A cluster of Ankyrin and Ankyrin-TPR repeat genes is associated with panicle branching diversity in rice.

The number of grains per panicle is an important yield-related trait in cereals which depends in part on panicle branching complexity. One component of this complexity is the number of secondary branches per panicle. Previously, a GWAS site associated with secondary branch and spikelet numbers per panicle in rice was identified. Here we combined gene capture, bi-parental genetic population analysis, expression profiling and transgenic approaches in order to investigate the functional significance of a cluster of 6 ANK and ANK-TPR genes within the QTL. Four of the ANK and ANK-TPR genes present a differential expression associated with panicle secondary branch number in contrasted accessions. These differential expression patterns correlate in the different alleles of these genes with specific deletions of potential cis-regulatory sequences in their promoters. Two of these genes were confirmed through functional analysis as playing a role in the control of panicle architecture. Our findings indicate that secondary branching diversity in the rice panicle is governed in part by differentially expressed genes within this cluster encoding ANK and ANK-TPR domain proteins that may act as positive or negative regulators of panicle meristem's identity transition from indeterminate to determinate state.

Evaluating the satisfaction and utility of social networks in medical practice and continuing medical education.

BACKGROUND: Digital health has surged during the Covid health crisis, and the use of social media, already prevalent in medicine, has significantly increased. There are Social Networks groups dedicated to physicians with an educational purpose. These groups also facilitate peer discussions on medical questions and the sharing of training materials. OBJECTIVES: The aim of our study was to assess the value of these new tools and their contribution to medical education. METHODS: An anonymous questionnaire was conducted among members of a Social Networks community group for physicians. The survey received responses from 1451 participants. RESULTS: The majority of participants believed they had enriched their medical knowledge and accessed documents they would not have accessed without the group. Subgroup analysis showed that the contribution of this tool is more pronounced for general practitioners and doctors practicing in limited healthcare access. CONCLUSION: It is essential to develop digital tools that enhance physician training, and social networks represent a valuable educational tool.

Dietary patterns and child, parental, and societal factors associated with being overweight and obesity in Vietnamese children living in Ho Chi Minh city.

Childhood overweight and obesity are rapidly increasing in urban Vietnam. Dietary patterns are understudied for their association with obesity risk in these children, and it is unclear which parental and societal factors should be targeted in prevention efforts. The study assessed child characteristics, dietary patterns, parental and societal factors for associations with childhood overweight and obesity status in Ho Chi Minh City, Vietnam. A sample of 221 children aged 9-11 years was randomly selected from four Ho Chi Minh City primary schools. Weight, height and waist circumference were measured using standardized methods. Three 24-h dietary recalls were collected from 124 children, which were used to assess dietary patterns using principal component analysis (PCA). Parents completed a questionnaire about child, parental and societal factors. The overall prevalence of obesity was 31.7% and of combined overweight and obesity 59.3%. Three main dietary patterns from 10 food groups were identified by PCA: traditional (grains, vegetables, meat and meat alternatives), discretionary (snacks and sweetened beverages), and industrialized (fast food and processed meat). Children with higher discretionary diet scores had higher odds of being overweight. Being a boy, screen time over 2 h/day, parental underestimation of child weight status, father's obesity, and household income in the lowest quintile were positively associated with childhood obesity. Future intervention programmes in Vietnam need to consider targeting children's unhealthy diets and parental perceptions of child weight status, as well as focusing on upstream approaches that reduce inequities contributing to childhood obesity and concomitant dietary patterns.

A comparison between the enzymatic oxidation method and headspace gas chromatography with a flame ionization detector in the determination of postmortem blood ethanol.

Ethanol is the most commonly encountered substance in forensic toxicology. Determining blood alcohol concentration (BAC) in autopsies accounts for the majority of work in forensic diagnosis. The most common method to assess BAC is the enzymatic oxidation method because of its low cost, easy operation, and high throughput. Still, the elevated lactate and lactate dehydrogenase (LDH) levels in postmortem blood may affect accuracy. This study uses headspace gas chromatography with a flame ionization detector (HS-GC/FID) to assess the interference of lactate and LDH levels on BAC in 110 autopsied blood samples determined by the enzymatic oxidation method. The results showed that lactate and LDH levels in postmortem blood were higher than in normal blood. There was a weak correlation between the lactate levels and BAC difference (r = 0.23, p < 0.05) and a strong correlation between LDH levels and BAC difference (r = 0.67, p < 0.001). The differentiation of BAC between the enzymatic oxidation method and HS-GC/FID was significant (p < 0.001), confirming the interference significantly. All postmortem blood samples with lactate and LDH levels higher than regular lead to a positive error in determining BAC by enzymatic oxidation method. The study results suggest that the HS-GC/FID method should be used to determine BAC in postmortem blood samples instead of the enzymatic oxidation method to avoid mistakes in forensic diagnosis.

Expanded vaccination practice in 2-year-old children and maternal knowledge on expanded vaccination in Tien Giang, Vietnam.

Background: Vaccination plays a central role in protecting children against severe diseases and preventing child mortality. Objectives: This study aimed to determine the rate and factors associated with complete and timely vaccination in 2-year-old children, as well as maternal knowledge on expanded vaccination in Go Cong Tay district, Tien Giang province, Vietnam. Methods: A cross-sectional descriptive study was conducted on 558 2-year-old children and their mothers residing in Go Cong Tay district, Tien Giang province, Vietnam. The study employed a systematic random sampling method from June to September 2021. Results: The rate of complete vaccination in children was 74.7%. Factors associated with the rate of complete vaccination were occupation (OR=0.3; 95%CI: 0.1-0.7; p=0.006), economic status (OR=3.8; 95%CI: 1.7-8.6; p=0.001), and maternal general knowledge on expanded vaccination (OR=1.7; 95%CI: 1.1-2.6; p=0.01). The rate of timely vaccination was 47.8%. Factors associated with the rate of timely vaccination were maternal age group (OR=3.1; 95%CI: 1.6-6.0; p=0.001; OR=3.0; 95%CI: 1.3-6.6; p=0.006) and economic status (OR=0.4; 95%CI: 0.2-0.9; p=0.04). The rate of both complete and timely vaccination was 22.6%. Factors associated with the rate of complete and timely vaccination were maternal age group (OR=3.1; 95%CI: 1.3-7.2; p=0.009; OR=3.3; 95%CI: 1.2-9.1; p=0.02) and maternal general knowledge on expanded vaccination (OR=1.5; 95%CI: 1.0-2.4; p=0.03). The rate of maternal general knowledge on expanded vaccination was 57.5%. Conclusion: The rates of complete and timely vaccination are still low, and various factors influence expanded vaccination. The-refore, it is crucial to continue health education campaigns to improve knowledge on expanded vaccination, remind mothers of vaccination schedules, strengthen confidence in vaccination programs and vaccine safety, attract customers to vaccination services, provide adequate healthcare for children, and ensure vaccination activities during disease outbreaks.

High-Precision Tailored Polymer Molecular Weights for Specific Photovoltaic Applications through Ultrasound-Induced Simultaneous Physical and Chemical Events.

It is highly challenging to reproducibly prepare semiconducting polymers with targeted molecular weight tailored for next-generation photovoltaic applications. Once such an easily accessible methodology is established, which can not only contribute to overcome the current limitation of the statistically determined nature of semiconducting polymers, but also facilitate rapid incorporation into the broad synthetic chemists' toolbox. Here, we describe a simple yet robust ultrasonication-assisted Stille polymerization for accessing semiconducting polymers with high-precision tailored molecular weights (from low to ultrahigh molecular weight ranges) while mitigating their interbatch variations. We propose that ultrasound-induced simultaneous physical and chemical events enable precise control of the semiconducting polymers' molecular weights with high reproducibility to satisfy all the optical/electrical and morphological demands of diverse types of high-performance semiconducting polymer-based devices; as demonstrated in in-depth experimental screenings in applications of both organic and perovskite photovoltaics. We believe that this methodology provides a fast development of new and existing semiconducting polymers with the highest-level performances possible on various photovoltaic devices.

Structure and elasticity of healthy and Alzheimer's disease cell membranes revealed by molecular dynamics simulations.

Interactions of amyloid-ß (Aß) peptides with neuronal membrane are associated with the development of Alzheimer's disease (AD). Ganglioside monosialotetrahexosylganglioside (GM1) lipids have been shown to form clusters that induce the structural conversion of Aß and promote the incorporation of Aß into the membrane via the membrane surface electrical potential. Prior to the onset of AD symptoms, GM1 clusters may not have formed but the concentration of GM1 may have already changed, and our question is whether this early concentration modification affects the structure and mechanical properties of the membrane. Using one model for healthy cell membranes and three models for AD cell membranes, we carry out 2 µs all-atom molecular dynamics simulations for each model to compare the structure and elasticity of the two membrane types. The simulations show that at the physiological concentration, 1%-3%, GM1 does not form clusters. The reduction of the GM1 lipid does not significantly alter the area per lipid, the membrane thickness, and the lipid order parameters of the AD membranes. However, the dipole potential, the bending, and twist moduli are decreased for the AD membranes. We suggest that these changes in the AD membranes are factors that could trigger the interaction and incorporation of Aß to the membranes. Finally, we show that changes in the sphingomyelin lipid concentrations do not affect the membrane structure and elasticity.

Astrocytic FoxO1 in the hypothalamus regulates metabolic homeostasis by coordinating neuropeptide Y neuron activity.

The forkhead box transcription factor O1 (FoxO1) is expressed ubiquitously throughout the central nervous system, including in astrocytes, the most prevalent glial cell type in the brain. While the role of FoxO1 in hypothalamic neurons in controlling food intake and energy balance is well-established, the contribution of astrocytic FoxO1 in regulating energy homeostasis has not yet been determined. In the current study, we demonstrate the essential role of hypothalamic astrocytic FoxO1 in maintaining normal neuronal activity in the hypothalamus and whole-body glucose metabolism. Inhibition of FoxO1 function in hypothalamic astrocytes shifts the cellular metabolism from glycolysis to oxidative phosphorylation, enhancing astrocyte ATP production and release meanwhile decreasing astrocytic export of lactate. As a result, specific deletion of astrocytic FoxO1, particularly in the hypothalamus, causes a hyperactivation of hypothalamic neuropeptide Y neurons, which leads to an increase in acute feeding and impaired glucose regulation and ultimately results in diet-induced obesity and systemic glucose dyshomeostasis.

Disrupting Sc-uORFs of a transcription factor bZIP1 using CRISPR/Cas9 enhances sugar and amino acid contents in tomato (Solanum lycopersicum).

MAIN CONCLUSION: Induced mutations in the SC-uORF of the tomato transcription factor gene SlbZIP1 by the CRISPR/Cas9 system led to the high accumulation of sugar and amino acid contents in tomato fruits. Tomato (Solanum lycopersicum) is one of the most popular and consumed vegetable crops in the world. Among important traits for tomato improvement such as yield, biotic and abiotic resistances, appearance, post-harvest shelf life and fruit quality, the last one seems to face more challenges because of its genetic and biochemical complexities. In this study, a dual-gRNAs CRISPR/Cas9 system was developed to induce targeted mutations in uORF regions of the SlbZIP1, a gene involved in the sucrose-induced repression of translation (SIRT) mechanism. Different induced mutations in the SlbZIP1-uORF region were identified at the T0 generation, stably transferred to the offspring, and no mutation was found at potential off-target sites. The induced mutations in the SlbZIP1-uORF region affected the transcription of SlbZIP1 and related genes in sugar and amino acid biosynthesis. Fruit component analysis showed significant increases in soluble solid, sugar and total amino acid contents in all SlbZIP1-uORF mutant lines. The accumulation of sour-tasting amino acids, including aspartic and glutamic acids, raised from 77 to 144%, while the accumulation of sweet-tasting amino acids such as alanine, glycine, proline, serine, and threonine increased from 14 to 107% in the mutant plants. Importantly, the potential SlbZIP1-uORF mutant lines with desirable fruit traits and no impaired effect on plant phenotype, growth and development were identified under the growth chamber condition. Our result indicates the potential utility of the CRISPR/Cas9 system for fruit quality improvement in tomato and other important crops.

The mutation spectrum of SLC25A13 gene in citrin deficiency: identification of novel mutations in Vietnamese pediatric cohort with neonatal intrahepatic cholestasis.

BACKGROUND: Citrin deficiency (CD), a disorder caused by mutations in the SLC25A13 gene, may result in neonatal intrahepatic cholestasis. This study was purposely to explore the mutation spectrum of SLC25A13 gene in Vietnamese CD patients. METHODS: The 292 unrelated CD patients were first screened for four high-frequency mutations by PCR/PCR-RFLP. Then, Sanger sequencing was performed directly for heterozygous or undetected patients. Novel mutations identified would need to be confirmed by their parents. RESULTS: 12 pathogenic SLC25A13 mutations were identified in all probands, including three deletions c.851_854del (p.R284Rfs*3), c.70-63_133del (p.Y24_72Ifs*10), and c.[1956C>A;1962del] (p.[N652K;F654Lfs*45]), two splice-site mutations (IVS6+5G>A and IVS11+1G>A), one nonsense mutations c.1399C>T (p.R467*), one duplication mutation c.1638_1660dup (p.A554fs*570), one insertion IVSl6ins3kb (p.A584fs*585), and four missense mutation c.2T>C (p.M1T), c.1231G>A (p.V411M), c.1763G>A (p.R588Q), and c.135G>C (p.L45F). Among them, c.851_854del (mut I) was the most identified mutant allele (91.78%) with a total of 247 homozygous and 42 heterozygous genotypes of carriers. Interestingly, two novel mutations were identified: c.70-63_133del (p.Y24_72Ifs*10) and c.[1956C>A;1962del] (p.[N652K;F654Lfs*45]). CONCLUSION: The SLC25A13 mutation spectrum related to intrahepatic cholestasis infants in Vietnam revealed a quite similar pattern to Asian countries' reports. This finding supports the use of targeted SLC25A13 mutation for CD screening in Vietnam and contributed to the SLC25A13 mutation spectra worldwide. It also helps emphasize the role of DNA analysis in treatment, genetic counseling, and prenatal diagnosis.

Impact of clinical pharmacist-led interventions on switching from intravenous-to-oral antibiotics in patients with infectious diseases at a Vietnamese hospital.

OBJECTIVES: To evaluate the impact of clinical pharmacist-led interventions on the switch from intravenous (IV) to oral (PO) antibiotics among inpatients with infectious diseases. METHODS: A before-and-after study was conducted among inpatients aged 18 or older who were diagnosed with infectious diseases and received IV antibiotics for at least 24 h at the Thong Nhat Hospital during the pre-intervention (between January 2021 and June 2021) and intervention (between January 2022 and June 2022) periods. Information on patient characteristics, antibiotic usage, length of hospital stay and treatment outcomes was obtained from medical records. The interventions included introducing IV-to-PO switch guidelines to physicians and clinical pharmacists' feedback on eligible cases. The impact of the pharmacists' interventions was evaluated by comparing primary outcomes (switch rate and appropriateness of switching) and secondary outcomes (duration of IV therapy, length of hospital stay and treatment outcomes) between the two study periods. RESULTS: We included 99 patients in the pre-intervention and 80 patients in the intervention period. The proportion of patients who switched from IV-to-PO antibiotics increased from 44.4% in the pre-intervention period to 67.8% in the intervention period (p = 0.008). The overall rate of appropriate conversion increased significantly from 43.8% to 67.5% (p = 0.043). There were no statistically significant differences between the two periods with respect to the median duration of IV therapy (9 days vs. 8 days), length of hospital stay (10 days vs. 9 days) and treatment outcomes. Logistic regression analysis showed that the interventions resulted in a higher switch rate, whereas age was negatively associated with the switching rate. CONCLUSIONS: The implementation of clinical pharmacist-led interventions was effective in promoting IV-to-PO antibiotic conversion.

Lot-to-lot variation and verification.

Lot-to-lot verification is an integral component for monitoring the long-term stability of a measurement procedure. The practice is challenged by the resource requirements as well as uncertainty surrounding experimental design and statistical analysis that is optimal for individual laboratories, although guidance is becoming increasingly available. Collaborative verification efforts as well as application of patient-based monitoring are likely to further improve identification of any differences in performance in a relatively timely manner. Appropriate follow up actions of failed lot-to-lot verification is required and must balance potential disruptions to clinical services provided by the laboratory. Manufacturers need to increase transparency surrounding release criteria and work closer with laboratory professionals to ensure acceptable reagent lots are released to end users. A tripartite collaboration between regulatory bodies, manufacturers, and laboratory medicine professional bodies is key to developing a balanced system where regulatory, manufacturing, and clinical requirements of laboratory testing are met, to minimize differences between reagent lots and ensure patient safety. Clinical Chemistry and Laboratory Medicine has served as a fertile platform for advancing the discussion and practice of lot-to-lot verification in the past 60 years and will continue to be an advocate of this important topic for many more years to come.

Method evaluation in the clinical laboratory.

Method evaluation is one of the critical components of the quality system that ensures the ongoing quality of a clinical laboratory. As part of implementing new methods or reviewing best practices, the peer-reviewed published literature is often searched for guidance. From the outset, Clinical Chemistry and Laboratory Medicine (CCLM) has a rich history of publishing methods relevant to clinical laboratory medicine. An insight into submissions, from editors' and reviewers' experiences, shows that authors still struggle with method evaluation, particularly the appropriate requirements for validation in clinical laboratory medicine. Here, we consider through a series of discussion points an overview of the status, challenges, and needs of method evaluation from the perspective of clinical laboratory medicine. We identify six key high-level aspects of clinical laboratory method evaluation that potentially lead to inconsistency. 1. Standardisation of terminology, 2. Selection of analytical performance specifications, 3. Experimental design of method evaluation, 4. Sample requirements of method evaluation, 5. Statistical assessment and interpretation of method evaluation data, and 6. Reporting of method evaluation data. Each of these areas requires considerable work to harmonise the practice of method evaluation in laboratory medicine, including more empirical studies to be incorporated into guidance documents that are relevant to clinical laboratories and are freely and widely available. To further close the loop, educational activities and fostering professional collaborations are essential to promote and improve the practice of method evaluation procedures.

Mutual association between family history of gastric and colorectal cancer and risk of gastric and colorectal cancer.

BACKGROUND AND AIM: We evaluated the associations between gastric cancer (GC) family history (FH) and colorectal cancer (CRC) risk and between CRC FH and GC/gastric adenoma risk. METHODS: We used data of participants who underwent national cancer screening between 2013 and 2014. Participants with GC or CRC FH in first-degree relatives (n = 1 172 750) and those without cancer FH (n = 3 518 250) were matched 1:3 by age and gender. RESULTS: Of the 1 172 750 participants with a FH, 871 104, 264 040, and 37 606 had FHs of only GC, only CRC, and both GC and CRC, respectively. The median follow-up time was 4.8 years. GC and CRC FHs were associated with increased GC and CRC risks, respectively. GC FH was associated with CRC risk (adjusted hazard ratio 1.05; 95% confidence interval [CI] 1.01-1.10), whereas CRC FH was not associated with the risk of GC or gastric adenoma. However, gastric adenoma risk increased 1.62-fold (95% CI 1.40-1.87) in participants with FHs of both GC and CRC, demonstrating a significant difference with the 1.39-fold (95% CI 1.34-1.44) increase in participants with only GC FH. Furthermore, GC risk increased by 5.32 times (95% CI 1.74-16.24) in participants with FHs of both GC and CRC in both parents and siblings. CONCLUSIONS: GC FH was significantly associated with a 5% increase in CRC risk. Although CRC FH did not increase GC risk, FH of both GC and CRC further increased the risk of gastric adenoma. FHs of GC and CRC may affect each other's neoplastic lesion risk.

Isopropyl alcohol inhalation versus 5-HT3 antagonists for treatment of nausea: a meta-analysis of randomised controlled trials.

PURPOSE: Nausea is a common and unpleasant sensation for which current therapies such as serotonin (5-HT3) antagonists are often ineffective, while also conferring a risk of potential adverse events. Isopropyl alcohol (IPA) has been proposed as a treatment for nausea. We aimed to compare IPA with 5-HT3 antagonists for the treatment of nausea across all clinical settings. METHODS: MEDLINE, EMBASE, PubMed, CENTRAL and CINAHL were searched from inception to 17 July 2023 for randomised controlled trials (RCTs) comparing inhaled IPA and a 5-HT3 antagonist for treatment of nausea. Severity and duration of nausea, rescue antiemetic use, adverse events and patient satisfaction were the outcomes sought. Risk of bias (RoB) was assessed using Cochrane RoB 2. Random-effects model was used for meta-analysis. Combination of meta-analyses and narrative review was used to synthesise findings. The evidence was appraised using GRADE. RESULTS: From 1242 records, 4 RCTs were included with 382 participants. Participants receiving IPA had a significantly lower mean time to 50% reduction in nausea (MD - 20.06; 95% CI - 26.26, - 13.85). Nausea score reduction at 30 min was significantly greater in the IPA group (MD 21.47; 95% CI 15.47, 27.47). IPA led to significantly reduced requirement for rescue antiemetics (OR 0.60; 95% CI 0.37, 0.95; p = 0.03). IPA led to no significant difference in patient satisfaction when compared with a 5-HT3 antagonist. The overall GRADE assessment of evidence quality ranged from very low to low. CONCLUSION: IPA may provide rapid, effective relief of nausea when compared with 5-HT3 antagonists.

The Orphan GPCR Receptor, GPR88, Interacts with Nuclear Protein Partners in the Cerebral Cortex.

GPR88 is an orphan G-protein-coupled receptor (GPCR) highly expressed in striatal medium spiny neurons (MSN), also found in cortical neurons at low level. In MSN, GPR88 has a canonical GPCR plasma membrane/cytoplasmic expression, whereas in cortical neurons, we previously reported an atypical intranuclear localization. Molecular size analysis suggests that GPR88, expressed in plasma membrane of MSN or in nuclear compartment of cortical neurons, corresponds to the full-length protein. By transfection of cortical neurons, we showed that GPR88 fluorescent chimeras exhibit a nuclear localization. This localization is contingent on the third intracytoplasmic loop and C-terminus domains, even though these domains do not contain any known nuclear localization signals (NLS). Using yeast two-hybrid screening with these domains, we identified the nuclear proteins ATRX, TOP2B, and BAZ2B, all involved in chromatin remodeling, as potential protein partners of GPR88. We also validated the interaction of GPR88 with these nuclear proteins by proximity ligation assay on cortical neurons in culture and coimmunoprecipitation experiments on cortical extracts from GPR88 wild-type (WT) and knockout (KO) mice. The identification of GPR88 subcellular partners may provide novel functional insights for nonclassical modes of GPCR action that could be relevant in the maturating process of neocortical neurons.

Therapeutic plasma exchange and continuous renal replacement therapy in pediatric dengue-associated acute liver failure: A case series from Vietnam.

BACKGROUND AND OBJECTIVES: Paediatric dengue-associated acute liver failure (PALF) is a rare and fatal complication. To date, clinical data regarding the combination of therapeutic plasma exchange (TPE) and continuous renal replacement therapy (CRRT) for the treatment of dengue-associated PALF are limited. METHODS: We conducted a single-center, retrospective study of all children with dengue-associated PALF admitted to the paediatric intensive care unit of Children Hospital No.2, Vietnam, who were treated with TPE+CRRT between January 2021 and March 2022. The main study outcomes were in-hospital survival, normalisation of hepatic function, and hepatic encephalopathy improvement. RESULTS: Twelve patients aged from 06 to 12 years underwent TPE+CRRT procedures. Among them, three (25 %) patients died of severe sepsis and septic shock confirmed by Enterobacteriaceae spp. haemocultures (stable on maintenance treatment of COVID-19-associated MIS-C with low dose of oral steroids on hospital admission), acute respiratory distress syndrome (ARDS), and clinically apparent intracranial haemorrhage. Nine patients (75 %) survived. The paediatric mortality risk score improved significantly at discharge compared with PICU admission (P < 0.01). Markedly, all twelve patients were diagnosed with hepatoencephalopathy of grades III and IV on PICU admission. After the combined TPE+CRRT interventions, there were substantial improvements in liver transaminases levels, coagulation profiles, and metabolic biomarkers. Normal neurological functions were observed in nine alive patients at hospital discharge. Only one patient experienced an adverse event of slightly low blood pressure, which rapidly self-resolved. INTERPRETATION AND CONCLUSIONS: Combined TPE+CRRT significantly improved survival outcome, neurological status, and rapid normalisation of liver functions in dengue-associated PALF.

Targeting of pancreatic cancer cells and stromal cells using engineered oncolytic Salmonella typhimurium.

Pancreatic cancer is resistant to conventional therapeutic interventions, mainly due to abundant cancer stromal cells and poor immune cell infiltration. Here, we used a targeted cancer therapy approach based on attenuated Salmonella typhimurium engineered to express cytolysin A (ClyA) to target cancer stromal cells and cancer cells and treat pancreatic cancer in mice. Nude mice bearing subcutaneous or orthotopic human pancreatic cancers were treated with engineered S. typhimurium expressing ClyA. The tumor microenvironment was monitored to analyze stromal cell numbers, stromal cell marker expression, and immune cell infiltration. The attenuated bacteria accumulated and proliferated specifically in tumor tissues after intravenous injection. The bacteria secreted ClyA into the tumor microenvironment. A single dose of ClyA-expressing Salmonella markedly inhibited growth of pancreatic cancer both in subcutaneous xenograft- and orthotopic tumor-bearing nude mice. Histological analysis revealed a marked decrease in expression of stromal cell markers and increased immune cell (neutrophils and macrophages) infiltration into tumors after colonization by ClyA-expressing bacteria. ClyA-expressing S. typhimurium destroyed cancer stromal cells and cancer cells in mouse models of human pancreatic cancer. This approach provides a novel strategy for combining anticancer and anti-stromal therapy to treat pancreatic cancer.

Study protocol for type II hybrid implementation-effectiveness trial of strategies for depression care task-sharing in community health stations in Vietnam: DEP Project.

BACKGROUND: It is not clear what the most effective implementation strategies are for supporting the enactment and sustainment of depression care services in primary care settings. This type-II Hybrid Implementation-Effectiveness study will compare the effectiveness of three system-level strategies for implementing depression care programs at 36 community health stations (CHSs) across 2 provinces in Vietnam. METHODS: In this cluster-randomized controlled trial, CHSs will be randomly assigned to one of three implementation conditions: (1) Usual Implementation (UI), which consists of training workshops and toolkits; (2) Enhanced Supervision (ES), which includes UI combined with bi-weekly/monthly supervision; and (3) Community-Engaged Learning Collaborative (CELC), which includes all components of ES, combined with bi-monthly province-wide learning collaborative meetings, during which cross-site learning and continuous quality improvement (QI) strategies are implemented to achieve better implementation outcomes. The primary outcome will be measured based on the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation quality, and Maintenance) using indicators on implementation, provider, and client factors. The secondary outcome examines factors associated with barriers and facilitators of quality implementation, while the tertiary outcome evaluates the incremental cost-effectiveness ratio of services provided in the ES and CELC conditions, relative to UI condition for depression care. A total of 1,296 clients receiving depression care at CHSs will be surveyed at baseline and 6-month follow-up to assess mental health and psychosocial outcomes (e.g., depression and anxiety severity, health function, quality of life). Additionally, 180 CHS staff and 180 non-CHS staff will complete pre- and post-training evaluation and surveys at baseline, 6, 12, and 24 months. DISCUSSION: We hypothesize that the additional implementation supports will make mental health service implementation superior in the ES and CELC arms compared to the UI arm. The findings of this project could identify effective implementation models and assess the added value of specific QI strategies for implementing depression care in primary care settings in Vietnam, with implications and recommendations for other low- and middle-income settings. More importantly, this study will provide evidence for key stakeholders and policymakers to consider policies that disseminate, scale up, and advance quality mental health care in Vietnam. TRIAL REGISTRATION: NCT04491045 on Clinicaltrials.gov. Registered July 29, 2020.

Optical Glucose Sensors Based on Chitosan-Capped ZnS-Doped Mn Nanomaterials.

The primary goal of glucose sensing at the point of care is to identify glucose concentrations within the diabetes range. However, lower glucose levels also pose a severe health risk. In this paper, we propose quick, simple, and reliable glucose sensors based on the absorption and photoluminescence spectra of chitosan-capped ZnS-doped Mn nanomaterials in the range of 0.125 to 0.636 mM glucose corresponding to 2.3 mg/dL to 11.4 mg/dL. The detection limit was 0.125 mM (or 2.3 mg/dL), much lower than the hypoglycemia level of 70 mg/dL (or 3.9 mM). Chitosan-capped ZnS-doped Mn nanomaterials retain their optical properties while improving sensor stability. This study reports for the first time how the sensors' efficacy was affected by chitosan content from 0.75 to 1.5 wt.%. The results showed that 1 %wt chitosan-capped ZnS-doped Mn is the most-sensitive, -selective, and -stable material. We also put the biosensor through its paces with glucose in phosphate-buffered saline. In the same range of 0.125 to 0.636 mM, the sensors-based chitosan-coated ZnS-doped Mn had a better sensitivity than the working water environment.