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Frailty in end-stage liver disease:Understanding pathophysiology,tools for assessment,and strategies for management

World Journal of Gastroenterology 2023年第46期29卷 6028-6048页

作者： Mazen Elsheikh Ahmed El Sabagh Islam B Mohamed megha bhongade Manal M Hassan Prasun Kumar Jalal Department of Gastroenterology and Hepatology Baylor College of MedicineHoustonTX 77030United States Department of Epidemiology Division of Cancer Prevention and Population SciencesThe University of TexasMD Anderson Cancer CenterHoustonTX 77030United States

Frailty and sarcopenia are frequently observed in patients with end-stage liver *** is a complex condition that arises from deteriorations across various physiological systems,including the musculoskeletal,cardiovascular,and immune systems,resulting in a reduced ability of the body to withstand *** condition is associated with declined resilience and increased vulnerability to negative outcomes,including disability,hospitalization,and *** cirrhotic patients,frailty is influenced by multiple factors,such as hyperammonemia,hormonal imbalance,malnutrition,ascites,hepatic encephalopathy,and alcohol *** frailty is crucial in predicting morbidity and mortality in cirrhotic *** can aid in making critical decisions regarding patients’eligibility for critical care and ***,in turn,can guide the development of an individualized treatment plan for each patient with cirrhosis,with a focus on prioritizing exercise,proper nutrition,and appropriate treatment of hepatic complications as the primary lines of *** this review,we aim to explore the topic of frailty in liver diseases,with a particular emphasis on pathophysiology,clinical assessment,and discuss strategies for preventing frailty through effective treatment of hepatic ***,we explore novel assessment and management strategies that have emerged in recent years,including the use of wearable technology and telemedicine.

关键词： End-stage liver disease Frailty Liver cirrhosis Malnutrition Sarcopenia

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The Largest Chinese Cohort Study Indicates Homologous Recombination Pathway Gene Mutations as Another Major Genetic Risk Factor for Colorectal Cancer with Heterogeneous Clinical Phenotypes

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Research 2024年第3期6卷 191-203页

作者： Yun Xu Kai Liu Cong Li Minghan Li Fangqi Liu Xiaoyan Zhou Menghong Sun megha Ranganathan Liying Zhang Sheng Wang Xin Hu Ye Xu Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghaiP.R.China Department of Pathology Fudan University Shanghai Cancer CenterShanghaiP.R.China Department of Pathology Tissue BankFudan University Shanghai Cancer CenterShanghaiP.R.China Department of Medicine Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Department of Pathology and Laboratory Medicine David Geffen School of MedicineUniversity of CaliforniaLos AngelesCAUSA Precision Cancer Medical Center Fudan University Shanghai Cancer CenterShanghaiP.R.China

While genetic factors were associated with over 30% of colorectal cancer (CRC) patients, mutations in CRC-susceptibility genes were identified in only 5% to 10% of these patients. Besides, previous studies on hereditary CRC were largely designed to analyze germline mutations in patients with single genetic high-risk factor, which limited understanding of the association between genotype and phenotypes. From January 2015 to December 2018, we retrospectively enrolled 2,181 patients from 8,270 consecutive CRC cases, covering 5 categories of genetic high-risk factors. Leukocyte genomic DNA was analyzed for germline mutations in cancer predisposition genes. The germline mutations under each category were detected and analyzed in association with CRC susceptibility, clinical phenotypes, and prognoses. A total of 462 pathogenic variants were detected in 19.3% of enrolled CRC patients. Mismatch repair gene mutation was identified in 9.1% of patients, most prevalent across all high-risk groups. Homologous recombination (HR) gene mutations were detected in 6.5% of cases, penetrated in early-onset and extra-colonic cancer risk groups. Mutations in HR genes, including BARD1, RAD50, and ATM, were found to increase CRC risk with odds ratios of 2.8-, 3.1-, and 3.1-fold, respectively. CRC patients with distinct germline mutations manifested heterogeneous phenotypes in clinicopathology and long-term prognoses. Thus, germline mutation screenings should be performed for CRC patients with any of those genetic risk factors. This study also reveals that HR gene mutations may be another major driver for increased CRC risk.

关键词： susceptibility category Major

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On the road to new treatments for multiple sclerosis: targeting dendritic cell migration into the central nervous system

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Neural Regeneration Research 2019年第12期14卷 2088-2090页

作者： megha Meena Nathalie Cools Laboratory of Experimental Hematology Vaccine & Infectious Disease Institute (VAXINFECTIO) Faculty of Medicine and Health Sciences University of Antwerp

Distinct migratory pathways and trafficking of dendritic cells to the central nervous system (CNS): The immune system is a host defense mechanism protecting against invaders, such as bacteria and viruses, while maintaining tolerance to self. Nonetheless, a few sites throughout the body are believed to be immunologically inert, such as the testes, the eye and the brain. Indeed, experiments in the mid-20th century gave rise to the concept of the brain as a site of immune privilege. Originally, the immune privilege of the brain was thought to be absolute, attributed by a physical blood-brain barrier (BBB) protecting the CNS from the entry of pathogens and circulating immune cells. These views have changed and currently, the CNS is seen as an immune-specialized site regulated by immunological components into and within the CNS.

关键词： new treatments multiple sclerosis nervous system

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Potential cotton aphid, Aphis gossypii, population suppression by arthropod predators in upland cotton

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Insect Science 2013年第6期20卷 778-788页

作者： Ram B. Shrestha megha N. Parajulee Texas A&M University AgriLife Research and Extension Center 1102 E. FM 1294 Lubbock TX 79403 United States

The cotton aphid, Aphis gossypii Glover, predation rate of convergent lady beetle, Hippodamia convergens Guerin-Meneville, was determined by assigning a single predator randomly to each of four prey density treatments in the laboratory. Prey densities included 25, 50, 100, and 200 aphids per Petri dish arena. Predation response was recorded at 1, 4, 8, 16, 24, and 48 h after assigning predators to their prey treatments. Rate of consumption increased through time, with all 25 aphids consumed during the first 4 h of the experiment. At the highest density, adult lady beetle consumed on average 49, 99, 131, 163, 183, and 200 aphids within 1, 4, 8, 16, 24 and 48 h, respectively. Predators showed a curvilinear feeding response in relation to total available time, indicating that convergent lady beetles have the potential to suppress larger populations of aphids through continuous feeding by regulating their predation efficiency during feeding. The analysis of age-specific mortality in absence of prey revealed that lady beetles could survive for an extended period of time （more than 2 weeks） without prey. The ability of a predator to survive without prey delays or prevents the rebound of pest populations that is a significant factor in natural biological control. A two-year field sampling of 10 cotton arthropod predator species showed that spiders （27%） were the most dominant foliage dwelling predators in the Texas High Plains cotton followed by convergent lady beetles （23.5%）, hooded beetles （13.5%）, minute pirate bugs （11%）, green lacewings （9.5%）, bigeyed bugs （7.5%）, scymnus beetles （3%）, soft-winged flower beetles （2%）, damsel bugs （1.5%）, and assassin bugs （1.5%）. A field cage study showed that one H. convergens adult per plant released at prey density of one aphid per leaf kept the aphid population below economic threshold for the entire growing season.

关键词： Aphis gossypii biological control cotton IPM functional response Hippo-damia convergens natural suppression

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Development and validation of Hyperacusis Handicap Questionnaire in individuals with tinnitus associated with hyperacusis

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Journal of Otology 2020年第4期15卷 124-128页

作者： Prashanth Prabhu megha Kondli Nagaraj All India Institute of Speech and Hearing ManasagangothriMysuru570006India

Introduction:Hypersensitivity to sound and tinnitus are often co-morbid and can influence emotional well-being,hearing,sleep,concentration,cause anxiety,and interfere with speech perception in ***:A clear measure of sensitivity to sound is important as there is dearth in standard protocol for evaluating hyperacusis in individuals with *** there are a few questionnaires to assess hyperacusis,a direct application of these questionnaires in the Indian context would be ***:The study attempts to develop and validate an indigenous Hyperacusis Handicap Questionnaire(HHQ)for individuals with tinnitus associated with ***:A total of 25 questions were considered for ***,21 questions were subdivided into three sections of seven questions each,tapping,‘Functional,’‘Social,’and‘Emotional’aspects of the *** was administered on 77 individuals with tinnitus associated with hyperacusis in the age range of 20e55 years for further validation.A total score was obtained by adding all the three ***:The internal consistency of the questionnaire was determined by Cronbach’s Alpha(a)was a?0.85;and,a?0.83 for Functional,a?0.81 for Social,a?0.7 for Emotional subscales suggesting that the questionnaire can be used for the assessment of handicap associated with hyperacusis in individuals with ***,no significant difference in terms of gender and duration of tinnitus comparisons were ***:The obtained results suggest that HHQ will aid in the characterization and quantification of the handicap associated with hyperacusis in individuals with tinnitus.

关键词： Quality of life Annoyance Reduced tolerance Hypersensitivity

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Effects of environmental humidity on the survival and development of pine caterpillars, Dendrolimus tabulaeformis （Lepidoptera： Lasiocampidae）

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Insect Science 2008年第2期15卷 147-152页

作者： Rui-Dong Han megha Parajulee Zhong He Feng Ge State Key Laboratory of Integrated Management of Pest Insects and Rodents Institute of Zoology Chinese Academy of Sciences Beijing Weifang Forestry Bureau of Shandong Province Weifang City Shandong Province China Texas Agricultural Experiment Station Lubbock Texas USA

The pine caterpillar, Dendrolimus tabulaeformis is one of the most important pests on Pinus tabulaeformis and other pine species in North China. In the present study, effects of relative humidity （RH） on the development and survival of pine caterpillars and soil moisture （SM） on their diapausing larvae were investigated. Low RH （20%） deferred the development of eggs and larvae, reduced egg hatching and larval surviving compared to 40%, 60% and 80% RH. Both low （20%） and high （100%） RH reduced egg hatching, but only 20% RH deferred the development of larvae, prolonged developmental duration and reduced the body mass and body length of larvae. The SM influenced the survival of diapausing larvae significantly. The dry treatment significantly reduced the supercooling points （SCPs）, whereas increased the mortality and reduced body mass from 56.9 to 36.5 mg and body water content from 78% to 63% after 2 weeks＇ exposure. Therefore, higher RH is more favorable for the development of early instars and survival of diapausing larvae of the pine caterpillars.

关键词： cold hardiness Dendrolimus tabulaeformis development mortality relative humidit y

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Metapopulation approach for landscape level management of western tarnished plant bug,Lygus hesperus,in Texas( Hemiptera,Miridae)

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植物保护学报 2014年第6期41卷 761-768页

作者： Parajulee megha N Shrestha Ram B Texas A & M University System AgriLife Research and Extension Center

Insect source-sink dynamics are vital to ecologically intensive pest management. Maintaining sink plant hosts,or "trap crops",and destroying alternate hosts or breeding places adjacent to the field crop are effective pest management strategies for some arthropods. However,determining whether a host acts as a source or a sink is challenging, especially when the pest species is highly mobile and polyphagous. The western tarnished plant bug,Lygus hesperus,is highly polyphagous,and can utilize >300 hosts. Its presence has been documented in 26 roadside weed hosts in the Texas High *** studies demonstrated that L. hesperus prefer alfalfa over cotton and several alternate weed hosts.A four-year project involved surveying and sampling for L. hesperus in the agricultural landscapes of several sub-regions of the southwestern United States,including the Texas High Plains. In Texas,geographic information of the landscape vegetation complex was compiled from a 150 km radius in the Texas High Plains. In one study,fifty irrigated cotton fields representing the crop diversity within this region were sampled via sweep-net for 10 weeks. This effort also included sampling of up to six noncotton insect habitats within a 3 km radius of each field. Seasonal average L. hesperus abundance data were regressed with 27 field characteristics( variables),including habitat-specific land cover,distance between focal cotton fields and non-cotton habitats,longitude,latitude,elevation,habitat heterogeneity index,and several environmental / ecological variables. Significant variables were selected using a stepwise regression at 15% probability rate. A 10-parameter linear model explained 93% of the variation in the data. Major parameters contributing significantly to variation in L. hesperus abundance in cotton were corn and sunflower acreages,focal cotton field distances from several non-cotton hosts,and habitat heterogeneity index. In addition,field marking-and-capture studies were cond

关键词： western tarnished plant bug cotton IPM ecological pest management alternate host management

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Understanding the interaction of hepatitis C virus with host DEAD-box RNA helicases

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World Journal of Gastroenterology 2014年第11期20卷 2913-2926页

作者： megha Haridas Upadya Jude Juventus Aweya Yee-Joo Tan Department of Microbiology Yong Loo Lin School of MedicineNational University Health System (NUHS)National University of SingaporeSingapore 117597Singapore Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research (A*STAR)Singapore 138673Singapore

The current therapeutic regimen to combat chronic hepatitis C is not optimal due to substantial side effects and the failure of a significant proportion of patients to achieve a sustained virological response. Recently developed direct-acting antivirals targeting hepatitis C virus (HCV) enzymes reportedly increase the virologic response to therapy but may lead to a selection of drug-resistant variants. Besides direct-acting antivirals, another promising class of HCV drugs in development include host targeting agents that are responsible for interfering with the host factors crucial for the viral life cycle. A family of host proteins known as DEAD-box RNA helicases, characterized by nine conserved motifs, is known to play an important role in RNA metabolism. Several members of this family such as DDX3, DDX5 and DDX6 have been shown to play a role in HCV replication and this review will summarize our current knowledge on their interaction with HCV. As chronic hepatitis C is one of the leading causes of hepatocellular carcinoma, the involvement of DEAD-box RNA helicases in the development of HCC will also be highlighted. Continuing research on the interaction of host DEAD-box proteins with HCV and the contribution to viral replication and pathogenesis could be the panacea for the development of novel therapeutics against HCV.

关键词： Hepatitis C virus Chronic hepatitis C Hepatitis C virus therapy DEAD-box helicases Host factors Hepatocellular carcinoma

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The link between olfactory ensheathing cell survival and spinal cord injury repair: a commentary on common limitations of contemporary research

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Neural Regeneration Research 2020年第10期15卷 1848-1849页

作者： Ronak Reshamwala megha Shah James St.John Jenny Ekberg Griffith Institute for Drug Discovery Griffith UniversityBrisbaneQLDAustralia Menzies Health Institute Queensland Griffith UniversitySouthportQLDAustraliaClem Jones Centre for Neurobiology and Stem Cell ResearchGriffith UniversityBrisbaneQLDAustralia

Olfactory ensheathing cells(OECs)are crucial players in the continuous regeneration of the olfactory nervous system that occurs through out life and are thought to have unique growth-promoting *** this reason,OEC transplantation has been thoroughly explored for the potential to promote neural repair after both central and peripheral nervous system *** studies have shown that OEC transplantation is safe and can promote recovery after spinal cord injury(SCI),both in animal models and in human clinical *** date,a variety of injury types and time-points after injury,as well as different delivery methods,have been *** have been encouraging(in rodent models including,for example,restoration of locomotion,breathing and climbing ability along with induction of axonal sprouting and some axonal regeneration)but highly variable(Barnett and Riddell,2007;Gomez et al.,2018).

关键词： injuries injury limitations

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Relative preference of Lygus hesperus （Hemiptera： Miridae） to selected host plants in the field

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Insect Science 2010年第6期17卷 542-548页

作者： Apurba K. Barman megha N. Parajulee Stanley C. Carroll Department of Entomology Texas A&M University College Station Texas AgriLife Research Center Lubbock Texas USA

Information on host plant preference of agriculturally important insect pests, such as Lygus hesperus （Knight）, can be helpful in predicting its occurrence and future movement among crop and nonrop host plants. A field study was conducted during 2005 and 2006 to evaluate the host preference of Lygus to cotton and four other host plants in the Texas High Plains, including alfalfa （Medicago sativa L.）, wild sunflower （Helianthus annuus L.）, Russian thistle （Salsola iberica L.） and pigweed （Amaranthus palmeri L.）. Sampling for both nymphs and adults during 2005 （July to November） and 2006 （June to November） showed that alfalfa and Russian thistle were the two most preferred hosts out of the five hosts evaluated. Abundance of nymphs （numbers per 50 sweeps per host plant） during the sampling period also indicated the superior reproductive suitability of alfalfa and Russian thistle. Cotton appeared to be the least attractive host plant for Lygus when Russian thistle and alfalfa were available in the host mosaic. Seasonal abundance of Lygus was found to be lower during 2006 compared to 2005, which may be explained by the difference in rainfall patterns during these two years. In terms of species dominance, L. hesperus was the most dominant species in the sampled population followed by an inconsiderable fraction ofL. elisus and L. lineolaris.

关键词： cotton crop host-plant preference Lygus hesperus non-cotton crops

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