Clinical features of patients with systemic sclerosis positive for anti-SS-A antibody: a cohort study of 156 patients.

BACKGROUND: Anti-SS-A/Ro antibody (anti-SSA), the diagnostic marker of Sjögren's syndrome (SS), is often detected in systemic sclerosis (SSc). Some patients are diagnosed with SSc/SS overlap syndromes, while there are anti-SSA-positive SSc cases without SS. In this study, we investigated the clinical characteristics of SSc with anti-SSA and clarified the clinical impact of this antibody in SSc. METHODS: A retrospective chart review was conducted of 156 patients with SSc at Yokohama City University Hospital from 2018 to 2021. Clinical data, laboratory data, imaging, and autoantibody positivity status were collected and analysed to assess the association between these variables and anti-SSA using multivariable logistic regression analysis. RESULTS: This cohort included 18 men and 138 women with SSc (median age, 69.0 years). Thirty-nine patients had diffuse cutaneous SSc (dcSSc) (25%), and 117 patients had limited cutaneous SSc (75%). Forty-four patients were anti-SSA-positive. Among them, 24 fulfilled the SS criteria. Multivariable logistic regression revealed that anti-SSA was statistically associated with interstitial lung disease (ILD; odds ratio [OR] = 2.67; 95% confidence interval [CI], 1.14-6.3; P = 0.024). Meanwhile, anti-SSA positivity tended to increase the development of digital ulcer (OR = 2.18; 95% CI, 0.99-4.82, P = 0.054). In the comparative analysis of the autoantibody single-positive and anti-SSA/SSc-specific autoantibody double-positive groups, the anti-SSA single-positive group showed a significantly increased risk of ILD (OR = 12.1; 95% CI, 2.13-140.57; P = 0.003). Furthermore, patients with SSc and anti-SSA indicated that anti-SSA-positive SSc without SS was strongly associated with dcSSc when compared to that in patients with SS (OR = 6.45; 95% CI, 1.23-32.60; P = 0.024). CONCLUSIONS: Anti-SSA positivity increases the risk of organ involvement, such as ILD, in patients with SSc. Additionally, the anti-SSA-positive SSc without SS population may have more severe skin fibrosis than others. Anti-SSA may be a potential marker of ILD and skin severity in SSc.

Food-dependent exercise-induced anaphylaxis caused by leek and several allergens of the allium family.

Exercise-induced anaphylaxis (EIA) is a relatively rare condition but can be a diagnostic pitfall in daily practice. Leek allergy is extremely rare, and there have been no reports, to our knowledge, of leek-dependent EIA. Here, we report the first case of exercise- and leek-induced anaphylaxis. An 18-year-old woman presented with symptoms of anaphylaxis after exercise in the morning. Prick-to-prick tests for leek was 1+ and challenge test for heated leek was negative, but leek-dependent physical exertion challenge test evoked anaphylaxis. We diagnosed food-dependent EIA by some additional tests including immunoblotting assay with patient's serum. Leek allergy is an extremely rare condition, so careful interview and investigation of allergens is important to eliminate causative substances of anaphylaxis.

Periostin-An inducer of pro-fibrotic phenotype in monocytes and monocyte-derived macrophages in systemic sclerosis.

Enhanced circulating blood periostin levels positively correlate with disease severity in　patients with systemic sclerosis (SSc). Monocytes/macrophages are predominantly associated with the pathogenesis of SSc, but the effect of periostin on immune cells, particularly monocytes and macrophages, still remains to be elucidated. We examined the effect of periostin on monocytes and monocyte-derived macrophages (MDM) in the pathogenesis of SSc. The modified Rodnan total skin thickness score in patients with dcSSc was positively correlated with the proportion of CD80-CD206+ M2 cells. The proportion of M2 macrophages was significantly reduced in rPn-stimulated MDMs of HCs compared to that of SSc patients. The mRNA expression of pro-fibrotic cytokines, chemokines, and ECM proteins was significantly upregulated in rPn-stimulated monocytes and MDMs as compared to that of control monocytes and MDMs. A similar trend was observed for protein expression in the respective MDMs. In addition, the ratio of migrated cells was significantly higher in rPn-stimulated as compared to control monocytes. These results suggest that periostin promotes inflammation and fibrosis in the pathogenesis of SSc by possible modulation of monocytes/macrophages.

Copper-catalyzed [1,3]-nitrogen rearrangement of O-aryl ketoximes via oxidative addition of N-O bond in inverse electron flow.

The [1,3]-nitrogen rearrangement reactions of O-aryl ketoximes were promoted by N-heterocyclic carbene (NHC)-copper catalysts and BF3·OEt2 as an additive, affording ortho-aminophenol derivatives in good yields. The reaction of substrates with electron-withdrawing substituents on the phenol moiety are accelerated by adding silver salt and modifying the substituent at the nitrogen atom. Density functional theory calculations suggest that the rate-determining step of this reaction is the oxidative addition of the N-O bond of the substrate to the copper catalyst. The negative ρ values of the substituent at both the oxime carbon and phenoxy group indicate that the donation of electrons by the oxygen and nitrogen atoms accelerates the oxidative addition.

Competing Frames in Global Health Governance: An Analysis of Stakeholder Influence on the Political Declaration on Non-communicable Diseases.

BACKGROUND: Non-communicable diseases (NCDs) are increasingly recognized as a significant threat to health and development globally, and United Nations (UN) Member States adopted the Political Declaration of the Third High-level Meeting (HLM) on the prevention and control of NCDs in 2018. The negotiation process for the Declaration included consultations with Member States, intergovernmental organizations (IGOs), and non-state actors such as non-governmental organizations (NGOs) and the private sector. With NCD responses facing charges of inadequacy, it is important to scrutinize the governance process behind relevant high-level global decisions and commitments. METHODS: Through a review of 159 documents submitted by stakeholders during the negotiation process, we outline a typology of policy positions advocated by various stakeholders in the development of the Declaration. We document changes in text from the draft to the final version of the Declaration to analyse the extent to which various positions and their proponents were influential. RESULTS: NGOs and low- and middle-income countries (LMICs) generally pursued 'stricter' governance of NCD risk factors including stronger regulation of unhealthy products and improved management of conflicts of interest that arise when health-harming industries are involved in health policy-making. The private sector and high-income countries generally opposed greater restrictions on commercial factors. The pattern of changes between the draft and final Declaration indicate that advocated positions tended to be included in the Declaration if there was no clear opponent, whereas opposed positions were either not included or included with ambiguous language. CONCLUSION: Many cost-effective policy options to address NCDs, such as taxation of health-harming products, were opposed by high-income countries and the private sector and not well-represented in the Declaration. To ensure robust political commitments and action on NCDs, multi-stakeholder governance for NCDs must consider imbalances in power and influence amongst constituents as well as biases and conflicts in positioning.

Congenital Hypothyroidism and Brain Development: Association With Other Psychiatric Disorders.

Thyroid hormones play an important role in brain development, and thyroid hormone insufficiency during the perinatal period results in severe developmental delays. Perinatal thyroid hormone deficiency is clinically known as congenital hypothyroidism, which is caused by dysgenesis of the thyroid gland or low iodine intake. If the disorder is not diagnosed or not treated early, the neuronal architecture is perturbed by thyroid hormone insufficiency, and neuropathological findings, such as abnormal synapse formation, defects in neuronal migration, and impairment of myelination, are observed in the brains of such patients. Furthermore, the expression of psychiatric disorder-related molecules, especially parvalbumin, is significantly decreased by thyroid hormone insufficiency during the perinatal period. Animal experiments using hypothyroidism models display decreased parvalbumin expression and abnormal brain architecture, and these experimental results show reproducibility and stability. These basic studies reinforce the results of epidemiological studies, suggesting the relevance of thyroid dysfunction in psychiatric disorders. In this review, we discuss the disruption of brain function associated with congenital hypothyroidism from the perspective of basic and clinical research.

Arabidopsis EGY1 Is Critical for Chloroplast Development in Leaf Epidermal Guard Cells.

In Arabidopsis thaliana, the Ethylene-dependent Gravitropism-deficient and Yellow-green 1 (EGY1) gene encodes a thylakoid membrane-localized protease involved in chloroplast development in leaf mesophyll cells. Recently, EGY1 was also found to be crucial for the maintenance of grana in mesophyll chloroplasts. To further explore the function of EGY1 in leaf tissues, we examined the phenotype of chloroplasts in the leaf epidermal guard cells and pavement cells of two 40Ar17+ irradiation-derived mutants, Ar50-33-pg1 and egy1-4. Fluorescence microscopy revealed that fully expanded leaves of both egy1 mutants showed severe chlorophyll deficiency in both epidermal cell types. Guard cells in the egy1 mutant exhibited permanent defects in chloroplast formation during leaf expansion. Labeling of plastids with CaMV35S or Protodermal Factor1 (PDF1) promoter-driven stroma-targeted fluorescent proteins revealed that egy1 guard cells contained the normal number of plastids, but with moderately reduced size, compared with wild-type guard cells. Transmission electron microscopy further revealed that the development of thylakoids was impaired in the plastids of egy1 mutant guard mother cells, guard cells, and pavement cells. Collectively, these observations demonstrate that EGY1 is involved in chloroplast formation in the leaf epidermis and is particularly critical for chloroplast differentiation in guard cells.

Differential Diagnosis between Oral Metastasis of Renal Cell Carcinoma and Salivary Gland Cancer.

Renal cell carcinoma, which has clear cells in 70% of cases, has a high frequency of hematogenous distant metastases to lung, bone, liver, and other areas. Metastatic cancer accounts for 1 to 3% of malignant tumors in the stomatognathic region, and the metastasis of renal cell carcinoma to the oral mucosal tissue, though extremely rare, does occur. In addition, clear cells have been observed in some salivary gland cancers in the oral cavity. Therefore, the differential diagnosis of metastatic renal cell carcinoma and salivary gland cancer is important. This review discusses the differential diagnosis between metastatic renal cell carcinoma and malignant tumors of the salivary gland.

Thyroid hormone insufficiency alters the expression of psychiatric disorder-related molecules in the hypothyroid mouse brain during the early postnatal period.

The functional role of thyroid hormone (TH) in the cortex and hippocampus of mouse during neuronal development was investigated in this study. TH insufficiency showed a decrease in the expression of parvalbumin (PV) in the cortex and hippocampus of pups at postnatal day (PD) 14, while treatment with thyroxine from PD 0 to PD 14 ameliorated the PV loss. On the other hand, treatment with antithyroid agents in adulthood did not result in a decrease in the expression of PV in these areas. These results indicate the existence of a critical period of TH action during the early postnatal period. A decrease in MeCP2-positive neuronal nuclei was also observed in the cortical layers II-IV of the cerebral cortex. The brains were then stained with CUX1, a marker for cortical layers II-IV. In comparison with normal mice, CUX1 signals were decreased in the somatosensory cortex of the hypothyroid mice, and the total thickness of cortical layers II-IV of the mice was lower than that of normal mice. These results suggest that TH insufficiency during the perinatal period strongly and broadly affects neuronal development.