropediatric disorders; 5 of them (4 male, 1 female) have an abnormally large head, mild/moderate developmental delay, and seizures. *Correspondence to: Piero Pavone, University-Hospital “Policlinico-Vittorio Emanuele”, University of Catania, Italy, Via Plebiscito n. 667, 95100 Catania, Tel: 095 3781821; Fax: 0953782940; E-mail: ppavone@unict.it
We propose that Alzheimer's disease (AD) progression is largely caused by excess reactive oxygen species (ROS) or free radicals created by iron dysregulation.An AD brain is struggling with damage control creating harmful tau tangles and amyloid plaques to deal with the dysregulated iron.We hypothesized that transgenic APP/PS1 (Amyloid precursor protein/ Presenilin-1) and Tau mice would exhibit higher levels of deposits in the brain which can be detected through MRI as well as decreased behavioral performance in radial arm maze tasks.We bred APP/PS1 transgenic mice overexpressing chimeric mouse/human APP-695 with mutations and human PSEN1 carrying the exon-9-deleted variant (PSEN1dE9), and Tau mice overexpressing all six isoforms of hyper-phosphorylated human MAPT (Microtubule associated protein Tau), which were compared with age controlled wild type mice.Mice received a diet of either regular or methionine rich chow as an oxidative stressor.Subgroups received a rescue treatment of either zinc, metformin or clioquinol chow.MRI (Magnetic Resonance Imaging) scans were performed using a Siemens 3 Tesla scanner.Behavioral data was collected using a radial arm maze (RAM) for 2 weeks at each point.Data collection time points were: 1 (baseline), 3, 6 and 9 months.Mean T2 TSE signals from scans on these mice revealed significant signal loss in bilateral hippocampi when compared by age.We also found a significant main effect of genotype and a trend toward significance for genotype and treatment interaction in the mean time mice spent in the RAM.Pairwise comparison showed a significant difference between the time male and female mice spent in the RAM.There was, however, no effect of signal loss or behavior deficit when comparing rescue treatments with or without oxidative insults.The decrease in signal and RAM performance is due to plaque increase and accompanying iron, which offers a possibility to refine the imaging techniques in pursuit of a noninvasive diagnostic biomarker.
Young male Zucker rats with a leptin receptor mutation are obese, have a non-insulin-dependent diabetes mellitus (NIDDM), and other endocrinopathies. Tibial branches of the sciatic nerve reveal a progressive demyelination that progresses out of the Schwann cells (SCs) where electron-contrast deposits are accumulated while the minor lines or intermembranous SC contacts display exaggerated spacings. Cajal bands contain diversely contrasted vesicles adjacent to the abaxonal myelin layer with blemishes; they appear dispatched centripetally out of many narrow electron densities, regularly spaced around the myelin annulus. These anomalies widen and yield into sectors across the stacked myelin layers. Throughout the worse degradations, the adaxonal membrane remains along the axonal neuroplasm. This peripheral neuropathy with irresponsive leptin cannot modulate hypothalamic-pituitary-adrenal axis and SC neurosteroids, thus exacerbates NIDDM condition. Additionally, the ultrastructure of the progressive myelin alterations may have unraveled a peculiar, centripetal mode of trafficking maintenance of the peripheral nervous system myelin, while some adhesive glycoproteins remain between myelin layers, somewhat hindering the axon mutilation. Heading title: Peripheral neuropathy and myelin.
This study reviews current understanding of relationship of paraoxonase1 polymorphisms and activity of paraoxonase1 in Parkinson’s Disease (PD). Paraoxonase 1 (PON1) is involved in the detoxification of insecticides and pesticides and metabolisms of these toxins. Two polymorphisms within the gene affect the activity of paraoxonase. In One of them a methionine replaces with leucine at position 54 (M54L) and the other a glutamine change to arginine variant at position 192 (Q192R). There are some evidences show the genetic polymorphisms of PON1 can protect against organophosphates such as paraoxon and diazinon. Results of studies that investigate these associations are controversial. There was no significant association between PON1-1 92Q/R alleles and risk of developing PD and also there is no evidence for an association between PON 1-192 polymorphism and development of PD, however, a study found that the 192R alleles were risk factor for developing PD. These polymorphisms explain only some of the variations in serum PON1 activity; thus, the other critical test of the hypothesis is likely to be whether low serum PON1 activity is associated with Parkinson disease or not. In this review we summarize current knowledge from PON1 association studies regarding the interaction between gene polymorphisms and activity of PON1 with the risk of PD. *Correspondence to: Mohammad Valilo, Department of Clinical Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran, Tel: +989380540895; E-mail: valilo.biomed@gmail.com
The development of the dural venous complex of the skull base formed by the cavernous, intercavernous, and petrous dural sinuses and their connections with the intraand extracranial veins and venous plexuses, was investigated on 112 premature stillborn human fetuses from 16 to 36 weeks of gestation by methods of vascular corrosion casting. It was established that the main intracranial dural canals approach similar to the mature arrangement at the very beginning of the early fetal period. In fetuses 16 weeks of gestation, the parasellar dural venous complex appeared as a plexiform venous ring draining the venous plexus of the orbits into the petrous sinuses. The average diameter of dural canals progressively enlarged and reached its maximum value 2.2 ± 0.53 mm approaching the 24th week of gestation. This developmental stage is characterized by the intensive formation of the emissary veins connecting the cavernous sinus with the extracranial venous plexuses. Due to the particular fusion of the intraluminal canals, the average diameter of the lumen gradually declined to reach 1.9 ± 0.54 mm in 36-week-old fetuses. By the end of the fetal development, 21.3% of fetuses featured a considerable reduction of the primary venous system with the formation of the one-canal shaped dural venous sinuses, obliteration of several tributaries, and decreased density of the extracranial venous plexuses. In the other third of fetuses, the enhanced venous basal complex with the multi-canal shape of dural sinuses, and abundance of tributaries and anastomoses persisted thought the whole antenatal period. Thus, the genetically determined pace of reduction of the primary venous plexuses determines the final shape of the dural venous system and its compensatory abilities. *Correspondence to: Maryna Kornieieva, American University of Caribbean School of Medicine, Lowlands, Sint Maarten, Netherlands Antilles, Tel: 721-5452298 Ext: 4042355, Cell: +1(721)5591342; E-mail: mkornieieva@aucmed.edu
We describe Pre-Action Games & Exercises (PAGEs) a prototype for supplemental tele-rehabilitation.PAGEs are therapist-guided exercises for chronically impaired stroke survivors: basically a computer-based platform of brain exercises based on control of virtual limbs.Survivors control virtual limbs, simultaneously actuating wearable, motorized orthoses which physically manipulate impaired limbs.Physical manipulations mirror survivor controlled virtual limb movements.PAGEs are designed to assist physical and occupational therapists to treat increased numbers of stroke survivors (estimated, in the US, Canada, Mexico and Europe to be 18 million individuals).Key elements of PAGEs tele-rehabilitation are outlined.Tele-rehabilitation is suggested as a modality for therapist-supervised, survivor-selfadministered and repetitive brain-to-body exercises either in clinics and/or at home or anywhere at any time.Thus, the genetically determined pace of reduction of the primary venous plexuses determines the final shape of the dural venous system and its compensatory abilities.
First paragraph... I think that there must be very few books that live up to the promise implicit in their title. It is very tempting to exaggerate, in order to get people to buy the book. (By contrast, Walt Whitman's Leaves of Grass, one of my favorite books, does discuss leaves of grass, but also a lot more!) As far as I can tell, Evan Harris Walker's The Physics of Consciousness: Quantum Minds and the Meaning of Life discusses neither the physics of consciousness, quantum minds, nor the meaning of life.
Introduction:The objective of this study was to review the literature and analyze the clinical presentation and response to therapy of late onset myasthenia gravis (LOMG) in our center.Methods: Previous reports of LOMG and the records of 24 cases of LOMG seen in our neuromuscular clinic were reviewed, and the demographic data, clinical presentations, and responses to therapy were studied.The definition of LOMG's age of onset varies, but we have defined the cases in our center as LOMG when symptoms first appear at 65 years of age or older. Results:In our center, the age range was 65-82 years--the male sex predominated in 16 patients (67%) while 8 patients (33%) were women; the presenting symptom was ocular in 12 patients (50%), generalized (not confined to a specific muscle group) in 7 (29%), and bulbar in 5 (21%); this is similar to statistics reported previously.The most common comorbidities were diabetes, essential hypertension, and thyroid disease.The treatment consisted of acetylcholinesterase inhibitors (monotherapy) in two patients; prednisone plus acetylcholinesterase inhibitors were administered in 20 patients (83%); 17 subjects (71%) needed immunosuppression with azathioprine / mycophenolate mofetil (due to lack of response or for steroid sparing).Ten patients (42%) in our center required plasma exchange or intravenous immunoglobulin infusions; thymectomy was performed in three cases, and one of these had a thymoma; otherwise, no patients experienced thymic hyperplasia. Conclusions:As in the literature, we found LOMG to have a clear male predominance; ocular presentation was the most common manifestation.Clinically, antibody positivity and response to therapy in LOMG were similar to younger myasthenia patients (non-LOMG patients) as evidenced by previous studies.Thymoma was rare.
The aim of the paper was to estimate histologically the effect of alcohol consumption by rats during pregnancy on the parietal cortex neurons development in their offspring.Female Wistar rats consumed a 15% solution of ethanol as a single source of drinking (3.64 ± 2.2 g/kg/day) throughout pregnancy, control rats received equivolume amounts of water.The offspring were decapitated on the 2-, 5-, 10-, 20-, 45-, and 90 th days after birth and the samples of the brain parietal cortex were prepared for histological examination in combination with morphometry to examine the 5 th layer inner pyramidal neurons.Results: Antenatal alcohol exposure in rats increased (on the 2 nd and 5 th postnatal days), and then reduced (on the 10 th and 90 th days) the parietal cortex thickness, decreased the amount of parietal cortex inner pyramidal neurons and increased the number of their pathological forms at all time intervals of the examination.Starting from the 20 th postnatal day the shrinkage and cessation of the growth of inner pyramidal neurons was observed.Conclusion: Alcohol consumption by rats during pregnancy induces deep and long-term histological changes in the parietal cortex neurons in postnatal ontogenesis in rat offspring including early swelling and postpone shrinkage and the cessation of growth of the brain cortex inner pyramidal neurons.
Background: People living with Schizophrenia are often associated with obesity due to a fairly sedentary lifestyle.However, there are less study findings about body composition of normal weight chronic schizophrenia inmates.The aim of this study is to compare body composition variables between normal weight chronic schizophrenia inmates and age-gender matched healthy control subjects in Malaysia.Methods: People with chronic schizophrenia, based on DSM-IV, and with normal weight were recruited from the pool of patients in a large hospital.Body fat percentage (%), Body fat mass (kg), fat free mass (kg), body muscle mass (kg), visceral fat rating and total body water were measured using bioelectrical impedance analysis (BIA) method.Comparative analysis was performed between the normal BMI schizophrenia inmates and healthy control subjects.Results: There were 247 consented subjects with normal BMI (164 males and 83 females).Their age range between 18-91 years old (mean/SD=58+13.17)were compared to 64 normal weight healthy controls (25 males and 39 females (mean/SD=34 ± 10.87) years old; age range of 21-58 years old.Among males, fat free mass and body muscle mass are significantly higher in normal BMI healthy control subjects compared to chronic schizophrenia inmates (p-value <0.05).Among females, fat free mass and body muscle mass are significantly higher in normal BMI healthy control subjects compared to chronic schizophrenia inmates.Meanwhile, visceral fat rating is significantly higher in normal BMI chronic schizophrenia inmates than healthy controls for both males and females with Mean ± SD (8 ± 2.91 and 7 ± 1.58) respectively.Age, weight, were significant for the schizophrenic inmates (both gender), whist only BMI was significantly higher in male healthy control subjects (p<0.05) Conclusions:The findings show that normal BMI schizophrenia patients have higher visceral fat rating and lower fat free mass and body muscle mass compared to healthy controls.In addition, the longer the duration of illness the higher the visceral fat rating among the inmates.These results indicate that community rehabilitation program should be individualised even for Chronic Schizophrenia with normal BMI, to ensure better health and wellbeing.
Background:The aim was to investigate the relation between cognitive functions and thyroid hormone levels among patients with untreated Graves' disease and to explore the influence of mild traumatic brain injury (mTBI) on the results.Patients: A cohort of forty-four patients (mean age: 39.3 ± 10.2) with untreated Graves' disease were investigated and compared to a healthy control group (n=31, mean age: 36.7 ± 8.8).Six patients had a history of mTBI.Methods: Neuropsychological tests were used to assess cognitive functions of attention, memory, executive and psychomotor performance.Results: Within the patient group high free triiodothyronine levels were associated with higher cognitive performance.This was particularly the case if patients with a history of mTBI were excluded.However, the patients showed lower performance on several tests compared to the control group. Conclusion:At the same time as cognitive dysfunction in untreated Graves' disease is present it parallels with a positive relation between thyroxine hormone levels and cognitive performance.This may explain previous conflicting research results.A history of mTBI, however, seems to prevent these positive thyroxine effects, indicating that an mTBI might be related to a subtle persistent impact on cognition.
