How to experimentally evaluate the adiabatic condition for quantum annealing.

We propose an experimental method for evaluating the adiabatic condition during quantum annealing (QA), which will be essential for solving practical problems. The adiabatic condition consists of the transition matrix element and the energy gap, and our method simultaneously provides information about these components without diagonalizing the Hamiltonian. The key idea is to measure the power spectrum of a time domain signal by adding an oscillating field during QA, and we can estimate the values of the transition matrix element and energy gap from the measurement output. Our results provides a powerful experimental basis for analyzing the performance of QA.

Low on-treatment blood pressure and cardiovascular events in patients without elevated risk: a nationwide cohort study.

Insufficient blood pressure control among patients with hypertension without elevated risk is a global concern, suggesting the need for treatment optimization. However, the potential harm of excessive blood pressure lowering among these patients is understudied. This study addressed this evidence gap by using nationally representative public health insurer database covering 30 million working-age population. Patients who were continuously using antihypertensive drugs with 10-year cardiovascular risk <10% were identified. They were categorized by on-treatment systolic and diastolic blood pressures. The primary outcome was a composite of myocardial infarction, stroke, heart failure hospitalization, and peripheral artery disease. Of 920,533 participants (mean age, 57.3 years; female, 48.3%; mean follow-up, 2.75 years), the adjusted hazard ratios for systolic blood pressure of <110, 110-119, 120-129 (reference), 130-139, 140-149, 150-159, and ≥160 mmHg were 1.05 (95% confidence interval: 0.99-1.12), 0.97 (0.93-1.02), 1 (reference), 1.05 (1.01-1.09), 1.15 (1.11-1.20), 1.30 (1.23-1.37), and 1.76 (1.66-1.86), respectively; and for diastolic blood pressure of <60, 60-69, 70-79 (reference), 80-89, 90-99, and ≥100 mmHg were 1.25 (1.14-1.38), 0.99 (0.95-1.04), 1 (reference), 1.00 (0.96-1.03), 1.13 (1.09-1.18), and 1.66 (1.58-1.76), respectively. Among low-risk patients with hypertension, diastolic blood pressure <60 mmHg was associated with increased cardiovascular events, while systolic blood pressure <110 mmHg was not. Compared to previous investigations in high-risk patients, the potential harm of excessive blood pressure lowering was less pronounced in low-risk patients with hypertension. The association between low on-treatment blood pressure and cardiovascular events has been understudied in low-risk patients with hypertension. In our study with nationally representative working-age adults from general population with hypertension without elevated risk, increased risk of cardiovascular events was observed in diastolic blood pressure of <60 mmHg, but not in systolic blood pressure of <110 mmHg. Those results contrasted with previous investigations in high-risk patients where the risk of low on-treatment blood pressure was more pronounced.

Early-Stage Chronic Kidney Disease and Related Health Care Spending.

Importance: The global burden of chronic kidney disease (CKD) is substantial and potentially leads to higher health care resource use. Objective: To examine the association between early-stage CKD and health care spending and its changes over time in the general population. Design, Setting, and Participants: Cohort study using nationwide health checkup and medical claims data in Japan. Participants included individuals aged 30 to 70 years with estimated glomerular filtration rates (eGFR) of 30 mL/min/1.73 m2 or greater at the baseline screening in 2014. Data analyses were conducted from April 2021 to October 2023. Exposure: The CKD stages at baseline, defined by the eGFR and proteinuria, were as follows: eGFR of 60 mL/min/1.73 m2 or greater without proteinuria, eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. Main Outcome and Measures: The primary outcome was excess health care spending, defined as the absolute difference in health care spending according to the baseline CKD stages (reference group: eGFR ≥60 mL/min/1.73 m2 without proteinuria) in the baseline year (2014) and in the following 5 years (2015 to 2019). Results: Of the 79 988 participants who underwent a health checkup (mean [SD] age, 47.0 [9.4] years; 22 027 [27.5%] female), 2899 (3.6%) had an eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, 1116 (1.4%) had an eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and 253 (0.3%) had an eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. At baseline, the presence of proteinuria and an eGFR less than 60 mL/min/1.73 m2 were associated with greater excess health care spending (adjusted difference, $178; 99% CI, $6-$350 for proteinuria; $608; 99% CI, $233-$983 for an eGFR of 30-59 mL/min/1.73 m2; and $1254; 99% CI, $134-$2373 for their combination). The study consistently found excess health care spending over the following 5 examined years. Conclusions and Relevance: In this cohort study of nationwide health checkup and medical claims data in Japan, early-stage CKD was associated with excess health care spending over the 5 examined years, and the association was more pronounced with a more advanced disease stage.

[Creation of 3D Stereo and MPR Color Anatomical Charts in the Hepatic Segments].

We used the Voronoi diagram of a computed tomography (CT) application (i.e., CT liver volume measurement) to depict the liver area, and we obtained depictions of the hepatic segments as a three-dimensional (3D) image based on clinical data; this information can be used for the patient's education and for surgical planning. The hepatic segments use the inter-relationships among the eight subsegments illustrated by Couinaud, those indicated by the portal veins and those provided by hepatic veins. The liver has dual portal and arterial innervation, with the thick portal vein intertwined with thin arteries similar to the intertwining of ivy plants. Couinaud divided the liver into eight segments (S1 to S8) based on portal vein casts. The Voronoi diagram estimates the dominant region of the portal vein, divides the liver into segments, and produces 3D images and multiplanar reconstruction (MPR) images in color. To support understanding of Couinaud's eight hepatic segments (which are explained only in the illustration of the frontal view of the liver), using 3D images created by the Voronoi diagram, we created 3D stereo color anatomical charts of the liver that Couinaud's eight hepatic segments can be confirmed from multiple directions. In addition, we created the MPR color anatomical charts of the liver (S1 to S8) that can be confirmed by color from three directions: axial images, coronal images, and sagittal images in the same way. We converted the data of this anatomical chart into an electronic file that provides a tool that can be easily used in radiological examinations, and we were able to make improvements based on requests from users.

Risk of cardiovascular disease associated with repeated proteinuria across annual kidney function screening among the middle-aged and older general population in Japan: a retrospective cohort study.

OBJECTIVES: We aimed to investigate the association between repetitive proteinuria and cardiovascular events among the middle-aged and older general Japanese population. DESIGN: Retrospective cohort study. SETTING: We used repeated health screening results and medical claim data from one of the largest health insurers in Japan. PARTICIPANTS: Among the middle-aged and older participants (40-74 years, n=179 840), 90 752 were excluded for undergoing health screening fewer than two times and 344 were excluded for having a history of cardiovascular diseases; 88 744 who underwent kidney function screenings at least two times (from April 2011 to March 2015) were included in the analysis. Based on dipstick proteinuria test results, the participants were divided into 'Repetitively-positive' (positive two times or more (positive proteinuria was defined as≥1+)), 'Once-positive' and 'All-negative' groups. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome of major cardiovascular events from baseline screening to June 2021 was hospitalisation or death due to acute myocardial infarction (AMI), cerebrovascular diseases, heart failure (HF) or peripheral vascular diseases (PVDs). The association between proteinuria and major cardiovascular events was assessed using a Cox proportional hazards model. RESULTS: Of the 88 744 participants, 8775 (9.9%) and 5498 (6.2%) had Once-positive and Repetitively-positive proteinuria, respectively. During the follow-up period of 402 799 person-years (median 5.25 years), 660 cardiovascular events were observed, with an incidence of 1.64 per 1000 person-years (95% CI 1.52 to 1.77). Despite adjusting for major cardiovascular risk factors, we observed a high incidence of cardiovascular events in the Repetitively-positive (HR 2.08, 95% CI 1.67 to 2.59) and Once-positive groups (HR 1.36, 95% CI 1.07 to 1.72). We found similar associations for AMI, cerebrovascular disease, HF and PVD. CONCLUSIONS: Proteinuria is often repeatedly detected during annual renal screening in the general population. Repetitive proteinuria is a risk factor for major cardiovascular events.

Patterns and predictors of adherence to follow-up health guidance invitations in a general health check-up program in Japan: A cohort study with an employer-sponsored insurer database.

BACKGROUND: Japan has conducted a nationwide annual health check-up program since 2008, focusing on metabolic syndrome and subsequent health guidance in individuals at high risk for cardiovascular disease. However, the adherence rate to health guidance invitations was assumed to be low in previous reports. Therefore, this study aimed to characterize adherence patterns in the program and identify major predictors of adherence to health guidance invitations. METHODS: We studied 186,316 adults (aged 40-74 years) who were included in a nationwide employer-sponsored insurer's database in Japan at the beginning of the fiscal year 2017. We first described adherence to health check-ups, the proportion of individuals with high cardiovascular risk, and adherence to health guidance invitations. Predictors of adherence to the invitation were then identified among eligible high-risk individuals. RESULTS: In 2017, 71.7% of the study population (n = 133,573) underwent health check-ups, among whom 23.2% (n = 30,979) were invited for health guidance because of their high cardiovascular risk. Among those individuals, 35.2% (n = 10,614) received health guidance. Predictors of improved adherence to health guidance invitation were older age, more concerning blood pressure or laboratory data results, and self-reported motivation for a lifestyle change. CONCLUSION: Though 70% of eligible adults attended Japan's annual cardiovascular risk check-ups, only 35% of individuals with high cardiovascular risk adhered to health guidance invitations. Future policy reforms to improve adherence to this program should target younger individuals and those with mild stages of hypertension, diabetes, or dyslipidemia.

Image Quality Assessment of Deep Learning Image Reconstruction in Torso Computed Tomography Using Tube Current Modulation.

Novel deep learning image reconstruction (DLIR) reportedly changes the image quality characteristics based on object contrast and image noise. In clinical practice, computed tomography image noise is usually controlled by tube current modulation (TCM) to accommodate changes in object size. This study aimed to evaluate the image quality characteristics of DLIR for different object sizes when the in-plane noise was controlled by TCM. Images acquisition was performed on a GE Revolution CT system to investigate the impact of the DLIR algorithm compared to the standard reconstructions of filtered-back projection (FBP) and hybrid iterative reconstruction (hybrid-IR). The image quality assessment was performed using phantom images, and an observer study was conducted using clinical cases. The image quality assessment confirmed the excellent noise- reduction performance of DLIR, despite variations due to phantom size. Similarly, in the observer study, DLIR received high evaluations regardless of the body parts imaged. We evaluated a novel DLIR algorithm by replicating clinical behaviors. Consequently, DLIR exhibited higher image quality than those of FBP and hybrid-IR in both phantom and observer studies, albeit the value depended on the reconstruction strength, and proved itself capable of providing stable image quality in clinical use.

[Accuracy of Virtual Non-contrast Image Reconstruction Using Material Decomposition for Fast kV-switching Dual-energy CT].

PURPOSE: Dual-energy computed tomography (DECT) system can generate virtual non-contrast (VNC) images. Although several reconstruction algorithms are defined, there are not many researches using deep learning image reconstruction (DLIR) algorithm. In this study, we evaluated the accuracy of the VNC image reconstruction under various conditions using DLIR algorithm. METHODS: At first, each iodine insert with variable concentrations (2.0, 5.0, 10.0, 15.0 mg/ml) or diameters (2.0, 5.0, 10.0, 28.5 mm), or mixed insert including blood-mimicking material with iodine (iodine concentrations: 2.0, 4.0 mg/ml) was put in the center of the multi-energy CT phantom (Gammex, USA). This phantom was placed in the isocenter of DECT, and it scanned and reconstructed the VNC images. In addition, the VNC images were reconstructed with various display field of view (DFOV) sizes (240, 350 mm) or reconstruction algorithms (filtered back projection, advanced statistical iterative reconstruction, deep learning image reconstruction) for each iodine diameter. Attenuation values of these images (CTVNC) were measured and assessed by placing a circular region of interest (ROI) on each insert. RESULTS: CTVNC form iodine inserts increased with iodine concentration became lower, whereas CTVNC form blood plus iodine inserts were stable regardless of low iodine concentration. As iodine diameter became smaller, CTVNC increased remarkably. CTVNC remained steady even though reconstruction parameters were varied. CONCLUSION: In our study, the VNC image reconstruction using DLIR algorithm was affected by various conditions such as iodine concentration and size. In particular, its accuracy was reduced by the size of target.

Sodium-Glucose Cotransporter 2 Inhibitors and New-onset Type 2 Diabetes in Adults With Prediabetes: Systematic Review and Meta-analysis of Randomized Controlled Trials.

CONTEXT: The preventive effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors for new-onset diabetes was investigated in secondary analyses of several randomized controlled trials (RCTs). However, the results were inconsistent. OBJECTIVE: This work aimed to synthesize available evidence and evaluate whether SGLT2 inhibitors are effective in preventing new-onset diabetes. METHODS: In this systematic review and meta-analysis of RCTs, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched through February 11, 2022. Two independent authors screened the search results and extracted summary data from eligible RCTs (including original and post hoc analyses) comparing SGLT2 inhibitors and placebo for the risk of new-onset diabetes among adults with prediabetes. Meta-analysis was conducted using random-effects models to calculate risk ratios and 95% CIs. RESULTS: We included 4 RCTs with 5655 participants who had prediabetes. Based on the random-effects meta-analysis, SGLT2 inhibitors were significantly associated with a lower risk of new-onset diabetes (relative risk, 0.79; 95% CI, 0.68-0.93). The relative risks of new-onset diabetes in dapagliflozin and empagliflozin were 0.68 (95% CI, 0.52-0.89) and 0.87 (95% CI, 0.72-1.04), respectively (P-for-heterogeneity = .14). The frequency of severe hypoglycemia was not elevated in the SGLT2 inhibitors group compared to the placebo group. CONCLUSION: In this meta-analysis, SGLT2 inhibitors were associated with a reduced risk of new-onset type 2 diabetes among adults with prediabetes and heart failure or chronic kidney disease. These findings indicate the potential usefulness of SGLT2 inhibitors in preventing diabetes among high-risk populations with prediabetes.

[Creation of Bone X-ray Radiography Manual Using Human Bone Specimens for Bone X-ray Radiography Education].

Senior radiological technologists have made various improvements and have supported the clinical and educational fields by explaining bone X-ray radiography to students and junior radiological technologists to understand the procedure using illustrations, X-ray images, and photographs in a way that corresponds to the design software available for that era. Because human bone specimens are only available in the anatomy laboratory of medical schools, they could not be used for the explanation of bone X-ray radiography until now. Therefore, we have developed a bone X-ray radiography manual using bone specimens for the bone X-ray radiography education, which helps students to understand the procedure of bone X-ray radiography. Previous bone X-ray radiography manuals had not been illustrated by bone specimens and bone specimen X-ray images, but this bone X-ray radiography manual using bone specimens has made it possible to understand the surface morphology of bone specimens and X-ray images of them. In addition, the data of bone X-ray radiography using this bone specimen were made into an electronic file, which can be easily used at the place of radiological examination or at home through electronic media.

[Creation of Stereo-paired Color Vascular Anatomical Charts Using 3-dimentional Images].

Three-dimensional (3D) images of blood vessels in the human body, which are acquired by X-ray computed tomography (CT) and cone-beam CT of Angiography devices, are widely used in medical diagnosis and treatment. Using the 3DCT images of blood vessels, we created stereo-paired color vascular anatomical charts for better understanding of vascular anatomy in clinical settings, patient explanations, and student education. Since it is difficult to distinguish branches of blood vessels that show three-dimensionally complicated running such as cerebral blood vessels, we made it easier to identify them anatomically by color-coding each branch of the blood vessel. Also, by using stereo-paired images, we can see the three-dimensional blood vessel running. In the past anatomical books and vascular anatomy atlas, there was no anatomical chart of the whole body blood vessels that could be color-coded and stereoscopically viewed. We have made it possible to identify blood vessels by the stereoscopic vision of the blood vessels using this stereo-paired color anatomical chart. In addition, this vascular anatomical chart can be additionally revised according to the needs of the clinical and educational settings to be used, and the data can be converted into an electronic file so that it can be easily used in the field of radiological examination or at home through electronic media.

Polymyxin B and low-dose hydrocortisone treatment in a patient with uroseptic shock in a rural health unit.

Sepsis has a high mortality rate; thus, in the intensive care unit, early diagnosis and adjunctive treatments are crucial. However, generally, most patients with sepsis from rural area initially visit the emergency department at a rural hospital and are managed in general medical wards in Japan. Here we report on an 81-year-old Japanese female manifesting septic shock caused by the upper urinary tract infection of extended-spectrum beta-lactamase-producing Escherichia coli secondary to the left ureter obstruction by the urothelial carcinoma. Broad-spectrum antibiotics were administered. Although critical for the source control of infection, drainage of the ureteropelvic junction could not be performed immediately because of catecholamine-resistant hypotension. Hence, we administered polymyxin B-immobilized fiber column direct hemoperfusion, followed by low-dose hydrocortisone administration. After 8 hours of infusion, she recovered from the septic shock and successfully underwent emergency percutaneous nephrostomy. This presented strategy may provide a new resolution of catecholamine-resistant patients in urosepsis.

Listeria monocytogenes Ankle Osteomyelitis in a Patient with Rheumatoid Arthritis on Adalimumab: A Report and Literature Review of Listeria monocytogenes Osteomyelitis.

Localized Listeria infection predominantly occurs in the prosthetic and hip joints. We herein report a case of Listeria monocytogenes ankle osteomyelitis in a 73-year-old man receiving adalimumab who was transferred to our hospital because of suspected rheumatoid arthritis (RA) flare. He reported a four-month history of left ankle swelling. A surgical biopsy revealed L. monocytogenes osteomyelitis in the left tibia and talus bones. The patient was successfully treated with antibiotics and surgical debridement. Thus, infection due to L. monocytogenes can present as ankle osteomyelitis in immunocompromised patients and may mimic an RA flare.

Behavior of light elements in iron-silicate-water-sulfur system during early Earth's evolution.

Hydrogen (H) is considered to be one of the candidates for light elements in the Earth's core, but the amount and timing of delivery have been unknown. We investigated the effects of sulfur (S), another candidate element in the core, on deuteration of iron (Fe) in iron-silicate-water system up to 6-12 GPa, ~ 1200 K using in situ neutron diffraction measurements. The sample initially contained saturated water (D2O) as Mg(OD)2 in the ideal composition (Fe-MgSiO3-D2O) of the primitive Earth. In the existence of water and sulfur, phase transitions of Fe, dehydration of Mg(OD)2, and formation of iron sulfide (FeS) and silicates occurred with increasing temperature. The deuterium (D) solubility (x) in iron deuterides (FeDx) increased with temperature and pressure, resulting in a maximum of x = 0.33(4) for the hydrous sample without S at 11.2 GPa and 1067 K. FeS was hardly deuterated until Fe deuteration had completed. The lower D concentrations in the S-containing system do not exceed the miscibility gap (x < ~ 0.4). Both H and S can be incorporated into solid Fe and other light elements could have dissolved into molten iron hydride and/or FeS during the later process of Earth's evolution.

Impact of Frailty on Bleeding Events Related to Anticoagulation Therapy in Patients With Atrial Fibrillation.

BACKGROUND: Although anticoagulation is the key treatment to prevent stroke in patients with atrial fibrillation (AF), including elderly patients, anticoagulation is sometimes withheld for elderly people because of concerns about frailty. However, it remains unknown whether frailty increases bleeding events.Methods and Results:A total of 120 consecutive non-valvular AF patients admitted with symptoms of AF or congestive heart failure were included in this study. Frailty was assessed using the Cardiovascular Health Study (CHS) frailty index. We performed a retrospective analysis of the risk factors associated with major bleeding events. After a median follow-up of 518 days, major bleeding events occurred in 17 (14.2%) patients. Patients with major bleeding events had a higher CHS frailty index (P=0.015). The cutoff value for high-risk CHS frailty index was 2 (area under the ROC curve: 0.68 [95% confidence interval (CI): 0.57-0.78]). The event-free rates at 2 years were 97.6% (95% CI: 83.9-99.7) in patients with a CHS frailty index <2 and 59.6% (95% CI: 27.9-81.0) for those with a CHS frailty index ≥2 (P<0.001). CONCLUSIONS: Frailty is associated with increased bleeding events related to anticoagulant therapy in patients previously hospitalized with AF. Greater care should be taken with patients with a CHS frailty index ≥2.

Culture-negative group B streptococcal pericarditis: A case report and literature review of the diagnostic use of polymerase chain reaction.

Although conventional microbiology cultures may be negative, polymerase chain reaction (PCR) can effectively identify both typical and atypical microorganisms. With careful interpretation, PCR could become the gold-standard diagnostic test for culture-negative bacterial pericarditis.

Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection.

The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009-2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza - i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden.

La formulation de définitions précises de cas cliniques fait partie intégrante d'un processus efficace de surveillance de la santé publique. Alors que ces définitions devraient, dans l'idéal, s'appuyer sur un ensemble standardisé et fixe de critères de définition, elles nécessitent souvent une révision pour tenir compte des nouvelles connaissances relatives à la maladie concernée et des améliorations apportées aux tests diagnostiques. Pour être optimales, les définitions de cas doivent aussi établir un équilibre entre sensibilité et spécificité qui reflète leur utilisation aux fins prévues. À la suite de la pandémie de grippe H1N1 de 2009-2010, l'Organisation mondiale de la Santé (OMS) a lancé une consultation technique sur la surveillance mondiale de la grippe. Cela a conduit à des améliorations concernant la sensibilité et la spécificité de la définition de cas pour la grippe ­ c'est-à-dire une maladie respiratoire dont seule la symptomatologie reste à définir. Le processus de révision n'a pas seulement modifié la définition du syndrome de type grippal pour inclure une liste simplifiée des critères le mieux à même de prédire une infection grippale, il a également permis de clarifier le langage utilisé dans la définition pour en améliorer l'interprétation. Par ailleurs, afin de tenir compte des cas sévères de grippe qui nécessitaient une hospitalisation, une nouvelle définition de cas a été introduite concernant l'infection aigüe sévère des voies respiratoires dans tous les groupes d'âge. Il a été constaté que les nouvelles définitions reflétaient davantage de cas, sans pour autant compromettre la spécificité. S'il est vrai que la distinction clinique de la grippe des autres infections respiratoires continue de poser problème, l'utilisation mondiale des nouvelles définitions de cas de l'OMS devrait permettre de dégager des tendances mondiales concernant les caractéristiques et la transmission des virus grippaux ainsi que la charge de morbidité qui leur est associée.

La elaboración de definiciones precisas de los casos clínicos es una parte fundamental de un proceso efectivo de la vigilancia de la salud pública. Aunque tales definiciones deberían, idealmente, estar basadas en una recopilación estandarizada y fija de criterios de definición, a menudo necesitan una revisión para reflejar el nuevo conocimiento de la enfermedad existente y las mejoras en las pruebas de diagnóstico. Las definiciones óptimas de los casos también deben tener un equilibrio entre sensibilidad y especificidad que refleje su uso previsto. Después de la pandemia de gripe H1N1 en 2009-2010, la Organización Mundial de la Salud (OMS) inició una consulta técnica para la vigilancia mundial de la gripe. Esto dio lugar a mejoras en la sensibilidad y la especificidad de las definiciones de los casos de gripe, es decir, una enfermedad respiratoria que carece de una sintomatología definitoria singular. El proceso de revisión no solo modificó la definición de las enfermedades similares a la gripe para incluir una lista simplificada de los criterios que demostraron ser más predictivos de la infección por gripe, sino que también aclaró el lenguaje utilizado para la definición, con el fin de mejorar su interpretación. Para englobar los casos graves de gripe que requirieron hospitalización, también se desarrolló una nueva definición de los casos de la infección respiratoria aguda grave en todos los grupos de edad. Se ha descubierto que las nuevas definiciones engloban más casos sin comprometer la especificidad. A pesar del desafío que todavía plantea la separación clínica de la gripe de otras infecciones respiratorias, el uso global de las nuevas definiciones de los casos de la OMS debería ayudar a determinar las tendencias mundiales en las características y transmisión de los virus de la gripe y la carga de la enfermedad asociada.

Electric current-induced lymphatic activation.

The lymphatic system in skin plays important roles in drainage of wastes and in the afferent phase of immune response. We previously showed that activation of vascular endothelial growth factor receptor (VEGFR), specifically the VEGFC/VEGFR-3 pathway, attenuates oedema and inflammation by promoting lymphangiogenesis, suggesting a protective role of lymphatic vessels against skin inflammation. However, it remains unknown how physical stimuli promote lymphatic function. Here, we show that lymphatic endothelial cells (LECs) are activated by direct-current (DC) electrical stimulation, which induced extension of actin filaments of LECs, increased calcium influx into LECs, and increased phosphorylation of p38 mitogen-activated protein kinase (MAPK). An inhibitor of focal adhesion kinase, which plays a role in cellular adhesion and motility, diminished the DC-induced extension of F-actin and abrogated p38 phosphorylation. Time-lapse imaging revealed that pulsed-DC stimulation promoted proliferation and migration of LECs. Overall, these results indicate that electro-stimulation activates lymphatic function by activating p38 MAPK.