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2021 ◽  
Vol 23 (3) ◽  
Author(s):  
Ahmad Reza Shahraki ◽  
Ali Reza Khazayi ◽  
Mahdi Mohammadi ◽  
Elham Shahraki ◽  
Elahe Shahraki ◽  
...  

Background: Laparoscopic cholecystectomy, one of the most common elective surgical procedures, is a minimally invasive surgical procedure for patients with gallbladder diseases. Objectives: This study aimed to evaluate the effect of laparoscopic cholecystectomy on coagulation tests among patients undergoing the surgery in Ali Ibn Abi Taleb Hospital in Zahedan. Methods: Following a quasi-experimental design, 21 cases scheduled for laparoscopic cholecystectomy for whatever reasons at Ali Ibn Abi Taleb Hospital in Zahedan (Iran) were selected. To study the serum levels of blood factors, blood samples were collected at three stages, i.e., before the surgery (time point 1), 30 minutes after pumping the carbon dioxide gas into the abdomen (time point 2), and 30 minutes after removing the last port from the abdomen (time point 3). Data were analyzed using repeated measures. Results: According to the findings, laparoscopic cholecystectomy surgery only had a significant effect on the PT coagulation factor at the 99% confidence level. Also, PT was increased and significantly differed at time points 2 (30 minutes after pumping) and 3 (30 minutes after removing the port) compared to time point 1 (30 minutes before the surgery). Conclusions: Generally, it can be argued that despite observing some variations in the PT coagulation factor during the laparoscopic surgery, the INR level did not change. Hence, it can be considered as a safe surgical intervention for renal and liver functions.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Joshua D Greenlee ◽  
Maria Lopez-Cavestany ◽  
Nerymar Ortiz-Otero ◽  
Kevin Liu ◽  
Tejas Subramanian ◽  
...  

Colorectal cancer (CRC) remains a leading cause of cancer death, and its mortality is associated with metastasis and chemoresistance. We demonstrate that oxaliplatin-resistant CRC cells are sensitized to TRAIL-mediated apoptosis. Oxaliplatin-resistant cells exhibited transcriptional downregulation of caspase-10, but this had minimal effects on TRAIL sensitivity following CRISPR-Cas9 deletion of caspase-10 in parental cells. Sensitization effects in oxaliplatin-resistant cells were found to be a result of increased DR4, as well as significantly enhanced DR4 palmitoylation and translocation into lipid rafts. Raft perturbation via nystatin and resveratrol significantly altered DR4/raft colocalization and TRAIL sensitivity. Blood samples from metastatic CRC patients were treated with TRAIL liposomes, and a 57% reduction of viable circulating tumor cells (CTCs) was observed. Increased DR4/lipid raft colocalization in CTCs was found to correspond with increased oxaliplatin resistance and increased efficacy of TRAIL liposomes. To our knowledge, this is the first study to investigate the role of lipid rafts in primary CTCs.


2021 ◽  
Vol 19 (2) ◽  
pp. 229-236
Author(s):  
Nguyen Thi Xuân ◽  
Dang Thanh Chung ◽  
Can Van Mao

Acute lymphoblastic leukemia (ALL) is the most common pediatric hematologic malignancy characterized by aberrant proliferation of immature lymphoid cells. A20 is a deubiquitinase gene that inhibits functional activation of immune cells mediated through nuclear factor κB (NFκB)/signal transducers and activators of transcription (STAT) pathways. A20 is frequently inactivated in leukemia/lymphoma. Little is known about the involvement between A20 and STAT signalling in regulating the function of ALL blasts. The present study, therefore, explored whether migration and apoptosis of peripheral blood mononuclear cells (PBMCs) and ALL blasts in high glucose conditions is regulated by A20. To this end, ALL blasts from blood samples of fifteen patients and PBMCs from healthy individuals in the absence of A20 were examined. Gene expression profile was determined by quantitative RT-PCR, cell apoptosis by flow cytometry, and cell migration by a transwell migration assay. As a result, the expression of A20 was inactivated in ALL blasts. Cell migration, but not apoptosis of ALL-blasts was enhanced when the cells were exposed to high glucose and dependent on A20 expression, the effects were abolished by using Nifuroxazide, a STAT inhibitor. In conclusion, A20 inhibited glucose-induced migration of ALL blasts through the STAT pathway. The effect might contribute to poorer survival of ALL patients, who develop hyperglycemia during therapy.


2021 ◽  
Author(s):  
Weijia Cheng ◽  
Kai Wu ◽  
Xiaonan Song ◽  
Wang Wei ◽  
Weixing Du ◽  
...  

Abstract BackgroundMolecular markers for monitoring resistance could help improve malaria treatment policies. Delayed clearance of Plasmodium falciparum by Artemisinin-based Combination Therapies (ACTs) has been reported in several countries. In addition to the PfKelch13 (pfk13), new drug resistance genes, the ubiquitin-specific protease 1 (pfubp1) and the eadaptor protein complex 2 mu subunit (pfap2mu) have been identified as being linked to ACTs. This study investigated the prevalence of single-nucleotide polymorphisms (SNPs) in clinical Plasmodium falciparum isolates pfubp1 and pfap2mu imported from Africa and Southeast Asia (SEA) to Wuhan, China, to provide baseline data for antimalarial resistance monitoring in this region.MethodsPeripheral Blood samples were collected in Wuhan, China, from August 2011 to December 2019. The SNPs of Pfubp1 and pfap2mu of P. falciparum were determined by nested PCR and Sanger sequencing. ResultsIn total, 296 samples were collected. Subsequently, 92.23% (273/296) were successfully amplified and sequenced for the Pfubp1. There were 60.07% (164/273) wild strains and 39.93% (109/273) mutant strains. For the pfap2mu gene, it was divided into three fragments for amplification, 82.77% (245/296), 90.20% (267/296) and 94.59% (280/296) were sequenced successfully respectively. Genotypes reportedly associated with ACTs resistance detected in this study included pfubp1 D1525E as well as E1528D and pfap2mu S160N. The mutation prevalence rates were 10.99% (30/273), 13.19% (36/273) and 11.24% (30/267), respectively. ConclusionsThe existence of mutation sites of known clearance genes detected in the isolates in this study, including D1525E and E1528D in the pfubp1 gene, and S160N in the pfap2mu gene, further proved the risk of ACTs resistance. Constant vigilance is therefore needed to protect the effectiveness of ACTs, and to prevent the spread of drug-resistant P. falciparum. Further studies in malaria-endemic countries are needed to further validate potential genetic markers for monitoring parasite populations in Africa and SEA.


2021 ◽  
Author(s):  
Ahmed M. Soliman ◽  
Nagwa M. Elhawary ◽  
Nashwa M. Helmy ◽  
Sahar M. Gadelhaq

Abstract Equine piroplasmosis (EP) is an ixodid tick-borne disease caused by Theileria equi and/or Babesia caballi that can lead to severe health issues and economic losses among equine population. This study aimed to determine the prevalence of T. equi and B. caballi among Egyptian equines based on microscopy and conventional PCR. Also, to determine the effect of season, age, and sex of on their prevalence and determining the difference in sensitivity between microscopy and conventional PCR in the diagnosis of EP. This study was carried out on 432 blood samples randomly collected from 146 horses and 286 donkeys during a period from April 2016 to March 2018. Microscopic examination revealed that among horses, 13 (8.9%) and 4 (2.7%) were infected by T. equi and B. caballi respectively. While among donkeys, 22 (7.7%), 16 (5.6%) respectively. While mixed infections were detected in 4 (1.4%) donkeys. There was a statistically nonsignificant relation between prevalence of infection and season and sex of equines but the highest prevalence was recorded in age group less than 5 years old. By conventional PCR, among 64 horses, 15 (23.4%) and 8 (12.5%) were infected by T. equi and B. caballi, respectively. While among 76 donkeys, 36 (47.4%), 16 (21.1%), and 5 (6.6%) were infected by T. equi, B. caballi, and mixed infection, respectively. Our finding proved the existence of T. equi and B. caballi among equines.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mohammad Mahdavi ◽  
Abdoulreza Esteghamati ◽  
Khadijeh Khanaliha ◽  
Shirin Sayyahfar ◽  
Elahe Orang ◽  
...  

Background: Toxoplasmosis is an opportunistic infection that affects solid organ transplant (SOT) recipients. The parasite transmission may be occurred from a Toxoplasma-seropositive donor to a Toxoplasma-seronegative recipient by organ transplantation. Objectives: In this study, a nested PCR was carried out using different primers targeting the B1, SAG4, and MAG1 genes to assess Toxoplasma infection in pediatric heart transplantation at Shahid Rajaei Heart Center in Tehran. Methods: Blood samples were collected from 46 pediatric heart transplant patients aged 1 - 17 years referring to Rajaei Cardiovascular and Medical Research Center from 2018 - 2019. All patients were on oral administration of Trimethoprim-sulfamethoxazole (cotrimoxazole). Blood samples were collected, and peripheral blood mononuclear cell (PBMC) isolation using the Ficoll gradient method was performed. DNA was extracted from PBMC, and nested PCR was carried out. Serologic tests were performed using ELISA to determine IgG and IgM anti - Toxoplasma gondii antibodies. Results: The results of serologic tests showed that all 46 patients had negative anti-T. gondii IgM antibody. Furthermore, 6 (13.05%) and 3 (6.5 %) out of the 46 patients were positive for IgG T. gondii antibody before and after transplantation, respectively. All 46 patients were evaluated using PCR using B1, MAG-1, and SAG-4 genes, and PCR results were negative. Conclusions: In general, due to the negative results of Toxoplasma with PCR using B1 and bradyzoite-specific genes (SAG-4 and MAG-1), it is possible that the results obtained in this study are because of prophylaxis with cotrimoxazole.


2021 ◽  
Author(s):  
Julia Greissl ◽  
Mitch Pesesky ◽  
Sudeb C. Dalai ◽  
Alison W. Rebman ◽  
Mark J. Soloski ◽  
...  

Lyme disease, the most common tick-borne illness in the United States, is most frequently caused by infection with Borrelia burgdorferi. Although early antibiotic treatment can prevent development of severe illness and late manifestations, diagnosis is challenging in patients who do not present with a typical erythema migrans rash. To support a diagnosis of Lyme disease in such cases, guidelines recommend 2-tiered serologic testing. However, 2-tiered testing has numerous limitations, including ambiguity in interpretation and lower sensitivity in early disease. We developed a diagnostic approach for Lyme disease based on the T-cell response to B. burgdorferi infection by immunosequencing T-cell receptor (TCR) repertoires in blood samples from 3 independent cohorts of patients with laboratory-confirmed or clinically diagnosed early Lyme disease, as well as endemic and non-endemic controls. We identified 251 public, Lyme-associated TCRs that were used to train a classifier for detection of early Lyme disease with 99% specificity. In a validation cohort of individuals with early Lyme disease, TCR testing demonstrated a 1.9-fold increase in sensitivity compared to standard 2-tiered testing (STTT; 56% versus 30%), with a 3.1-fold increase <=4 days from the onset of symptoms (44% versus 14%). TCR positivity predicted subsequent seroconversion in 37% of initially STTT-negative patients, suggesting that the T-cell response is detectable before the humoral response. While positivity for both tests declined after treatment, greater declines in posttreatment sensitivity were observed for STTT compared to TCR testing. Higher TCR scores were associated with clinical measures of disease severity, including abnormal liver function test results, disseminated rash, and number of symptoms. A subset of Lyme-associated TCRs mapped to B. burgdorferi antigens, demonstrating high specificity of a TCR immunosequencing approach. These results support the clinical utility of T-cell-based testing as a sensitive and specific diagnostic for early Lyme disease, particularly in the initial days of illness.


Author(s):  
Jennifer Byrne ◽  
Caitríona Murphy ◽  
Jennifer B. Keogh ◽  
Peter M. Clifton

Evidence supports an association between low magnesium (Mg) intake and coronary heart disease and between Mg intake and endothelial function. The aim of this study was to assess the effect of one week of Mg supplementation on endothelial function, assessed by flow mediated dilatation (FMD). Nineteen healthy men and women completed this cross-over pilot study in which participants were randomised to take an over-the-counter magnesium supplement for one week or to follow their usual diet. Weight, FMD and blood pressure (BP) were taken on completion of each intervention and 24 h urine collections and blood samples were taken to assess compliance. Baseline serum Mg was within normal range for all participants. Urinary Mg and urinary magnesium-creatinine ratio (Mg/Cr) significantly increased between interventions, (p = 0.03, p = 0.005, respectively). No significant differences in FMD or BP were found between the interventions. A significant negative correlation was seen between age and FMD (r = −0.496, p = 0.031). When adjusted for age, saturated fat was negatively associated with FMD (p = 0.045). One week of Mg supplementation did not improve FMD in a healthy population.


Diabetologia ◽  
2021 ◽  
Author(s):  
Naiara G. Bediaga ◽  
Connie S. N. Li-Wai-Suen ◽  
Michael J. Haller ◽  
Stephen E. Gitelman ◽  
Carmella Evans-Molina ◽  
...  

Abstract Aims/hypothesis Accurate prediction of disease progression in individuals with pre-symptomatic type 1 diabetes has potential to prevent ketoacidosis and accelerate development of disease-modifying therapies. Current tools for predicting risk require multiple blood samples taken during an OGTT. Our aim was to develop and validate a simpler tool based on a single blood draw. Methods Models to predict disease progression using a single OGTT time point (0, 30, 60, 90 or 120 min) were developed using TrialNet data collected from relatives with type 1 diabetes and validated in independent populations at high genetic risk of type 1 diabetes (TrialNet, Diabetes Prevention Trial–Type 1, The Environmental Determinants of Diabetes in the Young [1]) and in a general population of Bavarian children who participated in Fr1da. Results Cox proportional hazards models combining plasma glucose, C-peptide, sex, age, BMI, HbA1c and insulinoma antigen-2 autoantibody status predicted disease progression in all populations. In TrialNet, the AUC for receiver operating characteristic curves for models named M60, M90 and M120, based on sampling at 60, 90 and 120 min, was 0.760, 0.761 and 0.745, respectively. These were not significantly different from the AUC of 0.760 for the gold standard Diabetes Prevention Trial Risk Score, which requires five OGTT blood samples. In TEDDY, where only 120 min blood sampling had been performed, the M120 AUC was 0.865. In Fr1da, the M120 AUC of 0.742 was significantly greater than the M60 AUC of 0.615. Conclusions/interpretation Prediction models based on a single OGTT blood draw accurately predict disease progression from stage 1 or 2 to stage 3 type 1 diabetes. The operational simplicity of M120, its validity across different at-risk populations and the requirement for 120 min sampling to stage type 1 diabetes suggest M120 could be readily applied to decrease the cost and complexity of risk stratification. Graphical abstract


Author(s):  
Sydney Banton ◽  
Júlia G Pezzali ◽  
Adronie Verbrugghe ◽  
Marica Bakovic ◽  
Katie M Wood ◽  
...  

Abstract Grain based ingredients are replaced in part by pulse ingredients in grain-free pet foods. Pulse ingredients are lower in methionine and cysteine, amino acid (AA) precursors to taurine synthesis in dogs. While recent work has investigated plasma and whole blood taurine concentrations when feeding grain-free diets, supplementation of a grain-free diet with various nutrients involved in the biosynthesis of taurine has not been evaluated. This study aimed to investigate the effects of supplementing a complete grain-free dry dog food with either methionine (MET), taurine (TAU), or methyl donors (choline) and methyl receivers (creatine and carnitine; CCC) on postprandial AA concentrations. Eight healthy Beagle dogs were fed 1 of 3 treatments or the control grain-free diet (CON) for 7 d in a 4 × 4 Latin square design. On d7, cephalic catheters were placed and one fasted sample (0 min) and a series of 9 post-meal blood samples were collected at 15, 30, 60, 90, 120, 180, 240, 300 and 360 min. Data were analyzed as repeated measures using the PROC GLIMMIX function in SAS (Version 9.4). Dogs fed MET had greater plasma and whole blood methionine concentrations from 30 - 360 min after a meal (P &lt; 0.0001) and greater plasma homocysteine concentrations from 60 - 360 min after a meal (P &lt; 0.0001) compared to dogs fed CON, TAU and CCC. Dogs fed TAU had greater plasma taurine concentrations over time compared to dogs fed CON (P = 0.02), but were not different than dogs fed MET and CCC (P &gt; 0.05). In addition, most AA remained significantly elevated at 6 h post-meal compared to fasted samples across all treatments. Supplementation of creatine, carnitine and choline in grain-free diets may play a role in sparing the methionine requirement without increasing homocysteine concentrations. Supplementing these nutrients could also aid in the treatment of disease that causes metabolic or oxidative stress, including cardiac disease in dogs, but future research is required.


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