Lifestyle practices and associated factors among adults with hypertension: Conquering Hypertension in Vietnam-solutions at the grassroots level study.

BACKGROUND: Vietnam is experiencing an increasing prevalence of hypertension in its adult population. In addition to medical therapy, modifying adverse lifestyle practices is important for effective blood pressure control. There are limited data on unhealthy lifestyle practices in patients with chronic diseases, however, particularly among hypertensive patients living in rural Vietnam. Our study objectives were to examine the prevalence of unhealthy lifestyle practices and associated factors among rural Vietnamese adults with uncontrolled hypertension. METHODS: Data from the baseline survey of a cluster randomized trial among hypertensive Vietnamese adults (2017-2022) were utilized. Information on unhealthy lifestyle practices including smoking, excessive alcohol consumption, physical inactivity, and inadequate fruit and vegetable intake was collected from study participants. The primary study outcome was having ≥2 unhealthy lifestyle practices. A multivariable logistic regression model was used to examine factors associated with the primary study outcome. RESULTS: The mean age of the 671 patients was 67 years and 45.0% were men. Nearly three out of every four participants had one or fewer unhealthy practices, 24.0% had two, and 3.3% had three or all four unhealthy lifestyle practices. Men, individuals who did unpaid work or were unemployed, and individuals with hypertension level III were more likely to have ≥2 unhealthy lifestyle practices, whereas individuals with higher education were less likely to have ≥2 unhealthy lifestyle practices compared with respective comparison groups. CONCLUSIONS: We observed a high prevalence of unhealthy lifestyle practices among rural Vietnamese patients with uncontrolled hypertension. Several demographic factors were associated with a greater number of unhealthy lifestyle practices. Newer interventions and educational programs encouraging lifestyle modification practices are needed to control hypertension among adults living in rural settings of Vietnam.

The endometrial transcriptome transition preceding receptivity to embryo implantation in mice.

BACKGROUND: Receptivity of the uterus is essential for embryo implantation and progression of mammalian pregnancy. Acquisition of receptivity involves major molecular and cellular changes in the endometrial lining of the uterus from a non-receptive state at ovulation, to a receptive state several days later. The precise molecular mechanisms underlying this transition and their upstream regulators remain to be fully characterized. Here, we aimed to generate a comprehensive profile of the endometrial transcriptome in the peri-ovulatory and peri-implantation states, to define the genes and gene pathways that are different between these states, and to identify new candidate upstream regulators of this transition, in the mouse. RESULTS: High throughput RNA-sequencing was utilized to identify genes and pathways expressed in the endometrium of female C57Bl/6 mice at estrus and on day 3.5 post-coitum (pc) after mating with BALB/c males (n = 3-4 biological replicates). Compared to the endometrium at estrus, 388 genes were considered differentially expressed in the endometrium on day 3.5 post-coitum. The transcriptional changes indicated substantial modulation of uterine immune and vascular systems during the pre-implantation phase, with the functional terms Angiogenesis, Chemotaxis, and Lymphangiogenesis predominating. Ingenuity Pathway Analysis software predicted the activation of several upstream regulators previously shown to be involved in the transition to receptivity including various cytokines, ovarian steroid hormones, prostaglandin E2, and vascular endothelial growth factor A. Our analysis also revealed four candidate upstream regulators that have not previously been implicated in the acquisition of uterine receptivity, with growth differentiation factor 2, lysine acetyltransferase 6 A, and N-6 adenine-specific DNA methyltransferase 1 predicted to be activated, and peptidylprolyl isomerase F predicted to be inhibited. CONCLUSIONS: This study confirms that the transcriptome of a receptive uterus is vastly different to the non-receptive uterus and identifies several genes, regulatory pathways, and upstream drivers not previously associated with implantation. The findings will inform further research to investigate the molecular mechanisms of uterine receptivity.

Steroid Components of Marine-Derived Fungal Strain Penicillium levitum N33.2 and Their Biological Activities.

Genus Penicillium comprising the most important and extensively studied fungi has been well-known as a rich source of secondary metabolites. Our study aimed to analyze and investigate biological activities, including in vitro anti-cancer, anti-inflammatory and anti-diabetic properties, of metabolites from a marine-derived fungus belonging to P. levitum. The chemical compounds in the culture broth of P. levitum strain N33.2 were extracted with ethyl acetate. Followingly, chemical analysis of the extract leaded to the isolation of three ergostane-type steroid components, namely cerevisterol (1), ergosterol peroxide (2), and (3ß,5α,22E)-ergosta-6,8(14),22-triene-3,5-diol (3). Among these, (3) was the most potent cytotoxic against human cancer cell lines Hep-G2, A549 and MCF-7 with IC50 values of 2.89, 18.51, and 16.47 µg/mL, respectively, while the compound (1) showed no significant effect against tested cancer cells. Anti-inflammatory properties of purified compounds were evaluated based on NO-production in LPS-induced murine RAW264.7 macrophages. As a result, tested compounds performed diverse inhibitory effects on NO production by the macrophages, with the most significant inhibition rate of 81.37 ± 1.35% at 25 µg/mL by the compound (2). Interestingly, compounds (2) and (3) exhibited inhibitory activities against pancreatic lipase and α-glucosidase enzymes in vitro assays. Our study brought out new data concerning the chemical properties and biological activities of isolated steroids from a P. levitum fungus.

Right lumbar lymph trunk injury after right laparoscopic donor nephrectomy: a case report.

Laparoscopic donor nephrectomy (LDN) is increasingly popular because of its advantages over open surgery. Chyle leak after donor nephrectomy is a rare but potentially lethal complication if not treated appropriately. We describe a case of a 43-year-old female patient with no remarkable history who presented a chyle leak on day 2 after right transperitoneal LDN. Since conservative treatment failed, the patient underwent magnetic resonance imaging (MRI) and intranodal lipiodol lymphangiography, which confirmed the chyle leak from the right lumbar lymph trunk into the right renal fossa. The chyle leak was percutaneously embolized twice, on postoperative day (POD) 5 and POD 10, by a mixture of N-butyl-2-cyanoacrylate and lipiodol. The drainage fluid decreased significantly after the second embolization. The subhepatic drainage tube was withdrawn on POD 14, and the patient was discharged on POD 17. MRI lymphangiography and intranodal lipiodol lymphangiography effectively identified the chyle leak point. Percutaneous embolization seems to be a safe, effective method for treating high-output chyle leaks.

Neurite Outgrowth and Gene Expression Profile Correlate with Efficacy of Human Induced Pluripotent Stem Cell-Derived Dopamine Neuron Grafts.

Transplantation of human induced pluripotent stem cell-derived dopaminergic (iPSC-DA) neurons is a promising therapeutic strategy for Parkinson's disease (PD). To assess optimal cell characteristics and reproducibility, we evaluated the efficacy of iPSC-DA neuron precursors from two individuals with sporadic PD by transplantation into a hemiparkinsonian rat model after differentiation for either 18 (d18) or 25 days (d25). We found similar graft size and dopamine (DA) neuron content in both groups, but only the d18 cells resulted in recovery of motor impairments. In contrast, we report that d25 grafts survived equally as well and produced grafts rich in tyrosine hydroxylase-positive neurons, but were incapable of alleviating any motor deficits. We identified the mechanism of action as the extent of neurite outgrowth into the host brain, with d18 grafts supporting significantly more neurite outgrowth than nonfunctional d25 grafts. RNAseq analysis of the cell preparation suggests that graft efficacy may be enhanced by repression of differentiation-associated genes by REST, defining the optimal predifferentiation state for transplantation. This study demonstrates for the first time that DA neuron grafts can survive well in vivo while completely lacking the capacity to induce recovery from motor dysfunction. In contrast to other recent studies, we demonstrate that neurite outgrowth is the key factor determining graft efficacy and our gene expression profiling revealed characteristics of the cells that may predict their efficacy. These data have implication for the generation of DA neuron grafts for clinical application.

A sumoylation program is essential for maintaining the mitotic fidelity in proliferating mantle cell lymphoma cells.

BACKGROUND: Mantle cell lymphoma (MCL) is a rare, highly heterogeneous type of B-cell non-Hodgkin's lymphoma. The sumoylation pathway is known to be upregulated in many cancers including lymphoid malignancies. However, little is known about its oncogenic role in MCL. METHODS: Levels of sumoylation enzymes and sumoylated proteins were quantified in MCL cell lines and primary MCL patient samples by scRNA sequencing and immunoblotting. The sumoylation enzyme SAE2 was genetically and pharmacologically targeted with shRNA and TAK-981 (subasumstat). The effects of SAE2 inhibition on MCL proliferation and cell cycle were evaluated using confocal microscopy, live-cell microscopy, and flow cytometry. Immunoprecipitation and orbitrap mass spectrometry were used to identify proteins targeted by sumoylation in MCL cells. RESULTS: MCL cells have significant upregulation of the sumoylation pathway at the level of the enzymes SAE1 and SAE2 which correlated with poor prognosis and induction of mitosis associated genes. Selective inhibition of SAE2 with TAK-981 results in significant MCL cell death in vitro and in vivo with mitotic dysregulation being an important mechanism of action. We uncovered a sumoylation program in mitotic MCL cells comprised of multiple pathways which could be directly targeted with TAK-981. Centromeric localization of topoisomerase 2A, a gene highly upregulated in SAE1 and SAE2 overexpressing MCL cells, was lost with TAK-981 treatment likely contributing to the mitotic dysregulation seen in MCL cells. CONCLUSIONS: This study not only validates SAE2 as a therapeutic target in MCL but also opens the door to further mechanistic work to uncover how to best use desumoylation therapy to treat MCL and other lymphoid malignancies.

Effects of advanced platelet-rich fibrin combined with xenogenic bone on human periodontal ligament stem cells.

OBJECTIVES: In this study, we aimed to investigate the effects of a mixture of advanced platelet-rich fibrin (A-PRF) and xenogenic bone substitute material (XBSM) on the proliferation and migration of human periodontal ligament stem cells (hPDLSCs) based on the in vitro release of growth factors. MATERIAL AND METHODS: The concentrations of platelet-derived growth factor-AB (PDGF-AB) and vascular endothelial growth factor (VEGF) released by the A-PRF-XBSM mixture were estimated using enzyme-linked immunoassay for up to 7 d. The A-PRF-XBSM mixture exudate was incubated with hPDLSCs. At Days 1, 3, 5, and 7, cell proliferation and migration were investigated by cell counting and wound-healing assays. RESULTS: PDGD-AB and VEGF were released from the A-PRF-XBSM mixture exudate for up to 7 days. hPDLSCs were cultured in media with various concentrations of the A-PRF-XBSM mixture exudate and exhibited their proliferation and migration ability. Furthermore, the factors released from the 100% A-PRF-XBSM mixture exudate had a substantial effect on cell migration, whereas those released from 4% and 20% A-PRF-XBSM mixture exudates stimulated hPDLSC proliferation. CONCLUSIONS: A-PRF-XBSM mixture continuously released growth factors over 7 days and enhanced hPDLSC proliferation and migration. Therefore, A-PRF in combination with XBSM might provide potential advantages for periodontal tissue regeneration.

Curcuminoid Co-Loading Platinum Heparin-Poloxamer P403 Nanogel Increasing Effectiveness in Antitumor Activity.

Nanosized multi-drug delivery systems provide synergistic effects between drugs and bioactive compounds, resulting in increased overall efficiency and restricted side effects compared to conventional single-drug chemotherapy. In this study, we develop an amphiphilic heparin-poloxamer P403 (HP403) nanogel that could effectively co-load curcuminoid (Cur) and cisplatin hydrate (CisOH) (HP403@CisOH@Cur) via two loading mechanisms. The HP403 nanogels and HP403@CisOH@Cur nanogels were closely analyzed with 1H-NMR spectroscopy, FT-IR spectroscopy, TEM, and DLS, exhibiting high stability in spherical forms. In drug release profiles, accelerated behavior of Cur and CisOH at pH 5.5 compared with neutral pH was observed, suggesting effective delivery of the compounds in tumor sites. In vitro studies showed high antitumor activity of HP403@CisOH@Cur nanogels, while in vivo assays showed that the dual-drug platform prolonged the survival time of mice and prevented tail necrosis. In summary, HP403@CisOH@Cur offers an intriguing strategy to achieve the cisplatin and curcumin synergistic effect in a well-designed delivery platform that increases antitumor effectiveness and overcomes undesired consequences caused by cisplatin in breast cancer treatment.

Effects of Cadmium and Lead on Muscle and Liver Glycogen Levels of Climbing Perch (Anabas testudineus).

The aim of this study was to assess the glycogen content in the muscle and liver tissues of the climbing perch (Anabas testudineus) exposed to sublethal concentrations of Cd and Pb over 28 days of exposure and 14 days of depuration. Muscle and liver glycogen levels in A. testudineus after Pb or Cd treatment were significantly lower (p < 0.05) than that of A. testudineus in the control group during the exposure phase. In the recovery phase, muscle, and liver glycogen levels in A. testudineus increased in all Pb treatment groups, whereas they continuously decreased in all Cd treatment groups. Fish affected by Cd had obvious difficulties recovering from the stress response. It was concluded that exposure to the tested concentrations of Pb and Cd could be a potent endocrine activity disruptor, which may lead to adverse impacts on the health of A. testudineus.

The potential anti-African swine fever virus effects of medium chain fatty acids on in vitro feed model: An evaluation study using epidemic ASFV strain circulating in Vietnam.

Background: African swine fever (ASF) is an important disease affecting swine and has a significant economic loss in both the developed and developing world. Aim: In this study, we evaluated the potential effects of medium-chain fatty acids (MCFAs) in individual and synergistic forms to prevent and/or reduce ASF virus (ASFV) infection using in vitro feed model. Methods: The cytotoxicity of MCFAs on porcine alveolar macrophages cells was evaluated by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The potential effects of MCFAs, including C8 (caprylic acid), C8-C6-C10 (caprylic acid-caproic acid-capric acid; 1:1:1 ratio) and C8-C10-C12 (caprylic acid-capric acid-lauric acid; 1:1:1 ratio) against a field ASFV strain isolated in the capital Hanoi of Vietnam, were further examined by real-time PCR and haemadsorption assays in in vitro feed model. Results: Our results indicated that all tested products do not induce cytotoxicity at the dose of 100 µg/ml and are suitable for further in vitro examination. These products have shown a strong antiviral effect against ASFV infectivity at doses of 0.375% and 0.5%. Interestingly, the synergistic MCFAs have shown clearly their potential activities against ASFV in which at a lower dose of 0.25%, pre-treatment with product two and three induced significant increases at the level of Cq value when compared to positive control and/or product 1 (p < 0.05). However, the viral titre was not changed after 24 hours post-inoculation when compared to positive control. Our findings suggested that all tested products, both individual and synergistic forms of MCFAs, have possessed a strong anti-ASFV effect, and this effect is dose-dependence in in vitro feed model. Additionally, synergistic effects of MCFAs are more effective against ASFV when compared to individual forms. Conclusion: Together, the findings in this study indicate that MCFAs, both individual and synergistic forms, inhibit against a field ASFV strain in the feed model, which may support minimizing the risk of ASF transmission in the pig population. Further studies focusing on in vivo anti-ASFV effects of MCFAs are important to bring new insight into the mode of ASFV-reduced action by these compounds in swine feed.

Measuring Health-Related Quality of Life in Vietnamese Patients After Kidney Transplantation.

Objectives: To consider that the health-related quality of life (HRQOL) has become an inherent part of the patient outcomes in the care and treatment after kidney transplantation (KT). This study aimed to measure HRQOL among a representative sample size of patients after KT by using both the Short Form 36 (SF-36) and the Kidney Disease Quality of Life 36 (KDQOL-36). Methods and Results: Data of this cross-sectional design were collected in the Organ Transplant Center, Viet Duc University Hospital (Hanoi, Vietnam) from January 2020 to March 2020 and included the patients aged 18 years or over after KT at 6 months, 1 year, and 3 years postoperatively. HRQOL was evaluated through face-to-face interviews by means of the SF-36 and KDQOL-36 measurement tools. According to the SF-36, the overall mean score of HRQOL was 69.13 ± 15.55 and the two domains were the highest scores of "Mental Health" (81.23 ± 14.28) and "General Health" (80.06 ± 14.81). When measuring with the KDQOL-36, the overall mean score was 68.67 ± 13.75 and was the highest in the domain "Symptoms and Problems of Kidney Disease" (87.06 ± 16.00). Both instruments had good reliability for those after KT. The reliability of the SF-36 was high with Cronbach's coefficients α = 0.90. There were positive relationships between the dimensions measured by the KDQOL-36 and SF-36 (correlation coefficient: 0.03-0.69). Similarly, the domains of the SF-36 also had positive correlations with the KDQOL-36 (correlation coefficient: 0.18-0.51). The correlation coefficient between overall HRQOL scores of the SF-36 and KDQOL-36 was 0.62, indicating a strong correlation between the SF-36 and KDQOL-36. Conclusions: There were slight fluctuations in the HRQOL score in domains in the 3-year follow-up stages, suggesting not having clear change. The mean SF-36 score was consistent with the mean KDQOL-36 score. High reliability and strong correlation were found between two instruments of the SF-36 and KDQOL-36. This study provides the reliability and constructs validity in the combination of two sets of the SF-36 and KDQOL-36 scales for the assessment of HRQOL among post-KT patients, thereby assisting physicians and health professionals in the clinical decision-making, assessment of therapeutic efficacy, and understanding of treatment risk.

Potential health risks of toxic heavy metals and nitrate via commonly consumed bivalve and vegetable species in Ho Chi Minh City, Vietnam.

This study aimed to evaluate the health risks of cadmium (Cd), lead (Pb), inorganic arsenic (As), and nitrate exposure through the consumption of bivalves and vegetables collected from local markets in Ho Chi Minh City. The present study analyzed four favorite bivalve species (Meretrix lyrate; Perna viridis; Anadara subcrenata; Anadara granosa) for concentrations of Cd, Pb, and inorganic As and 9 vegetable species (Brassica juncea; Brassica integrifolia; Brassica rapa chinensis; Nasturtium officinale; Lactuca sativa; Ipomoea aquatica; Amaranthus gangeticus; Ipomoea batatas; Spinacia oleracea) for concentrations of Pb and nitrate. The target hazard quotient (THQ) and target cancer risk (TR) were calculated to estimate non-carcinogenic and carcinogenic health risks, respectively. For bivalves, Cd and inorganic As were present at relatively lower concentrations, whereas a relatively higher accumulation of Pb was recorded. The THQ for Cd, Pb, or inorganic As was below the threshold of 1, suggesting no potential health risks. In the case of vegetables, Pb was present at relatively low concentrations, while nitrate accumulation was at relatively high concentrations. The THQ for nitrate was higher than the threshold of 1, suggesting a potential health risk. The combined effects are estimated according to the hazard index (HI), which shows the health risks associated with the consumption of these bivalves and vegetable species. Therefore, continuous and excess consumption for a lifetime of more than 70 years has a probability of target cancer risk.

Development of local vancomycin delivery system from fibrin gel to prevent Staphylococcus aureus biofilms graft infection.

Prosthetic vascular graft infection is one of the most severe vascular surgery complications. Fibrin gel (FG) has many useful characteristics as biocompatibility, biodegradation, adhesion, and haemostasis to develop the local antibiotic delivery system. In this study, human plasma was collected from peripheral blood that was used to create fibrin gel by supplement ion Ca2+. Antibiotic-containing fibrin gel was then evaluated in some characteristics such as surface structure, biodegradation, antibiotic delivery, cytotoxicity, and bacterial biofilm prevention in vitro and in vivo. The results showed that fibrin gel was excellent material for the extended delivery of antibiotics. Most importantly, antibiotic-containing fibrin gel was not toxic for human fibroblast cells in vitro and inhibited bacterial biofilm growth in vitro and in vivo. This research is the first step in developing an antibiotic delivery system for effective graft infection treatments.

Efficacy and Safety of Expanded Hemodialysis with the Theranova 400 Dialyzer: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Expanded hemodialysis therapy enabled by medium cut-off membranes may promote greater clearance of larger middle molecules that comprise putative uremic solutes than conventional high-flux dialysis. This randomized trial evaluated the efficacy and safety of hemodialysis treatment with a medium cut-off dialyzer. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Clinically stable patients on maintenance hemodialysis were randomized to receive dialysis with either a medium cut-off dialyzer (Theranova 400) or a high-flux dialyzer (Elisio-17H) over 24 weeks of treatment. The primary safety end point was the predialysis serum albumin level after 24 weeks of treatment. The primary efficacy end point was the reduction ratio of free λ light chains at 24 weeks of treatment. RESULTS: Among 172 patients on maintenance hemodialysis, mean age was 59±13 years, 61% were men, 40% were Black, and mean dialysis vintage was 5±4 years. Of the 86 patients randomized to each dialyzer, 65 completed the trial in each group. The reduction ratio for the removal of free λ light chains was significantly higher in the Theranova 400 group compared with the Elisio-17H group after 4 weeks (39% versus 20%) and 24 weeks (33% versus 17%; both P<0.001). Among secondary end points, the Theranova 400 group demonstrated significantly larger reduction ratios at 4 and 24 weeks for complement factor D, free κ light chains, TNFα, and ß2-microglobulin (P<0.001 for all), but not for IL-6. Predialysis serum albumin levels were similar between groups after 24 weeks (4 g/dl with the Theranova 400 and 4.1 g/dl with the Elisio-17H), consistent with noninferiority of the Theranova 400 dialyzer in maintaining predialysis serum albumin levels after 24 weeks of treatment. CONCLUSIONS: Hemodialysis therapy with the Theranova 400 dialyzer provides superior removal of larger middle molecules, as exemplified by free λ light chains, compared with a similar size high-flux dialyzer, while maintaining serum albumin level. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: A Multi-Center, Prospective, Randomized, Controlled, Open-Label, Parallel Study to Evaluate the Safety and Efficacy of the Theranova 400 Dialyzer in End Stage Renal Disease (ESRD) Patients, NCT03257410.

O2-Dependent Protein Internalization Underlies Astrocytic Sensing of Acute Hypoxia by Restricting Multimodal TRPA1 Channel Responses.

Hypoxia sensors are essential for regulating local oxygen (O2) homeostasis within the body. This is especially pertinent within the CNS, which is particularly vulnerable to O2 deprivation due to high energetic demand. Here, we reveal hypoxia-monitoring function exerted by astrocytes through an O2-regulated protein trafficking mechanism within the CNS. Strikingly, cultured mouse astrocytes isolated from the parafacial respiratory group (pFRG) and retrotrapezoid nucleus (RTN) region are capable of rapidly responding to moderate hypoxia via the sensor cation channel transient receptor potential (TRP) A1 but, unlike multimodal sensory neurons, are inert to hyperoxia and other TRPA1 activators (carbon dioxide, electrophiles, and oxidants) in normoxia. Mechanistically, O2 suppresses TRPA1 channel activity by protein internalization via O2-dependent proline hydroxylation and subsequent ubiquitination by an E3 ubiquitin ligase, NEDD4-1 (neural precursor cell-expressed developmentally down-regulated protein 4). Hypoxia inhibits this process and instantly accumulates TRPA1 proteins at the plasma membrane, inducing TRPA1-mediated Ca2+ influx that triggers ATP release from pFRG/RTN astrocytes, potentiating respiratory center activity. Furthermore, astrocyte-specific Trpa1 disruption in a mouse brainstem-spinal cord preparation impedes the amplitude augmentation of the central autonomic respiratory output during hypoxia. Thus, reversible coupling of the TRPA1 channels with O2-dependent protein translocation allows astrocytes to act as acute hypoxia sensors in the medullary respiratory center.

Interleukin-dependent modulation of the expression of MHC class I and MHC class II genes in chicken HD11 cells.

Interleukins (ILs) regulate cell surface antigens known as activation markers, which have distinct functional roles. However, the regulation of major histocompatibility complex (MHC) class I, MHC class II, and related genes by cytokines in chickens is not well understood. In the present study, we evaluated the influence of certain recently discovered chicken interleukins-i.e., IL-11, IL-12B, IL-17A, IL-17B, IL-26, and IL-34-on the expression and regulation of genes related to MHC class I, MHC class II, and the associated proteins in an HD11 chicken macrophage cell line. We used quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunocytochemical, and flow cytometric analyses to assess dose- and time-dependent expression in the HD11 cell line and found that the ILs induced MHC class I, MHC class II, and associated protein. As NF-κB is actively involved in cell activation and is constitutively activated in many immune cells, we also determined whether NF-κB regulates MHC class I, MHC class II, and related gene expression in the HD11 cell line. The NF-κB inhibitor sulfasalazine (Sz) dose-dependently inhibited MHC class I and MHC class II in the HD11 cell line. Sz also downregulated the expression of MHC class I, MHC class II, and the associated proteins in the IL-induced HD11 cell line. The expression of MHC class I, MHC class II, and associated genes was accompanied by the Sz-sensitive degradation of the p65 (RelA) and p50 subunits of NF-κB and IκBα. Our results indicate that the different effects of each IL on the expression of genes related to MHC class I, MHC class II, and the associated proteins are involved with the regulation of the dose and duration of antigenic peptide presentation and, thus, also influence Th1, Th2, and Th17 production.

Genetic interaction between two VNTRs in the MAOA gene is associated with the nicotine dependence.

IMPACT STATEMENT: The present study combined the analysis of two transcriptional regulators, uVNTR and dVNTR, in the MAOA gene that is an enzyme responsible for the monoamine degradation and identified genetic interaction between these VNTRs in association with the nicotine dependence. The main impact is that when analyzing different populations in the genetic studies, the functionally meaningful variants should be combined rather than addressing individual elements separately (a mini polygenic risk score for a particular gene/locus). This combination is very rarely analyzed and therefore the study sets an example. Another impact is that we analyzed the genetic variability in the Asian population and therefore our data present a piece of information from underrepresented populations.

Delays to diagnosis among people with severe mental illness in rural Vietnam, a population-based cross-sectional survey.

BACKGROUND: People with severe mental illness (SMI) living in low and middle-income countries can experience extended delays to diagnosis, which hinder access to medical treatment. The aims of this study were to describe the interval to diagnosis among these people in rural Vietnam and its associated factors. METHODS: A population-based cross-sectional study was conducted among people with SMI in two provinces in Vietnam. The delay to diagnosis was defined as the time between the first abnormal behaviour being observed by family members and the formal diagnosis of psychosis. A multilevel linear regression was used to examine the factors associated with the delay to diagnosis. RESULTS: Among 404 people with SMI from 370 households, the median delay to diagnosis was 11.5 months (IQR 0-168.0). Overall, 53.7% had a delay to diagnosis of less than one year (95% CI: 48.81-58.54). The financial burden of these people on their families was nearly USD 470/year. After adjusting for other factors at individual and household levels, living in a Northern province; older age, and having psychotic diagnosis before the implementation of the National Community Mental Health program (2003) were associated with a delay of more than twelve months to diagnosis. CONCLUSIONS: These data indicate that the implementation of a national policy for community-based care has been effective in reducing the delay to diagnosis in rural Vietnam. Therefore, there is a need for strengthening the program and mental health policies, focusing on public communication to improve mental health literacy and reduce stigma against SMI.

Bioinformatic identification and expression analysis of the chicken B cell lymphoma (BCL) gene.

BACKGROUND: B cell lymphoma (BCL) families play an important role in apoptosis as a growth factor, cell death programming, cytokine expression and immune-related genes expression. OBJECTIVES: In this study, to investigate the roles of BCLs, we performed genome-wide identification, expression and functional analyses of the BCL family in chicken. METHODS: Chicken BCLs genes were identified and analyzed by using bioinformatics approach. Expression profiles and Hierarchical cluster analysis of the BCLs genes in different chicken tissues were obtained from the genome-wide RNA-seq in the GEO, and Cluster and Java Treeview, respectively. RESULTS: A total of 16 BCLs genes were identified from the chicken genome, which could be further classified into five distinct groups in the phylogenetic tree. On the other hand, the interaction among BCLs proteins and between BCLs proteins with NF-κB subunits are limited, indicating that the remaining the functions of BCLs protein could be investigated in chicken. Moreover, KEGG pathway analysis indicated that BCL gene family was involved in regulation of apoptotic and immune response. Finally, BCL gene family was differentially expressed in chicken tissues, pathogen infection and growth stages of early chicken early embryo. CONCLUSION: This study provides significant insights into the potential functions of BCLs in chicken, including the regulation of apoptosis, cell death and expression of immune-related genes.

Safety, pharmacokinetics, and pharmacodynamic activity of obinutuzumab, a type 2 anti-CD20 monoclonal antibody for the desensitization of candidates for renal transplant.

The limited effectiveness of rituximab plus intravenous immunoglobulin (IVIG) in desensitization may be due to incomplete B cell depletion. Obinutuzumab is a type 2 anti-CD20 antibody that induces increased B cell depletion relative to rituximab and may therefore be more effective for desensitization. This open-label phase 1b study assessed the safety, pharmacokinetics, and pharmacodynamics of obinutuzumab in highly sensitized patients with end-stage renal disease. Patients received 1 (day 1, n = 5) or 2 (days 1 and 15; n = 20) infusions of 1000-mg obinutuzumab followed by 2 doses of IVIG on days 22 and 43. Eleven patients received additional obinutuzumab doses at the time of transplant and/or at week 24. The median follow-up duration was 9.4 months. Obinutuzumab was well tolerated, and most adverse events were grade 1-2 in severity. There were 11 serious adverse events (SAEs) in 9 patients (36%); 10 of these SAEs were infections and 4 occurred after kidney transplant. Obinutuzumab plus IVIG resulted in profound peripheral B cell depletion and appeared to reduce B cells in retroperitoneal lymph nodes. Reductions in anti-HLA antibodies, number of unacceptable antigens, and the calculated panel reactive antibody score as centrally assessed using single-antigen bead assay were limited and not clinically meaningful for most patients (NCT02586051).