All-electrical skyrmionic magnetic tunnel junction.

Topological whirls or 'textures' of spins such as magnetic skyrmions represent the smallest realizable emergent magnetic entities1-5. They hold considerable promise as robust, nanometre-scale, mobile bits for sustainable computing6-8. A longstanding roadblock to unleashing their potential is the absence of a device enabling deterministic electrical readout of individual spin textures9,10. Here we present the wafer-scale realization of a nanoscale chiral magnetic tunnel junction (MTJ) hosting a single, ambient skyrmion. Using a suite of electrical and multimodal imaging techniques, we show that the MTJ nucleates skyrmions of fixed polarity, whose large readout signal-20-70% relative to uniformly magnetized states-corresponds directly to skyrmion size. The MTJ exploits complementary nucleation mechanisms to stabilize distinctly sized skyrmions at zero field, thereby realizing three non-volatile electrical states. Crucially, it can electrically write and delete skyrmions to both uniform states with switching energies 1,000 times lower than the state of the art. Here, the applied voltage emulates a magnetic field and, in contrast to conventional MTJs, it reshapes both the energetics and kinetics of the switching transition, enabling deterministic bidirectional switching. Our stack platform enables large readout and efficient switching, and is compatible with lateral manipulation of skyrmionic bits, providing the much-anticipated backbone for all-electrical skyrmionic device architectures9,10. Its wafer-scale realizability provides a springboard to harness chiral spin textures for multibit memory and unconventional computing8,11.

Safety and tolerability of the novel 2019 coronavirus disease (COVID-19) vaccines among people with epilepsy (PwE): A cross-sectional study.

BACKGROUND: People with epilepsy (PwE) were concerned about the safety of the novel 2019 Coronavirus Disease (COVID-19) vaccines. OBJECTIVE: This study aimed to assess the side effects experienced by PwE following vaccination with COVID-19 vaccines and to identify the causes of vaccine hesitation. METHODS: We administered a questionnaire to PwE, who visited the epilepsy clinic at Ibn Sina Hospital in Kuwait during the first two working weeks of April 2021. It included socio-demographic, epilepsy status, and vaccination data. In addition, we asked those who were not vaccinated yet about the reasons and their plan. RESULTS: A total of 111 PwE were surveyed, with 82 being vaccinated and 29 being unvaccinated. Out of the 82 vaccinated, 66 (80.5%) reported at least one side effect. Patients who received the Pfizer BioNTech mRNA vaccine (BNT162b2) (first, second dosage); and the Oxford-AstraZenecaa chimpanzee adenovirus-vectored vaccine (ChAdOx1nCoV-19) (first dose) had the following reactions: Pain at the injection site (40%, 67.6%), 43.8%, fatigue (47%, 32.4%), 46.9%, Headache (33.3%, 35.3%), 34.4% and Myalgia (40%, 35%), 50% respectively. Local site effects, including pain (67.6% vs. 40%, p = < 0.001) and redness (26.5% vs 6.7%, p = 0.019), were more statistically significantly after the second dose of BNT162b2 vaccine compared to the first dose of the same vaccine. While there was no significant difference in systemic side effects frequencies between the two doses of the BNT162b2 vaccine. The systemic side effects were more statistically significantly after the first dose of ChAdOx1nCoV-19 compared to the first dose of the BNT162b2 vaccine and those included fever (56.3% vs 13.3%, p = < 0.001), chills (37.5% vs 6.7%, p = < 0.001), myalgia (50% vs 40%, p = < 0.001) and arthralgia (25% vs 6.7%, p = 0.021). The local site reactions were not significantly different between the first doses of both vaccines. Among the subgroup who had vaccine-related side effects, 66.7% were females, 90.9% were 55 or younger, 63.6% were on polytherapy, 74% had side effects for one day or less, and 95% were symptoms free by the end of the first-week post-vaccination. Symptoms were mild in 68% of the patients and moderate in 29.3%. Most patients (93.9%) did not report seizure worsening after vaccination. The relative risk of seizure worsening after the first and second doses of BNT162b2 and the first dose of ChAdOx1nCoV-19 vaccines was 1.027 (95% CI 0.891-1.183), 1.019 (95% CI 0.928-1.119), and 1.026 (95% CI 0.929-1.134) respectively. After the first dose of BNT162b2, one patient reported the development of status epilepticus. Among the non-vaccinated group, 34.9% were still indecisive, while 37.9% rejected the vaccination. Fear of adverse effects (42.9%) and fear of epilepsy worsening (23.8%) were the main reasons for vaccine hesitation. CONCLUSIONS: This study shows that the two vaccines under consideration (BNT162b2 and ChAdOx1nCoV-19) have a good safety profile and a low risk of epilepsy worsening among a cohort of PwE in Kuwait.

Compressive Dorsal Myelopathy Secondary to Extramedullary Hematopoiesis in a Thalassemic Patient.

BACKGROUND: Extramedullary hematopoiesis (EMH) is one of the rare causes of spinal cord compression (SCC). It results from noncancerous proliferation of hematopoietic tissue outside the bone marrow as a compensatory mechanism for ineffective erythropoiesis. It occurs in the paraspinal area in 11-15% of thalassemic patients in intermediate and severe cases causing a paraspinal compressive mass. We present a rare case of spinal EMH with thoracic cord compression in a 22-year-old female with beta thalassemia who presented with paraparesis and we provide a review of literature. CASE REPORT: A 22-year-old female patient with a known history of beta thalassemia presented with subacute onset of weakness and numbness of both lower limbs with a sensory level at T6. Magnetic resonance imaging (MRI) of the dorsal spine showed cord compression secondary to paraspinal EMH from T2 to T9 with most prominent compression over T5. She was managed with blood transfusion and low-dose radiotherapy. CONCLUSION: Although rare, EMH should be suspected in thalassemic patients presenting with paraplegia. Treatment with blood transfusions is usually effective. Other options include radiotherapy, surgery, hydroxyurea or a combination of these modalities.

Consensus recommendations for the diagnosis and treatment of multiple sclerosis in Kuwait.

OBJECTIVES: We aim to develop consensus recommendations to guide neurologists in the community for the diagnosis and treatment of Multiple Sclerosis (MS). METHODS: After reviewing the available literature, a group of neurologists with expertise in MS met to discuss the evidence and develop consensus recommendations for the diagnosis and treatment of MS. RESULTS: The revised 2010 McDonald criteria is the established diagnostic criteria for MS and has wide international acceptance among international MS experts. Several red flags in the history and examination, along with certain laboratory tests were pointed out to exclude MS mimickers in the diagnostic phase. The available approved disease modifying therapies (DMTs) were listed in an algorithmic fashion based on initial assessment of disease severity and subsequent disease breakthrough while on DMTs. Risk stratification based on the benefit versus risk ratio was used to help choosing the appropriate therapy to MS patients using an "individualized therapy" approach. The requirements for initiation and monitoring of treated MS patients were highlighted with emphasis on early identification of disease breakthrough, adverse events, and safety concerns. The role of multi-disciplinary MS clinics was discussed and a guide for referral to specialized MS clinics was developed. CONCLUSIONS: Consensus recommendations have been developed to guide local neurologists on the diagnosis and treatment of patients with MS. Implementation of the revised 2010 McDonald diagnostic criteria was advised while a personalized treatment approach was recommended using a treatment algorithm based on risk stratification and patient-centered outcomes.

Increasing prevalence and incidence rates of multiple sclerosis in Kuwait.

BACKGROUND: Kuwait was considered as low to intermediate risk area for MS. OBJECTIVES: To determine the prevalence and incidence rates of MS among Kuwaiti nationals based on 2011 population census. METHODS: This cross-sectional study was conducted between October 2010 and April 2013 using the newly developed national MS registry in Kuwait. Patients with a diagnosis of MS according to 2010 revised McDonald criteria were identified. The crude, age- and sex-specific prevalence and incidence rates among Kuwaiti patients were calculated. RESULTS: 1176 MS patients were identified of which 927 (78.8%) were Kuwaitis and 249 (21.2%) were expatriates. Among Kuwaiti patients, female to male ratio was 1.8:1 with a mean age of 35.40 ± 10.99 years. The prevalence rate of MS was 85.05 per 100,000 persons (95% CI: 82.80 - 87.04). There was a peak in prevalence among patients aged 30-39 years. The incidence of MS was 6.88 per 100,000 persons (95% CI 5.52-8.55). Between 2003 and 2011, the incidence increased 3.22 and 2.54 times in women and men respectively. CONCLUSION: Kuwait is considered a high-risk area for MS. The significant increase in prevalence and incidence rates may represent a true increase despite the improvement in case ascertainment and case definition.

Crystal structure of human uroporphyrinogen III synthase.

Uroporphyrinogen III synthase, U3S, the fourth enzyme in the porphyrin biosynthetic pathway, catalyzes cyclization of the linear tetrapyrrole, hydroxymethylbilane, to the macrocyclic uroporphyrino gen III, which is used in several different pathways to form heme, siroheme, chlorophyll, F(430) and vitamin B(12). U3S activity is essential in all organisms, and decreased activity in humans leads to the autosomal recessive disorder congenital erythropoetic porphyria. We have determined the crystal structure of recombinant human U3S at 1.85 A resolution. The protein folds into two alpha/beta domains connected by a beta-ladder. The active site appears to be located between the domains, and variations in relative domain positions observed between crystallographically independent molecules indicates the presence of flexibility that may be important in the catalytic cycle. Possible mechanisms of catalysis were probed by mutating each of the four invariant residues in the protein that have titratable side chains. Additionally, six other highly conserved and titratable side chains were also mutated. In no case, however, did one of these mutations abolish enzyme activity, suggesting that the mechanism does not require acid/base catalysis.

Maintaining methylation activities during salt stress. The involvement of adenosine kinase.

Synthesis of the compatible osmolyte Gly betaine is increased in salt-stressed spinach (Spinacia oleracea). Gly betaine arises by oxidation of choline from phosphocholine. Phosphocholine is synthesized in the cytosol by three successive S-adenosyl-Met-dependent N-methylations of phosphoethanolamine. With each transmethylation, a molecule of S-adenosylhomo-Cys (SAH) is produced, a potent inhibitor of S-adenosyl-Met-dependent methyltransferases. We examined two enzymes involved in SAH metabolism: SAH hydrolase (SAHH) catabolizes SAH to adenosine plus homo-Cys and adenosine kinase (ADK) converts adenosine to adenosine monophosphate. In vitro SAHH and ADK activities increased incrementally in extracts from leaves of spinach plants subjected to successively higher levels of salt stress and these changes reflected increased levels of SAHH and ADK protein and transcripts. Another Gly betaine accumulator, sugar beet (Beta vulgaris), also showed salt-responsive increases in SAHH and ADK activities and protein whereas tobacco (Nicotiana tabacum) and canola (Brassica napus), which do not accumulate Gly betaine, did not show comparable changes in these enzymes. In spinach, subcellular localization positions SAHH and ADK in the cytosol with the phospho-base N-methyltransferase activities. Because SAHH activity is inhibited by its products, we propose that ADK is not a stress-responsive enzyme per se, but plays a pivotal role in sustaining transmethylation reactions in general by serving as a coarse metabolic control to reduce the cellular concentration of free adenosine. In support of this model, we grew Arabidopsis under a short-day photoperiod that promotes secondary cell wall development and found both ADK activity and transcript levels to increase severalfold.

An electromyographic investigation of 4 elastic-tubing closed kinetic chain exercises after anterior cruciate ligament reconstruction.

OBJECTIVE: To determine the electromyographic (EMG) activity of the vastus medialis oblique (VMO), vastus lateralis (VL), semitendinosus and semimembranosus (ST), and biceps femoris (BF) muscles during 4 elastic-tubing closed kinetic chain exercises in postoperative patients with anterior cruciate ligament (ACL)-reconstructed knees. DESIGN AND SETTING: A 4 x 4 repeated-measures analysis of variance design guided this study. Independent variables were type of exercise and muscle; the dependent variable was EMG activity. SUBJECTS: Fifteen patients, 5 to 24 weeks after ACL reconstruction. MEASUREMENTS: Subjects performed 4 exercises (front pull, back pull, crossover, reverse crossover) with elastic tubing attached to the foot of the uninjured leg. Time-and amplitude- normalized EMG activity was recorded from the VMO, VL, ST, and BF muscles of the injured leg. The hamstrings: quadriceps ratio was calculated. RESULTS: The normalized VMO, VL, and BF EMG activity ranged from 25% to 50% of maximum voluntary isometric contraction for the 4 exercises. The ST ranged from 12% on the back pull to 58% on the front pull. The hamstrings: quadriceps ratios were 137% (front pull), 115% (crossover), 70% (back pull), and 60% (reverse crossover). CONCLUSIONS: We suggest that clinicians use these exercises during early ACL rehabilitation since they incorporate early weightbearing with hamstring and quadriceps coactivation.

Sex differences in parental influences on children's story-telling skills.

Acquisition of story-telling skills is an aspect of language development that is influenced by hearing parental story telling. Because discourse between parent and child is affected by the sex of both parent and child, we hypothesized that sex differences would affect parental story telling and children's acquisition of story-telling skills. For this study, 24 children (12 girls, 12 boys) told a story from a picture book both before and after hearing a parent (12 mothers or 12 fathers) tell the story. Children's stories improved after hearing a parent tell the story. Sons told stories containing more evaluatives (linguistic forms believed to promote better comprehension and memory of stories) after hearing mother's rather than father's story telling, and daughters told stories containing more evaluatives after hearing father's, rather than mother's, story telling. There were no differences in mothers' and fathers' use of evaluatives when telling stories to sons as compared with daughters.

Implementation issues in home healthcare universal precautions.

Universal precautions in home healthcare are essential, yet cost and compliance monitoring are major barriers to their implementation. To help administrators ensure adherence to universal precautions, the authors present specific strategies, including management commitment, a comprehensive training program sensitive to the educational level of the employee, and participation of employees in the continuing implementation and evaluation of the universal precautions policy.

Ferret model for acquired subglottic stenosis.

Researchers continue to look for an improved animal model for the study of acquired subglottic stenosis. This report describes a ferret model that reliably produces 40% to 60% stenosis with a method analogous to the pathophysiology of prolonged endotracheal intubation. Unlike some previously developed animal models, this model has a low morbidity and a perioperative mortality of less than 5%. Ferrets are small, hardy animals that are inexpensive and easy to house, handle, and anesthetize. They are readily available from breeders in a uniform size, age, and sex. Their airway is disproportionately large for their body size, making them particularly well suited for the study of acquired subglottic stenosis and subsequent surgical therapy.