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Clostridioides difficile infection (CDI) is the major identifiable cause of antibiotic-associated diarrhea. The emergence of hypervirulent C. difficile strains has led to increases in both hospital- and community-acquired CDI. Furthermore, the rate of CDI relapse from hypervirulent strains can reach up to 25%. Thus, standard treatments are rendered less effective, making new methods of prevention and treatment more critical. Previously, the bile salt analog CamSA (cholic acid substituted with m -aminosulfonic acid) was shown to inhibit spore germination in vitro and protect mice and hamsters from C. difficile strain 630. Here, we show that CamSA was less active in preventing spore germination by other C. difficile ribotypes, including the hypervirulent strain R20291. The strain-specific in vitro germination activity of CamSA correlated with its ability to prevent CDI in mice. Additional bile salt analogs were screened for in vitro germination inhibition activity against strain R20291, and the most active compounds were tested against other strains. An aniline-substituted bile salt analog, CaPA (cholic acid substituted with phenylamine), was found to be a better antigerminant than CamSA against eight different C. difficile strains. In addition, CaPA was capable of reducing, delaying, or preventing murine CDI signs with all strains tested. CaPA-treated mice showed no obvious toxicity and showed minor effects on their gut microbiome. CaPA's efficacy was further confirmed by its ability to prevent CDI in hamsters infected with strain 630. These data suggest that C. difficile spores respond to germination inhibitors in a strain-dependent manner. However, careful screening can identify antigerminants with broad CDI prophylaxis activity.

Targeted therapy with tyrosine kinase inhibitors (TKI) provides survival benefits to a majority of patients with non-small cell lung cancer (NSCLC). However, resistance to TKI almost always develops after treatment. Although genetic and epigenetic alterations have each been shown to drive resistance to TKI in cell line models, clinical evidence for their contribution in the acquisition of resistance remains limited. Here, we employed liquid biopsy for simultaneous analysis of genetic and epigenetic changes in 122 Vietnamese NSCLC patients undergoing TKI therapy and displaying acquired resistance. We detected multiple profiles of resistance mutations in 51 patients (41.8%). Of those, genetic alterations in EGFR, particularly EGFR amplification (n = 6), showed pronounced genome instability and genome-wide hypomethylation. Interestingly, the level of hypomethylation was associated with the duration of response to TKI treatment. We also detected hypermethylation in regulatory regions of Homeobox genes which are known to be involved in tumor differentiation. In contrast, such changes were not observed in cases with MET (n = 4) and HER2 (n = 4) amplification. Thus, our study showed that liquid biopsy could provide important insights into the heterogeneity of TKI resistance mechanisms in NSCLC patients, providing essential information for prediction of resistance and selection of subsequent treatment., (© 2021. The Author(s).)

Pemphigus is a group of rare, lifethreatening bullous autoimmune diseases that affect the skin and mucous membranes and are associated with high morbidity and morbidity. HLA class II genes, particularly HLA-DRB1 and HLA-DQB1, play roles in pemphigus. The aim of this paper is to investigate the susceptibility of HLA class II DRB1 and DQB1 alleles in Vietnamese patients with pemphigus vulgaris (PV) or pemphigus foliaceus (PF). The study enrolled 31 participants (22 with PV, 9 with PF) with diagnoses confirmed by clinical manifestations, histopathology, and direct immunofluorescence from November 2019 to June 2020. The HLA polymorphisms were determined by Sanger sequencing. The HLA-DRB1 and HLA-DQB1 profiles of the 101 healthy individuals in the control group have been published previously. The frequencies of HLA-DRB1*14, DRB1*13:07, DRB1*04:04, DRB1*03:02, DQB1*02:02, and DQB1*05:03 were significantly higher, whereas those of DRB1*09:01, DRB1*12:02, DQB1*03:03, DQB1*05:01, and DQB1*06:01 were significantly lower, in the PV group than in the controls. The frequencies of DRB1*14:54, DRB1*13:07, and HLA-DQB1*03:02 were significantly higher in the PF group than in the controls. Alleles HLA-DRB1*14:54, DRB1*14:04, DRB1*14:03, DRB1*14:01, DRB1*14:12, DRB1*13:07, DRB1*04:04, DRB1*03:02, DQB1*02:02, and DQB1*05:03 were associated with an increased risk of PV, whereas alleles DRB1*09:01, DRB1*12:02, DQB1*03:03, DQB1*05:01, and DQB1*06:01 might protect against PV. In PF, DRB1*14:54, DRB1*13:07, and HLA-DQB1*03:02 are promising susceptibility alleles., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)

Objective: This study evaluated the presence and the levels of antibodies reactive to SARS-CoV-2 S1 and S2 subunits (S1 + S2), and nucleocapsid protein., Study Design: The levels of SARS-CoV-2 S1 + S2- and nucleocapsid-reactive SIgM/IgM, IgG and SIgA/IgA were measured in human milk samples from 41 women during the COVID-19 pandemic (2020-HM) and from 16 women 2 years prior to the outbreak (2018-HM)., Results: SARS-CoV-2 S1 + S2-reactive SIgA/IgA, SIgM/IgM and IgG were detected in 97.6%, 68.3% and 58.5% in human milk whereas nucleocapsid-reactive antibodies were detected in 56.4%, 87.2% and 46.2%, respectively. S1 + S2-reactive IgG was higher in milk from women that had symptoms of viral respiratory infection(s) during the last year than in milk from women without symptom. S1 + S2- and nucleocapsid-reactive IgG were higher in the 2020-HM group compared to the 2018-HM group., Conclusions: The presence of SARS-CoV-2-reactive antibodies in human milk could provide passive immunity to breastfed infants and protect them against COVID-19 diseases.

Background: Free secretory component (free SC) in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion, but its concentration in human milk is unknown. To evaluate the relationship between free SC and SIgA, the influence of maternal factors (vaccination during pregnancy, allergy, previous infections, nutrition, mode of delivery and active lifestyle) on the concentrations of those secretory immune components in human milk was investigated., Methods: Concentration of active free SC and SIgA in 124 milk samples from 91 mothers were measured via ELISA., Results: Free SC in milk from Tdap-vaccinated mothers was lower than the Tdap-flu-vaccinated, flu-vaccinated or Rhogam-vaccinated mothers. Free SC in mothers who had a cesarean delivery was higher than mothers who had a vaginal delivery. Free SC in the nonallergic group was higher than the allergic group. Free SC was higher in mothers who rarely/never eat junk food, than in mothers who always/frequently eat junk food. Free SC also was higher in the moderate exercise group (active lifestyle) compared with the group who rarely/never exercise (sedentary lifestyle). Free SC in human milk was not affected by previous maternal infection or probiotic supplementation whereas SIgA was not changed by all investigated maternal factors., Conclusion: This study suggests that active free SC is more impacted by maternal factors than active SIgA in human milk., Impact: Active free secretory component (free SC) is more impacted by maternal factors than active secretory IgA (SIgA) in human milk. Vaccination during pregnancy, allergy, nutrition, type of delivery and active lifestyle affect the secretion of free SC in human milk, but not SIgA secretion. Free SC in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion against pathogens and its active concentration in milk strongly varies between mothers, partially due to their specific maternal background.

In this article, the authors apply the relative air pollution index (RAPI) proposed by Pham Ngoc Ho for aggregate assessment of daily air pollution level (RAPI d ) using data from 3 daily standards (1, 8, and 24 h) of each country's standard, including Vietnam Technical Regulation QCVN 05:2013/MONRE. By using the automated data of ambient air at 3 monitoring stations in Cam Pha coal mining area, Quang Ninh province in 2018, results of the frequency of pollution by month (f%) have shown that overall, the air quality in dry season (October-March) is worse than that in rainy season (April-September). Results of pollution frequency by month in a year f% also indicate that air pollution in 2018 at 3 stations is mostly at level I (no pollution) with f% ranged from 10 to 58.3%, but pollution level II-IV (light pollution-very heavy pollution) also happened as f% fluctuated from 20 to 42% in some months. Comparing with air quality assessment in 2011-2015 at this area by periodic monitoring equipment of Quang Ninh Center for Environmental Monitoring, results in 2018 have shown that individual index of RAPI is consistent with the current status of air quality with high accuracy. To compare with RAPI d , we used VN_AQI d index of the Vietnam Environment Administration (VEA). Comparison results show that both indices do not encounter eclipsing effect. However, ambiguous effect occurred in the case of VN_AQI d index (warning not suitable for reality in some cases). In addition, advantages and limitations of these two methods have been analyzed and explained in detail.

Clostridioides difficile (formerly Clostridium difficile ) infection (CDI) can result from the disruption of the resident gut microbiota. Western diets and popular weight-loss diets drive large changes in the gut microbiome; however, the literature is conflicted with regard to the effect of diet on CDI. Using the hypervirulent strain C. difficile R20291 (RT027) in a mouse model of antibiotic-induced CDI, we assessed disease outcome and microbial community dynamics in mice fed two high-fat diets in comparison with a high-carbohydrate diet and a standard rodent diet. The two high-fat diets exacerbated CDI, with a high-fat/high-protein, Atkins-like diet leading to severe CDI and 100% mortality and a high-fat/low-protein, medium-chain-triglyceride (MCT)-like diet inducing highly variable CDI outcomes. In contrast, mice fed a high-carbohydrate diet were protected from CDI, despite the high levels of refined carbohydrate and low levels of fiber in the diet. A total of 28 members of the Lachnospiraceae and Ruminococcaceae decreased in abundance due to diet and/or antibiotic treatment; these organisms may compete with C. difficile for amino acids and protect healthy animals from CDI in the absence of antibiotics. Together, these data suggest that antibiotic treatment might lead to loss of C. difficile competitors and create a favorable environment for C. difficile proliferation and virulence with effects that are intensified by high-fat/high-protein diets; in contrast, high-carbohydrate diets might be protective regardless of the source of carbohydrate or of antibiotic-driven loss of C. difficile competitors. IMPORTANCE The role of Western and weight-loss diets with extreme macronutrient composition in the risk and progression of CDI is poorly understood. In a longitudinal study, we showed that a high-fat/high-protein, Atkins-type diet greatly exacerbated antibiotic-induced CDI, whereas a high-carbohydrate diet protected, despite the high monosaccharide and starch content. Our study results, therefore, suggest that popular high-fat/high-protein weight-loss diets may enhance CDI risk during antibiotic treatment, possibly due to the synergistic effects of a loss of the microorganisms that normally inhibit C. difficile overgrowth and an abundance of amino acids that promote C. difficile overgrowth. In contrast, a high-carbohydrate diet might be protective, despite reports on the recent evolution of enhanced carbohydrate metabolism in C. difficile ., (Copyright © 2020 Mefferd et al.)

The identification and quantification of actionable mutations are critical for guiding targeted therapy and monitoring drug response in colorectal cancer. Liquid biopsy (LB) based on plasma cell-free DNA analysis has emerged as a noninvasive approach with many clinical advantages over conventional tissue sampling. Here, we developed a LB protocol using ultra-deep massive parallel sequencing and validated its clinical performance for detection and quantification of actionable mutations in three major driver genes ( KRAS, NRAS and BRAF ). The assay showed a 92% concordance for mutation detection between plasma and paired tissues and great reliability in quantification of variant allele frequency.

Background: Mutations of GDAP1 gene cause autosomal dominant and autosomal recessive Charcot-Marie-Tooth (CMT) disease and over 80 different mutations have been identified so far. This study analyzed the clinical and genetic characteristics of a Vietnamese CMT family that was affected by a novel GDAP1 mutation., Methods: We present three children of a family with progressive weakness, mild sensory loss, and absent tendon reflexes. Electrodiagnostic analyses displayed an axonal type of neuropathy in affected patients. Sequencing of GDAP1 gene was requested for all members of the family., Results: All affected individuals manifested identical clinical symptoms of motor and sensory impairments within the first three years of life, and nerve conduction study indicated the axonal degeneration. A homozygous GDAP1 variant (c.667_671dup) was found in the three affected children as recessive inheritance pattern. The mutation leads to a premature termination codon that shortens GDAP1 protein (p.Gln224Hisfs∗37). Further testing showed heterozygous c.667_671dup variant in the parents., Discussion: Our study expands the mutational spectrum of GDAP1 -related CMT disease with the new and unreported GDAP1 variant. Alterations in GDAP1 gene should be evaluated as CMT causing variants in the Vietnamese population, predominantly axonal form of neuropathy in CMT disease.

A significant challenge in the design and development of biomaterial scaffolds is to incorporate mechanical and biochemical cues to direct organized tissue growth. In this study, we investigated the effect of hepatocyte growth factor (HGF) loaded, crosslinked fibrin (EDCn-HGF) microthread scaffolds on skeletal muscle regeneration in a mouse model of volumetric muscle loss (VML). The rapid, sustained release of HGF significantly enhanced the force production of muscle tissue 60 days after injury, recovering more than 200% of the force output relative to measurements recorded immediately after injury. HGF delivery increased the number of differentiating myoblasts 14 days after injury, and supported an enhanced angiogenic response. The architectural morphology of microthread scaffolds supported the ingrowth of nascent myofibers into the wound site, in contrast to fibrin gel implants which did not support functional regeneration. Together, these data suggest that EDCn-HGF microthreads recapitulate several of the regenerative cues lost in VML injuries, promote remodeling of functional muscle tissue, and enhance the functional regeneration of skeletal muscle. Further, by strategically incorporating specific biochemical factors and precisely tuning the structural and mechanical properties of fibrin microthreads, we have developed a powerful platform technology that may enhance regeneration in other axially aligned tissues., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Chronic kidney disease associated with hemodialysis can have a variety of musculoskeletal complications, in addition to repercussions in pulmonary function., Objective: To evaluate the effects of inspiratory muscle training on inspiratory muscle strength, pulmonary function, and functional capacity in patients with chronic kidney failure undergoing hemodialysis., Method: Non-controlled clinical trial, comprising 15 individuals diagnosed with chronic kidney failure and undergoing hemodialysis. Maximum inspiratory (PImax) and expiratory (PEmax) pressures were assessed by use of pressure vacuum meter reading. Pulmonary function was assessed by use of spirometry. Functional capacity was assessed by use of walked distance and oxygen consumption obtained in the six-minute walk test (6MWT). For eight weeks, the inspiratory muscle training (IMT) protocol was applied during hemodialysis sessions, with load set to 40% of PImax and weekly frequency of three alternate days., Results: A significant increase in the walked distance was observed after training (455.5 ± 98 versus 557.8 ± 121.0; p = 0.003). No statistically significant difference was observed in the other variables when comparing their pre- and posttraining values., Conclusion: The study showed no statistically significant difference in respiratory muscle strength, pulmonary function, and oxygen consumption. An increase in the walked distance was observed in the 6MWT.

Background: Little is known about cardiorespiratory and metabolic response in healthy children during progressive maximal exercise test., Objective: To test the hypothesis that children show different responses in cardiorespiratory and metabolic parameters during progressive maximal exercise test when compared with adults., Methods: Twenty-five healthy children (gender, 15M/10F; age, 10.2 +/- 0.2) and 20 healthy adults (gender, 11M/9F; age, 27.5 +/- 0.4) underwent a progressive treadmill cardiopulmonary test until exhaustion to determine the maximal aerobic capacity and ventilatory anaerobic threshold (VAT)., Results: The peak workload (5.9+/-0.1 vs 5.6+/-0.1 mph, respectively; p>0.05), exercise time (9.8+/-0.4 vs 10.2+/-0.4 min, respectively; p>0.05), and relative aerobic fitness (VO(2)peak, 39.4+/-2.1 vs 39.1+/-2.0 ml*kg(-1)*min-1, respectively; p>0.05) were similar in children and adults. At ventilatory anaerobic threshold, the heart rate, VO(2) ml*kg(-1)*min-1, respiratory rate (RR), functional estimate of dead space (VD/VT), ventilatory equivalent for oxygen (VE/VO(2)) and end-tidal pressure for oxygen (PETO2) were higher in children, while tidal volume (VT), O(2) pulse and end-tidal pressure for carbon dioxide (PETCO(2)) were lower. At peak of exercise, children showed higher RR and VD/VT. However, O(2) pulse, VT, pulmonary ventilation, PETCO(2) and respiratory exchange ratio were lower in children than adults., Conclusion: Cardiorespiratory and metabolic responses during progressive exercise test are different in children as compared to adults. Specifically, these differences suggest that children have lower cardiovascular and ventilatory efficiency. However, children showed higher metabolic efficiency during exercise. In summary, despite the differences observed, children showed similar levels of exercising capacity when compared with adults.