Antagonism of metabotropic glutamate receptor type 5 prevents levodopa-induced dyskinesia development in a male rat model of Parkinson's disease: Electrophysiological evidence.

Levodopa-induced dyskinesia (LID) is a common complication in patients with advanced Parkinson's disease (PD) undergoing treatment with levodopa. Glutamate receptor antagonists can suppress LID; however, the underlying mechanisms remain unclear. Here, we aimed to evaluate the effect of 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP), a metabotropic glutamate receptor 5 (mGluR5) antagonist, on dyskinesia. We recorded the neuronal activity of the entopeduncular nucleus and examined responses to cortical electric stimulation in the control group (n = 6) and three groups of rats (male PD model). Saline was intraperitoneally administered to dopamine lesioned (DL) rats (n = 6), levodopa/benserazide (L/B) was administered to LID rats (n = 8), and L/B combined with MTEP was administered to MTEP rats (n = 6) twice daily for 14 days. We administered L/B to LID and MTEP rats 48 h after the final administration of MTEP to examine the chronic effect of MTEP. The control and DL groups did not have LID. The MTEP group had less LID than the LID group (p < .01) on day 1 and day 18. The control group had a typical triphasic pattern consisting of early excitation (early-Ex), inhibition, and late excitation (late-Ex). However, the inhibition phase disappeared, was partially observed, and was fully suppressed in the DL, LID, and MTEP groups, respectively. The cortico-striato-entopeduncular pathway is important in the pathophysiology of LID. mGluR5 antagonism suppresses LID progression by preventing physiological changes in the cortico-striato-entopeduncular pathway. Future studies are required to validate these results.

Binding characteristics of the doxepin E/Z-isomers to the histamine H1 receptor revealed by receptor-bound ligand analysis and molecular dynamics study.

Doxepin is an antihistamine and tricyclic antidepressant that binds to the histamine H1 receptor (H1R) with high affinity. Doxepin is an 85:15 mixture of the E- and Z-isomers. The Z-isomer is well known to be more effective than the E-isomer, whereas based on the crystal structure of the H1R/doxepin complex, the hydroxyl group of Thr1123.37 is close enough to form a hydrogen bond with the oxygen atom of the E-isomer. The detailed binding characteristics and reasons for the differences remain unclear. In this study, we analyzed doxepin isomers bound to the receptor following extraction from a purified H1R protein complexed with doxepin. The ratio of the E- and Z-isomers bound to wild-type (WT) H1R was 55:45, indicating that the Z-isomer was bound to WT H1R with an approximately 5.2-fold higher affinity than the E-isomer. For the T1123.37V mutant, the E/Z ratio was 89:11, indicating that both isomers have similar affinities. Free energy calculations using molecular dynamics (MD) simulations also reproduced the experimental results of the relative binding free energy differences between the isomers for WT and T1123.37V. Furthermore, MD simulations revealed that the hydroxyl group of T1123.37 did not form hydrogen bonds with the E-isomer, but with the adjacent residues in the binding pocket. Analysis of the receptor-bound doxepin and MD simulations suggested that the hydroxyl group of T1123.37 contributes to the formation of a chemical environment in the binding pocket, which is slightly more favorable for the Z-isomer without hydrogen bonding with doxepin.

Study of the Structural Chemistry of the Inclusion Complexation of 4-Phenylbutyrate and Related Compounds with Cyclodextrins in Solution: Differences in Inclusion Mode with Cavity Size Dependency.

4-phenylbutyrate (PB) and structurally related compounds hold promise for treating many diseases, including cancers. However, pharmaceutical limitations, such as an unpleasant taste or poor aqueous solubility, impede their evaluation and clinical use. This study explores cyclodextrin (CD) complexation as a strategy to address these limitations. The structural chemistry of the CD complexes of these compounds was analyzed using phase solubility, nuclear magnetic resonance (NMR) spectroscopic techniques, and molecular modeling to inform the choice of CD for such application. The study revealed that PB and its shorter-chain derivative form 1:1 αCD complexes, while the longer-chain derivatives form 1:2 (guest:host) complexes. αCD includes the alkyl chain of the shorter-chain compounds, depositing the phenyl ring around its secondary rim, whereas two αCD molecules sandwich the phenyl ring in a secondary-to-secondary rim orientation for the longer-chain derivatives. ßCD includes each compound to form 1:1 complexes, with their alkyl chains bent to varying degrees within the CD cavity. γCD includes two molecules of each compound to form 2:1 complexes, with both parallel and antiparallel orientations plausible. The study found that αCD is more suitable for overcoming the pharmaceutical drawbacks of PB and its shorter-chain derivative, while ßCD is better for the longer-chain derivatives.

The effects of alendronate on the suppression of bone resorption and the promotion of cartilage formation in the human mosaicplasty donor site: A randomized, double-blind, placebo-controlled prospective study.

BACKGROUND: We previously reported that early alendronate administration accelerated bone formation and improved the quality of repaired cartilage in the donor site in rabbits. To investigate whether alendronate administration has effects in humans similar to those observed in rabbits. METHODS: The study cohort included 35 patients over the age of 12-years old who underwent mosaicplasty without osteoporotic therapy from March 2011 to October 2012. The donor sites were medial or lateral in the patellofemoral joint. Placebo (P) or Bonalon containing 35 mg of alendronate (A) was administered orally every week for 8 weeks. The cohort comprised 15 male and 20 female, including 14 right and 21 left knees. The mean age at the time of surgery was 57.1 years. Bone formation was examined using computer tomography and lateral knee radiography, and cartilage formation was examined using magnetic resonance imaging (MRI), second-look assessment, and intraoperative acoustic evaluation. The clinical outcomes were assessed using the Japanese Orthopaedic Association knee score and visual analog scale (VAS). Bone and cartilage formation in the donor site and clinical outcomes were assessed at 3, 6, and 12 months after mosaicplasty. RESULTS: The ratio of TRAP-5b in group A was significantly smaller than that in group P at 2 and 8 weeks after mosaicplasty. The extent of bone formation in the donor sites in group A was significantly greater than that in group P at 3 and 6 months after mosaicplasty. Cartilage formation did not differ significantly between the two groups as determined by MRI, macroscopic assessment, and intraoperative acoustic evaluation. Clinical outcomes did not differ significantly between the two groups, and no negative clinical outcomes were observed. CONCLUSION: Early alendronate administration accelerated bone formation but not cartilage formation in the mosaicplasty donor site in humans.

Feasibility and Safety of Microvascular Anastomoses Within Previously-Dissected Neck Regions.

The selection of appropriate recipient vessels is important for the success of head and neck reconstruction. Vessels located outside of previously-dissected neck regions tend to be more frequently selected due to relative ease of preparation. However, some advantages are offered regarding dead space filling and formation by using vascular anastomoses within regions previously dissected, or reusing former free flap pedicle due to their proximity to the defect. We analyzed microsurgical anastomoses in patients requiring oral reconstruction who had previously undergone neck dissection. Contralateral vascular anastomoses were preoperatively planned in 10 cases of which 9 could be successfully performed (achievement rate, 90%). Ipsilateral side anastomoses were planned in 28 cases, with 26 anastomosed as planned (achievement rate, 92.9%). There was no statistically significant difference between the two groups. Vascular anastomosis within the scar region can be performed safely, based on preoperative planning and intraoperative judgment.

Unique environmental Symbiodiniaceae diversity at an isolated island in the northwestern Pacific.

Dinoflagellates in the family Symbiodiniaceae are intensively investigated as algal symbionts of corals and other invertebrates, underpinning coral reef ecosystems as primary producers. Diversity, including regional diversification, of free-living communities is less studied. In this study, an environmental Symbiodiniaceae community at an isolated island, Okinotori Island, Japan, was investigated to determine whether the community is endemic or common with other locations near continents and major ocean currents. Symbiotic algae in common corals at the island were the same type as those of the corals from other Japanese waters. In the environmental samples, genera Symbiodinium (formerly clade A), Cladocopium (clade C), Durusdinium (clade D), and clades F (including Freudenthalidium), G, and I, were identified through analysis of internal transcribed spacer region 2 of nuclear ribosomal RNA gene (ITS2) sequences. Interestingly, some sequences found were genetically different from those of previously reported genera/clades. These unknown sequences were genetically included in the Symbiodiniaceae linage, but they were differentiated from the previously known nine clades. The sequences formed a cluster in the phylogenetic tree based on 28S nrDNA. These sequences were thus considered members of a novel clade in the family (clade J). In total, 120 kinds of ITS2 sequences were produced; while 10 were identical to previously reported sequences, the majority were highly divergent. These genetically unique Symbiodiniaceae types, including novel clade J, may have evolved in isolation and reflect the environmental characteristics of the Okinotori Island.

Reforms for financial protection schemes towards universal health coverage, Senegal.

Advancing the public health insurance system is one of the key strategies of the Senegalese government for achieving universal health coverage. In 2013, the government launched a universal health financial protection programme, la Couverture Maladie Universelle. One of the programme's aims was to establish a community-based health insurance scheme for the people in the informal sector, who were largely uninsured before 2013. The scheme provides coverage through non-profit community-based organizations and by the end of 2016, 676 organizations had been established across the country. However, the organizations are facing challenges, such as low enrolment rates and low portability of the benefit package. To address the challenges and to improve the governance and operations of the community-based health insurance scheme, the government has since 2018 planned and partly implemented two major reforms. The first reform involves a series of institutional reorganizations to raise the risk pool. These reorganizations consist of transferring the risk pooling and part of the insurance management from the individual organizations to the departmental unions, and transferring the operation and financial responsibility of the free health-care initiatives for vulnerable population to the community-based scheme. The second reform is the introduction of an integrated management information system for efficient and effective data management and operations of the scheme. Here we discuss the current progress and plans for future development of the community-based health insurance scheme, as well as discussing the challenges the government should address in striving towards universal health coverage in the country.

Faire progresser le système public d'assurance maladie est l'une des principales stratégies du gouvernement sénégalais, qui ambitionne de rendre les soins de santé accessibles à tous. En 2013, le gouvernement a lancé un programme de protection financière global en la matière, la Couverture Maladie Universelle. L'un des objectifs de ce programme consistait à établir un régime communautaire d'assurance maladie pour les personnes appartenant au secteur informel, encore largement non assurées auparavant. Ce régime fournit une couverture par le biais d'organismes communautaires sans but lucratif. Fin 2016, 676 organismes de ce type avaient été créés aux quatre coins du pays. Néanmoins, ces organismes sont confrontés à des défis tels que le faible taux d'inscription et la transférabilité réduite de la gamme d'avantages sociaux. Pour y remédier, mais aussi pour améliorer la gouvernance et les opérations du régime communautaire d'assurance maladie, le gouvernement a planifié et partiellement appliqué deux réformes d'envergure depuis 2018. La première implique une série de réorganisations institutionnelles afin d'accroître la mutualisation des risques. Ces réorganisations consistent à transférer la mutualisation des risques et une partie de la gestion de l'assurance de chacun des organismes vers les unions départementales, et à confier au régime communautaire la responsabilité financière et la mise en œuvre des initiatives destinées à prodiguer des soins de santé aux populations les plus vulnérables. La seconde prévoit l'introduction d'un système de gestion intégrée de l'information afin d'administrer les données et les opérations plus rapidement et avec davantage d'efficacité. Dans ce document, nous évoquons les progrès actuels et les projets de développement futur du régime communautaire d'assurance maladie. Nous traitons également des défis que le gouvernement doit relever, ainsi que des efforts déployés pour offrir une couverture maladie universelle à l'ensemble du territoire.

La promoción del sistema público de seguro médico es una de las estrategias clave del Gobierno senegalés para lograr la cobertura sanitaria universal. En 2013, el gobierno lanzó un programa de protección financiera universal de la salud, la Couverture Maladie Universelle. Uno de los objetivos del programa era establecer un sistema comunitario de seguro médico para las personas del sector informal, que en su mayoría no tenían seguro antes de 2013. El sistema proporciona cobertura a través de organizaciones comunitarias sin fines de lucro y, a finales de 2016, se habían establecido 676 organizaciones en todo el país. Sin embargo, las organizaciones se enfrentan a desafíos, como las bajas tasas de inscripción y la baja portabilidad del paquete de prestaciones. Para hacer frente a los desafíos y mejorar la gobernanza y el funcionamiento del sistema comunitario de seguro médico, desde 2018 el Gobierno ha planificado y aplicado parcialmente dos reformas importantes. La primera reforma implica una serie de reorganizaciones institucionales para elevar las fuentes de riesgo. Estas reorganizaciones consisten en la transferencia de la mancomunación de riesgos y parte de la gestión de los seguros de las distintas organizaciones a los sindicatos departamentales, y en la transferencia de la operación y la responsabilidad financiera de las iniciativas de atención gratuita de la salud para la población vulnerable al sistema comunitario. La segunda reforma consiste en la introducción de un sistema integrado de información de gestión para una gestión de datos y un funcionamiento eficientes y efectivos del sistema. Aquí se discuten los avances actuales y los planes para el desarrollo futuro del sistema comunitario de seguro médico, así como los desafíos que el gobierno debe abordar en su lucha por lograr la cobertura sanitaria universal en el país.

Differential Activation of Hepatic Invariant NKT Cell Subsets Plays a Key Role in Progression of Nonalcoholic Steatohepatitis.

Innate immune mechanisms play an important role in inflammatory chronic liver diseases. In this study, we investigated the role of type I or invariant NKT (iNKT) cell subsets in the progression of nonalcoholic steatohepatitis (NASH). We used α-galactosylceramide/CD1d tetramers and clonotypic mAb together with intracytoplasmic cytokine staining to analyze iNKT cells in choline-deficient l-amino acid-defined (CDAA)-induced murine NASH model and in human PBMCs, respectively. Cytokine secretion of hepatic iNKT cells in CDAA-fed C57BL/6 mice altered from predominantly IL-17+ to IFN-γ+ and IL-4+ during NASH progression along with the downmodulation of TCR and NK1.1 expression. Importantly, steatosis, steatohepatitis, and fibrosis were dependent upon the presence of iNKT cells. Hepatic stellate cell activation and infiltration of neutrophils, Kupffer cells, and CD8+ T cells as well as expression of key proinflammatory and fibrogenic genes were significantly blunted in Jα18-/- mice and in C57BL/6 mice treated with an iNKT-inhibitory RAR-γ agonist. Gut microbial diversity was significantly impacted in Jα18-/- and in CDAA diet-fed mice. An increased frequency of CXCR3+IFN-γ+T-bet+ and IL-17A+ iNKT cells was found in PBMC from NASH patients in comparison with nonalcoholic fatty liver patients or healthy controls. Consistent with their in vivo activation, iNKT cells from NASH patients remained hyporesponsive to ex-vivo stimulation with α-galactosylceramide. Accumulation of plasmacytoid dendritic cells in both mice and NASH patients suggest their role in activation of iNKT cells. In summary, our findings indicate that the differential activation of iNKT cells play a key role in mediating diet-induced hepatic steatosis and fibrosis in mice and its potential involvement in NASH progression in humans.

The physical activity at work (PAW) study protocol: a cluster randomised trial of a multicomponent short-break intervention to reduce sitting time and increase physical activity among office workers in Thailand.

BACKGROUND: High levels of sedentary behaviour (SB) are associated with non-communicable diseases. In 2016, the estimated total healthcare expenditure from physical activity (PA) in Thailand added up to $190 million in international dollars. The challenge to reduce SB and increase PA among office workers is more urgent now than ever as Thailand is transforming itself from a predominantly rural country to an increasingly urban one. This study will investigate the effectiveness of a multicomponent short break intervention on the reduction of SB during office hours. METHODS/DESIGN: This two-armed Physical Activity at Work (PAW) cluster randomised controlled trial will recruit 360 office workers from 18 offices in the Thailand's Ministry of Public Health (MOPH). Offices will be randomised to either the intervention group or the control group. The multicomponent intervention is informed by the Social Ecological Model and Behaviour Change Techniques (BCTs) and contains four components: (i) organisational, including heads of the participating divisions leading exercises, sending encouragement text messages and acknowledging efforts; (ii) social, including team movement breaks and team-based incentives; (iii) environmental, including posters to encourage exercise; and (iv) individual components including real-time PA feedback via an individual device. The main intervention component will be a short break intervention. The primary outcome of this study is the sedentary time of office workers. Secondary outcomes include time spent on PA, cardiometabolic outcomes, work productivity, musculoskeletal pain, and quality of life. The study also includes process and economic evaluations from the individual and societal perspective. DISCUSSION: The study will be the first experimental study in Thailand to investigate the effect of a short-break intervention at the workplace on SBs of office workers and health outcomes. The study will also include a cost-effectiveness analysis to inform investments on short break interventions under the Universal Healthcare Coverage in Thailand, which includes health promotion and disease prevention component. TRIAL REGISTRATION: The PAW study has been registered at the Thai Clinical Trials Registry (TCTR) under the study ID TCTR20200604007 . Registered 02 June 2020,.

Real-world data for health technology assessment for reimbursement decisions in Asia: current landscape and a way forward.

There is growing interest globally in using real-world data (RWD) and real-world evidence (RWE) for health technology assessment (HTA). Optimal collection, analysis, and use of RWD/RWE to inform HTA requires a conceptual framework to standardize processes and ensure consistency. However, such framework is currently lacking in Asia, a region that is likely to benefit from RWD/RWE for at least two reasons. First, there is often limited Asian representation in clinical trials unless specifically conducted in Asian populations, and RWD may help to fill the evidence gap. Second, in a few Asian health systems, reimbursement decisions are not made at market entry; thus, allowing RWD/RWE to be collected to give more certainty about the effectiveness of technologies in the local setting and inform their appropriate use. Furthermore, an alignment of RWD/RWE policies across Asia would equip decision makers with context-relevant evidence, and improve timely patient access to new technologies. Using data collected from eleven health systems in Asia, this paper provides a review of the current landscape of RWD/RWE in Asia to inform HTA and explores a way forward to align policies within the region. This paper concludes with a proposal to establish an international collaboration among academics and HTA agencies in the region: the REAL World Data In ASia for HEalth Technology Assessment in Reimbursement (REALISE) working group, which seeks to develop a non-binding guidance document on the use of RWD/RWE to inform HTA for decision making in Asia.

The educational gap in tar and nicotine content in purchases of cigarettes: An observational study using large-scale representative survey data from Japan.

The intensity of tobacco use is commonly measured by the number of cigarettes, which is inaccurate because it masks the heterogeneity and substances contained in tobacco. Unlike existing studies, this study adopted the tar and nicotine content of purchased cigarettes as proxies for smoking intensity and elicited socioeconomic disparities from the participants regarding tobacco use. Using a nationally representative consumer panel survey of Japan from 2010 to 2014, we found that socioeconomic disparities in smoking are more pronounced when tar and nicotine content in cigarettes is considered. University graduates purchased 26% fewer cigarettes, and 40% less tar or nicotine than their secondary school-educated counterparts. Low education groups purchased more tar-rich cigarettes, which cost less than low-tar cigarettes. The public health recommendations for reducing socioeconomic health inequalities might be understated because they are drawn from evidence based on the number of cigarettes smoked.

Landscape analysis of health technology assessment (HTA): systems and practices in Asia.

This paper explores the characteristics of health technology assessment (HTA) systems and practices in Asia. Representatives from nine countries were surveyed to understand each step of the HTA pathway. The analysis finds that although there are similarities in the processes of HTA and its application to inform decision making, there is variation in the number of topics assessed and the stakeholders involved in each step of the process. There is limited availability of resources and technical capacity and countries adopt different means to overcome these challenges by accepting industry submissions or adapting findings from other regions. Inclusion of stakeholders in the process of selecting topics, generating evidence, and making funding recommendations is critical to ensure relevance of HTA to country priorities. Lessons from this analysis may be instructive to other countries implementing HTA processes and inform future research on the feasibility of implementing a harmonized HTA system in the region.

Clinical and brain structural effects of the Illness Management and Recovery program in middle-aged and older patients with schizophrenia.

AIMS: In this study, we implemented the Illness Management and Recovery (IMR) program for middle-aged and older patients with schizophrenia hospitalized for long periods and assessed the effect of the IMR program on psychiatric symptoms and psychosocial function. The effects of the IMR program on brain structure were also evaluated. METHODS: The IMR program was implemented for 19 patients with schizophrenia; 17 patients with schizophrenia receiving treatment as usual (TAU) were also recruited as controls. In all patients, mean age was 61.4 years (range, 50-77 years) and mean hospitalization duration was 13.1 years (range, 1-31 years) at enrollment. Structural magnetic resonance images and Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) scores as clinical variables were obtained at the beginning and end of the IMR program. Longitudinal analyses were performed to compare the effects of the IMR program on clinical symptoms and cortical thickness in the superior temporal gyrus (STG) between the IMR and TAU groups. RESULTS: Significant improvements in GAF scores and the total, Insight and Judgment, and Positive components of the PANSS were found in the IMR group compared with the TAU group. Cortical thickness in the left STG was preserved in the IMR group compared with the TAU group. CONCLUSIONS: This is the first report demonstrating the effectiveness of the IMR program for improving psychotic symptoms and psychosocial function and protecting brain structure in middle-aged and older inpatients with schizophrenia hospitalized for long periods.

Evaluating the 2014 sugar-sweetened beverage tax in Chile: An observational study in urban areas.

BACKGROUND: In October 2014, Chile implemented a tax modification on sugar-sweetened beverages (SSBs) called the Impuesto Adicional a las Bebidas Analcohólicas (IABA). The design of the tax was unique, increasing the tax on soft drinks above 6.25 grams of added sugar per 100 mL and decreasing the tax for those below this threshold. METHODS AND FINDINGS: This study evaluates Chile's SSB tax, which was announced in March 2014 and implemented in October 2014. We used household-level grocery-purchasing data from 2011 to 2015 for 2,836 households living in cities representative of the urban population of Chile. We employed a fixed-effects econometric approach and estimated the before-after change in purchasing of SSBs controlling for seasonality, general time trend, temperature, and economic fluctuations as well as time-invariant household characteristics. Results showed significant changes in purchasing for the statistically preferred model: while there was a barely significant decrease in the volume of all soft drinks, there was a highly significant decrease in the monthly purchased volume of the higher-taxed, sugary soft drinks by 21.6%. The direction of this reduction was robust to different empirical modelling approaches, but the statistical significance and the magnitude of the changes varied considerably. The reduction in soft drink purchasing was most evident amongst higher socioeconomic groups and higher pretax purchasers of sugary soft drinks. There was no systematic, robust pattern in the estimates by household obesity status. After tax implementation, the purchase prices of soft drinks decreased for the items for which the tax rate was reduced, but they remained unchanged for sugary items, for which the tax was increased. However, the purchase prices increased for sugary soft drinks at the time of the policy announcement. The main limitations include a lack of a randomised design, limiting the extent of causal inference possible, and the focus on purchasing data rather than consumption or health outcomes. CONCLUSIONS: The results of subgroup analyses suggest that the policy may have been partially effective, though not necessarily in ways that are likely to reduce socioeconomic inequalities in diet-related health. It remains unclear whether the policy has had a major, overall population-level impact. Additionally, because the present study examined purchasing of soft drinks for only 1 year, a longer-term evaluation-ideally including an assessment of consumption and health impacts-should be conducted in future research. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02926001.

Effects of 5-HT and insulin on learning and memory formation in food-deprived snails.

The pond snail Lymnaea stagnalis learns conditioned taste aversion (CTA) and consolidates it into long-term memory (LTM). How well they learn and form memory depends on the degree of food deprivation. Serotonin (5-HT) plays an important role in mediating feeding, and insulin enhances the memory consolidation process following CTA training. However, the relationship between these two signaling pathways has not been addressed. We measured the 5-HT content in the central nervous system (CNS) of snails subjected to different durations of food deprivation. One-day food-deprived snails, which exhibit the best learning and memory, had the lowest 5-HT content in the CNS, whereas 5-day food-deprived snails, which do not learn, had a high 5-HT content. Immersing 1-day food-deprived snails in 5-HT impaired learning and memory by causing an increase in 5-HT content, and that the injection of insulin into these snails reversed this impairment. We conclude that insulin rescues the CTA deficit and this may be due to a decrease in the 5-HT content in the CNS of Lymnaea.

A CD46-like molecule functional in teleost fish represents an ancestral form of membrane-bound regulators of complement activation.

In the complement system, the regulators of complement activation (RCA) play crucial roles in controlling excessive complement activation and in protecting host cell from misdirected attack of complement. Several members of RCA family have been cloned from cyclostome and bony fish species and classified into soluble and membrane-bound type as in mammalian RCA factors. Complement-regulatory functions have been described only for soluble RCA of lamprey and barred sand bass; however, little is known on the biological function of the membrane-bound RCA proteins in the lower vertebrates. In this study, a membrane-bound RCA protein, designated teleost complement-regulatory membrane protein (Tecrem), was cloned and characterized for its complement-regulatory roles. Carp Tecrem, an ortholog of a zebrafish type 2 RCA, ZCR1, consists of four short consensus repeat modules, a serine/threonine/proline-rich domain, a transmembrane region, and a cytoplasmic domain, from the N terminus, as does mammalian CD46. Tecrem showed a ubiquitous mRNA expression in carp tissues, agreeing well with the putative regulatory role in complement activation. A recombinant Chinese hamster ovary cell line bearing carp Tecrem showed a significantly higher tolerance against lytic activity of carp complement and less deposition of C3-S, the major C3 isotypes acting on the target cell, than control Chinese hamster ovary (mock transfectant). Anti-Tecrem mAb enhanced the depositions of carp C3 and two C4 isotypes on autologous erythrocytes. Thus, the present findings provide the evidence of complement regulation by a membrane-bound group 2 RCA in bony fish, implying the host-cell protection is an evolutionarily conserved mechanism in regulation of the complement system.

Familial Mediterranean fever with P369S/R408Q exon3 variant in pyrin presenting as symptoms of PFAPA.

Familial Mediterranean fever (FMF) can be classified into typical and incomplete/atypical types. Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome-like symptoms have been found in atypical type carrying P369S-R408Q mutations in the responsible gene MEFV. A 28-year-old female with recurrent fever and her young sisters and mother, all of whom had tonsillectomy for tonsillitis, carried heterozygous alterations involving E148Q/P369S/R408Q. A diagnosis of atypical FMF, MEFV exon3 variants with PFAPA syndrome-like symptoms, was made.

Influenza-associated MOG antibody-positive longitudinally extensive transverse myelitis: a case report.

BACKGROUND: Myelin-oligodendrocyte glycoprotein antibody (MOG antibodies) was found in various demyelinated diseases. This is the first report of a patient with longitudinally extensive transverse myelitis with an extremely high titer of MOG antibodies after an influenza infection. This case supports the view that MOG antibodies are linked to longitudinally extensive transverse myelitis and that influenza infection might trigger the MOG antibodies. CASE PRESENTATION: A 32-year-old healthy male developed high fever, dysesthesia and paraesthesia below the C2 area, muscle weakness of the bilateral lower extremities, and urinary retention ten days after an influenza type A infection. Magnetic resonance imaging revealed a longitudinal lesion in the spinal cord extending from C2 to the spinal conus. There were no lesions in the brain or optic nerves. Established cell-based immunoassays revealed that he was positive for MOG antibodies (titer = 65,536) and negative for anti-aquaporin 4 antibodies (AQP4 antibodies). He fully recovered after steroid pulse therapy followed by 60 mg prednisolone. CONCLUSION: This is the first report of influenza A-associated longitudinally extensive transverse myelitis with a high titer anti-MOG antibodies. Our case report supports a relationship between anti-MOG antibodies and longitudinally extensive transverse myelitis, which was triggered by influenza infection. Further studies are needed to establish the clinical significance of anti-MOG antibodies for diagnosis, treatment, and prognosis.