Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid compositi...Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these forces.Intrinsic and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse formation.In the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called plasticity.Synaptic plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).展开更多
Prostate cancer is the most common non-cutaneous cancers occurring in American men,and whilemost men with early-stage prostate cancers are cured,up to a third might manifest with biochemical recurrence(BCR)of prostate...Prostate cancer is the most common non-cutaneous cancers occurring in American men,and whilemost men with early-stage prostate cancers are cured,up to a third might manifest with biochemical recurrence(BCR)of prostate cancer.BCR is a disease entitywhich is characterized by a rising prostate-specific antigen(PSA)in the setting of a previously treated localized prostate cancerwith either surgery or radiation therapywith curativeintent.展开更多
Low-frequency vibroseis acquisition has become a routine operation in land seismic surveys,given the advantages of low-frequency signals in characterizing geological structures and enhancing the imaging of deep explor...Low-frequency vibroseis acquisition has become a routine operation in land seismic surveys,given the advantages of low-frequency signals in characterizing geological structures and enhancing the imaging of deep exploration targets.The two key points of low-frequency sweep design techniques include controlling the distortion and improving the output energy during the low-frequency stage.However,the vibrators are limited by the maximum fl ow provided by the hydraulic systems at the low-frequency stage,causing difficulty in satisfying exploration energy requirements.Initially,a theoretical analysis of the low-frequency acquisition performance of vibrators is conducted.A theoretical maximum output force below 10 Hz is obtained by guiding through theoretical formulas and combining actual vibrator parameters.Then,the signal is optimized according to the surface characteristics of the operation area.Finally,detailed application quality control and operational procedures are established.The new low-frequency sweep design method has overcome the maximum flow limitations of the hydraulic system,increased the low-frequency energy,and achieved broadband acquisition.The designed signal has been tested and applied on various types of ground surfaces in the Middle East desert region,yielding good performance.The proposed low-frequency sweep design method holds considerable value for the application of conventional vibroseis in low-frequency acquisition.展开更多
In this study,naringin was encapsulated in microspheres and its simulated digestive behavior in vitro was examined.Then naringin microspheres was added in yogurt to investigate the rheology and antioxidant activities....In this study,naringin was encapsulated in microspheres and its simulated digestive behavior in vitro was examined.Then naringin microspheres was added in yogurt to investigate the rheology and antioxidant activities.The results indicated that encapsulating naringin in microspheres delayed its digestion in the stomach,allowing more release in the intestinal part.All kinds of yogurt were solid-like in nature and the addition of microspheres increased the elastic modulus and viscosity.The naringin and microspheres incorporation enhanced the total phenolic content of the yogurt to 6.7 and 8.8 mg of gallic acid equivalent/mL,respectively.All kinds of yogurt demonstrated more than 80%scavenging ability for hydroxyl radicals at 20μL whey/mL.The addition of microspheres improved the DPPH radical scavenging ability of yogurt.This study provides a new idea for the application of polyphenols in food and the development of functional yogurt.展开更多
AIM:To quantify and compare longitudinal thickness changes of the ganglion cell complex(GCC)and the choroid in patients with different patterns of age-related macular degeneration(AMD)progression.METHODS:Retrospective...AIM:To quantify and compare longitudinal thickness changes of the ganglion cell complex(GCC)and the choroid in patients with different patterns of age-related macular degeneration(AMD)progression.METHODS:Retrospective cohort analysis of anonymized data from participants aged 50y or more and diagnosed with early/intermediate AMD in at least one eye(with no evidence of advanced AMD).A total of 64 participants were included from the Instituto de Retina de Lisboa(IRL)study(IPL/2022/MetAllAMD_ESTeSL)and divided into 4 groups according to the Rotterdam classification for AMD.Spectral domain optical coherence tomography(SD-OCT)was used to assess and quantify GCC and choroid thickness at two time points(first visit vs last visit)with a minimum interval of 3y.RESULTS:In the GCC inner ring,a thinner thickness(P=0.001)was observed in the atrophic AMD group(51.3±21.4μm)compared to the early AMD(84.3±11.5μm),intermediate AMD(77.6±16.1μm)and neovascular AMD(88.9±16.3μm)groups.Choroidal thickness quantification showed a generalized reduction in the central circle(P=0.002)and inner ring(P=0.001).Slight reductions in retinal thickness were more accentuated in the inner ring in the atrophic AMD(-13%;P<0.01).CONCLUSION:The variation of the analyzed structures could be an indicator of risk of progression with neurodegenerative(GCC)or vascular(choroid)pattern in the intermediate and atrophic AMD.The quantification of both structures can provide important information about the risk of disease progression in the early and intermediate stages but also for the evolution pattern into late stages(atrophic or neovascular).展开更多
Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kines...Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.展开更多
Background Coronary atherectomy is used to treat severely calcified coronary artery lesions which are more frequent with increasing age,but its impact in older adults has not been sufficiently examined.Methods We comp...Background Coronary atherectomy is used to treat severely calcified coronary artery lesions which are more frequent with increasing age,but its impact in older adults has not been sufficiently examined.Methods We compared adults≥18 years old who underwent coronary atherectomy during inpatient PCI in 2016–2023 from the Vizient Clinical Data Base and compared outcomes in younger(<65 years),youngest-old(65–74 years),middle-old(75–84 years),and oldest-old(≥85 years)adults.Primary outcome was in-hospital mortality,and secondary outcomes included postprocedural complications.Results Among 47,337 patients who underwent coronary atherectomy,19,862(42.0%)were younger adults and 27,475(58.0%)were older adults,including 13,583 youngest-old,10,206 middle-old,and 3,686 oldest-old adults.Compared with younger adults,youngest-old adults had higher mortality(adjusted odds ratio[aOR]=1.37,P<0.001),ischemic stroke(aOR=1.35,P=0.005),gastrointestinal hemorrhage(GIH)(aOR=1.44,P<0.001),acute kidney injury(AKI)(aOR=1.43,P<0.001),tamponade(aOR=1.86,P<0.001),and pericardiocentesis(aOR=2.32,P<0.001).Middle-old adults had higher mortality(aOR=1.80,P<0.001),GIH(aOR=1.42,P=0.002),AKI(aOR=1.63,P<0.001),tamponade(aOR=2.52,P<0.001),and pericardiocentesis(aOR=3.13,P<0.001).Oldest-old adults had the highest odds for mortality(aOR=2.03,P<0.001),GIH(aOR=1.48,P=0.016),AKI(aOR=2.26,P<0.001),tamponade(aOR=3.86,P<0.001),and pericardiocentesis(aOR=4.21,P<0.001).There was a significant interaction(P-interaction=0.035)between atherectomy and age groups with regard to the odds of in-hospital mortality.Conclusions In this large claims-based study,in-hospital mortality,GIH,AKI,tamponade,and pericardiocentesis were higher in older adults compared with younger adults,in a stepwise manner by age group.展开更多
AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease(NAFLD) patients.METHODS: Ovid-Medline, Pub Med, EMBASE and Cochrane database were searched fo...AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease(NAFLD) patients.METHODS: Ovid-Medline, Pub Med, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "nonalcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "MR spectroscopy" and "liver biopsy". NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy(H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. RESULTS: Eight studies met selection criteria(6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared thetwo interventions. The beneficial effects of exercise on intrahepatic triglyceride(IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents.CONCLUSION: Prescribed exercise in subjects with NAFLD reduces IHTG independent of dietary intervention. Diet and exercise was more effective than exercise alone in reducing IHTG.展开更多
Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signali...Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited.展开更多
The panel of serologic markers for inflammatory bowel diseases （IBD） is rapidly expanding. Although antiSaccharornyces cerev/siae antibodies （ASCA） and atypical perinuclear antineutrophil cytoplasmic antibodies （...The panel of serologic markers for inflammatory bowel diseases （IBD） is rapidly expanding. Although antiSaccharornyces cerev/siae antibodies （ASCA） and atypical perinuclear antineutrophil cytoplasmic antibodies （P-ANCA） remain the most widely investigated, an increasing amount of experimental data is available on newly discovered antibodies directed against various microbial antigens. The role of the assessment of various antibodies in the current IBD diagnostic algorithm is often questionable due to their limited sensitivity. In contrast, the association of serologic markers with disease behavior and phenotype is becoming increasingly well-established. An increasing number of observations confirms that patients with Crohn＇s disease expressing multiple serologic markers at high titers are more likely to have complicated small bowel disease （e.g. stricture and/or perforation） and are at higher risk for surgery than those without, or with low titers of antibodies. Creating homogenous disease sub-groups based on serologic response may help develop more standardized therapeutic approaches and may help in a better understanding of the pathomechanism of IBD. Further prospective clinical studies are needed to establish the clinical role of serologic tests in IBD.展开更多
The mechanisms of fatigue in the group of people with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are protean. The liver is central in the pathogenesis of fatigue because it uniquely regulates ...The mechanisms of fatigue in the group of people with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are protean. The liver is central in the pathogenesis of fatigue because it uniquely regulates much of the storage, release and production of substrate for energy generation. It is exquisitely sensitive to the feedback controlling the uptake and release of these energy generation substrates. Metabolic contributors to fatigue, beginning with the uptake of substrate from the gut, the passage through the portal system to hepatic storage and release of energy to target organs (muscle and brain) are central to understanding fatigue in patients with chronic liver disease. Inflammation either causing or resulting from chronic liver disease contributes to fatigue, although inflammation has not been demonstrated to be causal. It is this unique combination of factors, the nexus of metabolic abnormality and the inflammatory burden of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis that creates pathways to different types of fatigue. Many use the terms central and peripheral fatigue. Central fatigue is characterized by a lack of self-motivation and can manifest both in physical and mental activities. Peripheral fatigue is classically manifested by neuromuscular dysfunction and muscle weakness. Therefore, the distinction is often seen as a difference between intention (central fatigue) versus ability (peripheral fatigue). New approaches to measuring fatigue include the use of objective measures as well as patient reported outcomes. These measures have improved the precision with which we are able to describe fatigue. The measures of fatigue severity and its impact on usual daily routines in this population have also been improved, and they are more generally accepted as reliable and sensitive. Several approaches to evaluating fatigue and developing endpoints for treatment have relied of biosignatures associated with fatigue. These have been used singly or in combination and include: physical performance measures, cognitive performance measures, mood/behavioral measures, brain imaging and serological measures. Treatment with non-pharmacological agents have been shown to be effective in symptom reduction, whereas pharmacological agents have not been shown effective.展开更多
Induction heating has been widely used by the heat treatment industry mainly in the wind-power and automotive sectors,in particular for hardening purposes,in a broad range of applications,its main advantages being the...Induction heating has been widely used by the heat treatment industry mainly in the wind-power and automotive sectors,in particular for hardening purposes,in a broad range of applications,its main advantages being the high repeatability and easy automation of the process,both factors leading to improved manufacturing efficiency and reduced CO;emissions.Though,traditional furnace-based case hardening treatments still represent the choice of reference when performance requirements are particularly demanding,either for the critical operating conditions or safety-related issues.The processes of CIH（Contour Induction Hardening）,compared to the traditional carburizing processes,allows to reduce the deformations after heat treatment.The main purpose of these treatments,as well as increases the surface hardness of the piece,is to induce compressive stresses in the superficial layer,improving the fatigue behavior.A multiphysics magneto-thermal simulation can be developed in order to calculate the temperature distribution in the gear,setting the input parameters such as currents,frequencies and treatment times.展开更多
Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibi...Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibitory environment for axonal regeneration. Among these inhibitory molecules, myelinassociated inhibitors, including neurite outgrowth inhibitor A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein, chondroitin sulfate proteoglycans and repulsive guidance molecule A are of particular importance. Due to their inhibitory nature, they represent exciting molecular targets to study axonal inhibition and regeneration after central injuries. These molecules are mainly produced by neurons, oligodendrocytes, and astrocytes within the scar and in its immediate vicinity. They exert their effects by binding to specific receptors, localized in the membranes of neurons. Receptors for these inhibitory cues include Nogo receptor 1, leucine-rich repeat, and Ig domain containing 1 and p75 neurotrophin receptor/tumor necrosis factor receptor superfamily member 19(that form a receptor complex that binds all myelin-associated inhibitors), and also paired immunoglobulin-like receptor B. Chondroitin sulfate proteoglycans and repulsive guidance molecule A bind to Nogo receptor 1, Nogo receptor 3, receptor protein tyrosine phosphatase σ and leucocyte common antigen related phosphatase, and neogenin, respectively. Once activated, these receptors initiate downstream signaling pathways, the most common amongst them being the Rho A/ROCK signaling pathway. These signaling cascades result in actin depolymerization, neurite outgrowth inhibition, and failure to regenerate after spinal cord injury. Currently, there are no approved pharmacological treatments to overcome spinal cord injuries other than physical rehabilitation and management of the array of symptoms brought on by spinal cord injuries. However, several novel therapies aiming to modulate these inhibitory proteins and/or their receptors are under investigation in ongoing clinical trials. Investigation has also been demonstrating that combinatorial therapies of growth inhibitors with other therapies, such as growth factors or stem-cell therapies, produce stronger results and their potential application in the clinics opens new venues in spinal cord injury treatment.展开更多
BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally de...BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells.As a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in hepatocytes.However,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in hepatocytes.So far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUANTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all patients.Two hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related disorders.The duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines.In particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of 632 patients(43.8%).GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4%vs 51.5%,P<0.001),decompensation of cirrhosis(60.3%vs 35.5%,P<0.001),presence of HCC(18.4%vs 7.9%,P<0.001)and advanced HCC stage(52.9%vs 14.8%,P=0.002).GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score[Area under the curve(AUC)(95%CI):0.909(0.885-0.934)vs 0.849(0.813-0.886),P=0.003].Combination of GP73 with APRI improved further the accuracy(AUC:0.925)compared to GP73(AUC:0.909,P=0.005)or APRI alone(AUC:0.849,P<0.001).GP73 levels were significantly higher in HCC patients compared to non-HCC[22.5(29.2)vs 16(20.3)units,P<0.001)and positively associated with BCLC stage[stage 0:13.9(10.8);stage A:17.1(16.8);stage B:19.6(22.3);stage C:32.2(30.8);stage D:45.3(86.6)units,P<0.001]and tumor dimensions[very early:13.9(10.8);intermediate:19.6(18.4);advanced:29.1(33.6)units,P=0.004].However,the discriminative ability for HCC diagnosis was relatively low[AUC(95%CI):0.623(0.570-0.675)].Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline,was prognostic of higher rates of decompensation(P=0.036),HCC development(P=0.08),and liver-related deaths(P<0.001)during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination.In combination with APRI,its diagnostic performance can be further improved.Most importantly,the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases.展开更多
<strong>Introduction:</strong><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;"> The true etiology of pelvic organ p...<strong>Introduction:</strong><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;"> The true etiology of pelvic organ prolapse and urinary incontinence and variations observed among individuals are not entirely understood. Tactile (stress) and ultrasound (anatomy, strain) image fusion may furnish new insights into the female pelvic floor conditions. This study aimed to explore imaging performance and clinical value of vaginal tactile and ultrasound image fusion for characterization of the female pelvic floor. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> A novel probe with 96 tactile and 192 ultrasound transducers was designed. Women scheduled for a urogynecological visit were considered eligible for enrollment to observational study. Intravaginal tactile and ultrasound images were acquired for vaginal wall deformations at probe insertion, elevation, rotation, Valsalva maneuver, voluntary contractions, involuntary relaxation, and reflex pelvic muscle contractions. Biomechanical mapping has included tactile/ultrasound imaging and functional imaging. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> Twenty women were successfully studied with the probe. Tactile and ultrasound images for tissues deformation as well as functional images were recorded. Tactile (stress) and ultrasound (strain) images allowed creation of stress-strain maps for the tissues of interest in absolute scale. Functional images allowed identification of active pelvic structures and their biomechanical characterization (anatomical measurements, contractive mobility and strength). Fusion of the modalities has allowed recognition and characterization of levator ani muscles (pubococcygeal, puborectal, iliococcygeal), perineum, urethral and anorectal complexes critical in prolapse and/or incontinence development. </span><b><span style="font-family:Verdana;">Conclusions:</span></b><span style="font-family:Verdana;"> Vaginal tactile and ultrasound image fusion provides unique data for biomechanical characterization of the female pelvic floor. Bringing novel biomechanical characterization for critical soft tissues/structures may provide extended scientific knowledge and improve clinical practice.</span></span></span></span>展开更多
We report a case of virus-induced acute respiratory distress syndrome(ARDS)treated with parenteral vitamin C in a patient testing positive for enterovirus/rhinovirus on viral screening.This report outlines the first u...We report a case of virus-induced acute respiratory distress syndrome(ARDS)treated with parenteral vitamin C in a patient testing positive for enterovirus/rhinovirus on viral screening.This report outlines the first use of high dose intravenous vitamin C as an interventional therapy for ARDS,resulting from enterovirus/rhinovirus respiratory infection.From very significant preclinical research performed at Virginia Commonwealth Universitywith vitamin C and with the very positive results of a previously performed phaseⅠsafety trial infusing high dose vitamin C intravenously into patients with severe sepsis,we reasoned that infusing identical dosing to a patient with ARDS from viral infection would be therapeutic.We report here the case of a 20-year-old,previously healthy,female who contracted respiratory enterovirus/rhinovirus infection that led to acute lung injury and rapidly to ARDS.She contracted the infection in central Italy while on an 8-d spring break from college.During a return flight to the United States,she developed increasing dyspnea and hypoxemia that rapidly developed into acute lung injury that led to ARDS.When support with mechanical ventilation failed,extracorporeal membrane oxygenation(ECMO)was initiated.Twelve hours following ECMO initiation,high dose intravenous vitamin C was begun.The patient's recovery was rapid.ECMO and mechanical ventilation were discontinued by day-7 and the patient recovered with no long-term ARDS sequelae.Infusing high dose intravenous vitamin C into this patient with virus-induced ARDS was associated with rapid resolution of lung injury with no evidence of post-ARDS fibroproliferative sequelae.Intravenous vitamin C as a treatment for ARDS may open a new era of therapy for ARDS from many causes.展开更多
Chemotherapy in prostate cancer （PCa） has undergone dramatic landscape changes. While earlier studies utilized varying chemotherapy regimens which were found to be largely palliative in nature and hardly resulted in...Chemotherapy in prostate cancer （PCa） has undergone dramatic landscape changes. While earlier studies utilized varying chemotherapy regimens which were found to be largely palliative in nature and hardly resulted in durable or meaningful responses, docetaxel resulted in the first chemotherapy agent that showed improvement in overall survival in metastatic castration-resistant prostate cancer （mCRPC）. However, combination chemotherapy or any agents added to docetaxel have failed to yield incremental benefits. The improvement in overall survival as well as secondary endpoints of prostate-specific antigen （PSA） and time to recurrence when using docetaxel in the metastatic hormone-sensitive state has changed the standard of care for treatment of newly diagnosed de novo metastatic PCa. There are also promising results in locally advanced PCa and high-risk PCa in both the neoadjuvant and adjuvant settings. This review summarizes the historical as well as the more contemporary use of chemotherapeutic agents in PCa in varying states and phases of disease.展开更多
AIM: To assess serum cartilage oligomeric matrix protein(COMP) as a marker of cirrhosis and risk of progression to hepatocellular carcinoma(HCC). METHODS: A COMP enzyme-linked immunosorbentassay was used to test 187 p...AIM: To assess serum cartilage oligomeric matrix protein(COMP) as a marker of cirrhosis and risk of progression to hepatocellular carcinoma(HCC). METHODS: A COMP enzyme-linked immunosorbentassay was used to test 187 patients with chronic liver diseases at the time point of first evaluation. The selected patients included 72 with chronic hepatitis B infection, 75 with chronic hepatitis C infection, 22 with primary biliary cirrhosis, 7 with autoimmune hepatitis type 1, and 11 with alcoholic liver disease. Demographic, biochemical, histological and clinical characteristics of the patients were recorded at the first evaluation. One hundred and forty-seven patients were followed for a median [interquartile range(IQR)] duration of 96.5(102) mo. The clinical, biochemical and histological data, as well as the development of cirrhosis, HCC according to internationally accepted criteria and in case of death, a liver-related cause during the follow-up period, were recorded at the electronic database of our clinic. COMP determination was also performed in 43 healthy individuals who served as the control study group.RESULTS: COMP positivity(> 15 U/L) was detected in 22%-36% among chronic liver disease groups. Strikingly, almost 83% of COMP-positive patients were cirrhotic at baseline, independently of cause of liver disease. Among the patients who developed HCC during follow-up, 73.7%(14/19) were COMP positive at baseline. COMP positivity was significantly associated with older age(P < 0.001), advanced fibrosis(P = 0.001) and necroinflammatory activity(P = 0.001), higher aspartate aminotransferase(P < 0.001), alanine aminotransferase(P < 0.02), γ-glutamyl transpeptidase(P = 0.003), alkaline phosphatase(P = 0.001), bilirubin(P < 0.05), international normalized ratio(P = 0.002) and alpha-fetoprotein levels(P < 0.02), and lower albumin(P < 0.001), and platelet count(P = 0.008). COMP levels [median(IQR)] were significantly higher in cirrhotics compared to non-cirrhotics [13.8(7.9) U/L vs 9.8(4.6) U/L, respectively; P < 0.001]. On multivariate logistic regression analysis, COMP-positivity was independently associated only with cirrhosis(OR = 4.40, 95%CI: 1.33-14.69, P = 0.015). Kaplan-Meier analysis showed that COMP positivity was significantly associated with HCC development(P = 0.007) and higher incidence of liver-related death(P < 0.001). CONCLUSION: Elevated COMP levels are strongly associated with cirrhosis and HCC progression. Serum COMP is a new promising non-invasive biomarker for HCC risk assessment in surveillance programs.展开更多
基金supported by PTDC-01778/2022-NeuroDev3D,iNOVA4Health(UIDB/04462/2020 and UIDP/04462/2020)LS4FUTURE(LA/P/0087/2020)。
文摘Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these forces.Intrinsic and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse formation.In the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called plasticity.Synaptic plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).
文摘Prostate cancer is the most common non-cutaneous cancers occurring in American men,and whilemost men with early-stage prostate cancers are cured,up to a third might manifest with biochemical recurrence(BCR)of prostate cancer.BCR is a disease entitywhich is characterized by a rising prostate-specific antigen(PSA)in the setting of a previously treated localized prostate cancerwith either surgery or radiation therapywith curativeintent.
基金The authors would like to express their sincere appreciation to the research project of CNPC Geophysical Key Lab(2022DQ0604-4)National Natural Science Foundation of China(Grant No.42074141).
文摘Low-frequency vibroseis acquisition has become a routine operation in land seismic surveys,given the advantages of low-frequency signals in characterizing geological structures and enhancing the imaging of deep exploration targets.The two key points of low-frequency sweep design techniques include controlling the distortion and improving the output energy during the low-frequency stage.However,the vibrators are limited by the maximum fl ow provided by the hydraulic systems at the low-frequency stage,causing difficulty in satisfying exploration energy requirements.Initially,a theoretical analysis of the low-frequency acquisition performance of vibrators is conducted.A theoretical maximum output force below 10 Hz is obtained by guiding through theoretical formulas and combining actual vibrator parameters.Then,the signal is optimized according to the surface characteristics of the operation area.Finally,detailed application quality control and operational procedures are established.The new low-frequency sweep design method has overcome the maximum flow limitations of the hydraulic system,increased the low-frequency energy,and achieved broadband acquisition.The designed signal has been tested and applied on various types of ground surfaces in the Middle East desert region,yielding good performance.The proposed low-frequency sweep design method holds considerable value for the application of conventional vibroseis in low-frequency acquisition.
基金funded by the People’s Livelihood Plan Project of Department of Science and Technology of Liaoning Province(2021JH2/10300069,2019-ZD-0845)the Department of Education of Liaoning Province(Natural Science,Strategic Industrialization Project,LJ212410163061)the Liaoning Province College Students Innovation and Entrepreneurship Training Program(S202410163077).
文摘In this study,naringin was encapsulated in microspheres and its simulated digestive behavior in vitro was examined.Then naringin microspheres was added in yogurt to investigate the rheology and antioxidant activities.The results indicated that encapsulating naringin in microspheres delayed its digestion in the stomach,allowing more release in the intestinal part.All kinds of yogurt were solid-like in nature and the addition of microspheres increased the elastic modulus and viscosity.The naringin and microspheres incorporation enhanced the total phenolic content of the yogurt to 6.7 and 8.8 mg of gallic acid equivalent/mL,respectively.All kinds of yogurt demonstrated more than 80%scavenging ability for hydroxyl radicals at 20μL whey/mL.The addition of microspheres improved the DPPH radical scavenging ability of yogurt.This study provides a new idea for the application of polyphenols in food and the development of functional yogurt.
基金Supported by FCT/MCTES UIDB/05608/2020(https://doi.org/10.54499/UIDB/05608/2020)UIDP/05608/2020(https://doi.org/10.54499/UIDP/05608/2020)+1 种基金IDI&CA grant IPL/2022/MetAllAMD_ESTeSL by H&TRC-Health&Technology Research Center,ESTeSL-Escola Superior de Tecnologia da Saúde,Instituto Politécnico de Lisboaby Retina Institute of Lisbon(IRL).
文摘AIM:To quantify and compare longitudinal thickness changes of the ganglion cell complex(GCC)and the choroid in patients with different patterns of age-related macular degeneration(AMD)progression.METHODS:Retrospective cohort analysis of anonymized data from participants aged 50y or more and diagnosed with early/intermediate AMD in at least one eye(with no evidence of advanced AMD).A total of 64 participants were included from the Instituto de Retina de Lisboa(IRL)study(IPL/2022/MetAllAMD_ESTeSL)and divided into 4 groups according to the Rotterdam classification for AMD.Spectral domain optical coherence tomography(SD-OCT)was used to assess and quantify GCC and choroid thickness at two time points(first visit vs last visit)with a minimum interval of 3y.RESULTS:In the GCC inner ring,a thinner thickness(P=0.001)was observed in the atrophic AMD group(51.3±21.4μm)compared to the early AMD(84.3±11.5μm),intermediate AMD(77.6±16.1μm)and neovascular AMD(88.9±16.3μm)groups.Choroidal thickness quantification showed a generalized reduction in the central circle(P=0.002)and inner ring(P=0.001).Slight reductions in retinal thickness were more accentuated in the inner ring in the atrophic AMD(-13%;P<0.01).CONCLUSION:The variation of the analyzed structures could be an indicator of risk of progression with neurodegenerative(GCC)or vascular(choroid)pattern in the intermediate and atrophic AMD.The quantification of both structures can provide important information about the risk of disease progression in the early and intermediate stages but also for the evolution pattern into late stages(atrophic or neovascular).
基金supported by the Portuguese Foundation for Science and Technology(FCT),Centro 2020 and Portugol2020 and the EU FEDER program,via the project GoBack to SIV(PTDC/CVT-CVT/32261/2017,CENTRO-01-0145-FEDER-032261)the doctoral grants of PDC(SFRH/BD/139974/2018)and BMS(2020.06525.BD and DOI 10.54499/2020.06525.BD)+5 种基金the post-doctoral grant to JPF(SFRH/BPD/113359/2015-program-contract described in paragraphs 4,5,6 of art.23 of Law no.100157/2016,of August 29,as amended by Law no.57/2017 of July 2019),the project PTDC/MED-NEU/1677/2021 to JBRthe Institute of Biomedicine iBiMED(UIDB/04501/2020 and DOI 10.54499/UIDB/04501/2020,UIDP/04501/2020 and DOI 10.54499/UIDP/04501/2020)its LiM Bioimaging Facility-a PPBI node(POCI-01-0145-FEDER-022122)supported by the Research Commission of the Medical Faculty of the Heinrich-Heine-University(HHU)Düsseldorf,of the Biologisch-Medizinisches Forschungszentrum(BMFZ)of HHUfinanced by the Spanish"Plan Nacional de Investigacion Cientifica,Desarrollo e Innovacion Tecnologica,Ministerio de Economia y Competitividad(Instituto de Salud CarlosⅢ)",co-financed by the European Union(FEDER program),(grant FIS P/20/00318 and FIS P23/00337 to VC)grant CPP2021-009070 to VC by the"Proyectos de colaboracion publico-privada,Plan de Investigacion Cientifica,Tecnica y de inovacion 2021-2023,Ministerio de Ciencia e Innovacion,Union Europea,Agencia Estatal de Investigacion,Espana"。
文摘Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.
文摘Background Coronary atherectomy is used to treat severely calcified coronary artery lesions which are more frequent with increasing age,but its impact in older adults has not been sufficiently examined.Methods We compared adults≥18 years old who underwent coronary atherectomy during inpatient PCI in 2016–2023 from the Vizient Clinical Data Base and compared outcomes in younger(<65 years),youngest-old(65–74 years),middle-old(75–84 years),and oldest-old(≥85 years)adults.Primary outcome was in-hospital mortality,and secondary outcomes included postprocedural complications.Results Among 47,337 patients who underwent coronary atherectomy,19,862(42.0%)were younger adults and 27,475(58.0%)were older adults,including 13,583 youngest-old,10,206 middle-old,and 3,686 oldest-old adults.Compared with younger adults,youngest-old adults had higher mortality(adjusted odds ratio[aOR]=1.37,P<0.001),ischemic stroke(aOR=1.35,P=0.005),gastrointestinal hemorrhage(GIH)(aOR=1.44,P<0.001),acute kidney injury(AKI)(aOR=1.43,P<0.001),tamponade(aOR=1.86,P<0.001),and pericardiocentesis(aOR=2.32,P<0.001).Middle-old adults had higher mortality(aOR=1.80,P<0.001),GIH(aOR=1.42,P=0.002),AKI(aOR=1.63,P<0.001),tamponade(aOR=2.52,P<0.001),and pericardiocentesis(aOR=3.13,P<0.001).Oldest-old adults had the highest odds for mortality(aOR=2.03,P<0.001),GIH(aOR=1.48,P=0.016),AKI(aOR=2.26,P<0.001),tamponade(aOR=3.86,P<0.001),and pericardiocentesis(aOR=4.21,P<0.001).There was a significant interaction(P-interaction=0.035)between atherectomy and age groups with regard to the odds of in-hospital mortality.Conclusions In this large claims-based study,in-hospital mortality,GIH,AKI,tamponade,and pericardiocentesis were higher in older adults compared with younger adults,in a stepwise manner by age group.
文摘AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease(NAFLD) patients.METHODS: Ovid-Medline, Pub Med, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "nonalcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "MR spectroscopy" and "liver biopsy". NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy(H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. RESULTS: Eight studies met selection criteria(6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared thetwo interventions. The beneficial effects of exercise on intrahepatic triglyceride(IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents.CONCLUSION: Prescribed exercise in subjects with NAFLD reduces IHTG independent of dietary intervention. Diet and exercise was more effective than exercise alone in reducing IHTG.
文摘Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited.
文摘The panel of serologic markers for inflammatory bowel diseases （IBD） is rapidly expanding. Although antiSaccharornyces cerev/siae antibodies （ASCA） and atypical perinuclear antineutrophil cytoplasmic antibodies （P-ANCA） remain the most widely investigated, an increasing amount of experimental data is available on newly discovered antibodies directed against various microbial antigens. The role of the assessment of various antibodies in the current IBD diagnostic algorithm is often questionable due to their limited sensitivity. In contrast, the association of serologic markers with disease behavior and phenotype is becoming increasingly well-established. An increasing number of observations confirms that patients with Crohn＇s disease expressing multiple serologic markers at high titers are more likely to have complicated small bowel disease （e.g. stricture and/or perforation） and are at higher risk for surgery than those without, or with low titers of antibodies. Creating homogenous disease sub-groups based on serologic response may help develop more standardized therapeutic approaches and may help in a better understanding of the pathomechanism of IBD. Further prospective clinical studies are needed to establish the clinical role of serologic tests in IBD.
文摘The mechanisms of fatigue in the group of people with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are protean. The liver is central in the pathogenesis of fatigue because it uniquely regulates much of the storage, release and production of substrate for energy generation. It is exquisitely sensitive to the feedback controlling the uptake and release of these energy generation substrates. Metabolic contributors to fatigue, beginning with the uptake of substrate from the gut, the passage through the portal system to hepatic storage and release of energy to target organs (muscle and brain) are central to understanding fatigue in patients with chronic liver disease. Inflammation either causing or resulting from chronic liver disease contributes to fatigue, although inflammation has not been demonstrated to be causal. It is this unique combination of factors, the nexus of metabolic abnormality and the inflammatory burden of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis that creates pathways to different types of fatigue. Many use the terms central and peripheral fatigue. Central fatigue is characterized by a lack of self-motivation and can manifest both in physical and mental activities. Peripheral fatigue is classically manifested by neuromuscular dysfunction and muscle weakness. Therefore, the distinction is often seen as a difference between intention (central fatigue) versus ability (peripheral fatigue). New approaches to measuring fatigue include the use of objective measures as well as patient reported outcomes. These measures have improved the precision with which we are able to describe fatigue. The measures of fatigue severity and its impact on usual daily routines in this population have also been improved, and they are more generally accepted as reliable and sensitive. Several approaches to evaluating fatigue and developing endpoints for treatment have relied of biosignatures associated with fatigue. These have been used singly or in combination and include: physical performance measures, cognitive performance measures, mood/behavioral measures, brain imaging and serological measures. Treatment with non-pharmacological agents have been shown to be effective in symptom reduction, whereas pharmacological agents have not been shown effective.
文摘Induction heating has been widely used by the heat treatment industry mainly in the wind-power and automotive sectors,in particular for hardening purposes,in a broad range of applications,its main advantages being the high repeatability and easy automation of the process,both factors leading to improved manufacturing efficiency and reduced CO;emissions.Though,traditional furnace-based case hardening treatments still represent the choice of reference when performance requirements are particularly demanding,either for the critical operating conditions or safety-related issues.The processes of CIH（Contour Induction Hardening）,compared to the traditional carburizing processes,allows to reduce the deformations after heat treatment.The main purpose of these treatments,as well as increases the surface hardness of the piece,is to induce compressive stresses in the superficial layer,improving the fatigue behavior.A multiphysics magneto-thermal simulation can be developed in order to calculate the temperature distribution in the gear,setting the input parameters such as currents,frequencies and treatment times.
基金a Ph D fellowship by FCT-Fundacao para a Ciência Tecnologia (SFRH/BD/135868/2018)(to SSC)。
文摘Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibitory environment for axonal regeneration. Among these inhibitory molecules, myelinassociated inhibitors, including neurite outgrowth inhibitor A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein, chondroitin sulfate proteoglycans and repulsive guidance molecule A are of particular importance. Due to their inhibitory nature, they represent exciting molecular targets to study axonal inhibition and regeneration after central injuries. These molecules are mainly produced by neurons, oligodendrocytes, and astrocytes within the scar and in its immediate vicinity. They exert their effects by binding to specific receptors, localized in the membranes of neurons. Receptors for these inhibitory cues include Nogo receptor 1, leucine-rich repeat, and Ig domain containing 1 and p75 neurotrophin receptor/tumor necrosis factor receptor superfamily member 19(that form a receptor complex that binds all myelin-associated inhibitors), and also paired immunoglobulin-like receptor B. Chondroitin sulfate proteoglycans and repulsive guidance molecule A bind to Nogo receptor 1, Nogo receptor 3, receptor protein tyrosine phosphatase σ and leucocyte common antigen related phosphatase, and neogenin, respectively. Once activated, these receptors initiate downstream signaling pathways, the most common amongst them being the Rho A/ROCK signaling pathway. These signaling cascades result in actin depolymerization, neurite outgrowth inhibition, and failure to regenerate after spinal cord injury. Currently, there are no approved pharmacological treatments to overcome spinal cord injuries other than physical rehabilitation and management of the array of symptoms brought on by spinal cord injuries. However, several novel therapies aiming to modulate these inhibitory proteins and/or their receptors are under investigation in ongoing clinical trials. Investigation has also been demonstrating that combinatorial therapies of growth inhibitors with other therapies, such as growth factors or stem-cell therapies, produce stronger results and their potential application in the clinics opens new venues in spinal cord injury treatment.
文摘BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells.As a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in hepatocytes.However,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in hepatocytes.So far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUANTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all patients.Two hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related disorders.The duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines.In particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of 632 patients(43.8%).GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4%vs 51.5%,P<0.001),decompensation of cirrhosis(60.3%vs 35.5%,P<0.001),presence of HCC(18.4%vs 7.9%,P<0.001)and advanced HCC stage(52.9%vs 14.8%,P=0.002).GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score[Area under the curve(AUC)(95%CI):0.909(0.885-0.934)vs 0.849(0.813-0.886),P=0.003].Combination of GP73 with APRI improved further the accuracy(AUC:0.925)compared to GP73(AUC:0.909,P=0.005)or APRI alone(AUC:0.849,P<0.001).GP73 levels were significantly higher in HCC patients compared to non-HCC[22.5(29.2)vs 16(20.3)units,P<0.001)and positively associated with BCLC stage[stage 0:13.9(10.8);stage A:17.1(16.8);stage B:19.6(22.3);stage C:32.2(30.8);stage D:45.3(86.6)units,P<0.001]and tumor dimensions[very early:13.9(10.8);intermediate:19.6(18.4);advanced:29.1(33.6)units,P=0.004].However,the discriminative ability for HCC diagnosis was relatively low[AUC(95%CI):0.623(0.570-0.675)].Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline,was prognostic of higher rates of decompensation(P=0.036),HCC development(P=0.08),and liver-related deaths(P<0.001)during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination.In combination with APRI,its diagnostic performance can be further improved.Most importantly,the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases.
文摘<strong>Introduction:</strong><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;"> The true etiology of pelvic organ prolapse and urinary incontinence and variations observed among individuals are not entirely understood. Tactile (stress) and ultrasound (anatomy, strain) image fusion may furnish new insights into the female pelvic floor conditions. This study aimed to explore imaging performance and clinical value of vaginal tactile and ultrasound image fusion for characterization of the female pelvic floor. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> A novel probe with 96 tactile and 192 ultrasound transducers was designed. Women scheduled for a urogynecological visit were considered eligible for enrollment to observational study. Intravaginal tactile and ultrasound images were acquired for vaginal wall deformations at probe insertion, elevation, rotation, Valsalva maneuver, voluntary contractions, involuntary relaxation, and reflex pelvic muscle contractions. Biomechanical mapping has included tactile/ultrasound imaging and functional imaging. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> Twenty women were successfully studied with the probe. Tactile and ultrasound images for tissues deformation as well as functional images were recorded. Tactile (stress) and ultrasound (strain) images allowed creation of stress-strain maps for the tissues of interest in absolute scale. Functional images allowed identification of active pelvic structures and their biomechanical characterization (anatomical measurements, contractive mobility and strength). Fusion of the modalities has allowed recognition and characterization of levator ani muscles (pubococcygeal, puborectal, iliococcygeal), perineum, urethral and anorectal complexes critical in prolapse and/or incontinence development. </span><b><span style="font-family:Verdana;">Conclusions:</span></b><span style="font-family:Verdana;"> Vaginal tactile and ultrasound image fusion provides unique data for biomechanical characterization of the female pelvic floor. Bringing novel biomechanical characterization for critical soft tissues/structures may provide extended scientific knowledge and improve clinical practice.</span></span></span></span>
基金supported by the Aubrey Sage McF arlane acute lung injury fund,the VCU Johnson Center for Critical Care and Pulmonary Research
文摘We report a case of virus-induced acute respiratory distress syndrome(ARDS)treated with parenteral vitamin C in a patient testing positive for enterovirus/rhinovirus on viral screening.This report outlines the first use of high dose intravenous vitamin C as an interventional therapy for ARDS,resulting from enterovirus/rhinovirus respiratory infection.From very significant preclinical research performed at Virginia Commonwealth Universitywith vitamin C and with the very positive results of a previously performed phaseⅠsafety trial infusing high dose vitamin C intravenously into patients with severe sepsis,we reasoned that infusing identical dosing to a patient with ARDS from viral infection would be therapeutic.We report here the case of a 20-year-old,previously healthy,female who contracted respiratory enterovirus/rhinovirus infection that led to acute lung injury and rapidly to ARDS.She contracted the infection in central Italy while on an 8-d spring break from college.During a return flight to the United States,she developed increasing dyspnea and hypoxemia that rapidly developed into acute lung injury that led to ARDS.When support with mechanical ventilation failed,extracorporeal membrane oxygenation(ECMO)was initiated.Twelve hours following ECMO initiation,high dose intravenous vitamin C was begun.The patient's recovery was rapid.ECMO and mechanical ventilation were discontinued by day-7 and the patient recovered with no long-term ARDS sequelae.Infusing high dose intravenous vitamin C into this patient with virus-induced ARDS was associated with rapid resolution of lung injury with no evidence of post-ARDS fibroproliferative sequelae.Intravenous vitamin C as a treatment for ARDS may open a new era of therapy for ARDS from many causes.
文摘Chemotherapy in prostate cancer （PCa） has undergone dramatic landscape changes. While earlier studies utilized varying chemotherapy regimens which were found to be largely palliative in nature and hardly resulted in durable or meaningful responses, docetaxel resulted in the first chemotherapy agent that showed improvement in overall survival in metastatic castration-resistant prostate cancer （mCRPC）. However, combination chemotherapy or any agents added to docetaxel have failed to yield incremental benefits. The improvement in overall survival as well as secondary endpoints of prostate-specific antigen （PSA） and time to recurrence when using docetaxel in the metastatic hormone-sensitive state has changed the standard of care for treatment of newly diagnosed de novo metastatic PCa. There are also promising results in locally advanced PCa and high-risk PCa in both the neoadjuvant and adjuvant settings. This review summarizes the historical as well as the more contemporary use of chemotherapeutic agents in PCa in varying states and phases of disease.
文摘AIM: To assess serum cartilage oligomeric matrix protein(COMP) as a marker of cirrhosis and risk of progression to hepatocellular carcinoma(HCC). METHODS: A COMP enzyme-linked immunosorbentassay was used to test 187 patients with chronic liver diseases at the time point of first evaluation. The selected patients included 72 with chronic hepatitis B infection, 75 with chronic hepatitis C infection, 22 with primary biliary cirrhosis, 7 with autoimmune hepatitis type 1, and 11 with alcoholic liver disease. Demographic, biochemical, histological and clinical characteristics of the patients were recorded at the first evaluation. One hundred and forty-seven patients were followed for a median [interquartile range(IQR)] duration of 96.5(102) mo. The clinical, biochemical and histological data, as well as the development of cirrhosis, HCC according to internationally accepted criteria and in case of death, a liver-related cause during the follow-up period, were recorded at the electronic database of our clinic. COMP determination was also performed in 43 healthy individuals who served as the control study group.RESULTS: COMP positivity(> 15 U/L) was detected in 22%-36% among chronic liver disease groups. Strikingly, almost 83% of COMP-positive patients were cirrhotic at baseline, independently of cause of liver disease. Among the patients who developed HCC during follow-up, 73.7%(14/19) were COMP positive at baseline. COMP positivity was significantly associated with older age(P < 0.001), advanced fibrosis(P = 0.001) and necroinflammatory activity(P = 0.001), higher aspartate aminotransferase(P < 0.001), alanine aminotransferase(P < 0.02), γ-glutamyl transpeptidase(P = 0.003), alkaline phosphatase(P = 0.001), bilirubin(P < 0.05), international normalized ratio(P = 0.002) and alpha-fetoprotein levels(P < 0.02), and lower albumin(P < 0.001), and platelet count(P = 0.008). COMP levels [median(IQR)] were significantly higher in cirrhotics compared to non-cirrhotics [13.8(7.9) U/L vs 9.8(4.6) U/L, respectively; P < 0.001]. On multivariate logistic regression analysis, COMP-positivity was independently associated only with cirrhosis(OR = 4.40, 95%CI: 1.33-14.69, P = 0.015). Kaplan-Meier analysis showed that COMP positivity was significantly associated with HCC development(P = 0.007) and higher incidence of liver-related death(P < 0.001). CONCLUSION: Elevated COMP levels are strongly associated with cirrhosis and HCC progression. Serum COMP is a new promising non-invasive biomarker for HCC risk assessment in surveillance programs.
