Prevalence and associated factors of bacterial vaginosis among pregnant women in Hue, Vietnam.

INTRODUCTION: Bacterial vaginosis (BV) is the most frequent vaginal infection affecting women of childbearing age worldwide. It is associated with significant adverse healthcare outcomes, especially during pregnancy. Although screening for BV could reduce potential pregnancy-related obstetric complications, there is no routine screening of pregnant women for BV in Vietnam. We aimed to identify the prevalence of BV among pregnant women and the associated factors in two tertiary hospitals in Hue, Vietnam. METHODOLOGY: This cross-sectional descriptive study included 885 pregnant women in third trimester, who received routine antenatal care in the Hue Central Hospital and Hue University Hospital of Medicine and Pharmacy, Hue city, Thua Thien Hue province, Vietnam. Gram-stained vaginal smears were used for calculating the Nugent score and recording the fungal elements. RESULTS: In total, 435 (49.1%) women had a normal BV score, 352 (39.8%) had intermediate vaginal microbiota, and 98 (11.1%) had BV. Among the 98 women with BV, 71 (72.4%) also had fungal infection. There was a significant association of BV with discharge (p = 0.004) and abnormal cervix (p = 0.014). BV was significantly more frequent among the women who reported previous abortion or miscarriage (p = 0.007). CONCLUSIONS: About a tenth of women in Thua Thien Hue province have BV in the third trimester of pregnancy being associated with previous adverse outcome. Discharge with fishy odour is still a characteristic feature among subtle clinical presentations of BV. Better awareness about this disease and routine test-and-treat management during pregnancy may improve pregnancy outcome.

Early Impressions and Adoption of the AtriAmp for Managing Arrhythmias Following Congenital Heart Surgery.

AtriAmp is a new medical device that displays a continuous real-time atrial electrogram on telemetry using temporary atrial pacing leads. Our objective was to evaluate early adoption of this device into patient care within our pediatric intensive care unit (PICU). This is a qualitative study using inductive analysis of semi-structured interviews to identify dominant themes. The study was conducted in a single-center, tertiary, academic 21-bed mixed PICU. The subjects were PICU multidisciplinary team members (Pediatric Cardiac Intensivists, PICU Nurse Practitioners, PICU nurses and Pediatric Cardiologists) who were early adopters of the AtriAmp (n = 14). Three prominent themes emerged: (1) Accelerated time from arrhythmia event to diagnosis and treatment; (2) Increased confidence in the accuracy of providers' arrhythmia diagnosis; and (3) Improvement in the ability to educate providers about post-operative arrhythmias. Providers also noted some learning curves, but none compromised medical care or clinical workflow. Insights from early adopters of AtriAmp signal the need for simplicity and fidelity in new PICU technologies. Our research suggests that such technologies can be pivotal to the support and growth of multi-disciplinary teams, even among those who do not participate in early implementation. Further research is needed to understand when and why novel technology adoption becomes widespread in high-stakes settings.

Early Impressions and Adoption of the AtriAmp for Managing Arrhythmias Following Congenital Heart Surgery.

Objective: AtriAmp is a new medical device that displays a continuous real-time atrial electrogram on telemetry using temporary atrial pacing leads. Our objective was to evaluate early adoption of this device into patient care, understand how it affected clinical workflow, and identify unforeseen benefits or limitations. Design: Qualitative study using inductive analysis of semi-structured interviews to identify dominant themes. Setting: Single center, tertiary, academic 21-bed mixed pediatric intensive care unit (PICU). Subjects: PICU multidisciplinary team members (Pediatric intensivists, PICU Nurse Practitioners, PICU nurses and Pediatric Cardiologists) who were early adopters of the AtriAmp (n=14). Results: Three prominent themes emerged from qualitative analysis of the early adopters' experiences. (1) Accelerated time from arrhythmia event to diagnosis, treatment, and determination of treatment effectiveness; (2) Increased confidence and security in the accuracy of providers' arrhythmia diagnosis; and (3) Improvement in the ability to educate providers about post-operative arrythmias where reliance on time consuming consultation is a default. Providers also noted some learning curves with the device; none of which compromised medical care or clinical workflow. Conclusions: Insights from early adopters of AtriAmp signal the need for simplicity and fidelity in new technologies within the PICU. Further research in the qualitative and observational sphere is needed to understand how technologies, such as AtriAmp, find expanded use in the PICU environment. Our research suggests that such technologies can be pivotal to the support and growth of multi-disciplinary teams, even among those who do not participate in early implementation.

Dendritic cell-targeted delivery of antigens using extracellular vesicles for anti-cancer immunotherapy.

Neoantigen delivery using extracellular vesicles (EVs) has gained extensive interest in recent years. EVs derived from tumour cells or immune cells have been used to deliver tumour antigens or antitumor stimulation signals. However, potential DNA contamination from the host cell and the cost of large-scale EV production hinder their therapeutic applications in clinical settings. Here, we develop an antigen delivery platform for cancer vaccines from red blood cell-derived EVs (RBCEVs) targeting splenic DEC-205+ dendritic cells (DCs) to boost the antitumor effect. By loading ovalbumin (OVA) protein onto RBCEVs and delivering the protein to DCs, we were able to stimulate and present antigenic OVA peptide onto major histocompatibility complex (MHC) class I, subsequently priming activated antigen-reactive T cells. Importantly, targeted delivery of OVA using RBCEVs engineered with anti-DEC-205 antibody robustly enhanced antigen presentation of DCs and T cell activation. This platform is potentially useful for producing personalised cancer vaccines in clinical settings.

Pathogenic/likely pathogenic mutations identified in Vietnamese children diagnosed with autism spectrum disorder using high-resolution SNP genotyping platform.

Among the most prevalent neurodevelopmental disorders, Autism Spectrum Disorder (ASD) is highly diverse showing a broad phenotypic spectrum. ASD also couples with a broad range of mutations, both de novo and inherited. In this study, we used a proprietary SNP genotyping chip to analyze the genomic DNA of 250 Vietnamese children diagnosed with ASD. Our Single Nucleotide Polymorphism (SNP) genotyping chip directly targets more than 800 thousand SNPs in the genome. Our primary focus was to identify pathogenic/likely pathogenic mutations that are potentially linked to more severe symptoms of autism. We identified and validated 23 pathogenic/likely pathogenic mutations in this initial study. The data shows that these mutations were detected in several cases spanning multiple biological pathways. Among the confirmed SNPs, mutations were identified in genes previously known to be strongly associated with ASD such as SLCO1B1, ACADSB, TCF4, HCP5, MOCOS, SRD5A2, MCCC2, DCC, and PRKN while several other mutations are known to associate with autistic traits or other neurodevelopmental disorders. Some mutations were found in multiple patients and some patients carried multiple pathogenic/likely pathogenic mutations. These findings contribute to the identification of potential targets for therapeutic solutions in what is considered a genetically heterogeneous neurodevelopmental disorder.

[Management strategy of femoral artery pseudoaneurysm combined with infectious wounds].

Objective: To investigate the surgical treatment methods of femoral artery pseudoaneurysm combined with infectious wounds and to evaluate the clinical effects. Methods: The retrospective observational research method was used. Twelve patients with femoral artery pseudoaneurysm combined with infectious wounds who met the inclusion criteria were admitted to Nanjing University of Chinese Medicine Wuxi Integrated Traditional Chinese and Western Medicine Hospital (Affiliated Hospital of Jiangnan University) from October 2014 to September 2022, including 6 males and 6 females, aged from 46 to 78 years. In the primary operation, debridement, tumor resection, and artery suture/venous grafting to repair the artery/artery ligation were performed, and the wound area after tumor resection ranged from 4.0 cm×1.5 cm to 12.0 cm×6.5 cm. Wounds that could be sutured were treated with tension reduction suture and extracutaneous continuous vacuum sealing drainage (VSD), while large wounds that could not be sutured were treated with VSD to control infection. In the secondary operation, tension reduction suture was performed to repair the wounds that could be sutured; large wounds were repaired with adjacent translocated flaps with area of 9.0 cm×5.0 cm to 15.0 cm×7.0 cm. Additionally, when the length of the exposed femoral artery was equal to or over 3.0 cm, the wounds were repaired with additional rectus femoris muscle flap with length of 15.0 to 18.0 cm. The donor areas of the flaps were directly sutured. The wound with artery ligation was treated with stamp skin grafting and continuous VSD. The bacterial culture results of the wound exudate samples on admission were recorded. The intraoperative blood loss, the location of femoral artery rupture, the artery treatment method, and the wound repair method in the primary operation were recorded, and the durations of catheter lavage, catheter drainage, and VSD treatment, and the drainage volume after the operation were recorded. The repair method of wounds in the secondary operation, the durations of catheter drainage and VSD treatment, and the total drainage volume after the operation were recorded. The survivals of flap/muscle flap/stamp skin grafts were observed, and the wound healing time was recorded. Follow-up after discharge was performed to evaluate the quality of wound healing and the walking function and to check whether the pulsatile mass disappeared. B-ultrasound or computed tomography angiography (CTA) was performed again to observe potential pseudoaneurysm recurrence and evaluate the patency of blood flow of the femoral artery. Results: The bacterial culture results of wound exudate samples of all the patients were positive on admission. The blood loss was 150 to 750 mL in the primary operation. The arterial ruptures were located in the femoral artery in 8 cases, in the external iliac artery in 2 cases, and in the femoral arteriovenous fistula in 2 cases. Six cases received direct artery suture, 4 cases received autologous great saphenous vein grafting to repair the artery, 1 case received autologous great saphenous vein bypass surgery, and 1 case received artery ligation. The primary wound suture was performed in 4 cases, along with catheter lavage for 3 to 5 days, catheter drainage for 4 to 6 days, VSD treatment for 5 to 7 days, and a total drainage volume of 80 to 450 mL after the surgery. In the secondary operation, the wounds were sutured directly in 3 cases along with catheter drainage for 2 to 3 days, the wound was repaired with scalp stamp skin graft and VSD treatment for 5 days in 1 case, the wounds were repaired with adjacent translocated flaps in 2 cases with catheter drainage for 2 to 3 days, and the wounds were repaired with rectus femoris muscle flaps+adjacent translocated flaps in 2 cases with catheter drainage for 3 to 5 days . The total drainage volume after the secondary operation ranged from 150 to 400 mL. All the skin flaps/muscle flaps/skin grafts survived after operation. The wound healing time ranged from 15 to 36 days after the primary operation. Follow-up of 2 to 8 months after discharge showed that the wounds of all patients healed well. One patient who underwent femoral artery ligation had calf amputation due to foot ischemic necrosis, and the rest of the patients regained normal walking ability. The pulsatile mass disappeared in inguinal region of all patients. B-ultrasound or CTA re-examination in 6 patients showed that the blood flow of femoral artery had good patency, and there was no pseudoaneurysm recurrence. Conclusions: Early debridement, tumor resection, and individualized artery treatment should be performed in patients with femoral artery pseudoaneurysm combined with infected wounds. Besides, proper drainage and personalized repair strategy should be conducted according to the wound condition to achieve a good outcome.

A promising approach using Fibonacci sequence-based optimization algorithms and advanced computing.

In this paper, the feasibility of Structural Health Monitoring (SHM) employing a novel Fibonacy Sequence (FS)-based Optimization Algorithms (OAs) and up-to-date computing techniques is investigated for a large-scale railway bridge. During recent decades, numerous metaheuristic intelligent OAs have been proposed and immediately gained a lot of momentum. However, the major concern is how to employ OAs to deal with real-world problems, especially the SHM of large-scale structures. In addition to the requirement of high accuracy, a high computational cost is putting up a major barrier to the real application of OAs. Therefore, this article aims at addressing these two aforementioned issues. First, we propose employing the optimal ability of the golden ratio formulated by the well-known FS to remedy the shortcomings and improve the accuracy of OAs, specifically, a recently proposed new algorithm, namely Salp Swarm Algorithm (SSA). On the other hand, to deal with the high computational cost problems of OAs, we propose employing an up-to-date computing technique, termed superscalar processor to conduct a series of iterations in parallel. Moreover, in this work, the vectorization technique is also applied to reduce the size of the data. The obtained results show that the proposed approach is highly potential to apply for SHM of real large-scale structures.

SMILE Downregulation during Melanogenesis Induces MITF Transcription in B16F10 Cells.

SMILE (small heterodimer partner-interacting leucine zipper protein) is a transcriptional corepressor that potently regulates various cellular processes such as metabolism and growth in numerous tissues. However, its regulatory role in skin tissue remains uncharacterized. Here, we demonstrated that SMILE expression markedly decreased in human melanoma biopsy specimens and was inversely correlated with that of microphthalmia-associated transcription factor (MITF). During melanogenesis, α-melanocyte-stimulating hormone (α-MSH) induction of MITF was mediated by a decrease in SMILE expression in B16F10 mouse melanoma cells. Mechanistically, SMILE was regulated by α-MSH/cAMP/protein kinase A signaling and suppressed MITF promoter activity via corepressing transcriptional activity of the cAMP response element-binding protein. Moreover, SMILE overexpression significantly reduced α-MSH-induced MITF and melanogenic genes, thereby inhibiting melanin production in melanocytes. Conversely, SMILE inhibition increased the transcription of melanogenic genes and melanin contents. These results indicate that SMILE is a downstream effector of cAMP-mediated signaling and is a critical factor in the regulation of melanogenic transcription; in addition, they suggest a potential role of SMILE as a corepressor in skin pigmentation.

αvß1 integrin is enriched in extracellular vesicles of metastatic breast cancer cells: A mechanism mediated by galectin-3.

Breast cancer cells release a large quantity of biocargo-bearing extracellular vesicles (EVs), which mediate intercellular communication within the tumour microenvironment and promote metastasis. To identify EV-bound proteins related to metastasis, we used mass spectrometry to profile EVs from highly and poorly metastatic breast cancer lines of human and mouse origins. Comparative mass spectrometry indicated that integrins, including αv and ß1 subunits, are preferentially enriched in EVs of highly metastatic origin over those of poorly metastatic origin. These results are consistent with our histopathological findings, which show that integrin αv is associated with disease progression in breast cancer patients. Integrin αv colocalizes with the multivesicular-body marker CD63 at a higher frequency in the tumour and is enriched in circulating EVs of breast cancer patients at late stages when compared with circulating EVs from early-stage patients. With a magnetic bead-based flow cytometry assay, we confirmed that integrins αv and ß1 are enriched in the CD63+ subsets of EVs from both human and mouse highly metastatic cells. By analysing the level of integrin αv on circulating EVs, this assay could predict the metastatic potential of a xenografted mouse model. To explore the export mechanism of integrins into EVs, we performed immunoprecipitation mass spectrometry and identified members of the galectin family as potential shuttlers of integrin αvß1 into EVs. In particular, knockdown of galectin-3, but not galectin-1, causes a reduction in the levels of cell surface integrins ß1 and αv, and decreases the colocalization of these integrins with CD63. Importantly, knockdown of galectin-3 leads to a decrease of integrin αvß1 export into the EVs concomitant with a decrease in the metastatic potential of breast cancer cells. Moreover, inhibition of the integrin αvß1 complex leads to a reduction in the binding of EVs to fibronectin, suggesting that integrin αvß1 is important for EV retention in the extracellular matrix. EVs retained in the extracellular matrix are taken up by fibroblasts, which differentiate into cancer associated fibroblasts. In summary, our data indicate an important link between EV-bound integrin αvß1 with breast cancer metastasis and provide additional insights into the export of integrin αvß1 into EVs in the context of metastasis.

The prevalence of JAK2 exon12 mutations in Vietnamese patients with JAK2 V617F-negative polycythemia vera: frequent or rare?

Purpose Polycythemia vera is a hematological malignancy characterized by the overproduction of red blood cells in the bone marrow. Pathogenesis of Polycythemia vera was thought to be caused by genetic mutations of the Janus kinase 2 (JAK2) gene, especially the JAK2 V617F and exon 12 mutations since those mutations were found frequently in the patients. The prevalence of JAK2 exon 12 mutations among Polycythemia Vera patients in Vietnam has not been studied yet. Objectives The overall study objective is to investigate the frequency of JAK2 exon 12 mutations among V617F-negative Polycythemia Vera patients in Vietnam. Methods In this study, the occurrence of these mutations was investigated in a clinical population of 76 Vietnamese Polycythemia Vera patients by PCR-RFLP and Sanger sequencing. Results The result showed that 53 of the patients were V617F-positive, and in 23 V617F-negative patients, only four individuals carried two JAK2 exon 12 mutations. Analysis by different in-silico tools predicted that all the two exon 12 mutations detected in this study (JAK2 c.1592A>G; p.H531R and c.1616A>G p.K539R) were benign. Conclusion These results suggested that the causative mutations in this V617F-negative subgroup might locate in another genetic region, and mutations in exon 12 might not be as common among the V617F-negative Polycythemia Vera patients as thought.

Safety and immunogenicity of Nanocovax, a SARS-CoV-2 recombinant spike protein vaccine: Interim results of a double-blind, randomised controlled phase 1 and 2 trial.

Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant. Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients. Findings: For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 [CI95%: 51·12-71·55], 49·11 [41·26-58·46], 57·18 [48·4-67·5] compared to 7·10 [6·32-13·92] of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 [52·2-152·3], 80·0 [50·8-125.9] and 95·1 [63·1-143·6], compared to 55·1 [33·4-91·0] of the convalescent group. Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. Funding: This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC.

Delineating charge and capacitance transduction in system-integrated graphene-based BioFETs used as aptasensors for malaria detection.

Despite significant eradication efforts, malaria remains a persistent infectious disease with high mortality due to the lack of efficient point-of-care (PoC) screening solutions required to manage low-density asymptomatic parasitemia. In response, we demonstrate a quantitative electrical biosensor based on system-integrated two-dimensional field-effect transistors (2DBioFETs) of reduced graphene oxide (rGO) as transducer for high sensitivity screening of the main malaria biomarker, Plasmodium falciparum lactate dehydrogenase (PfLDH). The 2DBioFETs were biofunctionalized with pyrene-modified 2008s aptamers as specific PfLDH receptors. While we systematically optimize biosensor interface for optimal performance, aptamer-protein transduction at 2DBioFETs is elucidated based on delineation of charge and capacitance in an updated analytical model for two-dimensional rGO/biofunctional layer/electrolyte (2DiBLE) interfaces. Our 2DBioFET-aptasensors display a limit-of-detection down to 0.78 fM (0.11 pg/mL), dynamic ranges over 9 orders of magnitude (subfemto to submicromolar), high sensitivity, and selectivity in human serum validating their diagnostic potential as rapid PoC tests for malarial management.

Damage assessment in structures using artificial neural network working and a hybrid stochastic optimization.

Artificial neural network (ANN) has been commonly used to deal with many problems. However, since this algorithm applies backpropagation algorithms based on gradient descent (GD) technique to look for the best solution, the network may face major risks of being entrapped in local minima. To overcome those drawbacks of ANN, in this work, we propose a novel ANN working parallel with metaheuristic algorithms (MAs) to train the network. The core idea is that first, (1) GD is applied to increase the convergence speed. (2) If the network is stuck in local minima, the capacity of the global search technique of MAs is employed. (3) After escaping from local minima, the GD technique is applied again. This process is applied until the target is achieved. Additionally, to increase the efficiency of the global search capacity, a hybrid of particle swarm optimization and genetic algorithm (PSOGA) is employed. The effectiveness of ANNPSOGA is assessed using both numerical models and measurement. The results demonstrate that ANNPSOGA provides higher accuracy than traditional ANN, PSO, and other hybrid ANNs (even a higher level of noise is employed) and also considerably decreases calculational cost compared with PSO.

Clinical study on the treatment of thoracolumbar fractures with single plane screw percutaneous internal fixation.

OBJECTIVE: The aim of the study was to investigate the clinical effect of single plane screw percutaneous internal fixation in the treatment of simple thoracolumbar fractures. PATIENTS AND METHODS: The subjects of this study were 84 patients with simple thoracolumbar fractures treated in our hospital from January 2018 to December 2020. The patients were grouped by different treatment methods (42 cases in each group). The single plane group was treated by percutaneous single plane screw internal fixation and the universal group was treated with percutaneous universal screw. The surgery completion status and the incidence of complications were recorded. The visual analogue scale (VAS) and the Oswestry Disability Index (ODI) of the two groups were recorded before the surgery, 3 days after the surgery, and 7 days after the surgery. The anterior edge height ratio of the fractured vertebra and the kyphotic Cobb angle were marked before the surgery, immediately after the operation, and at the last follow-up. RESULTS: Difference between groups in surgery time, blood loss and hospital stay was not statistically significant (p>0.05); the single plane group had a substantially lower incidence of complications than the universal group (p<0.05). At the last follow-up, the single plane group had greatly higher anterior edge height ratio of the injured vertebra than the universal group, while kyphotic Cobb angle was greatly higher in the universal group (p<0.05). CONCLUSIONS: Both single plane screw and universal screw percutaneous internal fixation were feasible for the treatment of simple thoracolumbar fractures, but single plane screw showed better vertebral height recovery and kyphosis correction effect, which could reduce postoperative correction loss.

Superficial vs. deep serratus anterior plane block for analgesia in patients undergoing mastectomy: A randomized prospective trial.

STUDY OBJECTIVE: In the initial description of the serratus anterior plane block (SAPB), both superficial and deep SAPB provided effective blockade. The purpose of this study was to investigate the difference in opioid consumption and postoperative analgesia between superficial and deep SAPB for patients undergoing mastectomy. DESIGN: Randomized prospective trial. SETTING: Academic hospital. PATIENTS: 64 women, >18 years of age, ASA I-III, undergoing single or bilateral mastectomy, with and without lymph node biopsy, with and without tissue expander reconstruction. INTERVENTION: Either superficial or deep SAPB by an ultrasound-guided technique in addition to multimodal analgesia. MEASUREMENTS: The primary outcome was opioid consumption in the first 24 h. Secondary outcomes were pain scores, satisfaction scores, incidence of PONV, length of stay and block performance time. RESULTS: Subjects who received a deep SAPB required 30% less oral morphine equivalents (OME) (113.5 mg vs. 147 mg, p = 0.009) and reported lower pain scores. There were no significant differences in satisfaction scores, incidence of PONV, LOS, or block performance time between the two groups. CONCLUSION: There was a significant difference in opioid consumption between the deep and superficial SAPB groups. Subjects in the deep SAPB group had lower pain scores at 12 h; however, the difference was not statistically significant at other time points. While both the superficial and the deep SAPB can be used for post-operative analgesia in patients undergoing mastectomy, our study suggests that the deep SAPB may improve analgesia to a greater degree than the superficial SAPB as shown through decreased opioid consumption of 30% over a 24-h period post-block. CLINICAL TRIAL NUMBER AND REGISTRY URL: clinicaltrials.gov: NCT03154658.

SREBP-1c impairs ULK1 sulfhydration-mediated autophagic flux to promote hepatic steatosis in high-fat-diet-fed mice.

A metabolic imbalance between lipid synthesis and degradation can lead to hepatic lipid accumulation, a characteristic of patients with non-alcoholic fatty liver disease (NAFLD). Here, we report that high-fat-diet-induced sterol regulatory element-binding protein (SREBP)-1c, a key transcription factor that regulates lipid biosynthesis, impairs autophagic lipid catabolism via altered H2S signaling. SREBP-1c reduced cystathionine gamma-lyase (CSE) via miR-216a, which in turn decreased hepatic H2S levels and sulfhydration-dependent activation of Unc-51-like autophagy-activating kinase 1 (ULK1). Furthermore, Cys951Ser mutation of ULK1 decreased autolysosome formation and promoted hepatic lipid accumulation in mice, suggesting that the loss of ULK1 sulfhydration was directly associated with the pathogenesis of NAFLD. Moreover, silencing of CSE in SREBP-1c knockout mice increased liver triglycerides, confirming the connection between CSE, autophagy, and SREBP-1c. Overall, our results uncover a 2-fold mechanism for SREBP-1c-driven hepatic lipid accumulation through reciprocal activation and inhibition of hepatic lipid biosynthesis and degradation, respectively.

Type 2 diabetes mellitus duration and obesity alter the efficacy of autologously transplanted bone marrow-derived mesenchymal stem/stromal cells.

Human bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) represent promising stem cell therapy for the treatment of type 2 diabetes mellitus (T2DM), but the results of autologous BM-MSC administration in T2DM patients are contradictory. The purpose of this study was to test the hypothesis that autologous BM-MSC administration in T2DM patient is safe and that the efficacy of the treatment is dependant on the quality of the autologous BM-MSC population and administration routes. T2DM patients were enrolled, randomly assigned (1:1) by a computer-based system into the intravenous and dorsal pancreatic arterial groups. The safety was assessed in all the treated patients, and the efficacy was evaluated based on the absolute changes in the hemoglobin A1c, fasting blood glucose, and C-peptide levels throughout the 12-month follow-up. Our data indicated that autologous BM-MSC administration was well tolerated in 30 T2DM patients. Short-term therapeutic effects were observed in patients with T2DM duration of <10 years and a body mass index <23, which is in line with the phenotypic analysis of the autologous BM-MSC population. T2DM duration directly altered the proliferation rate of BM-MSCs, abrogated the glycolysis and mitochondria respiration of BM-MSCs, and induced the accumulation of mitochondria DNA mutation. Our data suggest that autologous administration of BM-MSCs in the treatment of T2DM should be performed in patients with T2DM duration <10 years and no obesity. Prior to further confirming the effects of T2DM on BM-MSC biology, future work with a larger cohort focusing on patients with different T2DM history is needed to understand the mechanism underlying our observation.

Computational modeling - an approach to the development of blood grouping reagents.

Introduction: Blood group antigens are defined by an immune response that generates antibodies against a red blood cell molecule. Antibodies against these antigens can be associated with hemolytic transfusion reactions. However, difficulties can arise when developing antibodies against antigens through the use of peptide sequences alone. Three-dimensional representations (models) of the molecular structure of antigen-bearing proteins can provide valuable insights into tertiary structures and their consequent antigenicity. This can be achieved through predictive computational modeling to produce both structural and molecular dynamics models of blood group proteins.Areas covered: Authors discuss the use of molecular dynamic simulations on existing structures, as well as the use of computational modeling techniques in the development of protein models lacking preexisting data. Finally, the authors discuss specific examples of the use of computationally derived models of the MNS blood group system and its use in attempts to produce antibodies against MNS proteins.Expert opinion: Although in silico techniques have limitations, computer-based predictive models can inform the direction of research into blood group proteins. It is to be expected that as computer-based techniques grow more powerful these contributions will be even more significant.

[Expression of PTTG1 in gastric adenocarcinoma tissues and its relationship with prognosis].

Objective: To identify new prognostic markers and therapeutic targets for gastric adenocarcinoma. Methods: The public datasets of gastric adenocarcinoma collected from GEO database (GSE33335 and GSE63089) were downloaded for analysis. There were 70 GC tissues and paired normal tissues in the two profile datasets. Differentially expressed genes (DEGs) between GC tissues and normal stomach tissues were selected by the R software. Protein-protein interaction (PPI) of these DEGs were visualized by the Search Tool for the Retrieval of Interacting Genes (STRING). The key gene sets were analyzed by Cytoscape and Molecular Complex Detection (MCODE). The mRNA and protein expression levels of prognosis related genes identified by public database were confirmed by using GC tissues and paired normal tissues collected from July 2019 to September 2019 in Affiliated Hospital of Nantong University. Results: DEGs were identified in the two datasets by using R software. A total of 128 DEGs were detected, including 85 up-regulated genes (log(2)FC>1.2 and FDR<0.01) and 43 down-regulated genes (log(2)FC<-1.2 and FDR<0.01) in the GC tissues. PPI network model and MCODE model were established by using the Online String tool and Cytoscape software, and 27 key genes were obtained, including 25 genes related with prognosis of GC patients (P<0.05). We identified 14 significant DEGs in GC tissues, including cyclin B1 (CCNB1), polo-like kinase 1 (PLK1) and pituitary-tumor transforming gene (PTTG1), which were significantly enriched in the cell cycle pathway through KEGG pathway enrichment analysis. The positive expression rate of PTTG1 in GC tissues was 68.8% (22/32), significantly higher than 18.8% (6/32) in normal gastric tissues (P<0.05). Conclusions: The expression of PTTG1 is different in GC and gastric tissues, implicates it is the key gene in gastric carcinogenesis. The prognoses of GC patients with higher PTTG1 expression are worse. PTTG1 might participate in the development of gastric adenocarcinoma by regulating cell cycle.

A chain mediation model on COVID-19 symptoms and mental health outcomes in Americans, Asians and Europeans.

The novel Coronavirus-2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO) in March 2020, impacting the lifestyles, economy, physical and mental health of individuals globally. This study aimed to test the model triggered by physical symptoms resembling COVID-19 infection, in which the need for health information and perceived impact of the pandemic mediated the path sequentially, leading to adverse mental health outcomes. A cross-sectional research design with chain mediation model involving 4612 participants from participating 8 countries selected via a respondent-driven sampling strategy was used. Participants completed online questionnaires on physical symptoms, the need for health information, the Impact of Event Scale-Revised (IES-R) questionnaire and Depression, Anxiety and Stress Scale (DASS-21). The results showed that Poland and the Philippines were the two countries with the highest levels of anxiety, depression and stress; conversely, Vietnam had the lowest mean scores in these areas. Chain mediation model showed the need for health information, and the perceived impact of the pandemic were sequential mediators between physical symptoms resembling COVID-19 infection (predictor) and consequent mental health status (outcome). Excessive and contradictory health information might increase the perceived impact of the pandemic. Rapid COVID-19 testing should be implemented to minimize the psychological burden associated with physical symptoms, whilst public mental health interventions could target adverse mental outcomes associated with the pandemic.