Cachexia is Prevalent in Patients With Hepatocellular Carcinoma and Associated With Worse Prognosis.

BACKGROUND & AIMS: Cancer cachexia is a wasting syndrome associated with functional impairment and reduced survival that impacts up to 50% of patients with gastrointestinal cancers. However, data are limited on the prevalence and clinical significance of cachexia in patients with hepatocellular carcinoma (HCC). METHODS: We performed a retrospective cohort study of patients diagnosed with HCC at 2 United States health systems between 2008 and 2018. Patient weights were recorded 6 months prior to and at time of HCC diagnosis. Cachexia was defined as >5% weight loss (or >2% weight loss if body mass index <20 kg/m2), and precachexia was defined as 2% to 5% weight loss. We used multivariable logistic regression models to identify correlates of cachexia and multivariable Cox proportional hazard models to identify factors associated with overall survival. RESULTS: Of 604 patients with HCC, 201 (33.3%) had precachexia and 143 (23.7%) had cachexia at diagnosis, including 19.0%, 23.5%, 34.7%, and 34.0% of patients with Barcelona Clinic Liver Cancer stages 0/A, B, C, and D, respectively. Patients with cachexia were less likely to receive HCC treatment (odds ratio, 0.38; 95% confidence interval, 0.21-0.71) and had worse survival than those with precachexia or stable weight (11.3 vs 20.4 vs 23.5 months, respectively; P < .001). Cachexia remained independently associated with worse survival (hazard ratio, 1.43; 95% confidence interval, 1.11-1.84) after adjusting for age, sex, race, ethnicity, Child Pugh class, alpha-fetoprotein, Barcelona Clinic Liver Cancer stage, and HCC treatment. CONCLUSIONS: Nearly 1 in 4 patients with HCC present with cachexia, including many with compensated cirrhosis or early stage tumors. The presence of cancer-associated weight loss appears to be an early and independent predictor of worse outcomes in patients with HCC.

Randomized Clinical Trial of Inreach With or Without Mailed Outreach to Promote Hepatitis C Screening in a Difficult-to-Reach Patient Population.

INTRODUCTION: Hepatitis C virus (HCV) treatment can significantly reduce the risk of liver-related mortality; however, many patients remain unaware of their infection in clinical practice. The aim of this study is to compare the effectiveness of inreach, with and without mailed outreach, to increase HCV screening and follow-up in a large, difficult-to-reach patient population. METHODS: We conducted a pragmatic randomized clinical trial from August 2018 to May 2019 in a large safety-net health system. Patients born between 1945 and 1965 were randomly assigned (1:1) to inreach with an electronic health record reminder to providers (n = 6,195) or inreach plus mailed HCV screening outreach (n = 6,191) to complete HCV antibody screening. Outreach also included processes to promote HCV RNA testing among those with a positive HCV antibody and linkage to care among those with positive HCV RNA. The primary outcome was completion of HCV antibody testing within 3 months of randomization (ClinicalTrials.gov NCT03706742). RESULTS: We included 12,386 eligible patients (median age 60 years; 46.5% Hispanic, 33.0% Black, and 16.0% White). In intent-to-treat analyses, HCV screening completion was significantly higher among inreach-plus-outreach patients than inreach-alone patients at 3 months (14.6% vs 7.4%, P < 0.001) and 6 months (17.4% vs 9.8%, P < 0.001) after randomization. Among those who completed HCV screening within 6 months, a higher proportion of inreach-plus-outreach patients with positive antibody results completed RNA testing within 3 months than inreach-alone patients (81.1% vs 57.1%, respectively, P = 0.02); however, linkage to care within 3 months of HCV infection confirmation did not significantly differ between the 2 groups (48.1% vs 75.0%, respectively, P = 0.24). DISCUSSION: Among difficult-to-reach patients, a combination of inreach and mailed outreach significantly increased HCV screening compared with inreach alone. However, HCV screening completion in both arms remained low, highlighting a need for more intensive interventions.

Computational Methods and Tools in Antimicrobial Peptide Research.

The evolution of antibiotic-resistant bacteria is an ongoing and troubling development that has increased the number of diseases and infections that risk going untreated. There is an urgent need to develop alternative strategies and treatments to address this issue. One class of molecules that is attracting significant interest is that of antimicrobial peptides (AMPs). Their design and development has been aided considerably by the applications of molecular models, and we review these here. These methods include the use of tools to explore the relationships between their structures, dynamics, and functions and the increasing application of machine learning and molecular dynamics simulations. This review compiles resources such as AMP databases, AMP-related web servers, and commonly used techniques, together aimed at aiding researchers in the area toward complementing experimental studies with computational approaches.

SMART--Sunflower Mutant population And Reverse genetic Tool for crop improvement.

BACKGROUND: Sunflower (Helianthus annuus L.) is an important oilseed crop grown widely in various areas of the world. Classical genetic studies have been extensively undertaken for the improvement of this particular oilseed crop. Pertaining to this endeavor, we developed a "chemically induced mutated genetic resource for detecting SNP by TILLING" in sunflower to create new traits. RESULTS: To optimize the EMS mutagenesis, we first conducted a "kill curve" analysis with a range of EMS dose from 0.5% to 3%. Based on the observed germination rate, a 50% survival rate i.e. LD50, treatment with 0.6% EMS for 8 hours was chosen to generate 5,000 M2 populations, out of which, 4,763 M3 plants with fertile seed set. Phenotypic characterization of the 5,000 M2 mutagenised lines were undertaken to assess the mutagenesis quality and to identify traits of interest. In the M2 population, about 1.1% of the plants showed phenotypic variations. The sunflower TILLING platform was setup using Endo-1-nuclease as mismatch detection system coupled with an eight fold DNA pooling strategy. As proof-of-concept, we screened the M2 population for induced mutations in two genes related to fatty acid biosynthesis, FatA an acyl-ACP thioesterase and SAD the stearoyl-ACP desaturase and identified a total of 26 mutations. CONCLUSION: Based on the TILLING of FatA and SAD genes, we calculated the overall mutation rate to one mutation every 480 kb, similar to other report for this crop so far. As sunflower is a plant model for seed oil biosynthesis, we anticipate that the developed genetic resource will be a useful tool to identify novel traits for sunflower crop improvement.

Children at the Risk of Recurrent Wheezing: A Matched Case-Control Study in a Tertiary Care Center.

Introduction Wheezing is a common symptom in early childhood. Recurrent wheezing is defined as more than three episodes of wheezing in the past year. Many studies have been conducted to delineate the risk factors for recurrent wheezing and to predict which of these children will progress to asthma. Most studies about risk factors and the clinicodemographic profile of children with recurrent wheeze have been carried out in developed nations. Data in developing countries may differ. This study was carried out to identify risk factors associated with recurrent wheezing in children in a tertiary care center. Materials and methods It was a retrospective, matched case-control study conducted over a period of two years (July 2019 to July 2021). Records of children aged one month to 12 years who came to pediatric OPD or were admitted to a pediatric ward with a history of recurrent wheezing were included in the study. Cases with uncontrolled recurrent wheezing diagnosed by examination with an unreliable history and those with a global developmental delay were excluded from the study. The study involved the hospital records of 60 children. Of these, 30 were recurrent wheezers, and 30 were non-wheezers (controls). Data were collected with detailed proformas from case histories and examination sheets. The proforma had several known and suspected risk factors associated with wheezes. Each risk factor was studied and compared with the control group. The risk factors included in this study were male gender, not exclusively breastfed, history of bottle feeding, exposure to vehicles; exposure to pollen; exposure to animals; using an agarbatti or dhoop, passive smoking, or playing with a soft toy. Data were entered in an Excel sheet, and appropriate statistical analyses were done. Results The male-to-female ratio was 2:1. Out of the number of cases, 73.33% were younger than six years; 56.66% of cases were not exclusively breastfed, and 43.33% were exclusively breastfed for six months; 20% of the cases were bottle-fed, and 40% of the controls were bottle-fed. The percentage of cases exposed to vehicle smoke was 26.66%, while 20% of cases had exposure to pollen and 16% of controls were exposed to pollen. 30% of cases were exposed to animals, and 23% of controls were exposed to animals. With regard to passive smoking, 16.66% of cases were exposed to passive smoking, and 20% of controls were not exposed to passive smoking. Out of the study group, 26.66% of the children played with soft toys. Of all these risk factors, a significant difference between cases and controls was found in only one factor: not being exclusively breastfed for six months. All other risk factors showed no significant difference between cases and controls. Conclusion The present study concluded that the significant risk factor that was associated with recurrent wheezing was "not exclusively breastfeeding." The other factors studied that were suspected to be associated with recurrent wheezing cannot be ruled out entirely due to the relatively small size of the sample and the need to be studied further in detail.

LigTMap: ligand and structure-based target identification and activity prediction for small molecular compounds.

Target prediction is a crucial step in modern drug discovery. However, existing experimental approaches to target prediction are time-consuming and costly. Here, we introduce LigTMap, an online server with a fully automated workflow that can identify protein targets of chemical compounds among 17 classes of therapeutic proteins extracted from the PDBbind database. It combines ligand similarity search with docking and binding similarity analysis to predict putative targets. In the validation experiment of 1251 compounds, targets were successfully predicted for more than 70% of the compounds within the top-10 list. The performance of LigTMap is comparable to the current best servers SwissTargetPrediction and SEA. When testing with our newly compiled compounds from recent literature, we get improved top 10 success rate (66% ours vs. 60% SwissTargetPrediction and 64% SEA) and similar top 1 success rate (45% ours vs. 51% SwissTargetPrediction and 41% SEA). LigTMap directly provides ligand docking structures in PDB format, so that the results are ready for further structural studies in computer-aided drug design and drug repurposing projects. The LigTMap web server is freely accessible at https://cbbio.online/LigTMap . The source code is released on GitHub ( https://github.com/ShirleyWISiu/LigTMap ) under the BSD 3-Clause License to encourage re-use and further developments.

Clinical and Histopathologic Features Can Help Target Immunohistochemical Stain Use in the Diagnosis of Viral Esophagitis.

OBJECTIVES: Herpes simplex virus (HSV) and cytomegalovirus (CMV) immunohistochemical stains (IHC) are frequently applied on esophageal biopsies. Our aims were to identify IHC use patterns in viral esophagitis (VE), and clinicopathologic features of VE that could guide IHC use. METHODS: We included 58 VE cases and 60 controls, defined as patients with negative HSV/CMV IHC between January 2006 and July 2017. Biopsies were reviewed and histologic features and clinical data recorded. RESULTS: Thirteen cases required IHC for diagnosis. IHC was performed in 13 HSV and 5 CMV cases where diagnostic viral inclusions were present. VE patients were more likely to have endoscopic ulcer (P=0.002) and be immunocompromised (P<0.001). Pretest clinical concern for VE was common (P=0.006). Histologically, VE patients were more likely to have ulcer (P=0.004), ulcer exudate rich in neutrophils and histiocytes (P=0.001), neutrophils in squamous mucosa (P<0.001), histiocyte aggregates >15 (P<0.001) and spongiosis (P<0.001). Controls had frequent eosinophils, alone (P=0.008) or admixed with other inflammatory cells (P<0.0001). CONCLUSIONS: IHC is used in VE biopsies despite definite viral inclusions on hematoxylin and eosin and in patients without concerning histology or clinical concern for VE. History, endoscopic findings, and histology can be used to better target IHC use in VE.

Organelle transformation.

The source of genetic information in a plant cell is contained in nucleus, plastids, and mitochondria. Organelle transformation is getting a lot of attention nowadays because of its superior performance over the conventional and most commonly used nuclear transformation for obtaining transgenic lines. Absence of gene silencing, strong predictable transgene expression, and its application in molecular pharming, both in pharmaceutical and nutraceuticals, are some of many advantages. Other important benefits of utilizing this technology include the absence of transgene flow, as organelles are maternally inherited. This may increase the acceptability of organelle transformation technology in the development of transgenic crops in a wider scale all over the globe. As the need for crop productivity and therapeutic compounds increases, organelle transformation may be able to bridge the gap, thereby having a definite promise for the future.

Effects of sunlight and diet on vitamin D status of pulmonary tuberculosis patients in Tbilisi, Georgia.

OBJECTIVE: Vitamin D deficiency is common in tuberculosis (TB) and this may modulate immune responses. This study investigated vitamin D status in patients with TB and examined the sources of vitamin D in Tbilisi, Georgia. METHODS: We measured plasma 25-hydroxyvitamin D (25[OH]D) and dietary vitamin D intake in patients with pulmonary TB (n = 85) in Tbilisi, Georgia. To determine the impact of season on vitamin D status, we tested the in vitro conversion of 7-dehydrocholesterol (7-DHC) to previtamin D(3) after sunlight exposure. RESULTS: In subjects with TB, mean plasma 25(OH)D concentrations were 14.4 ± 7.0 ng/mL, and vitamin D insufficiency (25[OH]D <30 ng/mL) occurred in 97% of subjects. The dietary sources of vitamin D were mainly fish, eggs, and butter. The daily intake was well below recommended daily intakes in subjects with TB (172 ± 196 IU). The conversion of 7-DHC to previtamin D(3) was undetectable from October to March and highest in June and July from 11:00 to 14:00 h. CONCLUSION: An insufficient vitamin D dietary intake and a limited production of vitamin D from sunlight for most of the year may explain the high prevalence of vitamin D insufficiency in patients with TB in Tbilisi.

Vitamin D for treatment and prevention of infectious diseases: a systematic review of randomized controlled trials.

OBJECTIVE: To review the existing human controlled intervention studies of vitamin D as adjunctive therapy in settings of infection and provide recommendations for design and implementation of future studies in this field on the basis of the evidence reviewed. METHODS: We conducted a systematic review of randomized controlled clinical trials that studied vitamin D for treatment or prevention of infectious diseases in humans. Studies from 1948 through 2009 were identified through search terms in PubMed and Ovid MEDLINE. RESULTS: Thirteen published controlled trials were identified by our search criteria. Ten trials were placebo controlled, and 9 of the 10 were conducted in a rigorous double-blind design. The selected clinical trials demonstrated substantial heterogeneity in baseline patient demographics, sample size, and vitamin D intervention strategies. Serious adverse events attributable to vitamin D supplementation were rare across all studies. On the basis of studies reviewed to date, the strongest evidence supports further research into adjunctive vitamin D therapy for tuberculosis, influenza, and viral upper respiratory tract illnesses. In the selected studies, certain aspects of study design are highlighted to help guide future clinical research in the field. CONCLUSION: More rigorously designed clinical trials are needed for further evaluation of the relationship between vitamin D status and the immune response to infection as well as for delineation of necessary changes in clinical practice and medical care of patients with vitamin D deficiency in infectious disease settings.