Search

Aim To clarify the association between changes in the number of foundational medications for heart failure (FMHF) during hospitalization for worsening heart failure and post-discharge prognosis. Methods and results We retrospectively analyzed a combined dataset of three large-scale registries of hospitalized patients with heart failure in Japan (NARA-HF, WET-HF, and REALITY-AHF) and included patients already diagnosed with heart failure with reduced or mildly reduced left ventricular ejection fraction (HFr/mrEF) before admission. Patients were stratified by changes in the number of prescribed FMHF classes, namely angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta blockers, and mineralocorticoid receptor blockers, from admission to discharge. The primary endpoint was defined as the combined endpoint of heart failure rehospitalization and all-cause death within 1-year of discharge. The cohort consisted of 1,113 patients, and 482 combined endpoints were observed. In total, 413 (37.1%) patients were on increased FMHF (increased group), 607 (54.5%) remained unchanged (unchanged group), and 93 (8.4%) had a decreased number of FMHF (decreased group) at discharge compared to the time of admission. In multivariable analysis, the increased group was associated with a significantly lower incidence of the primary endpoint compared with the unchanged group (hazard ratio 0.56, 95% confidence interval 0.45–0.60; P Conclusion Increasing the number of FMHF cases during heart failure hospitalization is associated with a better prognosis in patients with HFr/mrEF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): REALITY registry was funded by the Cardiovascular Research Fund of Japan.WET-HF registry was supported by a Grant-in-Aid for Young Scientists (Y.S. JSPS KAKENHI, 18K15860).

The incidence and prognosis of Pacific Islanders with gastric cancer is not well documented as previous studies have often aggregated this population with Asians. The purpose of our study was to describe patient and tumor characteristics, as well as prognostic factors of Pacific Islanders with gastric cancer. Patients diagnosed with gastroesophageal junction or gastric adenocarcinoma between 2000 and 2014 were identified in the tumor registry of the largest hospital in Hawaii. Overall survival of Asians, Whites, and Pacific Islanders were calculated using the Kaplan-Meier method and log-rank test. Cox proportional hazards regression models were constructed to assess predictors of survival adjusting for clinical and pathological factors. A total of 615 patients were included in the final analysis. Pacific Islanders were found to present at a younger age, were more often uninsured or had Medicaid insurance, and were diagnosed with a higher stage of cancer compared to their Asian and White counterparts. Pacific Islanders were less likely to undergo surgery even after adjusting for stage. Race was a prognostic factor and survival was lowest among Pacific Islanders, but only if the model was unadjusted for treatment. We present an analysis of the largest cohort of Pacific Islander gastric cancer patients. Pacific Islanders have different sociodemographic characteristics and inferior survival compared to Asian patients and should be independently studied.

Coronavirus disease 2019 (COVID-19) is now an epidemic of global proportion, with major adverse impacts on older adults, persons with chronic diseases, and especially residents of long-term care facilities. This health catastrophe has challenged healthcare facilities' capacity to deliver care to not only COVID-19 patients but all patients who need hospital care. We report on a novel approach of utilizing long-term care beds at a Department of Veterans Affairs healthcare facility for managing recovering COVID-19 patients. J Am Geriatr Soc 68:2163-2166, 2020.

In infants with immunodeficiency, rotavirus (RV) vaccines can be continuously excreted in stool. We analysed nosocomial infection with RV vaccine strain in immunodeficient paediatric patients. RV1 RNAs were detected in stool and serum samples from case A, who was vaccinated with RV1, and case B, who was not. PAGE analysis of serial stool samples of case A revealed several rearrangements of the RV genome. In case B, the only band pattern detected was the same as a rearrangement detected in case A at the same time. In summary, RV vaccination of infants with immunodeficiency poses a risk of nosocomial infections.

Despite the current understanding of the pathophysiology of sepsis and advances in its treatment, the rate of sepsis is increasing globally. Sepsis is a common cause of hospitalization in older adults, and infections are among the most common diagnoses among residents transferred to the hospital from long-term care facilities (LTCFs). LTCFs and hospitals are facing financial and regulatory requirements to reduce potentially preventable emergency department visits, hospitalizations, and hospital readmissions due to infections and other causes. In addition, the human and financial costs of these events are substantial. Current criteria for early identification of sepsis have low sensitivity and specificity among LTCF residents. Early diagnosis must focus on changes in clinical, mental, and functional status, and vital signs including pulse oximetry. Laboratory data can increase the suspicion of sepsis, but the availability of testing and timing of results limits its usefulness in most LTCFs.While new diagnostic criteria for sepsis are being developed and validated in the LTCF setting, clinical practice and decision support tools are available to guide management. Most LTFCs do not have the capabilities to manage sepsis based on current guidelines despite availability of qualified nursing staff and clinicians. Thus excluding circumstances in which a resident's desire is palliative or hospice care without transfer to a hospital, most LTCFs will continue to transfer residents with severe infections at risk for evolving into sepsis to an acute hospital setting. J Am Geriatr Soc 67:2234-2239, 2019.

The incidence and prognosis of Pacific Islanders with gastric cancer is not well documented as previous studies have often aggregated this population with Asians. The purpose of our study was to describe patient and tumor characteristics, as well as prognostic factors of Pacific Islanders with gastric cancer.Patients diagnosed with gastroesophageal junction or gastric adenocarcinoma between 2000 and 2014 were identified in the tumor registry of the largest hospital in Hawaii. Overall survival of Asians, Whites, and Pacific Islanders were calculated using the Kaplan-Meier method and log-rank test. Cox proportional hazards regression models were constructed to assess predictors of survival adjusting for clinical and pathological factors.A total of 615 patients were included in the final analysis. Pacific Islanders were found to present at a younger age, were more often uninsured or had Medicaid insurance, and were diagnosed with a higher stage of cancer compared to their Asian and White counterparts. Pacific Islanders were less likely to undergo surgery even after adjusting for stage. Race was a prognostic factor and survival was lowest among Pacific Islanders, but only if the model was unadjusted for treatment.We present an analysis of the largest cohort of Pacific Islander gastric cancer patients. Pacific Islanders have different sociodemographic characteristics and inferior survival compared to Asian patients and should be independently studied.

The University of Tokyo Atacama Observatory Project is to construct a 6.5 m infrared-optimized telescope at the summit of Co. Chajnantor (5640 m altitude) in northern Chile. The telescope optics uses a Ritchey-Chretien type layout, with an under-sized secondary mirror to reduce stray light caused by thermal emission from the telescope structure. The primary mirror is a F/1.25 lightweight borosilicate glass (Ohara E6) mirror with honeycomb structure, which is developed by Steward Observatory Richard F. Caris Mirror Lab. The telescope has two Nasmyth foci and two folded-Cassegrain foci, which can be switched by rotating a tertiary mirror. The final focal ratio is 12.2 with a field of view of 25 arcmin in diameter. The telescope mount is a tripod-disk alt-azimuth mount. Both the azimuth and elevation axes are supported by and run on hydrostatic bearings, and they are driven by friction drives with servo motors, which are controlled by the telescope control system. It also controls the hexapod mount of the secondary mirror and the pneumatic actuators of the primary mirror support to keep good image quality during the observation. An off-axis Shack-Hartmann sensor installed in each focus measures the wavefront aberration of the telescope optics, then the misalignment between the secondary and primary mirrors is corrected by adjusting the hexapod mount while other aberrations are corrected by the deformation of the primary mirror. The force distribution of the actuators for correction will be calculated by fitting the wave-front errors with a series of bending modes of the primary mirror.

BackgroundIL-6 contributes significantly to the chronic inflammatory process of rheumatoid arthritis (RA) and is elevated in serum and synovial fluid of RA patients.Sarilumab (SRL), a human anti-human IL-6 receptor alpha monoclonal antibody that blocks the signaling originated by the IL-6/IL-6R complex like tocilizumab (TCZ),is an effective treatment. Recently, an association between the therapeutic effect of TCZ and neutropenia after TCZ initiation was reported[1]. Neutropenia is a common adverse event of SRL in patients with RA, but the relationship between reduced neutrophil count and clinical response to SRL is still inconclusive. In EULAR 2020, we reported the association between serum soluble gp130 levels before SRL treatment and the efficacy of SRL[2]. It is also unclear whether there is a relationship between IL-6 axis cytokines and SRL-induced neutropenia.ObjectivesThe purpose of this study was to determine whether neutropenia at 1 month by SRL predicts clinical remission within 3 months and whether there is an association between IL-6 axis cytokines levels and SRL-induced neutropenia.MethodsThis research is a retrospective study. We reviewed medical records of RA patients initiating SRL between February 2018 and August 2021 in our hospital. The Clinical Disease Activity Index (CDAI) was evaluated at baseline (before initiating SRL) and 3 months after administration. Clinical remission was defined when CDAI decreased ≤ 2.8. Of the 66 patients treated with SRL, 42 patients with 3 months follow-up, valid CDAI and serum available were enrolled. The ratio of neutrophil counts 1 month after initiating SRL to those at baseline (neutrophil ratio) was also calculated. Serum samples were tested for IL-6 (Human IL-6 Quantikine ELISA Kit, R&D systems), sIL-6R (Human soluble IL-6R alpha Quantikine ELISA Kit, R&D systems) and sgp130 (Human soluble gp130 Quantikine ELISA Kit, R&D systems) using specific ELISAs according to the manufacturer’s instructions. The statistical analyses were performed with EZR 1.55, and p values less than 0.05 were considered significant.ResultsThe median age of patients was 69.0 (IQR: 59.3 - 73.8) years and the median of disease duration was 9.0 (3.0 - 16.0) years. Eighteen (42.9%) patients were biologics and Jakinibs naive. The baseline CDAI was median 16.7 (11.5 - 25.8). When comparing CDAI-remission group (clinical remission: CR) and non-CR group, Patients in the CR group had significantly shorter disease duration, were more Biologic and JAKinib naive, and had greater neutropenia 1 month after starting SRL (0.71 vs 0.94, P=0.0252). There was no significant difference in the baseline serum levels of IL-6, sIL-6R between the CR and non-CR groups, but baseline serum sgp130 levels in the CR group tended to be higher than in the non-CR group (264.9 vs 234.2 ng/mL, P=0.0592). Univariate logistic regression analysis suggested Biologics and JAKinibs naive (odds ratio (OR) 6.68, p = 0.0317), baseline serum sgp130 levels (OR 8.608, P=0.0312) as predictors of CDAI remission treated with SRL at 3 months. Although not significant, neutrophil ratio ≤ 0.8 was associated with achieving remission (OR 6.67, P=0.0537). Univariate logistic regression for neutrophil ratio ≤ 0.8 did not show any relevant factors, including higher baseline serum sgp130 levels (OR 1.25, P=0.782).ConclusionA 20% or greater decrease in neutrophil count after 1 month of SRL treatment and a high baseline serum sgp130 level independently predict clinical remission within 3 months.References[1]Nakajima T, Watanabe R, Hashimoto M, Murata K, Murakami K, Tanaka M, et al. Neutrophil count reduction 1 month after initiating tocilizumab can predict clinical remission within 1 year in rheumatoid arthritis patients. Rheumatol Int. 2021;1rin[2]Yoshikawa T, Furukawa T, Tamura M, Hashimoto T, Morimoto M, Azuma N, et al. FRI0113 THE BASELINE SOLUBLE GP130 IS ASSOCIATED WITH THE RESPONSE OF RHEUMATOID ARTHRITIS PATIENTS TO SARILUMAB. Ann Rheum Dis. 2020;79(Suppl 1):637.1-637.Disclosure of InterestsNone declared

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the multiple joints.The elucidation of the pathogenesis of RA has progressed dramatically in recent decades, and among the many cytokines involved in the pathogenesis of RA, interleukin (IL)-6 and TNF-α are known to be the major pro-inflammatory cytokines that are abundant in the bloodstream and synovial tissue. JAK inhibitors (JAKinibs) such as tofacitinib and baricitinib are used in the treatment of RA by inhibiting JAK, which in turn inhibits the signaling of various cytokines including IL-6. However, predictors of the response to JAKinibs are still required.ObjectivesWe aimed to combine soluble TNF receptor (sTNFR) I, sTNFR II, IL-6, soluble IL-6R (sIL-6R) and soluble gp130 (sgp130) levels to identify groups of JAKinibs responses in RA patients.MethodsThis research is a retrospective study. We reviewed medical records of RA patients initiating JAKinibs between July 2013 and July 2021 in our hospital. The Simplified Disease Activity Index (SDAI) was evaluated at baseline and 3, 6 months after JAKinibs administration. Clinical remission was defined when SDAI decreased ≤ 3.3. Of the 125 patients treated with JAKinibs, 89 patients with 6 months follow-up, valid SDAI and serum available were enrolled. Serum samples were tested for IL-6 (Human IL-6 Quantikine ELISA Kit, R&D systems), sIL-6R (Human soluble IL-6R alpha Quantikine ELISA Kit, R&D systems) and sgp130 (Human soluble gp130 Quantikine ELISA Kit, R&D systems), sTNFR I (Human TNF RI/TNFRSF1A Quantikine ELISA Kit DRT100) and sTNFR II (Human sTNF RII/TNFRSF1B Quantikine ELISA Kit DRT200) using specific ELISAs according to the manufacturer’s instructions. The statistical analyses were performed with EZR 1.55, and p values less than 0.05 were considered significant.ResultsThe median age of patients was 62 (IQR: 51 - 72) years and the median of disease duration was 6.0 (2.0 - 16.0) years. Twenty-seven (30.3%) patients were biologics and Jakinibs naive. The baseline SDAI was median 18.9 (12.7 - 27.9). When comparing SDAI-remission group (clinical remission: CR) and non-remission group, there were no significant differences in any of the baseline clinical parameters. There was no significant difference in the serum levels of IL-6, sIL-6R and sgp130 between the CR and non-CR groups, but the serum levels of sTNFR I and sTNFR II in the CR group were significantly lower than non-CR group. Univariate logistic regression analysis suggested Biologics and JAKinibs naive (odds ratio (OR) 3.58, p = 0.015), baseline Log sTNFR II levels (OR 0.013, P=0.034) as predictors of SDAI remission treated with JAKinibs at 6 months. Although not significant, Stage IV (OR 0.211, P=0.082) and baseline Log sTNFR I serum levels (OR 0.013, P=0.065) were associated with clinical remission.ConclusionRA patients could be easily stratified prior to JAKinibs intervention with serum sTNFR II and sTNFR I levels, not but IL-6 axis cytokines (IL-6, sIL-6R and sgp130).Univariate logistic regression analysis for clinical remission in patients treated with JAKinibs. Odds Ratio[95% C.I.]P ValueAge, year0.973[0.942 - 1.010]0.104Female (%)0.820[0.231 - 2.910]0.759BMI0.968[0.847 - 1.110]0.627Duration, year0.952[0.897 - 1.010]0.110StageIreferrenceII0.857[0.218 - 3.370]0.825III0.444[0.072 - 2.740]0.382IV0.211[0.036 - 1.220]0.082Biologic/JAKi naïve3.580[1.280 - 9.950]0.015JAKi Drug-Baricitinibreferrence-Tofacitinib1.780[0.659 - 4.800]0.256MTX use1.640[0.532 - 5.30]0.390PSL use0.476[0.176 - 1.290]0.143SASP use0.783[0.268 - 2.290]0.654IGU use0.328[0.039 - 2.750]0.304BUC use0.436[0.051 - 3.760]0.450TAC use0.233[0.029 - 1.910]0.1750W IL-6, pg/mL0.991[0.977 - 1.000]0.1980W sIL-6R, ng/mL0.983[0.947 - 1.02]0.3690W sgp130, ng/mL0.998[0.994 - 1.000]0.4440W sTNFR II/I ratio0.808[0.222 - 2.940]0.7460W Log sTNFR II, pg/mL0.002[0.0000653 - 0.634]0.0340W Log sTNFR I, pg/mL0.013[0.000126 - 1.300]0.065Disclosure of InterestsNone declared

Two European phase III trials comparing D1 and D2 demonstrated that D2 did not improve the overall survival and was associated with a high mortality related to splenectomy. However, a long-term follow-up study showed that the gastric cancer-related death rate was significantly higher in D1 than D2. Based on these findings, the standard surgery in Europe became D2 without pancreatico-splenectomy to prevent mortality. In contrast, the JCOG9501 phase III comparing D2 and D2 plus para-aortic nodal dissection did not showed a survival efficacy of extended lymphadenectomy, but the mortality rate was quite low in both surgeries. Subsequently, the JCOG0110 phase III study comparing D2 and spleen-preserving D2 for upper gastric cancer not invading the greater curvature clearly showed the non-inferiority of spleen preservation. Thus, spleen-preserving D2 was made the standard surgery for these tumors in Japan. However, splenectomy is often selected for complete dissection of the splenic-hilar nodes, a frequent metastatic site for upper gastric tumors invading the greater curvature. Recently, an approach involving splenic hilar nodal dissection without splenectomy has been developed.

This study evaluated the effect of C-factor on the bond strength of a resin composite to floor and wall dentin using various adhesive systems.Four dentin substrates (flat wall, flat floor, cavity wall, or cavity floor) were prepared on human molars. Each specimen was restored with one of three adhesives; Clearfil SE Bond, Single Bond, or Clearfil tri-S Bond followed by buildup or filling using Z100 resin composite. The specimen was cut perpendicular to the bonded surface parallel to the floor or wall to obtain beams after light curing at 24,000 mJ/cmAll adhesive systems exhibited the highest bond strength to flat wall group (p0.05). The bond strength to the cavity group was significantly lower than that to the respective flat group regardless of the bonding system (p0.05). There was no significant difference in bond strength with Clearfil SE Bond and Clearfil tri-S Bond between the cavity wall and cavity floor (p0.05).The findings suggested that the strength of bonding to the cavity floor and cavity wall was affected by C-factor regardless of the adhesive system. Bonding to flat wall was higher than flat floor regardless of the adhesive system. Self-etching system provided uniform bond to the cavity wall and cavity floor dentin. However, total etching system reduced bond to the cavity floor than to the cavity wall.

Author(s): Winnett, Alexander; Jatt, Lauren P; Sohn, Linda; Lysaght, Marcia; Yoshikawa, Thomas; Simon, Steven R; Graber, Christopher J; Goetz, Matthew Bidwell

Inappropriate antibiotic use is common in older adults (aged >65 y), and they are particularly vulnerable to serious antibiotic-associated adverse effects such as cardiac arrhythmias, delirium, aortic dissection, drug-drug interactions, and Clostridioides difficile. Antibiotic prescribing improvement efforts in older adults have been primarily focused on inpatient and long-term care settings. However, the ambulatory care setting is where the vast majority of antibiotic prescribing to older adults occurs. To help improve the clinical care of older adults, we review drivers of antibiotic prescribing in this population, explore systems aspects of ambulatory care that can create barriers to optimal antibiotic use, discuss existing stewardship interventions, and provide guidance on priority areas for future inquiry. J Am Geriatr Soc 68:244-249, 2020.

The reinstatement of the Journal of the American Geriatrics Society Section on Ethnogeriatrics coincides with more rapid growth in older populations that are classified as ethnic and racial minorities in the United States than those classified as non-Hispanic white. By 2060, 40% of older Americans are predicted to belong to a minority. Important needs for ethnogeriatric research and publication include: making sure research populations are meaningful and precise rather than using categories that include many unrelated groups; and increasing research among smaller ethnic populations of older adults. Topics in need of attention include epidemiology of common geriatric illness among the smaller populations, and social determinants for those in which disparities have been established; the extent and effectiveness of use of Culturally and Linguistically Appropriate Services Standards in geriatric care; examination of communication strategies used in provider/patient interaction, especially use of interpreters; ethnic differences in treatment of older patients; and models of use of community health workers from older patients' own cultural communities. Stresses related to caregiving in cultures emphasizing the importance of family care are important to understand acceptable models of long-term care for diverse families. The new Ethnogeriatric Section opens the opportunity for geriatric researchers, especially those from diverse backgrounds, to explore important issues in cross-cultural geriatric care; their findings can then form the basis of expanded ethnogeriatric curriculum for training future providers for the growing population of diverse older Americans.

Compared with female mate choice, male mate choice has been an important but minor topic in the past two decades. In the guppy, Poecilia reticulata, a male approaching a female abandons his courtship when a rival male appears next to the focal female; however, the effect of the relative quality of the males on this behavioural change is unknown. We show here that male guppies abandon their approach to a female only when the rival male is phenotypically superior. Both natural and artificially induced brightly coloured males continued to approach a female even when the rival male was brightly coloured, but both natural and induced dull-coloured males abandoned their approach to a female when the rival was brightly coloured. Males decided their behaviours on the basis of their own appearance, not on their genotypes, because artificially induced brightly and dull- coloured brothers differed in their behaviour. Our results show that male mate choice behaviour is finely tuned to maximize the probability of acceptance by the approached female. (C) 2016 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Norovirus infection usually results in acute gastroenteritis, often with incapacitating nausea, vomiting, and diarrhea. It is highly contagious and resistant to eradication with alcohol-based hand sanitizer. Appropriate preventative and infection control measures can mitigate the morbidity and mortality associated with norovirus infection. Clostridium difficile infection is the leading cause of health care-associated diarrhea in the United States. Antibiotic use is by far the most common risk factor for C difficile colonization and infection. Appropriate preventive measures and judicious use of antibiotics can help mitigate the morbidity and mortality associated with C difficile infection.

Noroviruses have emerged as one of the leading causes of viral gastroenteritis worldwide, affecting community-dwelling and institutionalized older adults. Recent global epidemics present a growing challenge to the healthcare system and to long-term care facilities. Noroviruses spread readily and rapidly through multiple routes (e.g., person-to-person contact, contact with contaminated surfaces, airborne dissemination of vomitus) and thus are able to sustain an epidemic efficiently and successfully. Although norovirus gastroenteritis is a short self-limited illness in healthy immunocompetent individuals, it can result in significant morbidity and mortality in vulnerable compromised persons such as frail elderly persons and older residents of nursing homes. Diagnosis is made by clinical assessment and confirmed primarily by stool evaluation using polymerase chain reaction. Treatment is confined to supportive measures. Public health prevention and control strategies provide guidance regarding surveillance and the necessary steps to curb the clinical effect and spread of norovirus infections in various settings, including long-term care.

Introduction Multiple chemical sensitivity (MCS), often called idiopathic environmental intolerance, is a chronic acquired disorder characterised by nonspecific symptoms attributed to exposure to common odorous chemicals. We previously reported significant activations in the prefrontal cortex (PFC) during olfactory stimulation using several different odorants in patients with MCS compared with controls. Previous clinical observations demonstrated differences in oxygen partial pressure in peripheral venous blood between patients with MCS and controls. Our objective is to investigate peripheral blood oxygen levels during olfactory stimulation to characterise patients with MCS. Methods We investigated changes in the prefrontal area using near-infrared spectroscopic (NIRS) imaging and those in peripheral arterial blood oxygen saturation (SpO2) using a pulse oximeter during olfactory stimulation with odorants (γ-undecalactone) at three concentrations (zero, odour recognition threshold, and normal perceived odour level) in 11 patients with MCS and 10 controls. We also examined their oxygen partial pressures in peripheral venous blood at normal condition before the test. Results We observed significant activations in the PFC during olfactory stimulation in patients with MCS. The SpO2 in peripheral arterial blood in patients with MCS remained higher than that in controls during olfactory stimulation tests. The SpO2 remarkably decreased in patients with MCS compared with that in controls during olfactory stimulus at normal perceived odour level and the recovery of the SpO2 after the stimulus was delayed in these patients. No significant differences in oxygen partial pressures of peripheral venous blood were observed. Conclusion Patients with MCS exhibited stronger brain responses to odours at normally perceived levels. Changes in SpO2 in the peripheral arterial blood suggest that MCS might result in poor oxygen supply to the peripheral tissues or inadequately control the oxygen supply.

Background Oesophageal (OeC) and gastric (GC) cancer patients are treated with similar multimodal therapy and have poor survival. There remains an urgent clinical need to identify biomarkers to individualise patient management and improve outcomes. Therapy with immune checkpoint inhibitors has shown promising results in other cancers. Proposed biomarkers to predict potential response to immune checkpoint inhibitors include DNA mismatch repair (MMR) and/or Epstein–Barr virus (EBV) status. The aim of this study was to establish and compare EBV status and MMR status in large multi-centre series of OeC and GC. Methods EBV was assessed by EBV-encoded RNA (EBER) in situ hybridisation and MMR protein expression by immunohistochemistry (IHC) in 988 OeC and 1213 GC from multiple centres. In a subset of OeC, microsatellite instability (MSI) was tested in parallel with MMR IHC. Results Frequency of MMR deficiency (MMRdef) and MSI was low in OeC (0.8% and 0.6%, respectively) compared with GC (10.3%). None of the OeCs were EBER positive in contrast to 4.8% EBER positive GC. EBV positive GC patients were younger (p = 0.01), more often male (p = 0.001) and had a better overall survival (p = 0.012). MMRdef GC patients were older (p = 0.001) and showed more often intestinal-type histology (p = 0.022). Conclusions This is the largest study to date indicating that EBV and MMRdef do not play a role in OeC carcinogenesis in contrast to GC. The potential clinical usefulness of determining MMRdef/EBV status to screen patients for eligibility for immune-targeting therapy differs between OeC and GC patients., Highlights • In oesophageal cancer (OeC) the frequency of mismatch repair deficiency/microsatellite instability (MSI) was extremely low. • Epstein-Barr Virus infection does not play a role in OeC carcinogenesis. • Determination of EBV/MSI status for immunotherapy eligibility cannot be recommended for OeC patients. • Future trials involving immunotherapy require disease specific design and selection criteria.

International audience; Background: Dumping syndrome is a prevalent complication of oesophageal and gastric surgery characterised by early (postprandial tachycardia) and late (hypoglycaemia) postprandial symptoms. Aim: To evaluate efficacy and safety of the somatostatin analogue, pasireotide in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery. Methods: A single-arm, open-label, multicentre, intrapatient dose-escalation, phase 2 study with 4 phases: screening, 3-month SC (subcutaneous), 3-month IM (intramuscular) and 6-month optional extension IM phase. Primary endpoint was the proportion of patients without hypoglycaemia (plasma glucose \textless3.3 mmol/L [60 mg/dL] during an oral glucose tolerance test, OGTT) at the end of 3-month SC phase. A \textgreater= 50% response rate was considered clinically relevant. Results: Forty-three patients with late dumping were enrolled; 33 completed the 3-month SC phase and 23 completed the 12-month study. The proportion of patients without hypoglycaemia at month 3 (primary endpoint) was 60.5% (26 of 43; 95% confidence interval, 44.4%-75.0%). Improvement in quality of life was observed during SC phase, which was maintained in the IM phase. The proportion of patients with a rise in pulse rate of \textgreater= 10 beats/min during OGTT reduced from baseline (60.5%) to month 3 (18.6%) and month 12 (27.3%). Overall (month 0-12), the most frequent (\textgreater20% of patients) adverse events were headache (34.9%); diarrhoea, hypoglycaemia (27.9% each); fatigue, nausea (23.3% each); and abdominal pain (20.9%). Conclusion: These results suggest that pasireotide is a promising option in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery.

High levels (μM) of beta amyloid (Aβ) oligomers are known to trigger neurotoxic effects, leading to synaptic impairment, behavioral deficits, and apoptotic cell death. The hydrophobic C-terminal domain of Aβ, together with sequences critical for oligomer formation, is essential for this neurotoxicity. However, Aβ at low levels (pM-nM) has been shown to function as a positive neuromodulator and this activity resides in the hydrophilic N-terminal domain of Aβ. An N-terminal Aβ fragment (1-15/16), found in cerebrospinal fluid, was also shown to be a highly active neuromodulator and to reverse Aβ-induced impairments of long-term potentiation. Here, we show the impact of this N-terminal Aβ fragment and a shorter hexapeptide core sequence in the Aβ fragment (Aβcore: 10-15) to protect or reverse Aβ-induced neuronal toxicity, fear memory deficits and apoptotic death. The neuroprotective effects of the N-terminal Aβ fragment and Aβcore on Aβ-induced changes in mitochondrial function, oxidative stress, and apoptotic neuronal death were demonstrated via mitochondrial membrane potential, live reactive oxygen species, DNA fragmentation and cell survival assays using a model neuroblastoma cell line (differentiated NG108-15) and mouse hippocampal neuron cultures. The protective action of the N-terminal Aβ fragment and Aβcore against spatial memory processing deficits in amyloid precursor protein/PSEN1 (5XFAD) mice was demonstrated in contextual fear conditioning. Stabilized derivatives of the N-terminal Aβcore were also shown to be fully protective against Aβ-triggered oxidative stress. Together, these findings indicate an endogenous neuroprotective role for the N-terminal Aβ fragment, while active stabilized N-terminal Aβcore derivatives offer the potential for therapeutic application.

We demonstrate the generation of alternating spin current (SC) via spin-rotation coupling (SRC) using a surface acoustic wave (SAW) in a Cu film. Ferromagnetic resonance caused by injecting SAWs was observed in a Ni-Fe film attached to a Cu film, with the resonance further found to be suppressed through the insertion of a SiO_{2} film into the interface. The intensity of the resonance depended on the angle between the wave vector of the SAW and the magnetization of the Ni-Fe film. This angular dependence is explicable in terms of the presence of spin transfer torque from a SC generated via SRC.

Background Plaintiffs of the gefitinib (Iressa) lawsuits in Japan started in 2004 were defeated in the Supreme Court in 2013. The Court judged it was not possible to foresee the outbreak of deaths caused by interstitial pneumonia due to gefitinib from death cases before approval of this drug. Objective We attempted to verify validity of this judgment. Methods We estimated the 95% confidence interval (CI) of the proportion of onset and death cases among 23 onset and 13 death cases occurring from "within 1 week" to "within 4 weeks" from clinical data before approval of this drug using data admitted to the Court. Results For death cases, all of the upper limits of the 95% CI exceeded 50% within 1-4 weeks. This fact suggested that the cases of acute interstitial pneumonia were included in the clinical trial before the approval of gefitinib. Conclusion It was possible to foresee the outbreak of death cases after drug approval. This conclusion showed the Court's ruling was not reasonable and was unscientific.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tickborne virus in the Bunyaviridae family. This virus has recently been found in China, Japan and Korea. The risk of transfusion-transmitted SFTSV infection (TTI-SFTSV) is a concern because person-to-person transmission resulting from contact with SFTSV-contaminated blood has been reported. Therefore, we investigated the efficacy of the Mirasol pathogen reduction technology (PRT) system for inactivating SFTSV in vitro. The Mirasol PRT system achieved a > 4.11 log10 reduction value (LRV) for SFTSV. In conclusion, we showed that the Mirasol PRT system could potentially be used to reduce the risk of TTI-SFTSV.

Home energy management system (HEMS) is expected as one of the promising technologies to satisfy the demand. We are developing HEMS assisted by a sensor network having an efficient wireless power supply in order to be spreading around the people. Then we have studied the resonant-type wireless power transmission applying for HEMS because the transmitting power is comparatively high in the middle range by using resonant way. In our study, we have derived the formula of transmitting power efficiency in the system of including exciting coil and resonant coil. And the transmitting characteristic using single loop coil is measured. The calculated value with derived equation and measured value are in good agreement. Also we have tried to calculate using electromagnetic numerical method. After showing the validation of both calculation methods, we have examined the way of coil arrangement that transmitting distance is more than 1 m under the condition of human body safety protection guideline from electromagnetic wave. Finally we have arrived at the design of using the pair resonant coils which are very large coil for transmitting and the small coil for receiving. Then we have calculated the transmitting characteristic using electromagnetic numerical method and concluded this design is very useful for HEMS.