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Phenological synchrony can promote population growth in species with positive density dependence. Variation among life stages in the thermal thresholds for development can foster phenological synchrony under thermal regimes that include frequent occurrence of temperatures between developmental thresholds. The southern pine beetle is an insect with positive density dependence that has recently undergone important shifts in population abundance at the northern extremes of their distribution. We evaluated the hypothesis that cooler winter temperatures in their northern range cause a convergence of the population life stage structure that leads to synchrony in spring flight phenology. We used a combination of approaches. First, in situ laboratory experiments demonstrated a threshold temperature for pupation that was greater than was required for larval development; rearing larvae at lower temperatures increased the pooling of individuals at the end stage of larval development and synchrony in adult emergence. Second, a development rate model showed a similar convergence of the majority of the population at the end stage of larval development when brood experienced the cooler temperatures of the northern region, but not with temperatures from the southern region, or as a null model. Finally, field trapping of wild beetles showed greater synchrony in the pine forests of New Jersey than in the warmer, historically occupied forests of Georgia and Mississippi. Given these results, pine-dominated forests in the northern edge of the southern pine beetle’s range may experience more frequent occurrence of outbreaks, due to the positive feedbacks associated with a synchronous spring emergence of this insect.

Brain decoding with multivariate classification and regression has provided a powerful framework for characterizing information encoded in population neural activity. Classification and regression models are respectively used to predict discrete and continuous variables of interest. However, cognitive and behavioral parameters that we wish to decode are often ordinal variables whose values are discrete but ordered, such as subjective ratings. To date, there is no established method of predicting ordinal variables in brain decoding. In this study, we present a new algorithm, sparse ordinal logistic regression (SOLR), that combines ordinal logistic regression with Bayesian sparse weight estimation. We found that, in both simulation and analyses using real functional magnetic resonance imaging (fMRI) data, SOLR outperformed ordinal logistic regression with non-sparse regularization, indicating that sparseness leads to better decoding performance. SOLR also outperformed classification and linear regression models with the same type of sparseness, indicating the advantage of the modeling tailored to ordinal outputs. Our results suggest that SOLR provides a principled and effective method of decoding ordinal variables.

In this study, we are focused on Garcinia celebica as anti-HCV activity against JFH1 strain genotype 2a. The extraction process employed the use of maceration method. Starting from n-hexane solvent and another residue. The extracts were then analysed with various doses of 20, 10, 5, 2.5, and 1.25 μg/mL for anti-HCV against JFH1 strain genotype 2a and anticancer against Huh7it-1 cell line. The extracts exhibited anti-HCV on 1.25 μg/mL and no sign of toxicity to Huh7it-1 cells. The extracts also expressed anticancer activity on 20, 10, 5, and 2.5 μg/mL with a high level of toxicity to Huh7it-1 cells. The results from this study suggest that Garcinia celebica may be necessary as an add-on therapy candidate for treating HCV infections and HCC.

Stereopsis is a fundamental visual function that has been studied extensively. However, it is not clear why depth discrimination (stereoacuity) varies more significantly among people than other modalities. Previous studies have reported the involvement of both dorsal and ventral visual areas in stereopsis, implying that not only neural computations in cortical areas but also the anatomical properties of white matter tracts connecting those areas can impact stereopsis. Here, we studied how human stereoacuity relates to white matter properties by combining psychophysics, diffusion MRI (dMRI), and quantitative MRI (qMRI). We performed a psychophysical experiment to measure stereoacuity and, in the same participants, we analyzed the microstructural properties of visual white matter tracts on the basis of two independent measurements, dMRI (fractional anisotropy, FA) and qMRI (macromolecular tissue volume; MTV). Microstructural properties along the right vertical occipital fasciculus (VOF), a major tract connecting dorsal and ventral visual areas, were highly correlated with measures of stereoacuity. This result was consistent for both FA and MTV, suggesting that the behavioral–structural relationship reflects differences in neural tissue density, rather than differences in the morphological configuration of fibers. fMRI confirmed that binocular disparity stimuli activated the dorsal and ventral visual regions near VOF endpoints. No other occipital tracts explained the variance in stereoacuity. In addition, the VOF properties were not associated with differences in performance on a different psychophysical task (contrast detection). These series of experiments suggest that stereoscopic depth discrimination performance is, at least in part, constrained by dorso-ventral communication through the VOF.

Summary To clarify the contribution of osteoporosis to future immobilization, a prospective observational study was carried out on Japanese postmenopausal women. The prevalence of low bone mineral density (BMD) and vertebral fracture were independent risks for future immobilization. Introduction Immobilization by hip fracture requires more medical care and higher costs. Osteoporosis increases the risk of hip fracture, but there is little data linking osteoporosis and immobilization in postmenopausal Japanese women. Methods The study participants consisted of postmenopausal ambulatory volunteers. Baseline information such as BMD, prevalent fractures, comorbidities, pain in the body, and variables were obtained from 1993, and time course of occurrence of immobilization was observed until 2008. Results A total of 1,312 participants were enrolled and were observed for a total of 6.7 ± 4.1 years. A total of 75 subjects suffered immobilization. In multivariate analysis to calculate the Cox's hazard ratio of baseline parameters for immobilization, four independent variables were observed: age (hazard ratio, 1.52 [95% CI, 1.29 to 1.80], p = 0.000), pain in the body (2.54 [1.42 to 4.89, p = 0.001]), low BMD (1.83 [1.10 to 3.13, p = 0.020]), and dementia (3.58 [91.80 to 6.76, p = 0.001]). The hazard ratio of prevalent vertebral fracture was 1.98 (1.20 to 3.30, p = 0.007) instead of low BMD of above model. Conclusion These results indicate that low BMD and prevalent vertebral fracture pose an independent risk for future immobilization in postmenopausal Japanese women.

Objectives:Systemic juvenile idiopathic arthritis (sJIA) is a rheumatic disease in childhood characterised by systemic symptoms and a relatively poor prognosis. Peripheral leukocytes are thought to play a pathological role in sJIA although the exact cause of the disease is still obscure. In this study, we aimed to clarify cellular functional abnormalities in sJIA.Methods:We analysed the gene expression profile in peripheral leukocytes from 51 patients with sJIA, 6 patients with polyarticular type JIA (polyJIA) and 8 healthy children utilising DNA microarrays. Gene ontology analysis and network analysis were performed on the genes differentially expressed in sJIA to clarify the cellular functional abnormalities.Result:A total of 3491 genes were differentially expressed in patients with sJIA compared to healthy individuals. They were functionally categorised mainly into a defence response group and a metabolism group according to gene ontology, suggesting the possible abnormalities in these functions. In the defence response group, molecules predominantly constituting interferon (IFN)γ and tumour necrosis factor (TNF) network cascades were upregulated. In the metabolism group, oxidative phosphorylation-related genes were downregulated, suggesting a mitochondrial disorder. Expression of mitochondrial DNA-encoded genes including cytochrome c oxidase subunit 1(MT-CO1) and MT-CO2 were suppressed in patients with sJIA but not in patients with polyJIA or healthy children. However, nuclear DNA-encoded cytochrome c oxidases were intact.Conclusion:Our findings suggest that sJIA is not only an immunological disease but also a metabolic disease involving mitochondria disorder.

The underpinning of Chronic Venous Insufficiency (CVI) is valvular dysfunction, which manifests on a spectrum depending on the severity of insufficiency and duration of the disease. The mainstay of treatment relies on compression therapy of a proper type and intensity. In older adults, special consideration must be taken during the patient encounter to account for age-related factors. This review discusses the clinical presentation, diagnosis, and mimicking of CVI, focusing mainly on older adults. The epidemiology, risk factors, disease burden, and grave complications -- such as thrombosis and ulceration, are reviewed. The physiological impacts of CVI are described, providing the background for treatment strategies, including non-invasive, medical, and surgical therapies. The findings show advanced age to be an important risk factor contributing to CVI and that other age-related factors add to the risk of severe complications. Clinical assessments combined with objective measurements that assess localized skin water using tissue dielectric constant values or whole limb assessments may aid in the differential diagnosis. Furthermore, understanding the mechanism of action of compression therapy, the mainstay of CVI treatment, and its physiological impacts, allows for its informed use in geriatric patients with increased risks of potential compression-related side effects.

Background Tocilizumab (TCZ), a humanised anti-interleukin (IL)6 receptor antibody, was shown to be therapeutically effective in RA patients but the biological effect of TCZ on the immune response was not fully understood. DNA microarray can be amenable to exhaustively analyse the gene expression (GE) including immune response related genes. Objectives To investigate the effect of TCZ on the immune response related GE profiles and to elucidate the changes of immune response functions in RA patients before and after treatments. Methods Two-color microarray was performed by using whole blood samples here. The baseline GE profiles of the 112 RA patients in the Japanese phase III SATORI study (1), in which active RA patients were allocated to receive either TCZ 8mg/kg every 4 weeks (TCZ group: 54 patients) or MTX 8mg/week (MTX/control group: 58 patients) for 24 weeks, and 45 healthy individuals (HI) were obtained. The effect of treatments was investigated by directly comparing the samples before versus after the treatment. Each investigation was performed in duplicate with DNA labeling color reversal (dye swap). The average values of log2 (after/before) were used for further analysis. The genes with median expression levels of 1.2-fold changed after TCZ treatment were functionally categorized using Expression Analysis Systematic Explorer (EASE) version 2.0 bioinformatics software. Significant differences of GE levels between 112 RA at baseline and 45 HI, and between 54 TCZ and 58 MTX treated RA patients were defined by Mann-Whitney test. Results The expressions of 491 genes were identified to have 1.2-fold changed in TCZ group. EASE analysis revealed that these genes mainly related to protein biosynthesis (EASE Score =1.64E-41), ribosome biogenesis (4.23E-10), and response to biotic stimulus (4.19E-04). 44 genes out of the 45 genes categorized to response to biotic stimulus were included in defense response category, in which 36 genes also belonged to immune response category. Arachidonate 5-lipoxygenase-activating protein, defensin alpha (DEFA)3, DEFA4, complement component 8 gamma polypeptide, platelet factor 4 (chemokine (C-X-C motif) ligand 4), pro-platelet basic protein (chemokine (C-X-C motif) ligand 7), S100A9, S100A12, IL-1 receptor type II, peptidoglycan recognition protein 1, and C-type lectin domain family 4 member E in this category were found significantly overexpressed in RA patients before TCZ treatment when compared to HI. Most remaining other genes such as major histocompatibility complex (MHC) class II molecules (HLA-DPA1, HLA-DPB1, HLA-DPQA1, HLA-DPQB1, HLA-DRA, and HLA-DMA), killer cell lectin-like receptor subfamily members (KLRB1, KLRD1, KLRK1, and KLRF1), granulysin, immunoglobulin J, and chemokine (C-C motif) ligand 5 were found significantly underexpressed. All the GEs were normalised after TCZ treatment whereas these were unchanged in MTX group. Conclusions TCZ treatment normalised the expressions of immune response related genes in RA patients. The therapeutic effect of TCZ may be partly contributed by normalisation of these genes. References Nishimoto N, et al. Mod Rheumatol. 2009;19:12-9 Disclosure of Interest N. Nishimoto Grant/Research support from: Chugai Pharamaceutical Co. Ltd., Consultant for: Chugai Pharamaceutical Co. Ltd., Roche group, H.-M. Lee: None Declared, M. Murakami: None Declared, C. Aoki: None Declared, Y. Li: None Declared, T. Matsutani: None Declared

Background Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder characterized by systemic lymphadenopathy, constitutional inflammatory symptoms, and abnormal laboratories such as hyper-γ-globulinemia, increases in various auto-antibodies as well as acute phase proteins. While the symptoms are closely associated with dysregulated overproduction of interleukin (IL)-6, an increase in serum IgG4 and/or IgE levels in MCD patients is frequently observed. Blocking IL-6 with anti-IL-6 receptor antibody, tocilizumab (TCZ), ameliorates not only systemic inflammatory symptoms but also abnormal laboratories including hyper-γ-globulinemia. Objectives 1) To clarify differences in clinical features between MCD patients with high serum IgG4 and those with normal serum IgG4. 2) To analyze changes in serum IgG subclasses as well as IgE levels of MCD patients with TCZ treatment. Methods Serum levels of total IgG and four IgG subclasses as well as IgE of 18 MCD patients were measured. Eleven of 18 patients were treated with TCZ. Serum IgG subclass levels (n=11) and serum IgE levels (n=9) were compared before and after the treatment. Results Serum IgG4 levels at baseline were elevated in 12 of 18 MCD patients (542.2±387.7 mg/dl, n=12 vs. 45.2±39.8 mg/dl, n=6; the normal range is less than 105 mg/dl). Clinical features between MCD patients with high serum IgG4 and those with normal serum IgG4 were not distinct. Serum IgE levels at baseline were elevated in 12 of 16 MCD patients (3414.0±7198.2 IU/ml, n=12 vs. 95.8±66.4 IU/ml, n=4). All the 12 patients with high serum IgG4 showed elevated levels of IgE while only 2 out of 4 patients with normal IgG4 showed high IgE levels. IgG4 and IgE levels were significantly correlated. The mean absolute numbers of all IgG subclasses were significantly decreased after TCZ treatment. Furthermore, the mean ratio of IgG4 to total IgG was significantly decreased (7.4% vs. 5.5%, p<0.05, n=11), while those of the other subclasses did not change. The mean absolute number of IgE levels was also significantly decreased by TCZ treatment (1316.7 IU/ml vs. 481.0 IU/ml, p<0.05, n=9). Conclusions Decreases in the serum IgG4/IgG ratios and IgE levels after TCZ treatment suggests that IL-6 may be involved in the class switch to IgG4 and IgE. Disclosure of Interest M. Murakami: None Declared, T. Matsutani: None Declared, C. Aoki: None Declared, H.-M. Lee: None Declared, Y. Li: None Declared, N. Nishimoto Grant/Research support from: Chugai and Roche group, the product company of TCZ., Consultant for: Chugai and Roche group, the product company of TCZ.

Standard pulse oximeters estimate arterial blood saturation (SaO ) non-invasively by emitting and detecting light of a specific wavelength through a cutaneous vascular bed, such as a digit or the ear lobe. The quantity measured at these peripheral sites is designated as oxygen saturation (SpO ). Most reliable pulse oximeters are calibrated from measurements of healthy volunteers using some form of oxygen desaturation method. As the degree of inducible hypoxemia is limited, the calibration below achievable desaturation levels is usually extrapolated, leading to potential measurement error at low SaO values, especially in highly pigmented skin. Such skin color-related errors (SCRE) are the topic of this scoping review. Specifically, this study aimed to identify the combined impact of skin color and reduced SaO on the non-invasive assessment of SpO and report the consequences of potential inaccuracies. Three databases were searched (Cumulated Index to Nursing and Allied Health Literature (CINAHL), PubMed, and Web of Science) for peer-reviewed prospective and retrospective studies published in English between 2000 and 2022 involving human patients with hypoxemia that included a measure of skin color (Fitzpatrick scale or race/ethnicity). Ten studies met the criteria and were included in the final review. Eight of these studies reported statistically significant higher pulse oximeter readings in darker-skinned patients with hypoxia compared to their arterial blood gas measurements. Occult hypoxia was more prevalent in Black and Hispanic patients than in White patients. Minority patients overall (Black, Asian, and American Indian) were more likely to have a SaO < 88% that was not detected by pulse oximetry (occult hypoxemia) during hospitalization. With greater levels of hypoxemia, the differences between SpO and SaO were greater. If SaO was < 90%, then SpO was overestimated in all ethnicities but worse in minorities. In conclusion, the bias found in pulse oximeter readings in the skin of color broadly impacts patients with hypoxemia. The failure of SpO measuring devices to detect occult hypoxemia can delay the delivery of life-saving treatment to critically ill patients requiring respiratory rehabilitation and supplemental oxygen therapy. This may lead to adverse health outcomes, increased in-hospital mortality, and complications such as organ dysfunction. An improvement in pulse oximeter detection mechanisms that would include all skin pigmentations is therefore much desired to optimize individual healthcare status and minimize disparities in treatment.