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1.
ACG Case Rep J ; 11(5): e01336, 2024 May.
Article in English | MEDLINE | ID: mdl-38682079

ABSTRACT

Porphyria caused by inherited disorders in heme biosynthesis can lead to accumulation of porphyrins in various organs. Liver involvement due to porphyria mostly results in cholestasis leading to liver cirrhosis or hepatocellular carcinoma. Congenital erythropoietic porphyria (CEP), a rare porphyria due to deficiency of uroporphyrinogen III synthase, mostly results in cutaneous manifestations. There are reports of liver involvement including varying degree of fibrosis in patients with CEP. We report a unique case of a patient with CEP who developed porto-sinusoidal vascular disease with complications of portal hypertension that necessitated liver transplantation.

2.
Biochemistry ; 63(9): 1162-1169, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38668883

ABSTRACT

Parkinson's disease (PD) is characterized by the toxic oligomeric and fibrillar phases formed by monomeric alpha-synuclein (α-syn). Certain nanoparticles have been demonstrated to promote protein aggregation, while other nanomaterials have been found to prevent the process. In the current work, we use nuclear magnetic resonance spectroscopy in conjunction with isothermal titration calorimetry to investigate the cause and mechanism of these opposing effects at the amino acid protein level. The interaction of α-syn with two types of nanomaterials was considered: citrate-capped gold nanoparticles (AuNPs) and graphene oxide (GO). In the presence of AuNPs, α-syn aggregation is accelerated, whereas in the presence of GO, aggregation is prevented. The study indicates that GO sequesters the NAC region of α-syn monomers through electrostatic and hydrophobic interactions, leading to a reduced elongation rate, and AuNPs leave the NAC region exposed while binding the N-terminus, leading to higher aggregation. The protein's inclination toward quicker aggregation is explained by the binding of the N-terminus of α-syn with the gold nanoparticles. Conversely, a comparatively stronger interaction with GO causes the nucleation and growth phases to be postponed and inhibits intermolecular interactions. Our finding offers novel experimental insights at the residue level regarding the aggregation of α-syn in the presence of various nanomaterials and creates new opportunities for the development of suitably functionalized nanomaterial-based therapeutic reagents against Parkinson's and other neurodegenerative diseases.


Subject(s)
Metal Nanoparticles , Protein Aggregates , alpha-Synuclein , Humans , alpha-Synuclein/chemistry , alpha-Synuclein/metabolism , Citric Acid/chemistry , Citric Acid/metabolism , Gold/chemistry , Graphite/chemistry , Hydrophobic and Hydrophilic Interactions , Metal Nanoparticles/chemistry , Nanostructures/chemistry , Parkinson Disease/metabolism , Protein Aggregates/drug effects
3.
Front Hum Neurosci ; 18: 1354143, 2024.
Article in English | MEDLINE | ID: mdl-38435744

ABSTRACT

In this study, we explore the potential of using functional near-infrared spectroscopy (fNIRS) signals in conjunction with modern machine-learning techniques to classify specific anatomical movements to increase the number of control commands for a possible fNIRS-based brain-computer interface (BCI) applications. The study focuses on novel individual finger-tapping, a well-known task in fNIRS and fMRI studies, but limited to left/right or few fingers. Twenty-four right-handed participants performed the individual finger-tapping task. Data were recorded by using sixteen sources and detectors placed over the motor cortex according to the 10-10 international system. The event's average oxygenated Δ HbO and deoxygenated Δ HbR hemoglobin data were utilized as features to assess the performance of diverse machine learning (ML) models in a challenging multi-class classification setting. These methods include LDA, QDA, MNLR, XGBoost, and RF. A new DL-based model named "Hemo-Net" has been proposed which consists of multiple parallel convolution layers with different filters to extract the features. This paper aims to explore the efficacy of using fNRIS along with ML/DL methods in a multi-class classification task. Complex models like RF, XGBoost, and Hemo-Net produce relatively higher test set accuracy when compared to LDA, MNLR, and QDA. Hemo-Net has depicted a superior performance achieving the highest test set accuracy of 76%, however, in this work, we do not aim at improving the accuracies of models rather we are interested in exploring if fNIRS has the neural signatures to help modern ML/DL methods in multi-class classification which can lead to applications like brain-computer interfaces. Multi-class classification of fine anatomical movements, such as individual finger movements, is difficult to classify with fNIRS data. Traditional ML models like MNLR and LDA show inferior performance compared to the ensemble-based methods of RF and XGBoost. DL-based method Hemo-Net outperforms all methods evaluated in this study and demonstrates a promising future for fNIRS-based BCI applications.

4.
Alcohol Clin Exp Res (Hoboken) ; 48(2): 273-282, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38123167

ABSTRACT

BACKGROUND: Acute alcohol-associated hepatitis (AH) is associated with high mortality. CT-derived liver surface nodularity (LSN) is a robust prognostic biomarker in other chronic liver diseases. The aim of this study was to determine relationships between LSN, disease severity, and mortality in AH. METHODS: Adults hospitalized with AH from January 2016 to March 2020 were included if an abdominal CT was performed between 8 weeks prior to 72 h after hospitalization. LSN was measured using quantitative methods (Liver Surface Nodularity Software version 0.88, Birmingham, AL, USA). Cox proportional hazards models, logistic regression and AUROC analysis were used to examine relationships between LSN and 180-day transplant-free survival. RESULTS: Of 386 patients hospitalized with AH during the study period, 230 had CT scans performed, and 205 met inclusion criteria. Mean transplant-free survival was 127 days (95% CI 118-137). Within each cohort, patients were grouped into low [LSN-LOW, N = 109 (53.2%)] and high [LSN-HIGH, N = 96 (46.8%)] LSN strata based on an optimal cutoff of 2.86 derived from unadjusted ROC curves. Patients with high LSN had features of portal hypertension, which included encephalopathy [53 (55.2%) vs. 43 (39.4%), p = 0.017], ascites on CT [81 (84.4%) vs. 69 (63.3%), p = 0.001] and portosystemic shunts [78 (81.2%) vs. 69 (63.3%), p = 0.003]. High LSN, ascites and MELD were independently associated with lower likelihood of 180-day transplant-free survival, and inclusion of a score assigning 1 point each for high LSN or ascites on CT (AHRADS score) to MELD enhanced diagnostic accuracy of AUROC for 180-day survival compared to MELD alone [AUROC 0.782 (95% CI 0.719-0.845) vs. 0.735 (0.667-0.802), p = 0.023]. CONCLUSIONS: CT-derived factors that include LSN and ascites are radiographic biomarkers associated with 180-day transplant-free survival in alcohol-associated hepatitis.

5.
Clin Transplant ; 37(10): e15130, 2023 10.
Article in English | MEDLINE | ID: mdl-37698469

ABSTRACT

Cirrhosis is usually regarded as a contraindication to isolated lung transplantation (ILT). We sought to determine which patients with cirrhosis could safely undergo ILT. Based on a retrospective analysis of patients with cirrhosis who underwent ILT at our center between 2007 and 2020, we developed an exclusionary algorithm (PENS-CEPT: Pittsburgh ExclusioN Score in Cirrhotics Evaluated for Pulmonary Transplant) to help determine which patients can undergo ILT with minimal incurred risk from their underlying liver disease. The score utilizes a combination of readily available clinical data and the presence (or absence) of spontaneous portosystemic shunts on preoperative cross-sectional imaging. Sixteen patients underwent ILT with a diagnosis of cirrhosis: nine with cystic fibrosis. On univariate analysis, only our model was able to predict 1 year survival. Of the nine patients that would have been approved using our model, there was only one short term death. Of the seven patients that would have been rejected by the model, all but one died within the first year with six dying of complications from liver failure. We are proposing a simple score utilizing routine clinical parameters and pre-operative imaging to determine the safety of ILT in cirrhotic patients. Further studies are required to validate this scoring system with the goal of safely increasing the opportunity for cirrhotic patients who would otherwise be rejected for ILT.


Subject(s)
Liver Failure , Liver Transplantation , Lung Transplantation , Humans , Retrospective Studies , Lung Transplantation/adverse effects , Liver Cirrhosis/complications , Liver Cirrhosis/surgery , Liver Transplantation/adverse effects
6.
Hepatol Commun ; 7(7)2023 07 01.
Article in English | MEDLINE | ID: mdl-37395730

ABSTRACT

BACKGROUND: HCC can develop in the absence of cirrhosis in patients with NAFLD. We aimed to estimate the incidence of HCC in patients with NAFLD with and without cirrhosis or advanced liver fibrosis. METHODS: We performed a cohort study to determine the incidence of HCC in patients with NAFLD identified by the International Classification of Diseases 9/10 codes in the electronic health records of a US health care system between 2004 and 2018. The incidence of HCC was stratified by the presence or absence of cirrhosis and by the Fibrosis-4 index (FIB-4) at the time of HCC diagnosis. RESULTS: Of 47,165 patients with NAFLD aged 40-89 years, 981 (2.1%) developed HCC (mean follow-up 3.4 y). Among patients with HCC, 842 (85.8%) had cirrhosis, while 139 (14.2%) did not. Of the 139 patients with HCC without cirrhosis-related diagnostic codes, 26 (2.7%) had FIB-4 >2.67 (advanced fibrosis likely), whereas 43 (4.4%) had FIB-4 < 1.30 (excluding advanced fibrosis). The annual incidence of HCC in patients with NAFLD with and without cirrhosis was 23.6 and 1.1 per 1000 person-years, respectively. Among patients without cirrhosis, the annual incidence of HCC was 2.8 per 1000 person-years with FIB-4 >2.67 and 0.7 per 1000 person-years with FIB-4 <1.30. Patients with NAFLD and cirrhosis were 31.8 times (95% CI, 23.3-43.4) more likely to develop HCC than those without cirrhosis and FIB-4 <1.30, after adjustment for age and sex. CONCLUSIONS: Patients with NAFLD without cirrhosis nor advanced fibrosis have a low incidence of HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Humans , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Cohort Studies , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Liver Neoplasms/etiology , Risk Factors , Incidence , Retrospective Studies , Liver Cirrhosis/complications , Liver Cirrhosis/epidemiology , Liver Cirrhosis/diagnosis
7.
ACG Case Rep J ; 10(4): e01038, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37091208

ABSTRACT

A 58-year-old woman developed new-onset recurrent ascites after the recent initiation of cemiplimab for the treatment of advanced basal cell carcinoma. A comprehensive serological workup for viral, metabolic, and autoimmune causes was unrevealing. Transjugular liver biopsy demonstrated parenchymal changes consistent with a diagnosis of sinusoidal obstruction syndrome. While this is a condition commonly observed in patients after hematopoietic stem cell transplantation or use of chemotherapeutic agents, it should also be considered in patients who develop new-onset liver dysfunction after the initiation of checkpoint inhibitors.

8.
Ann Thorac Surg ; 116(6): 1277-1284, 2023 12.
Article in English | MEDLINE | ID: mdl-37000464

ABSTRACT

BACKGROUND: Hepatic dysfunction is a morbid complication of lung transplantation. Little is known about risk factors for postoperative hepatic dysfunction or its impact on survival after lung transplantation. METHODS: This retrospective analysis of 1406 adult lung transplant recipients was performed at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania between January 1, 2007 and December 1, 2019. Patients were excluded for redo lung transplantation, concomitant cardiac surgery, or concurrent solid organ transplantation. Postoperative liver dysfunction was classified as either ischemic liver injury or nonischemic dysfunction (transaminitis, hyperbilirubinemia). RESULTS: Among the 1155 primary lung transplant recipients included, postoperative hepatic dysfunction developed in 96 (8.3%) after lung transplantation. A history of liver disease was the greatest predictor of postoperative hepatic dysfunction (odds ratio, 6.19; CI, 2.13-17.4; P < .001). Patients with postoperative hepatic dysfunction had a greater need for intraoperative blood products (ischemic, 12 U [range, 6-21 U]; nonischemic, 10 U [range, 4-28 U]; vs none, 4 U [range, 1-12 U]; P < .001) and an increased need for postoperative circulatory support (ischemic, 16 [76%]; nonischemic, 25 [33%]; none, 117 [11%]; P < .001). Both ischemic liver injury and nonischemic dysfunction were associated with diminished 1-, 3-, and 5-year term survival (ischemic, 27.5%, 16.5%, and 0%, respectively; nonischemic, 60%, 49.6%, and 46.9%, respectively; none, 87.3%, 72.3%, and 59.5%, respectively; P < .001). CONCLUSIONS: Hepatic dysfunction after lung transplantation is associated with significant morbidity and mortality. A history of liver disease was the best positive predictor for postoperative dysfunction. Additional studies are necessary to identify the best treatment algorithm to avoid hepatic dysfunction more effectively in the postoperative setting after lung transplantation.


Subject(s)
Liver Diseases , Lung Transplantation , Adult , Humans , Retrospective Studies , Risk Factors , Liver Diseases/surgery , Ischemia/etiology , Lung Transplantation/adverse effects , Postoperative Complications/etiology
9.
Clin Transplant ; 36(11): e14786, 2022 11.
Article in English | MEDLINE | ID: mdl-35993599

ABSTRACT

BACKGROUND: The increasingly favorable outcomes of live donor liver transplant warrant development of screening techniques to expand current donor pool. Transient elastography (TE) with controlled attenuation parameter (CAP) is accessible and has promising diagnostic performance in non-obese individuals. Here, we demonstrate its utility in grading donor steatosis for risk assessment in living liver donors (LLD). STUDY DESIGN: In a prospective study of LLD and recipients, accuracy was determined using MRI-derived proton density fat fraction (PDFF) as reference. RESULTS: One hundred and one LLD underwent TE, 95 of whom had available PDFF. Median CAP and MRI-PDFF were 233 dB/m (206-270) and 2.9% (2.3-4.0), respectively. A CAP threshold of 270 dB/m captured all steatosis which was present in 13 (13%) LLD (AUROC .942, 100% sensitivity and 83% specificity). Performance further improved when excluding obese LLD and limiting analysis to M-probe (AUROC .971 and .974, respectively, with 87% specificity). There was no difference in CAP and MRI-PDFF between LLD and nondonors (P = .26 and .21, respectively). Early allograft dysfunction was observed in one recipient (CAP 316, PDFF 9.5%), zero underwent retransplant, and one died from sepsis. CONCLUSION: The specific role of CAP in living liver donation warrants further study, beginning with its use as screening tool across peripheral clinics.


Subject(s)
Elasticity Imaging Techniques , Liver Transplantation , Non-alcoholic Fatty Liver Disease , Humans , Elasticity Imaging Techniques/methods , Protons , Living Donors , Prospective Studies , ROC Curve , Liver/diagnostic imaging , Magnetic Resonance Imaging/methods
10.
HPB (Oxford) ; 24(11): 1994-2005, 2022 11.
Article in English | MEDLINE | ID: mdl-35981946

ABSTRACT

BACKGROUND: Socio-economic inequalities among different racial/ethnic groups have increased in many high-income countries. It is unclear, however, whether increasing socio-economic inequalities are associated with increasing differences in survival in liver transplant (LT) recipients. METHODS: Adults undergoing first time LT for hepatocellular carcinoma (HCC) between 2002 and 2017 recorded in the Scientific Registry of Transplant Recipients (SRTR) were included and grouped into three cohorts. Patient survival and graft survival stratified by race/ethnicity were compared among the cohorts using unadjusted and adjusted analyses. RESULTS: White/Caucasians comprised the largest group (n=9,006, 64.9%), followed by Hispanic/Latinos (n=2,018, 14.5%), Black/African Americans (n=1,379, 9.9%), Asians (n=1,265, 9.1%) and other ethnic/racial groups (n=188, 1.3%). Compared to Cohort I (2002-2007), the 5-year survival of Cohort III (2012-2017) increased by 18% for Black/African Americans, by 13% for Whites/Caucasians, by 10% for Hispanic/Latinos, by 9% for patients of other racial/ethnic groups and by 8% for Asians (All P values<0.05). Despite Black/African Americans experienced the highest survival improvement, their overall outcomes remained significantly lower than other ethnic∕racial groups (adjusted HR for death=1.20; 95%CI 1.05-1.36; P=0.005; adjusted HR for graft loss=1.21; 95%CI 1.08-1.37; P=0.002). CONCLUSION: The survival gap between Black/African Americans and other ethnic/racial groups undergoing LT for HCC has significantly decreased over time. However, Black/African Americans continue to have the lowest survival among all racial/ethnic groups.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Adult , United States/epidemiology , Humans , Liver Transplantation/adverse effects , Hispanic or Latino , Black or African American
11.
Proteins ; 90(9): 1732-1743, 2022 09.
Article in English | MEDLINE | ID: mdl-35443068

ABSTRACT

Functional regulation via conformational dynamics is well known in structured proteins but less well characterized in intrinsically disordered proteins and their complexes. Using NMR spectroscopy, we have identified a dynamic regulatory mechanism in the human insulin-like growth factor (IGF) system involving the central, intrinsically disordered linker domain of human IGF-binding protein-2 (hIGFBP2). The bioavailability of IGFs is regulated by the proteolysis of IGF-binding proteins. In the case of hIGFBP2, the linker domain (L-hIGFBP2) retains its intrinsic disorder upon binding IGF-1, but its dynamics are significantly altered, both in the IGF binding region and distantly located protease cleavage sites. The increase in flexibility of the linker domain upon IGF-1 binding may explain the IGF-dependent modulation of proteolysis of IGFBP2 in this domain. As IGF homeostasis is important for cell growth and function, and its dysregulation is a key contributor to several cancers, our findings open up new avenues for the design of IGFBP analogs inhibiting IGF-dependent tumors.


Subject(s)
Insulin-Like Growth Factor Binding Protein 2 , Insulin-Like Growth Factor I , Intrinsically Disordered Proteins , Humans , Insulin-Like Growth Factor Binding Protein 2/metabolism , Insulin-Like Growth Factor I/metabolism , Intrinsically Disordered Proteins/metabolism , Peptide Hydrolases/metabolism , Protein Binding
12.
Transplant Proc ; 53(5): 1682-1689, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33931249

ABSTRACT

BACKGROUND AND AIMS: Liver transplantation is the most effective treatment for end-stage liver disease (ESLD). Whether moderately macrosteatotic livers (30%-60%) represent a risk for worsened graft function is controversial. The uncertainty, in large part, is owing to the heterogeneous steatosis grading. Our aim was to determine the short- and long-term outcomes of moderately macrosteatotic allografts that were graded according to a standardized institutional protocol. METHODS: We performed a retrospective analysis of transplants performed between 1994 and 2014. All patients with allografts biopsied pretransplantation were included. Relevant donor and recipient variable were recorded. Moderately macrosteatotic livers were compared with mildly macrosteatotic and nonsteatotic livers. Primary outcomes of interest were patient survival at 90 days, 1 year, and 5 years. Cox regression analyses were carried out to compare survival between the 2 groups. RESULTS: We compared 65 allografts with moderate macrosteatosis and 810 with no or mild macrosteatosis. Patients with moderately macrosteatotic allografts were 2.69 times as likely to die within the first 90 days after transplant (75.1% vs 91.6% survival) after adjusting for donor age, donor race, recipient age, recipient race, recipient body mass index, recipient diabetes, presence of hepatocellular carcinoma, days on waitlist, Model for End-Stage Liver Disease (MELD) score at transplantation, cold ischemia time. However, for recipients who survive 90 days, moderately macrosteatotic allografts had comparable long-term survival. CONCLUSION: Our study shows that moderate macrosteatosis is a strong predictor of early but not late mortality. Further studies are needed to distinguish the specific cohort of patients for whom moderately macrosteatotic allografts will lead to acceptable outcomes.


Subject(s)
End Stage Liver Disease/mortality , Fatty Liver/pathology , Liver Transplantation , Adult , Aged , Body Mass Index , End Stage Liver Disease/surgery , Female , Humans , Kaplan-Meier Estimate , Liver/pathology , Liver Transplantation/methods , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Severity of Illness Index , Transplantation, Homologous , Treatment Outcome
13.
IEEE Trans Biomed Circuits Syst ; 14(4): 867-878, 2020 08.
Article in English | MEDLINE | ID: mdl-32746346

ABSTRACT

Sensing implants that can be deployed by catheterization or by injection are preferable over implants requiring invasive surgery. However, present powering methods for active implants and present interrogation methods for passive implants require bulky parts within the implants that hinder the development of such minimally invasive devices. In this article, we propose a novel approach that potentially enables the development of passive sensing systems overcoming the limitations of previous implantable sensing systems in terms of miniaturization. In this approach implants are shaped as thread-like devices suitable for implantation by injection. Their basic structure consists of a thin elongated body with two electrodes at opposite ends and a simple and small circuit made up of a diode, a capacitor and a resistor. The interrogation method to obtain measurements from the implants consists in applying innocuous bursts of high frequency (≥1 MHz) alternating current that reach the implants by volume conduction and in capturing and processing the voltage signals that the implants produce after the bursts. As proof-of-concept, and for illustrating how to put in practice this novel approach, here we describe the development and characterization of a system for measuring the conductivity of tissues surrounding the implant. We also describe the implementation and the in vitro validation of a 0.95 mm-thick, flexible injectable implant made of off-the-shelf components. For conductivities ranging from about 0.2 to 0.8 S/m, when compared to a commercial conductivity meter, the accuracy of the implemented system was about ±10%.


Subject(s)
Electric Conductivity , Miniaturization/instrumentation , Monitoring, Physiologic/instrumentation , Prostheses and Implants , Electronics, Medical , Humans , Leg/physiology , Muscle, Skeletal/physiology , Prosthesis Design , Transducers
14.
Nanoscale Adv ; 2(5): 1904-1912, 2020 May 19.
Article in English | MEDLINE | ID: mdl-36132498

ABSTRACT

The degree of oxidation of graphene oxide (GO) has been shown to be important for its toxicity and drug-loading efficiency. However, the effect of its variations on GO-protein interaction remains unclear. Here, we evaluate the effect of the different oxidation degrees of GO on its interaction with human ubiquitin (8.6 kDa) using solution state nuclear magnetic resonance (NMR) spectroscopy in combination with other biophysical techniques. Our findings show that the interaction between the protein and the different GO samples is weak and electrostatic in nature. It involves fast dynamic exchange of the protein molecules from the surface of the GO. As the oxidation degree of the GO increases, the extent of the interaction with the protein changes. The interaction of the protein with GO can thus be modulated by tuning the degree of oxidation. This study opens up new avenues to design appropriate graphenic materials for use in various biomedical fields such as drug delivery, biomedical devices and imaging.

15.
J Gastroenterol Hepatol ; 35(6): 1065-1068, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31692099

ABSTRACT

BACKGROUND AND AIM: Few case reports exist that link lactulose use with pneumatosis intestinalis in cirrhotics. This study investigates the relationship between lactulose use and idiopathic pneumatosis intestinalis in a cohort of cirrhotic patients. METHODS: This case series considers several notable cases of patients with idiopathic pneumatosis intestinalis and concurrent lactulose use. Idiopathic pneumatosis intestinalis was defined as pneumatosis intestinalis with no identifiable etiology. A cohort of 119 patients with cirrhosis and pneumatosis intestinalis were identified in a tertiary care setting, via chart review by a multidisciplinary team. Eleven of these patients were found to have idiopathic pneumatosis intestinalis. Nine of these patients were being treated with lactulose. RESULTS: Six out of 9 patients with idiopathic pneumatosis intestinalis that were being treated with lactulose saw resolution of pneumatosis intestinalis following discontinuation of treatment. CONCLUSIONS: The etiology of idiopathic pneumatosis intestinalis is likely multifactorial, but lactulose might play a preventable role in its formation.


Subject(s)
Gastrointestinal Agents/adverse effects , Lactulose/adverse effects , Liver Cirrhosis/drug therapy , Pneumatosis Cystoides Intestinalis/etiology , Aged , Cohort Studies , Female , Humans , Male , Middle Aged
16.
Front Plant Sci ; 10: 1340, 2019.
Article in English | MEDLINE | ID: mdl-31736995

ABSTRACT

Mungbean [Vigna radiata (L.) R. Wilczek var. radiata] is an important food and cash legume crop in Asia. Development of short duration varieties has paved the way for the expansion of mungbean into other regions such as Sub-Saharan Africa and South America. Mungbean productivity is constrained by biotic and abiotic factors. Bruchids, whitefly, thrips, stem fly, aphids, and pod borers are the major insect-pests. The major diseases of mungbean are yellow mosaic, anthracnose, powdery mildew, Cercospora leaf spot, halo blight, bacterial leaf spot, and tan spot. Key abiotic stresses affecting mungbean production are drought, waterlogging, salinity, and heat stress. Mungbean breeding has been critical in developing varieties with resistance to biotic and abiotic factors, but there are many constraints still to address that include the precise and accurate identification of resistance source(s) for some of the traits and the traits conferred by multi genes. Latest technologies in phenotyping, genomics, proteomics, and metabolomics could be of great help to understand insect/pathogen-plant, plant-environment interactions and the key components responsible for resistance to biotic and abiotic stresses. This review discusses current biotic and abiotic constraints in mungbean production and the challenges in genetic improvement.

17.
Chem Commun (Camb) ; 55(54): 7820-7823, 2019 Jul 02.
Article in English | MEDLINE | ID: mdl-31215563

ABSTRACT

An approach for rapid backbone resonance assignments in proteins using only two 2D NMR experiments is presented. The new method involves a combination of high-resolution 13Cα-detected NMR experiments and selective unlabeling of amino acid residues. The 13C detected 2D hNCA and 2D hNcoCA spectra of a uniformly labeled sample of the protein are analysed in concert with the 2D hNCA spectrum obtained for a selectively unlabeled sample. The combinatorial set of amino acid residues for selective unlabeling is chosen optimally to maximize the assignments. The method is useful for rapid assignment of proteins with low stability such as intrinsically disordered proteins and is applicable to deuterated proteins. This approach helped in assignments of 14.5 kDa human α-synuclein during the course of its aggregation.

18.
J Surg Res ; 235: 1-7, 2019 03.
Article in English | MEDLINE | ID: mdl-30691782

ABSTRACT

BACKGROUND: The rising incidence of liver disease has complicated the management of common surgical pathologies. Hernias, in particular, are problematic given the shortage of high-quality data and differing expert opinions. We aim to provide a narrative review of hernia management in cirrhosis as a first step toward developing evidence-based recommendations for the care of these patients. MATERIALS AND METHODS: A literature review using separate search strings was conducted for PubMed and Cochrane Central Register of Controlled Trials databases. Review articles, conference abstracts, randomized clinical trials, and observational studies were included. Articles without a focus on patients with end-stage liver disease were excluded. Manuscripts were selected based on relevance to perioperative risk assessment, medical optimization, surgical decision-making, and considerations of hernia repair in patients with cirrhosis. RESULTS: The existing literature is varied with regard to focus and quality of data. Of the 4516 articles identified, 51 full-text articles were selected for review. In general, there is evidence to suggest that individuals with compensated cirrhosis may successfully undergo and benefit from hernia repair. Patients at high risk for decompensated cirrhosis may be best served by nonoperative management. CONCLUSIONS: Carefully selected patients with cirrhosis may proceed with herniorrhaphy. A multidisciplinary approach is essential to provide high-quality care and improve outcomes.


Subject(s)
Herniorrhaphy/adverse effects , Herniorrhaphy/methods , Liver Cirrhosis/complications , Perioperative Care , Risk Assessment , End Stage Liver Disease/etiology , Hernia, Ventral/surgery , Humans , Portasystemic Shunt, Transjugular Intrahepatic
19.
RSC Adv ; 9(49): 28746-28753, 2019 Sep 09.
Article in English | MEDLINE | ID: mdl-35529627

ABSTRACT

Intrinsically disordered proteins (IDPs), being sensitive to proteolytic degradation both in vitro and in vivo, can be stabilized by the interactions with various binding partners. Here, we show for the first time that silver nanoparticles (AgNPs) have the ability to enhance the half-life of an IDP, thereby rendering it stable for a month against proteolytic degradation. The conjugate of the unstructured linker domain of human insulin-like growth factor binding protein-2 (L-hIGFBP2) with 10 nm citrate-capped AgNPs was studied using two-dimensional NMR spectroscopy and other biophysical techniques. Our studies reveal the extent and nature of residue-specific interactions of the IDP with AgNPs. These interactions mask proteolysis-prone sites of the IDP and stabilize it. This study opens new avenues for the design of appropriate nanoparticles targeting IDPs and for storage, stabilization and delivery of IDPs into cells in a stable form.

20.
World J Hepatol ; 11(12): 752-760, 2019 Dec 27.
Article in English | MEDLINE | ID: mdl-31966907

ABSTRACT

BACKGROUND: Giant cell hepatitis in the adult population remains very poorly defined with only 100 case reports published in the literature over the last three decades. AIM: To present our center's experience in an attempt to learn about the predisposing factors, outcomes and efficacy of proposed therapeutic interventions for giant cell hepatitis. METHODS: A retrospective chart review was conducted through the electronic records of the University of Pittsburgh Medical Center. We queried 36726 liver biopsy reports from January 1, 1991 to December 6, 2016. Our search yielded 50 patients who were identified as carrying a definite diagnosis of post-infantile giant cell hepatitis (PIGCH) by pathology. The data collected included demographic information, laboratory data (liver function tests, autoimmune markers) and transplant status. In order to better analyze patient characteristics and outcomes, subjects were separated into a non-transplant (native) liver group and a post-liver transplant (allograft) group. RESULTS: The incidence of PIGCH was approximately 0.14% of all biopsies queried in the 25-year period. The mean age was 48 years with 66% females. Liver function tests were classified as 38.2% cholestatic, 35.3% hepatocellular and 26.5% mixed. Autoimmune hepatitis was found to be the most prevalent predisposing factor leading to PIGCH constituting 32% of cases. Management consisted mainly of immunosuppression, viral targeted therapy, supportive care and in six cases liver transplantations. CONCLUSION: The diagnosis of PIGCH remains clinically challenging and requires a high index of suspicion as well as a thorough history, physical examination, serological workup and liver biopsy. Treatment of the underlying cause can result in clinical stability in a large number of cases.

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