Inventory study of an early pandemic COVID-19 cohort in South-Eastern Sweden, focusing on neurological manifestations.

BACKGROUND: Neurological manifestations in patients with COVID-19 have been reported previously as outcomes of the infection. The purpose of current study was to investigate the occurrence of neurological signs and symptoms in COVID-19 patients, in the county of Östergötland in southeastern Sweden. METHODS: This is a retrospective, observational cohort study. Data were collected between March 2020 and June 2020. Information was extracted from medical records by a trained research assistant and physician and all data were validated by a senior neurologist. RESULTS: Seventy-four percent of patients developed at least one neurological symptom during the acute phase of the infection. Headache (43%) was the most common neurological symptom, followed by anosmia and/or ageusia (33%), confusion (28%), hallucinations (17%), dizziness (16%), sleep disorders in terms of insomnia and OSAS (Obstructive Sleep Apnea) (9%), myopathy and neuropathy (8%) and numbness and tingling (5%). Patients treated in the ICU had a higher male presentation (73%). Several risk factors in terms of co-morbidities, were identified. Hypertension (54.5%), depression and anxiety (51%), sleep disorders in terms of insomnia and OSAS (30%), cardiovascular morbidity (28%), autoimmune diseases (25%), chronic lung diseases (24%) and diabetes mellitus type 2 (23%) founded as possible risk factors. CONCLUSION: Neurological symptoms were found in the vast majority (74%) of the patients. Accordingly, attention to neurological, mental and sleep disturbances is warranted with involvement of neurological expertise, in order to avoid further complications and long-term neurological effect of COVID-19. Furthermore, risk factors for more severe COVID-19, in terms of possible co-morbidities that identified in this study should get appropriate attention to optimizing treatment strategies in COVID-19 patients.

Real-world study of relapsing-remitting multiple sclerosis patients treated with Teriflunomide in Nordic countries: Quality-Of-Life, efficacy, safety and adherence outcomes.

BACKGROUND: Teriflunomide 14 mg (Aubagio®) is a once-daily, oral drug approved for the treatment of relapsing forms of multiple sclerosis (MS). While the efficacy and safety of teriflunomide have been thoroughly characterised across an extensive clinical program, we were interested in studying performance of the drug with respect to quality-of-life (QoL) outcomes in persons with MS in a real-world setting. METHODS: Teri-LIFE was a prospective, open label, non-interventional, observational, multi-centre study that enrolled 200 teriflunomide-treated patients from three Nordic countries. The primary outcome measure changes in patient-reported QoL over 24 months as measured by the Short Form-36 (SF-36) questionnaire. Secondary endpoints included clinical efficacy, fatigue, safety, treatment satisfaction (Treatment Satisfaction Questionnaire for Medication version 1.4 (TSQM-1.4)), treatment adherence, and health economic outcomes. Most assessments were made at baseline and then at 6-monthly intervals. RESULTS: Overall, changes in SF-36 scores from baseline to last visit indicated a stable QoL during treatment with teriflunomide for up to 24 months. Relapse activity decreased during the study compared to the pre-baseline period (p<0.001), patient-reported disability increased marginally, and no substantial change was seen in fatigue scores. The mean scores for TSQM domains increased nominally though not significantly from Month 6 to Month 24. The convenience and side effects TSQM domains recorded the highest median scores, indicating the acceptability of oral teriflunomide in this cohort. This was reflected in a generally high treatment adherence and decreased healthcare utilization during the study period. Some differences were seen between treatment-naïve and previously treated patients, likely reflecting different patient demographics and disease status at study entry, along with different treatment expectations. CONCLUSION: Teri-LIFE offers a reliable snapshot of QoL, efficacy, safety, and health economic outcomes in persons with relapsing MS treated with teriflunomide in routine clinical practice in Nordic countries The results were consistent with previous clinical trials and real-world studies.

Impact of CYBA genotypes on severity and progression of multiple sclerosis.

BACKGROUND AND PURPOSE: The NOX2 enzyme of myeloid cells generates reactive oxygen species (ROS) that have been implicated in the pathology of multiple sclerosis (MS). We aimed to determine the impact of genetic variation within CYBA, which encodes the functional CYBA/p22phox subunit of NOX2, on MS severity and progression. METHODS: One hundred three MS patients with up to 49 (median = 17) years follow-up time from first MS diagnosis were genotyped at the single nucleotide polymorphisms rs1049254 and rs4673 within CYBA. Results were matched with disease severity and time to diagnosis of secondary progressive MS (SPMS). NOX2-mediated formation of ROS was measured by chemiluminescence in blood myeloid cells from healthy donors (n = 55) with defined genotypes at rs1049254 and rs4673. RESULTS: The rs1049254/G and rs4673/A CYBA alleles were associated with reduced formation of ROS and were thus defined as low-ROS alleles. Patients carrying low-ROS alleles showed reduced multiple sclerosis severity score (p = 0.02, N = 103, linear regression) and delayed onset of SPMS (p = 0.02, hazard ratio [HR] = 0.46, n = 100, log-rank test). In a cohort examined after 2005, patients carrying low-ROS CYBA alleles showed >20 years longer time to secondary progression (p = 0.003, HR = 0.29, n = 59, log-rank test). CONCLUSIONS: These results implicate NOX2 in MS, in particular for the development of secondary progressive disease, and point toward NOX2-reductive therapy aiming to delay secondary progression.

Follow-up after infectious mononucleosis in search of serological similarities with presymptomatic multiple sclerosis.

BACKGROUND: A two- to three-fold increase in the risk of multiple sclerosis (MS) after infectious mononucleosis (IM) has been observed in cohort and case control studies. However, this association has not been investigated prospectively from IM. It remains to be determined whether long-term immunospecific sequelae with features consistent with presymptomatic MS occur after IM. METHODS: Sera were obtained from individuals with acute IM from 2003-2007 (n = 42) and from the same individuals at a follow-up (FU) study approximately 10 years after IM. These were assayed for antibodies against a variety of Epstein-Barr virus (EBV) antigens, including gp350, a novel recombinant glycoprotein from the EBV envelope. Similarly, single-protein antigens were used to assess measles and varicella-zoster reactivity (Ncore and varicella-zoster glycoprotein E [VZVgE]). The FU study also included cerebrospinal fluid (CSF) samples from 21 of these individuals to test for IgG antibodies against the same viral antigens. As controls, CSF and serum samples were obtained from 15 EBV-seropositive volunteers who denied a history of IM, and serum samples were obtained from 24 EBV-seropositive blood donors. Anti-gp350, anti-Ncore and anti-VZVgE IgG levels were also analysed in sera and CSF samples from 22 persons with MS. RESULTS: The FU assays showed higher anti-gp350 IgG (p = 0.007, univariate) than among healthy controls, with no difference in serum anti-VCA or anti-EBNA1 IgG levels and no difference in anti-gp350 in the CSF samples. Anti-Ncore IgG and anti-VZVgE were higher in acute IM samples (p < 0.001 and p < 0.0001, respectively) than at FU, although anti-Ncore remained heightened in an age-adjusted analysis at FU (p = 0.014) compared to the control group. In the MS group, the serum anti-gp350 and anti-Ncore IgG levels were significantly higher than among the control group, but the anti-VZVgE levels were not. The CSF anti-gp350 and VZVgE levels were slightly higher among persons with MS than among the control group, whereas anti-Ncore IgG was markedly higher in persons with MS than in the control group. CONCLUSION: In the present study IM showed certain similarities with MS. Increased anti-gp350 reactivity persisted more than a decade after IM, reminiscent of the established increased anti-EBV reactivity in presymptomatic MS. Acute IM was associated with increased anti-measles and anti-VZV immunoreactivity, similar to the MRZ reaction in MS, with some evidence suggesting that this measles reactivity persisted after a decade.

Open-label study with the monoamine stabilizer (-)-OSU6162 in myalgic encephalomyelitis/chronic fatigue syndrome.

OBJECTIVES: The purpose of the present study was to investigate the safety and tolerability of the monoaminergic stabilizer (-)-OSU6162 in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In addition, a potential therapeutic effect of (-)-OSU6162 in ME/CFS was evaluated by means of observer-rated scales and self-assessment rating scales. MATERIALS AND METHODS: In the current study using an open-label single-arm design ME/CFS patient received treatment with (-)-OSU6162 during 12 weeks. The patients received the following doses of (-)-OSU6162: 15 mg b.i.d. during the first 4-week period, up to 30 mg b.i.d. during the second 4-week period and up to 45 mg b.i.d. during the third 4-week period, with follow-up visits after 16 and 20 weeks. RESULTS: Out of 33 included patients, 28 completed the 12 weeks treatment period. (-)-OSU6162 was well tolerated; only one patient discontinued due to an adverse event. Vital signs and physical examinations showed no abnormal changes. Blood analyses showed an increase in serum prolactin. Therapeutically, improvements were seen on the Clinical Global Impression of Change scale, the FibroFatigue scale, the Mental Fatigue Scale, the Fatigue Severity Scale, Beck Depression Inventory, and the Short Form 36 Health Survey Questionnaire. CONCLUSIONS: (-)-OSU6162 is well tolerated in ME/CFS patients and shows promise as a novel treatment to mitigate fatigue and improve mood and health-related quality of life in ME/CFS. Obviously, the present results need to be confirmed in future placebo-controlled double-blind trials.

RebiQoL: A randomized trial of telemedicine patient support program for health-related quality of life and adherence in people with MS treated with Rebif.

RebiQoL was a phase IV multicenter randomized study to assess the impact of a telemedicine patient support program (MSP) on health-related quality of life (HRQoL) in patients with relapsing-remitting MS (RRMS) being administered with Rebif with the RebiSmart device. The primary endpoint was to assess the impact of MSP compared to patients only receiving technical support for RebiSmart on HRQoL at 12 months, using the psychological part of Multiple Sclerosis Impact Scale (MSIS-29), in patients administered with Rebif. A total of 97 patients diagnosed with RRMS were screened for participation in the study of which 3 patients did not fulfill the eligibility criteria and 1 patient withdrew consent. Of the 93 randomized patients, 46 were randomized to MSP and 47 to Technical support only. The demographic characteristics of the patients were well-balanced in the two arms. There were no statistical differences (linear mixed model) in any of the primary (difference of 0.48, 95% CI: -8.30-9.25, p = 0.91) or secondary outcomes (p>0.05). Although the study was slightly underpowered, there was a trend towards better adherence in the MSP group (OR 3.5, 95% CI 0.85-14.40, p = 0.08) although not statistically significant. No unexpected adverse events occurred. This study did not show a statistically significant effect of the particular form of teleintervention used in this study on HRQoL as compared to pure technical support, for MS patients already receiving Rebif with the RebiSmart device. Trial Registration: ClinicalTrials.gov: NCT01791244.

Cobalt-Catalyzed Hydroboration of Alkenes, Aldehydes, and Ketones.

An operationally convenient and general method for hydroboration of alkenes, aldehydes, and ketones employing Co(acac)3 as a precatalyst is reported. The hydroboration of alkenes in the presence of HBpin, PPh3, and NaO tBu affords good to excellent yields with high Markovnikov selectivity with up to 97:3 branched/linear selectivity. Moreover, Co(acac)3 could be used effectively to hydroborate aldehydes and ketones in the absence of additives under mild reaction conditions. Inter- and intramolecular chemoselective reduction of the aldehyde group took place over the ketone functional group.

Open study with (-)-OSU6162 in multiple sclerosis-related fatigue.

OBJECTIVES: The main objective of this study was to investigate the tolerability and safety of the monoaminergic stabilizer (-)-OSU6162 in patients with multiple sclerosis (MS). In addition, a potential therapeutic effect of (-)-OSU6162 with focus on MS-related fatigue was estimated by means of various self-assessment rating scales as well as a clinical investigator-rated scale. MATERIALS AND METHODS: In this open-label, single-arm study, 30 MS patients received treatment with the monoaminergic stabilizer (-)-OSU6162 during 12 weeks. The dose of (-)-OSU6162 was 15 mg twice daily during the first 4-week period, up to 30 mg twice daily during the second 4-week period and up to 45 mg twice daily during the third 4-week period, with follow-up visits after 16 and 20 weeks. MS-related fatigue was rated by the clinical investigator or by self-assessments, using mainly established rating scales. Twenty-five patients completed the study. RESULTS: (-)-OSU6162 was well tolerated by all patients, and no serious adverse events were observed. Therapeutically, improvements were observed with respect to fatigue and mood, as judged by ratings on the Mental Fatigue Scale (MFS), Short Form-36 (SF-36) scale and Beck Depression Inventory (BDI). Furthermore, the large majority of patients were rated as globally improved in the medical observers' rating scale Clinical Global Impression of Change (CGI-C). CONCLUSIONS: In view of its good tolerability, (-)-OSU6162 may offer a new treatment option for alleviating mental fatigue, as well as depression, in MS. Larger, randomized double-blind controlled trials are warranted to confirm the present preliminary observations.

Effect of Pt and Au current collector in LiMn2O4 thin film for micro-batteries.

The crystal orientation and morphology of sputtered LiMn2O4 thin films is strongly affected by the current collector. By substituting Pt with Au, it is possible to observe in the x-ray diffraction pattern of LiMn2O4 a change in the preferential orientation of the grains from (111) to (400). In addition, LiMn2O4 thin films deposited on Au show a higher porosity than films deposited on Pt. These structural differences cause an improvement in the electrochemical performances of the thin films deposited on Au, with up to 50% more specific charge. Aqueous cells using thin film based on LiMn2O4 sputtered on Au or Pt as the cathode electrode present a similar retention of specific charge, delivering 85% and 100%, respectively, of the initial values after 100 cycles. The critical role of the nature of the substrate used in the morphology and electrochemical behaviour observed could permit the exploration of similar effects for other lithium intercalation electrodes.

Wet Nanoindentation of the Solid Electrolyte Interphase on Thin Film Si Electrodes.

The solid electrolyte interphase (SEI) film formed at the surface of negative electrodes strongly affects the performance of a Li-ion battery. The mechanical properties of the SEI are of special importance for Si electrodes due to the large volumetric changes of Si upon (de)insertion of Li ions. This manuscript reports the careful determination of the Young's modulus of the SEI formed on a sputtered Si electrode using wet atomic force microscopy (AFM)-nanoindentation. Several key parameters in the determination of the Young's modulus are considered and discussed, e.g., wetness and roughness-thickness ratio of the film and the shape of a nanoindenter. The values of the Young's modulus were determined to be 0.5-10 MPa under the investigated conditions which are in the lower range of those previously reported, i.e., 1 MPa to 10 GPa, pointing out the importance of the conditions of its determination. After multiple electrochemical cycles, the polymeric deposits formed on the surface of the SEI are revealed, by force-volume mapping in liquid using colloidal probes, to extend up to 300 nm into bulk solution.