Detection of current-sheet and bipolar ion flows in a self-generated antiparallel magnetic field of laser-produced plasmas for magnetic reconnection research.

Magnetic reconnection in laser-produced magnetized plasma is investigated by using optical diagnostics. The magnetic field is generated via the Biermann battery effect, and the inversely directed magnetic field lines interact with each other. It is shown by self-emission measurement that two colliding plasmas stagnate on a midplane, forming two planar dense regions, and that they interact later in time. Laser Thomson scattering spectra are distorted in the direction of the self-generated magnetic field, indicating asymmetric ion velocity distribution and plasma acceleration. In addition, the spectra perpendicular to the magnetic field show different peak intensity, suggesting an electron current formation. These results are interpreted as magnetic field dissipation, reconnection, and outflow acceleration. Two-directional laser Thomson scattering is, as discussed here, a powerful tool for the investigation of microphysics in the reconnection region.

Sarcopenic Dysphagia with Low Tongue Pressure Is Associated with Worsening of Swallowing, Nutritional Status, and Activities of Daily Living.

OBJECTIVES: According to the recently proposed diagnostic criteria for sarcopenic dysphagia, sarcopenic dysphagia can be classified as probable or possible based on tongue pressure. However, it is unclear whether patients with probable and possible sarcopenic dysphagia have different characteristics. Therefore, this study aimed to investigate whether patients with possible and probable sarcopenic dysphagia have different clinical characteristics. DESIGN: A cross-sectional study. SETTING: A rehabilitation hospital. PARTICIPANTS: In total, 129 patients aged ≥65 years with sarcopenic dysphagia were included. METHODS: A tongue pressure of <20 kPa was indicative of probable sarcopenic dysphagia, and a tongue pressure of ≥20 kPa was indicative of possible sarcopenic dysphagia. Kuchi-Kara Taberu (KT) index scores were compared between the probable or possible sarcopenic dysphagia groups. RESULTS: According to the tongue pressure, 76 and 53 patients were classified into the probable and possible sarcopenic dysphagia groups, respectively. In multiple linear regression analysis, the presence of probable sarcopenic dysphagia was independently associated with the total KT index score (standardized coefficient: -0.313, regression coefficient: -4.500, 95% confidence interval [CI], -6.920 to -2.080, P < 0.001). The presence of probable sarcopenic dysphagia was independently associated with some subitems of the KT index (willingness to eat, cognitive function while eating, oral preparatory and propulsive phase, severity of pharyngeal dysphagia, eating behavior, and daily living activities). CONCLUSIONS: Patients with probable sarcopenic dysphagia were characterized by poor overall eating-related conditions, especially poor swallowing ability, ability to perform activities of daily living, and nutritional status.

SARC-F Predicts Mortality Risk of Older Adults during Hospitalization.

OBJECTIVES: To determine the association between SARC-F scores and the in-hospital mortality risk among older patients admitted to acute care hospitals. DESIGN: Single-center retrospective study. SETTING: A university hospital. PARTICIPANTS: All consecutive patients aged older than 65 were admitted and discharged from the study hospital between July 2019 and September 2019. MEASUREMENTS: Relevant patient data included age, sex, body mass index, nutritional status, fat-free mass, disease, activities of daily living (ADL), duration of hospital stay, SARC-F, and occurrence of death within 30 days of hospitalization. The diseases that caused hospitalization and comorbidities (Charlson Comorbidity Index; CCI) were obtained from medical records. The Eastern Cooperative Oncology Group-performance status (PS) was used to determine ADL, and the in-hospital mortality rate within 30 days of hospitalization as the outcome. RESULTS: We analyzed 2,424 patients. The mean age was 75.9±6.9 and 55.5% were male. Fifty-three in-hospital mortalities occurred among the participants within the first 30 days of hospitalization. Patients who died in-hospital were older, had poorer nutritional status and severer PS scores, and more comorbidities than those who did not. A SARC-F score of ≥4 predicted a higher mortality risk within those 30 days with the following precision: sensitivity 0.792 and specificity 0.805. There were significantly more deaths in Kaplan-Meier curves regarding a score of SARC-F≥4 than a score of SARC-F<4 (p<0.001). Cox proportional hazard analysis was used to identify the clinical indicators most associated with in-hospital mortality. SARC-F≥4 (Hazard Ratio: HR 5.65, p<0.001), CCI scores (HR1.11, p=0.004), and infectious and parasitic diseases (HR3.13, p=0.031) were associated with in-hospital mortality. The SARC-F items with significant in-hospital mortality effects were assistance with walking (HR 2.55, p<0.001) and climbing stairs (HR 2.46, p=0.002). CONCLUSION: The SARC-F questionnaire is a useful prognostic indicator for older adults because a SARC-F ≥4 score during admission to an acute care hospital predicts in-hospital mortality within 30 days of hospitalization.

The influence of mechanical Circulatory support on post-transplant outcomes in pediatric patients: A multicenter study from the International Society for Heart and Lung Transplantation (ISHLT) Registry.

BACKGROUND: Mechanical circulatory support (MCS) is increasingly being used as a bridge to transplant in pediatric patients. We compare outcomes in pediatric patients bridged to transplant with MCS from an international cohort. METHODS: This retrospective cohort study of heart-transplant patients reported to the International Society for Heart and Lung Transplantation (ISHLT) registry from 2005-2017 includes 5,095 patients <18 years. Pretransplant MCS exposure and anatomic diagnosis were derived. Outcomes included mortality, renal failure, and stroke. RESULTS: 26% of patients received MCS prior to transplant: 240 (4.7%) on extracorporeal membrane oxygenation (ECMO), 1,030 (20.2%) on ventricular assist device (VAD), and 54 (1%) both. 29% of patients were <1 year, and 43.8% had congenital heart disease (CHD). After adjusting for clinical characteristics, compared to no-MCS and VAD, ECMO had higher mortality during their transplant hospitalization [OR 3.97 & 2.55; 95% CI 2.43-6.49 & 1.42-4.60] while VAD mortality was similar [OR 1.55; CI 0.99-2.45]. Outcomes of ECMO+VAD were similar to ECMO alone, including increased mortality during transplant hospitalization compared to no-MCS [OR 4.74; CI 1.81-12.36]. Patients with CHD on ECMO had increased 1 year, and 10 year mortality [HR 2.36; CI 1.65-3.39], [HR 1.82; CI 1.33-2.49]; there was no difference in survival in dilated cardiomyopathy (DCM) patients based on pretransplant MCS status. CONCLUSION: Survival in CHD and DCM is similar in patients with no MCS or VAD prior to transplant, while pretransplant ECMO use is strongly associated with mortality after transplant particularly in children with CHD. In children with DCM, long term survival was equivalent regardless of MCS status.

Respiratory Sarcopenia and Sarcopenic Respiratory Disability: Concepts, Diagnosis, and Treatment.

The condition of muscle fiber atrophy and weakness that occurs in respiratory muscles along with systemic skeletal muscle with age is known as respiratory sarcopenia. The Japanese Working Group of Respiratory Sarcopenia of the Japanese Association of Rehabilitation Nutrition narratively reviews these areas, and proposes the concept and diagnostic criteria. We have defined respiratory sarcopenia as "whole-body sarcopenia and low respiratory muscle mass followed by low respiratory muscle strength and/or low respiratory function." Respiratory sarcopenia can be caused by various factors such as aging, decreased activity, undernutrition, disease, cachexia, and iatrogenic causes. We have also created an algorithm for diagnosing respiratory sarcopenia. Respiratory function decreases with age in healthy older people, along with low respiratory muscle mass and strength. We have created a new term, "Presbypnea," meaning a decline in respiratory function with aging. Minor functional respiratory disability due to aging, such as that indicated by a modified Medical Research Council level 1 (troubled by shortness of breath when hurrying or walking straight up hill), is an indicator of presbypnea. We also define sarcopenic respiratory disability as "a disability with deteriorated respiratory function that results from respiratory sarcopenia." Sarcopenic respiratory disability is diagnosed if respiratory sarcopenia is present with functional disability. Cases of respiratory sarcopenia without functional disability are diagnosed as "at risk of sarcopenic respiratory disability." Functional disability is defined as a modified Medical Research Council grade of 2 or more. Rehabilitation nutrition, treatment that combines rehabilitation and nutritional management, may be adequate to prevent and treat respiratory sarcopenia and sarcopenic respiratory disability.

The SARC-F Score on Admission Predicts Falls during Hospitalization in Older Adults.

OBJECTIVES: Community-dwelling older adults with sarcopenia are likely to fall. However, few studies have investigated whether sarcopenia is associated with falls during hospitalization in older adults. The purpose of this study was to determine whether the SARC-F when used as a simple screening tool for sarcopenia at the time of admission, predicts in-hospital falls. DESIGN: A retrospective, observational study. SETTING: A 900-bed university hospital. PARTICIPANTS: A total of 9,927 patients aged 65 years and older were hospitalized at the hospital between April 2019 and March 2020. MEASUREMENTS: The SARC-F contains five items: strength, assistance in walking, rise from a chair, climb stairs, and falls were evaluated at hospital admission. To investigate the relationship between the SARC-F score and falls, a ROC curve analysis was performed. Multivariate analysis adjusted for fall-related confounding factors such as age, gender, ADL, and disease were performed. RESULTS: Mean age: 75.9±6.7 years; male: 56.2% were analyzed, and 159 patients (1.6%) fell during hospitalization. SARC-F scores at admission were significantly higher in the fall group than in the control group (3 [1-6] points vs. 0 [¬0-2] point, p<0.001). Statistical association was observed between the SARC-F and in-hospital fall (area under the curve = 0.721 [0.678-0.764], p < 0.001). The cut-off value for the highest sensitivity and specificity of the SARC-F score for in-hospital falls was two (sensitivity = 0.679, specificity = 0.715). Among the subitem of the SARC-F, the hazard ratios for climbing stairs were significantly higher (HR = 1.52 [1.10-2.09], p = 0.011) and for a history of fall was significantly higher (HR = 1.41 [1.02-1.95], p = 0.036). A SARC-F score ≥ 2 had a significantly higher incidence of in-hospital falls compared to a SARC-F score <2 (3.7% vs. 0.7%, p < 0.001). Also, a SARC-F score ≥ 2 had a significantly higher hazard ratio for falls (2.11 [1.37-3.26], p < 0.001). CONCLUSION: SARC-F can help predict falls among hospitalized older adults.

SARC-F as a Screening Tool for Sarcopenia and Possible Sarcopenia Proposed by AWGS 2019 in Hospitalized Older Adults.

OBJECT: The SARC-F questionnaire is a sarcopenia screening tool. However, the validity of the SARC-F score ≥4 (SARC-F≥4) for the evaluation of sarcopenia in the hospital setting has not been investigated. This study investigated the validity of SARC-F≥4 as a screening tool for sarcopenia among hospitalized older adults. DESIGN: Cross-sectional retrospective study. SETTING: A university hospital. PARTICIPANTS: This study included older adult patients (age ≥65 years) who were hospitalized at, and subsequently discharged from, the hospital between April and September 2019 and underwent a nutritional assessment by the nutrition support team during their hospitalization. MEASUREMENTS: SARC-F was recorded at the time of admission, and the criteria specified by the Asia Working Group for Sarcopenia in 2019 (AWGS 2019) were applied to diagnose sarcopenia and possible sarcopenia. Appendicular muscle mass was estimated through validated equations, and three different models were developed for sarcopenia diagnosis. The sensitivity, specificity, and positive/negative likelihood ratios were calculated to analyze the accuracy of the SARC-F≥4 for sarcopenia and possible sarcopenia. Receiver-operating characteristic analyses were conducted to calculate the area under the curve (AUC). RESULTS: In total, 1,689 patients (mean age: 77.2±7.3 years; male: 54.4%) were analyzed, and 636 patients (37.7%) had SARC-F≥4. Patients with SARC-F≥4 had a statistically significant higher prevalence of AWGS 2019-defined sarcopenia than patients with SARC-F <4 in the models (65.4-78.9% vs 40.9-45.2%, p<0.001). The sensitivity, specificity, and positive/negative likelihood ratios of SARC-F≥4 for sarcopenia and possible sarcopenia were 49.1-51.3%, 73.9-81.2%, and 1.88-2.72/0.60-0.69 and 48.0%, 84.5%, and 3.11/0.62, respectively. The AUC for sarcopenia and possible sarcopenia were 0.644-0.695 and 0.708, respectively. The AUC of SARC-F for possible sarcopenia was equivalent to or larger than that for sarcopenia (DeLong test p=0.438, 0.088, and <0.001 vs the three models). CONCLUSIONS: SARC-F≥4 is suitable as a screening tool for sarcopenia in hospitalized older adults. SARC-F assessment could facilitate the detection and exclusion of sarcopenia at hospitalization and may lead to early adoption of a therapeutic and preventive approach.

Enhancing the thermoelectric power factor of nanostructured ZnCo2O4 by Bi substitution.

Bi x ZnCo2-x O4 (0 ≤ x ≤ 0.2) nanoparticles with different x values have been prepared by the sol-gel method; the structural, morphological, thermal and thermoelectric properties of the prepared nanomaterials are investigated. XRD analysis confirms that Bi is completely dissolved in the ZnCo2O4 lattice till the x values of ≤0.1 and the secondary phase of Bi2O3 is formed at higher x value (x > 0.1). The synthesized nanomaterials are densified and the thermoelectric properties are studied as a function of temperature. The electrical resistivity of the Bi x ZnCo2-x O4 decreased with x value and it fell to 4 × 10-2 Ω m for the sample with x value ≤ 0.1. The Seebeck coefficient value increased with the increase of Bi substitution till the x value of 0.1 and decreased for the sample with higher Bi content (x ≤ 0.2) as the resistivity of the sample increased due to secondary phase formation. With the optimum Seebeck coefficient and electrical resistivity, Bi0.1ZnCo1.9O4 shows the high-power factor (α 2 σ 550 K) of 2.3 µW K-2 m-1 and figure of merit of 9.5 × 10-4 at 668 K respectively, compared with other samples. The experimental results reveal that Bi substitution at the Co site is a promising approach to improve the thermoelectric properties of ZnCo2O4.

Assignment of Dental Hygienists Improves Outcomes in Japanese Rehabilitation Wards: A Retrospective Cohort Study.

OBJECTIVES: To clarify the effectiveness of ward-assigned dental hygienists (DHs) on rehabilitation outcomes in rehabilitation wards. DESIGN: Retrospective cohort study. SETTING: The registry data from the Japanese Rehabilitation Nutrition Database. PARTICIPANTS: 656 patients with hip fracture or stroke admitted to convalescent rehabilitation wards. MEASUREMENTS: The main outcome measures were the Functional Independence Measure (FIM), the Food Intake Level Scale (FILS), and the home discharge rate. Patients were divided into two groups based on the ward setting: with an assigned DH (DH group) and without an assigned DH (NDH group). Clinical characteristics and outcomes were compered between the groups. Between-facility differences were adjusted by generalized estimating equation. We performed post-hoc power analysis to confirm that there were enough samples included in this study to detect a significant difference. RESULTS: Of 656 patients (mean age, 77 years; 57.1% female; 65.5% stroke) from 10 facilities, 454 patients (69.2%) from 4 facilities were in the DH group. FIM score at discharge (107 vs 90, P<0.001), percentage improvement in FILS score from admission to discharge (44.5% vs 22.8%, P<0.001) and home discharge rate (72.5% vs 61.4%, P<0.001) were significantly higher in the DH group than in the NDH group. After multivariate analysis, the FIM score at discharge (P=0.007), FILS score at discharge (P=0.024), and home discharge rate (P=0.007) were significantly higher in the DH group than in the NDH group. CONCLUSIONS: ADL and swallowing function were significantly improved at discharge and the home discharge rate was higher among patients in rehabilitation wards with DHs. Having a ward-assigned DH may lead to better rehabilitation outcomes in rehabilitation wards.

Impact of Energy intake at One Week after Hospitalization on Prognosis for Older Adults with Pneumonia.

OBJECTIVES: This study objectives to investigate the influence of average energy intake at 1 week of hospitalization on prognosis for older adults with pneumonia. DESIGN: Retrospective observational cohort study. SETTING: The Japan Rehabilitation Nutrition Database comprise those with pneumonia in acute care hospitals. PARTICIPANTS: The study included 329 pneumonia patients (aged over 65 years) who entered into the Japan Rehabilitation Nutrition Database (JRND) from November 2015 to March 2018. MEASUREMENTS: Logistic regression analysis was performed to confirm the relationship of energy intake with the rate of mortality, discharge home, and pneumonia recurrence during hospitalization. Variables included in the multiple regression analysis model were age, sex, Mini Nutritional Assessment-Short Form score (MNA-SF) at hospitalization, A-DROP, Charlson comorbidity index (CCI), and presence or absence of rehabilitation. RESULTS: Of 315 patients with pneumonia (median age 85 years), 63.8% were men. 57.7% were assigned to the lack of energy intake (LEI) at 1 week after admission. Patients in the LEI group were older (p = 0.033), had higher A-DROP score (p < 0.001), and showed higher malnutrition rate in MNA-SF at hospitalization (p < 0.001) than those in the control group. Mortality, pneumonia recurrence (p = 0.001), median body mass index (p = 0.012), and low malnutrition in MNA-SF (p < 0.001) at discharge were significantly higher in the LEI group than in the control group. Logistic regression analysis showed that LEI was an independent risk factor for mortality (Odds ratio: 5.07, p = 0.002), discharge home (Odds ratio: 0.33, p = 0.007), and pneumonia recurrence (Odds ratio: 3.26, p = 0.007). CONCLUSIONS: LEI at 1 week after hospitalization in older adults with pneumonia was an independent risk factor for mortality, difficult at-home recovery, and pneumonia recurrence. These findings suggest the importance of adequate energy intake from the early days of hospitalization.

Burden of Premorbid Consumption of Texture Modified Diets in Daily Life on Nutritional Status and Outcomes of Hospitalization.

OBJECTIVES: Due to the water-rich cooking process required to soften texture modified diets (TMDs), TMDs may have poorer nutrition. The aim of this study was to investigate the associations between daily premorbid TMD consumption and nutritional status at the time of hospitalization, and its burden on hospitalization outcomes. DESIGN: Retrospective observational study. SETTING: An academic hospital. PARTICIPANTS: The cohort comprised 3,594 older adult patients aged ≥65 years admitted to the hospital. MEASUREMENTS: Patients were interviewed on admission using a premorbid daily consumption meal form to determine whether the patient ate a TMD. Nutritional status was examined using nutritional screening tools (Mini-Nutritional Assessment Short Form [MNA-SF], Malnutrition Universal Screening Tool [MUST], Geriatric Nutritional Risk Index [GNRI]) and the European Society of Clinical Nutrition and Metabolism (ESPEN)-defined criteria of malnutrition at admission. Length of hospital stay (LOS) and in-hospital mortality were considered outcomes of hospitalization. Multivariate analyses were performed to detect associations between premorbid TMD consumption and nutritional status and outcomes. RESULTS: The mean age of the subjects was 75.9±7.0 years, including 58% males. Overall, 110 (3.1%) patients consuming a premorbid TMD were identified. They were older (p<0.001), had poor nutritional status (lower MNA-SF score [p<0.001] and GNRI value [p<0.001], higher MUST score [p<0.001], and more prevalent ESPEN-defined malnutrition [61.8% vs. 14.0%, p<0.001] than did patients without a TMD. The mortality rate and LOS of patients with TMD was higher (7.3% vs. 2.9%, p=0.017) and longer (19 days vs. 8 days, p<0.001) than those without TMD. Multivariate analyses showed that TMD consumption was independently associated with poor nutritional status and prolonged LOS after adjusting confounders. CONCLUSION: Daily consumption of a TMD during the premorbid period affects nutritional status at the time of hospitalization and outcomes. Further studies are necessary to investigate whether nutritional intervention can improve outcomes for people on a TMD.

Peripheral administration of κ-opioid receptor antagonist stimulates gonadotropin-releasing hormone pulse generator activity in ovariectomized, estrogen-treated female goats.

Pulsatile gonadotropin-releasing hormone (GnRH) secretion is indispensable for reproduction in mammals. Kisspeptin neurons in the hypothalamic arcuate nucleus (ARC), referred to as KNDy neurons because of the coexpression of neurokinin B and dynorphin A, are considered as components of the GnRH pulse generator that produces rhythmic GnRH secretion. The present study aimed to investigate if peripheral administration of PF-4455242, a κ-opioid receptor (KOR, a dynorphin A receptor) antagonist, facilitates pulsatile luteinizing hormone (LH) secretion and GnRH pulse generator activity in estrogen-treated ovariectomized Shiba goats to determine the possibility of using KOR antagonists to artificially control ovarian activities. PF-4455242 was intravenously infused for 4 h (1 or 10 µmol/kg body weight/4 h) or as a single subcutaneous injection (1 or 10 µmol/kg body weight). In a separate experiment, the same KOR antagonist (10 µmol/kg body weight/4 h) was intravenously infused during the recording of multiple unit activity (MUA) in the ARC that reflects the activity of the GnRH pulse generator to test the effects of KOR antagonist administration on GnRH pulse generator activity. Intravenous infusion and single subcutaneous injection of the KOR antagonist significantly increased the frequency of LH pulses compared with controls. Intravenous infusion of KOR antagonist also significantly increased the frequency of episodic bursts in the MUA. The present study demonstrates that peripherally administered KOR antagonist stimulates pulsatile LH secretion by acting on the GnRH pulse generator, and peripheral administration of PF-4455242 can be used to facilitate pulsatile LH secretion, which in turn facilitates ovarian activities in farm animals.

Impact of Body Mass Index on Activities of Daily Living in Inpatients with Acute Heart Failure.

OBJECTIVES: To investigate the impact of body mass index on activities of daily living in inpatients with acute heart failure. DESIGN: A retrospective cohort study. SETTING: A hospital-based database contains Diagnosis Procedure Combination survey data from 100 participating acute-care hospitals. PARTICIPANTS: 11,301 inpatients aged 20 year or older who were admitted to the participating hospitals with a diagnosis of acute heart failure. MEASUREMENTS: The Barthel Index score at discharge and hospital death. RESULTS: The number of patients with a body mass index of <18.5 kg/m2 (underweight), 18.5-22.9 kg/m2 (low-normal weight), 23.0-24.9 kg/m2 (high-normal weight), 25.0-29.9 kg/m2 (overweight), and ≥30.0 kg/m2 (obesity) were 1689 (15%), 4715 (42%), 1809 (16%), 2306 (20%), and 782 (7%), respectively. Median Barthel Index scores at admission and discharge were 65 and 100, respectively. Hospital death occurred in 101 (0.9%) patients. Lower body mass index was associated with lower Barthel Index score at discharge and higher mortality. Multivariable analysis adjusted for body mass index, age, sex, New York Heart Association classification, Barthel Index score at admission, the updated Charlson Comorbidity Index, length of hospital stay, number of drugs administered, and rehabilitation during hospitalization revealed that body mass index was independently associated with Barthel Index score at discharge (beta: 0.354; 95% confidence interval: 0.248-0.461) and hospital death (odds ratio: 0.926, 95% confidence interval: 0.877-0.978). CONCLUSION: Overweight and obese inpatients showed greater independence in activities of daily living at discharge and lower rates of mortality, indicating the obesity paradox. A combination of rehabilitation and improved nutrition seems to be important in underweight patients with acute heart failure.

Signatures of a jet cocoon in early spectra of a supernova associated with a γ-ray burst.

Long γ-ray bursts are associated with energetic, broad-lined, stripped-envelope supernovae1,2 and as such mark the death of massive stars. The scarcity of such events nearby and the brightness of the γ-ray burst afterglow, which dominates the emission in the first few days after the burst, have so far prevented the study of the very early evolution of supernovae associated with γ-ray bursts3. In hydrogen-stripped supernovae that are not associated with γ-ray bursts, an excess of high-velocity (roughly 30,000 kilometres per second) material has been interpreted as a signature of a choked jet, which did not emerge from the progenitor star and instead deposited all of its energy in a thermal cocoon4. Here we report multi-epoch spectroscopic observations of the supernova SN 2017iuk, which is associated with the γ-ray burst GRB 171205A. Our spectra display features at extremely high expansion velocities (around 115,000 kilometres per second) within the first day after the burst5,6. Using spectral synthesis models developed for SN 2017iuk, we show that these features are characterized by chemical abundances that differ from those observed in the ejecta of SN 2017iuk at later times. We further show that the high-velocity features originate from the mildly relativistic hot cocoon that is generated by an ultra-relativistic jet within the γ-ray burst expanding and decelerating into the medium that surrounds the progenitor star7,8. This cocoon rapidly becomes transparent9 and is outshone by the supernova emission, which starts to dominate the emission three days after the burst.

Thymidine kinase-1/CD31 double immunostaining for identifying activated tumor vessels.

Although angiogenesis plays a crucial role in cancer growth and progression, no reliable method for assessing angiogenesis in tumor tissue sections currently is available. Using biomarkers with high specificity for proliferating endothelial cells could help quantify angiogenic activity. Thymidine kinase-1 (TK1) is an enzyme involved in the salvage pathway of DNA synthesis and its activity is correlated with cell proliferation. We investigated the use of double immunostaining for TK1 and CD31 for identifying activated tumor vessels. Differences in TK1/CD31 positive vessel rates (PVRs) between tumor and adjacent normal tissues were evaluated in 39 colorectal carcinoma (CRC) samples and compared with those of Ki67/CD31 double stained tissues. Mean TK1/CD31 PVR (23.6%) in CRCs was 13.9 fold greater than in adjacent normal tissues (1.7%)). By comparison, mean Ki67/CD31 PVR in CRCs was 20.0%, i.e. only 4.8 fold greater than in normal tissues (4.2%). Also, mean TK1/CD31 PVR in normal tissues was significantly less than mean Ki67/CD31 PVR. Our findings indicate that double immunostaining for TK1/CD31 can detect activated tumor vessels more accurately than staining for Ki67/CD31 and potentially could identify tumors that will respond to anti-angiogenic therapy.

A surge of light at the birth of a supernova.

It is difficult to establish the properties of massive stars that explode as supernovae. The electromagnetic emission during the first minutes to hours after the emergence of the shock from the stellar surface conveys important information about the final evolution and structure of the exploding star. However, the unpredictable nature of supernova events hinders the detection of this brief initial phase. Here we report the serendipitous discovery of a newly born, normal type IIb supernova (SN 2016gkg), which reveals a rapid brightening at optical wavelengths of about 40 magnitudes per day. The very frequent sampling of the observations allowed us to study in detail the outermost structure of the progenitor of the supernova and the physics of the emergence of the shock. We develop hydrodynamical models of the explosion that naturally account for the complete evolution of the supernova over distinct phases regulated by different physical processes. This result suggests that it is appropriate to decouple the treatment of the shock propagation from the unknown mechanism that triggers the explosion.

Increased metabolite production by deletion of an HDA1-type histone deacetylase in the phytopathogenic fungi, Magnaporthe oryzae (Pyricularia oryzae) and Fusarium asiaticum.

Histone deacetylases (HDACs) play an important role in the regulation of chromatin structure and gene expression. We found that dark pigmentation of Magnaporthe oryzae (anamorph Pyricularia oryzae) ΔMohda1, a mutant strain in which an orthologue of the yeast HDA1 was disrupted by double cross-over homologous recombination, was significantly stimulated in liquid culture. Analysis of metabolites in a ΔMohda1 mutant culture revealed that the accumulation of shunt products of the 1,8-dihydroxynaphthalene melanin and ergosterol pathways were significantly enhanced compared to the wild-type strain. Northern blot analysis of the ΔMohda1 mutant revealed transcriptional activation of three melanin genes that are dispersed throughout the genome of M. oryzae. The effect of deletion of the yeast HDA1 orthologue was also observed in Fusarium asiaticum from the Fusarium graminearum species complex; the HDF2 deletion mutant produced increased levels of nivalenol-type trichothecenes. These results suggest that histone modification via HDA1-type HDAC regulates the production of natural products in filamentous fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: Natural products of fungi have significant impacts on human welfare, in both detrimental and beneficial ways. Although HDA1-type histone deacetylase is not essential for vegetative growth, deletion of the gene affects the expression of clustered secondary metabolite genes in some fungi. Here, we report that such phenomena are also observed in physically unlinked genes required for melanin biosynthesis in the rice blast fungus. In addition, production of Fusarium trichothecenes, previously reported to be unaffected by HDA1 deletion, was significantly upregulated in another Fusarium species. Thus, the HDA1-inactivation strategy may be regarded as a general approach for overproduction and/or discovery of fungal metabolites.