Voltage-based magnetization switching and reading in magnetoelectric spin-orbit nanodevices.

As CMOS technologies face challenges in dimensional and voltage scaling, the demand for novel logic devices has never been greater, with spin-based devices offering scaling potential, at the cost of significantly high switching energies. Alternatively, magnetoelectric materials are predicted to enable low-power magnetization control, a solution with limited device-level results. Here, we demonstrate voltage-based magnetization switching and reading in nanodevices at room temperature, enabled by exchange coupling between multiferroic BiFeO3 and ferromagnetic CoFe, for writing, and spin-to-charge current conversion between CoFe and Pt, for reading. We show that, upon the electrical switching of the BiFeO3, the magnetization of the CoFe can be reversed, giving rise to different voltage outputs. Through additional microscopy techniques, magnetization reversal is linked with the polarization state and antiferromagnetic cycloid propagation direction in the BiFeO3. This study constitutes the building block for magnetoelectric spin-orbit logic, opening a new avenue for low-power beyond-CMOS technologies.

Scalable energy-efficient magnetoelectric spin-orbit logic.

Since the early 1980s, most electronics have relied on the use of complementary metal-oxide-semiconductor (CMOS) transistors. However, the principles of CMOS operation, involving a switchable semiconductor conductance controlled by an insulating gate, have remained largely unchanged, even as transistors are miniaturized to sizes of 10 nanometres. We investigated what dimensionally scalable logic technology beyond CMOS could provide improvements in efficiency and performance for von Neumann architectures and enable growth in emerging computing such as artifical intelligence. Such a computing technology needs to allow progressive miniaturization, reduce switching energy, improve device interconnection and provide a complete logic and memory family. Here we propose a scalable spintronic logic device that operates via spin-orbit transduction (the coupling of an electron's angular momentum with its linear momentum) combined with magnetoelectric switching. The device uses advanced quantum materials, especially correlated oxides and topological states of matter, for collective switching and detection. We describe progress in magnetoelectric switching and spin-orbit detection of state, and show that in comparison with CMOS technology our device has superior switching energy (by a factor of 10 to 30), lower switching voltage (by a factor of 5) and enhanced logic density (by a factor of 5). In addition, its non-volatility enables ultralow standby power, which is critical to modern computing. The properties of our device indicate that the proposed technology could enable the development of multi-generational computing.

Rituximab induction without maintenance for granulomatosis with polyangiitis and dialysis - Case report and literature review.

ANCA-associated vasculitis (AAV) may lead to irreversible organ damage, particularly end-stage renal disease (ESRD) requiring dialysis. The chances of renal recovery diminish with prolonged dialysis. We describe a case of a 32-year-old woman admitted for pulmonary infiltrates and acute renal failure. Autoimmune workup revealed an elevated titer of proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA). The diagnosis of granulomatosis with polyangiitis (GPA) was confirmed by renal biopsy. The patient received induction therapy with IV rituximab (375 mg/m2 per week for 4 weeks) along with systemic high-dose IV corticosteroids and one pulse of IV cyclophosphamide (1000 mg). Rapid deterioration of her kidney function led to pulmonary edema requiring intensive care (ICU) hospitalization. Dialysis and plasmapheresis were initiated. Significant clinical improvement ensued, but the patient remained dialysis dependent. No immunosuppressive maintenance therapy other than prednisone was given. Chronic dialysis was discontinued successfully after eight months. At a follow-up of 30 months since her hospitalization, the patient is in complete remission without relapses. We suggest that rituximab induction without maintenance therapy for GPA ESRD may be adequate.

Vaccines as a trigger for myopathies.

Vaccines are considered to be among the greatest medical discoveries, credited with the virtual eradication of some diseases and the consequent improved survival and quality of life of the at-risk population. With that, vaccines are among the environmental factors implicated as triggers for the development of inflammatory myopathies. The sporadic reports on vaccine-induced inflammatory myopathies include cases of hepatitis B virus, bacillus Calmette-Guérin, tetanus, influenza, smallpox, polio, diphtheria, diphtheria-pertussis-tetanus, combination of diphtheria with scarlet fever and diphtheria-pertussis-tetanus with polio vaccines. However, a significant increase in the incidence of dermatomyositis or polymyositis after any massive vaccination campaign has not been reported in the literature. In study patients with inflammatory myopathies, no recent immunization was recorded in any of the patients. Moreover, after the 1976 mass flu vaccination, no increase in the incidence of inflammatory myopathies was observed. Although rare, macrophagic myofasciitis has been reported following vaccination and is attributed to the aluminium hydroxide used as an adjuvant in some vaccines. Prospective multicenter studies are needed to identify potential environmental factors, including vaccines, as potential triggers for inflammatory myopathies.

Churg-Strauss syndrome: a rare presentation with otological and pericardial manifestations: case report and review of the literature.

Churg-Strauss syndrome (CSS) is a rare multisystem autoimmune disease characterized by diffuse eosinophilic infiltration and necrotizing vasculitis. There are typical manifestations of longstanding rhinosinusitis and polyposis but otological manifestations are rare and characterized by dense aural discharge, granulomatous eosinophilic infiltrate in the mastoid and middle ear with conductive hearing loss, and progressive sensory neural hearing loss--all of which are not responsive to conventional treatment. We describe the case of a 59-year-old man with a rare presentation of CSS that included chronic bilateral otitis media with hearing loss and life-threatening pericardial tamponade. Treatment with pericardiocentesis, prednisone and cyclophosphamide was beneficial and resulted in an improvement of the pericardial and otological manifestations. Early recognition and treatment of otological involvement in CSS is extremely important because of the dramatic response to corticosteroids which may prevent progression of hearing loss.

The renin-angiotensin system in lupus: physiology, genes and practice, in animals and humans.

Although multiple studies suggest a potential role for angiotensin II in inflammation, most were performed either in vitro or in animals with non-immune-complex-mediated diseases. Extrapolation of these findings to humans, particularly patients with lupus, which involves multiple immunoregulatory pathways, is unclear. In autoimmune-prone MRL/lpr mice, angiotensin-converting-enzyme (ACE) inhibition improved survival although to a lesser degree than cyclophosphamide and diminished the glomerular histopathologic damage, proteinuria, lymphoid hyperplasia, dermatitis, and hypergammaglobulinemia, with a reduction in TGF-beta1 and beta 2 expression in the kidneys and renal chemokine mRNA expression. Spleen levels of IL-4 and IL-10 were also reduced. Uncontrolled studies in patients with treatment-refractory lupus nephritis showed a significant reduction in proteinuria with ACE-inhibitors and Angiotensin receptor blockers treatment. The 'masking' effect of ACE-inhibitors should be taken into consideration, as an exacerbation of lupus nephritis may be missed when estimated by the magnitude of proteinuria, which is decreased by these treatments. No single ACE genotype was consistently associated with subsets of SLE patients. In retrospective analyses, ACE-inhibitor use predicted a favourable outcome in 94 cases of pauci-immune vasculitis. The attenuating effect of angiotensin II inhibitors on the progression of chronic renal disease is well recognized. The data on the role of this intervention in lupus is limited.

An intradermal skin test for determination of immunity to varicella.

AIMS: To evaluate the usefulness of a diluted, inactivated solution of attenuated varicella vaccine in predicting susceptibility to varicella and its correlation with specific antibody titre to varicella. METHODS: In a prospective blinded study, 63 healthy subjects (aged 2-43 years) were studied. Skin test solution was prepared from vials of OKA strain virus which was inactivated by exposure of the vials to room temperature for 10 days; solution was diluted at 1/50 with normal saline and kept at 4 degrees C until used for skin testing. The material was injected intradermally. Serum samples were drawn prior to skin testing and kept at -70 degrees C until analysis for antibody assay by the indirect fluorescent antibody (IFA) method. RESULTS: Forty three patients were IFA antibody positive; 41 of them reacted to the skin test. One of the 20 IFA negative patients reacted to the skin test. Sixteen patients had two serological tests performed, one month apart. Four out of these 16 patients tested negative with the skin test. All four had negative serology on both samples. Six of the 12 IFA positive patients showed a boost in the antibody titre one month after application of the skin test. The specificity and sensitivity of the skin test compared to the IFA assay were both 95%, and the positive and negative predictive values were 97% and 90% respectively. CONCLUSIONS: Results suggest that a varicella skin test prepared using this simple and relatively cheap method is a safe, sensitive, and specific tool by which to assess immunity to varicella.

Computational expansion of genetic networks.

We present a new methodology for computational analysis of gene and protein networks. The aim is to generate new educated hypotheses on gene functions and on the logic of the biological network circuitry, based on gene expression profiles. The framework supports the incorporation of biologically motivated network constraints and rules to improve specificity. Since current data is insufficient for de-novo reconstruction, the method receives as input a known pathway core and suggests likely expansions to it. Network modeling is combinatorial, yet data can be probabilistic. At the heart of the approach are a fitness function which estimates the quality of suggested network expansions given the core and the data, and a specificity measure of the expansions. The approach has been implemented in an interactive software tool called GENESYS. We report encouraging results in preliminary analysis of yeast ergosterol pathway based on transcription profiles. In particular, the analysis suggests a novel ergosterol transcription factor.

Concentration and bactericidal activity of fusidic acid and cloxacillin in serum and synovial fluid.

Fusidic acid and cloxacillin were studied in patients who underwent joint aspiration for noninfectious disorders. Nine patients were given oral 500 mg fusidic acid tid for 72 h, the last dose being given 4, 8 or 12 h before the joint aspiration. Cloxacillin was administered in a single 2 g iv dose to 9 patients, 0.5, 4 or 8 h before the aspiration. Bactericidal activity was determined against five isolates each of methicillin-susceptible and methicillin-resistant Staphylococcus aureus. Satisfactory activity (> or = 1:3) was detected in the serum in patients who received fusidic acid, while in the synovial fluids titres reflected borderline effectiveness (c. 1:2). Despite drug concentrations and excellent MICs, fusidic acid demonstrated markedly lower inhibitory and bactericidal activity against S. aureus than did cloxacillin.

Nimesulide-induced hepatitis and acute liver failure.

BACKGROUND: Nimesulide is a relatively new non-steroidal anti-inflammatory drug that is gaining popularity in many countries because it is a selective cyclooxygenase 2 inhibitor. Occasionally, treatment is associated with mild elevation of liver enzymes, which return to normal upon discontinuation of the drug. Several cases of nimesulide-induced symptomatic hepatitis were also recently reported, but these patients all recovered. OBJECTIVES: To report the characteristics of liver injury induced by nimesulide. PATIENTS AND METHODS: We report retrospectively six patients, five of them females with a median age of 59 years, whose aminotransferase levels rose after they took nimesulide for joint pains. In all patients nimesulide was discontinued, laboratory tests for viral and autoimmune causes of hepatitis were performed, and sufficient follow-up was available. RESULTS: One patient remained asymptomatic. Four patients presented with symptoms, including fatigue, nausea and vomiting, which had developed several weeks after they began taking nimesulide (median 10 weeks, range 2-13). Hepatocellular injury was observed with median peak serum alanine aminotransferase 15 times the upper limit of normal (range 4-35), reversing to normal 2-4 months after discontinuation of the drug. The remaining patient developed symptoms, but continued taking the drug for another 2 weeks. She subsequently developed acute hepatic failure with encephalopathy and hepatorenal syndrome and died 6 weeks after hospitalization. In none of the cases did serological tests for hepatitis A, B and C, Epstein-Barr virus and cytomegalovirus, as well as autoimmune hepatitis reveal findings. CONCLUSIONS: Nimesulide may cause liver damage. The clinical presentation may vary from abnormal liver enzyme levels with no symptoms, to fatal hepatic failure. Therefore, monitoring liver enzymes after initiating therapy with nimesulide seems prudent.

The antidepressant fluvoxamine increases natural killer cell counts in cancer patients.

Knowing the negative effect of depression on lymphocyte number and activity in humans, we investigated the effect of antidepressant therapy on various lymphocyte subgroups. Cancer patients receiving treatment for at least 6 months were asked to take the antidepressant, fluvoxamine, for 28 days. Before and at the end of the study, physical and psychiatric examinations were performed, and the severity of depression was assessed by the Hamilton Scale for Depression (HAM-D). In addition, a sample of blood was withdrawn from the patients to quantify the following parameters: total leukocyte and lymphocyte counts, T4, T8, and Natural Killer (NK) cells, and lymphocyte response to the mitogens phytohemagglutinin (PHA) and pokeweed (PWM). Ten adult patients completed the study. Five of the 10 responded favorably to fluvoxamine treatment. Mean improvement was 50% from the score on day one. There was a significant correlation between the change in the HAM-D score of the "responders" and the change in NK cell counts (p = 0.02). The mean increment in NK cell number was 53%. In 4 of the 5 "non-responders", NK cell number dropped by 65% (mean). No correlation between the change in HAM-D score and any other immunological parameters was detected. Fluvoxamine increases NK cell counts in cancer patients, probably by its antidepressant effect.

Autologous umbilical cord blood transfusion.

The purpose of this study was to examine some aspects of umbilical cord blood collection for autologous transfusion in premature infants. All 120 microbacterial cultures (aerobic and anaerobic) of cord blood samples as well as 30 cultures of mycoplasma were treated. Cord prothrombin fragment (F 1 + 2) concentrations were quantified at one and 10 minutes after clamping of the cord. F 1 + 2 concentrations assessed on 25 newborn infants were similar and no linear association with time of clamping could be drawn. This means that cord blood thrombosis is not activated for at least 10 minutes following clamping of the cord. As far as is known, the first newborn infant to benefit from this method of transfusion is reported here. The premature infant received two portions of autologous blood (on days 5 and 7). No untoward effects were noted. Blood, collected from the umbilical cord, is a safe source for autotransfusion, provided that bacteriological testing has been carried out.

V gamma 9-V delta 2+ gamma delta T cells from a patient with Felty syndrome that exhibit aberrant response to triggering of the CD3 molecule can regulate immunoglobulin secretion by B cells.

Expanded populations of T lymphocytes bearing gamma delta T cell receptors have been detected in several patients with Felty syndrome. The goal of this study was to functionally characterize these lymphocytes in a newly described patient with this disease. For this, fluorescence-activated cell sorter analysis of T cell surface antigens, proliferation, and tumor necrosis factor alpha enzyme-linked immunosorbent assays, as well as quantitative assays of immunoglobulins secreted by pokeweed mitogen-driven B cells were performed. The gamma delta cells, that expressed a CD3+CD4-V gamma 9-V delta 2+C delta + phenotype, and constituted 60% of the peripheral blood T cells, did not proliferate after triggering with anti-CD3, but did secrete tumor necrosis factor alpha and the addition of these cells to pokeweed mitogen-stimulated B cells from the patient decreased their secretion of immunoglobulin M while augmenting IgG secretion. These data suggest that the expanded anergic V gamma 9-V delta 2+ gamma delta cells can play an immunoregulatory role in the patient.

[Serum striated muscle enzymes in autoimmune hypoparathyroidism].

Elevated serum levels of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) are generally present in cases of muscle or heart disease, though there are some exceptions. We treated a 56-year-old man diagnosed as suffering from primary idiopathic hypoparathyroidism (PIHP). The neurologic examination was normal, but serum levels of CPK and LDH, and especially isoenzymes of striated muscle, were elevated. Elevated levels of these enzymes in PIHP are rare. In this case they most probably leaked from muscle into the blood circulation after changes in the muscle cell membrane due to hypocalcemia.

Autoantibodies to DNA in multicase families with schizophrenia.

In an attempt to define the autoimmune status of members of multicase families with schizophrenia, sera of both patients and healthy relatives from 28 such cases were tested for antinuclear antibodies, anti-double-stranded DNA, and anti-single-stranded DNA autoantibodies. These autoantibodies were significantly more frequent in both schizophrenic patients and healthy relatives than in normal subjects. Immunoglobulin (Ig) M anti-DNA antibodies were more common in patients, whereas in healthy relatives, IgG anti-DNA antibodies were more common. No significant differences were found between schizophrenic patients and their healthy relatives. The data indicate that an autoimmune process may be involved in the etiology of a subset of patients with schizophrenia.

Allergic granulomatosis and angiitis (Churg-Strauss vasculitis) in pregnancy.

Allergic granulomatosis and angiitis is very rare in pregnancy. To the best of our knowledge, no such case has been reported in the English literature up to now. We describe a patient who developed multisystem disease with mononeuritis multiplex, dermal vasculitis, and pleuritis during gestation with an excellent response to therapy and a good pregnancy outcome.

Astemizole in perennial allergic rhinitis with seasonal exacerbations: a placebo-controlled double-blind study.

Astemizole is a nonsedative H1-antagonist. It was used in a randomized double-blind, placebo-controlled in-season trial to assess its efficacy in patients with perennial allergic rhinitis showing seasonal exacerbations. By the last (6th) week of the study, the mean overall symptomatology, as rated by a global composite score, was significantly mitigated in the astemizole-treated group (18 patients) compared with their first week's global composite score (P less than .01). No such improvement was observed in the placebo-treated group (18 patients). Side effects were not appreciable throughout this short-term study. We conclude that astemizole is effective in the treatment of patients with perennial allergic rhinitis showing seasonal enhancement of symptoms.

Long-term followup of rheumatoid arthritis patients treated with total lymphoid irradiation.

Total lymphoid irradiation was administered to 32 patients with intractable rheumatoid arthritis. Twenty-four patients showed at least a 25% improvement in 3 of 4 disease activity parameters, which persisted during the followup period of up to 48 months. Eight of the 32 patients required adjunctive immunosuppressive drug therapy to maintain improvement. Four patients died after total lymphoid irradiation; the causes of death were acute myocardial infarction (1 patient), pulmonary embolism (1 patient), and rheumatoid lung disease complicated by respiratory infection (2 patients). After therapy, patients exhibited a prolonged reduction in the number and function of circulating T helper cells.