Synthesis and Characterization of Bulky 1,3-Diamidopropane Complexes of Group 2 Metals (Be-Sr).

Reaction of lithium 1,3-diamidopropane Li2(TripNCN) (TripNCN=[{(Trip)NCH2}2CH2]2-, Trip=2,4,6-triisopropylphenyl) with BeBr2(OEt2)2 gave the diamido beryllium complex, [(TripNCN)Be(OEt2)]. Deprotonation reactions between the bulkier 1,3-diaminopropane (TCHPNCN)H2 (TCHPNCN=[{(TCHP)NCH2}2CH2]2-, TCHP=2,4,6-tricyclohexylphenyl) and magnesium alkyls afforded the adduct complexes [(TCHPNCN)Mg(OEt2)] and [(TCHPNCN)Mg(THF)2], depending on the reaction conditions employed. Treating [(TCHPNCN)Mg(THF)2] with the N-heterocyclic carbene :C{(MeNCMe)2} (TMC) gave [(TCHPNCN)Mg(TMC)2] via substitution of the THF ligands. Reactions of (ArNCN)H2 (Ar=Trip or TCHP) with Mg{CH2(SiMe3)}2, in the absence of Lewis bases, yielded the N-bridged dimers [{(ArNCN)Mg}2]. Salt metathesis reactions between alkali metal salts M2(TCHPNCN) (M=Li or K) and CaI2 or SrI2 led to the THF adduct compounds [(TCHPNCN)Ca(THF)3] and [(TCHPNCN)Sr(THF)4], the differing number of THF ligands in which is a result of the different sizes of the metals involved. The described complexes hold potential as precursors to kinetically protected, low oxidation state group 2 metal species.

Investigation of Markedly Elevated Liver Enzymes With Serendipitous Underlying Wilson's Disease With Chronic Alcohol Abuse.

Acute hepatitis can result from a wide variety of noninfectious causes that include, but are not limited to, drugs (drug-induced hepatitis), alcohol (alcoholic hepatitis), immunologic (autoimmune hepatitis, primary biliary cholangitis), or as a result of indirect insult secondary to biliary tract dysfunction (cholestatic hepatitis), pregnancy-related liver dysfunction, shock, or metastatic disease. In clinical settings, these causes are not uncommon to overlap with each other or are masked by obviously visible causes in medical history. We reported our scenario of a patient who has a heavy history of alcohol use and presented with alcohol withdrawal symptoms and a marked elevation of liver enzymes. Interestingly, further investigations suggested Wilson's disease could be an underlying culprit of acute hepatitis in this patient. This case again emphasized that Wilson's disease can be masked under multiple causes and various scenarios, which alerts clinicians that a broad approach should be made for every case of acute hepatitis.

A Comprehensive Evaluation of Dioxins and Furans Occurrence in River Sediments from a Secondary Steel Recycling Craft Village in Northern Vietnam.

This first study investigated the presence of dioxins and furans in river sediments around a craft village in Vietnam, focusing on Secondary Steel Recycling. Sediment samples were collected from various locations along the riverbed near the Da Hoi Secondary Steel Recycling village in Bac Ninh province. The analysis was conducted using a HRGC/HRMS-DFS device, detecting a total of 17 dioxin/furan isomers in all samples, with an average total concentration of 288.86 ng/kg d.w. The concentrations of dioxin/furan congeners showed minimal variation among sediment samples, ranging from 253.9 to 344.2 ng/kg d.w. The predominant compounds in the dioxin group were OCDD, while in the furan group, they were 1,2,3,4,6,7,8-HpCDF and OCDF. The chlorine content in the molecule appeared to be closely related to the concentration of dioxins and their percentage distribution. However, the levels of furan isomers did not vary significantly. The distribution of these compounds was not dependent on the flow direction, as they were mainly found in solid waste and are not water-soluble. Although the hepta and octa congeners had high concentrations, when converted to TEQ values, the tetra and penta groups (for dioxins) and the penta and hexa groups (for furans) contributed more to toxicity. Furthermore, the source of dioxins in sediments at Da Hoi does not only originate from steel recycling production activities but also from other combustion sites. The average total toxicity was 10.92 ng TEQ/kg d.w, ranging from 4.99 to 17.88 ng TEQ/kg d.w, which did not exceed the threshold specified in QCVN 43:2017/BTNMT, the National Technical Regulation on Sediment Quality. Nonetheless, these levels are still concerning. The presence of these toxic substances not only impacts aquatic organisms in the sampled water environment but also poses potential health risks to residents living nearby.

FOXO1 enhances CAR T cell stemness, metabolic fitness and efficacy.

Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of haematological malignancies such as acute lymphoblastic leukaemia, B cell lymphoma and multiple myeloma1-4, but the efficacy of CAR T cell therapy in solid tumours has been limited5. This is owing to a number of factors, including the immunosuppressive tumour microenvironment that gives rise to poorly persisting and metabolically dysfunctional T cells. Analysis of anti-CD19 CAR T cells used clinically has shown that positive treatment outcomes are associated with a more 'stem-like' phenotype and increased mitochondrial mass6-8. We therefore sought to identify transcription factors that could enhance CAR T cell fitness and efficacy against solid tumours. Here we show that overexpression of FOXO1 promotes a stem-like phenotype in CAR T cells derived from either healthy human donors or patients, which correlates with improved mitochondrial fitness, persistence and therapeutic efficacy in vivo. This work thus reveals an engineering approach to genetically enforce a favourable metabolic phenotype that has high translational potential to improve the efficacy of CAR T cells against solid tumours.

Alteration in the gut microbiome is associated with changes in bone metabolism after laparoscopic sleeve gastrectomy.

Laparoscopic sleeve gastrectomy (LSG), the most common bariatric surgical procedure, leads to durable weight loss and improves obesity-related comorbidities. However, it induces abnormalities in bone metabolism. One unexplored potential contributor is the gut microbiome, which influences bone metabolism and is altered after surgery. We characterized the relationship between the gut microbiome and skeletal health in severe obesity and after LSG. In a prospective cohort study, 23 adults with severe obesity underwent skeletal health assessment and stool collection preoperatively and 6 mo after LSG. Gut microbial diversity and composition were characterized using 16S rRNA gene sequencing, and fecal concentrations of short-chain fatty acids (SCFA) were measured with LC-MS/MS. Spearman's correlations and PERMANOVA analyses were applied to assess relationships between the gut microbiome and bone health measures including serum bone turnover markers (C-terminal telopeptide of type 1 collagen [CTx] and procollagen type 1 N-terminal propeptide [P1NP]), areal BMD, intestinal calcium absorption, and calciotropic hormones. Six months after LSG, CTx and P1NP increased (by median 188% and 61%, P < .01) and femoral neck BMD decreased (mean -3.3%, P < .01). Concurrently, there was a decrease in relative abundance of the phylum Firmicutes. Although there were no change in overall microbial diversity or fecal SCFA concentrations after LSG, those with greater within-subject change in gut community microbial composition (ß-diversity) postoperatively had greater increases in P1NP level (ρ = 0.48, P = .02) and greater bone loss at the femoral neck (ρ = -0.43, P = .04). In addition, within-participant shifts in microbial richness/evenness (α-diversity) were associated with changes in IGF-1 levels (ρ = 0.56, P < .01). The lower the postoperative fecal butyrate concentration, the lower the IGF-1 level (ρ = 0.43, P = .04). Meanwhile, the larger the decrease in butyrate concentration, the higher the postoperative CTx (ρ = -0.43, P = .04). These findings suggest that LSG-induced gut microbiome alteration may influence skeletal outcomes postoperatively, and microbial influences on butyrate formation and IGF-1 are possible mechanisms.

Laparoscopic sleeve gastrectomy (LSG), the most common bariatric surgical procedure, is a highly effective treatment for obesity because it produces dramatic weight loss and improves obesity-related medical conditions. However, it also results in abnormalities in bone metabolism. It is important to understand how LSG affects the skeleton, so that bone loss after surgery might be prevented. We studied adult men and women before and 6 mo after LSG, and we explored the relationship between the altered gut bacteria and bone metabolism changes. We found that: Those with greater shifts in their gut bacterial composition had more bone loss.Butyrate, a metabolite produced by gut bacteria from fermentation of dietary fiber, was associated with less bone breakdown and higher IGF-1 level (a bone-building hormone). We conclude that changes in the gut bacteria may contribute to the negative skeletal impact of LSG and reduced butyrate production by the gut bacteria leading to lower IGF-1 levels is a possible mechanism.

Synthetic mRNA delivered to human cells leads to expression of Cpl-1 bacteriophage-endolysin with activity against Streptococcus pneumoniae.

Endolysins are bacteriophage-encoded hydrolases that show high antibacterial activity and a narrow substrate spectrum. We hypothesize that an mRNA-based approach to endolysin therapy can overcome some challenges of conventional endolysin therapy, namely organ targeting and bioavailability. We show that synthetic mRNA applied to three human cell lines (HEK293T, A549, HepG2 cells) leads to expression and cytosolic accumulation of the Cpl-1 endolysin with activity against Streptococcus pneumoniae. Addition of a human lysozyme signal peptide sequence translocates the Cpl-1 to the endoplasmic reticulum leading to secretion (hlySP-sCpl-1). The pneumococcal killing effect of hlySP-sCpl-1 was enhanced by introduction of a point mutation to avoid N-linked-glycosylation. hlySP-sCpl-1N215D, collected from the culture supernatant of A549 cells 6 h post-transfection showed a significant killing effect and was active against nine pneumococcal strains. mRNA-based cytosolic Cpl-1 and secretory hlySP-sCpl-1N215D show potential for innovative treatment strategies against pneumococcal disease and, to our best knowledge, represent the first approach to mRNA-based endolysin therapy. We assume that many other bacterial pathogens could be targeted with this novel approach.

Enforcing Metal-Arene Interactions in Bulky p-Terphenyl Bis(anilide) Complexes of Group 2 Metals (Be-Ba): Potential Precursors for Low-Oxidation-State Alkaline Earth Metal Systems.

An extremely bulky p-terphenyl bis(aniline), p-C6H4{C6H4[N(H)TCHP]-2}2 (TCHP = 2,4,6-tricyclohexylphenyl) TCHPTerphH2, has been developed. Deprotonation of a less bulky analogue, DipTerphH2 (Dip = 2,6-diisopropylphenyl), with BePh2 affords the bimetallic system, [(BePh)2(µ-DipTerph)] 1. Treating either TCHPTerphH2 or DipTerphH2 with Mg{CH2(SiMe3)}2 gives the monomeric bis(anilide) complexes [Mg(ArTerph)] (Ar = Dip 2, TCHP 3) which display rare examples of η6-arene coordination to the metal center. Treating 2 with THF leads to partial dissociation of the Mg···arene interaction and formation of [Mg(DipTerph)(THF)] 4. Reactions of the bis(aniline)s with the group 2 metal amides [M{N(SiMe3)2}2] afford dimeric, structurally analogous compounds [{M(ArTerph)}2] (Ar = Dip, M = Ca 5, Sr 6, Ba 7; Ar = TCHP, M = Ca 8, Sr 9, Ba 10) which display intermolecular M···arene interactions in the solid state. Computational studies have shown that the intramolecular M···Î·6-arene interactions in models of the ether-free metal bis(anilide) compounds are largely electrostatic in nature. Reductions of these compounds with alkali metals led to mixtures of unidentified products.

Lack of SPNS1 results in accumulation of lysolipids and lysosomal storage disease in mouse models.

Accumulation of sphingolipids, especially sphingosines, in the lysosomes is a key driver of several lysosomal storage diseases. The transport mechanism for sphingolipids from the lysosome remains unclear. Here, we identified SPNS1, which shares the highest homology to SPNS2, a sphingosine-1-phosphate (S1P) transporter, functions as a transporter for lysolipids from the lysosome. We generated Spns1-KO cells and mice and employed lipidomic and metabolomic approaches to reveal SPNS1 ligand identity. Global KO of Spns1 caused embryonic lethality between E12.5 and E13.5 and an accumulation of sphingosine, lysophosphatidylcholines (LPC), and lysophosphatidylethanolamines (LPE) in the fetal livers. Similarly, metabolomic analysis of livers from postnatal Spns1-KO mice presented an accumulation of sphingosines and lysoglycerophospholipids including LPC and LPE. Subsequently, biochemical assays showed that SPNS1 is required for LPC and sphingosine release from lysosomes. The accumulation of these lysolipids in the lysosomes of Spns1-KO mice affected liver functions and altered the PI3K/AKT signaling pathway. Furthermore, we identified 3 human siblings with a homozygous variant in the SPNS1 gene. These patients suffer from developmental delay, neurological impairment, intellectual disability, and cerebellar hypoplasia. These results reveal a critical role of SPNS1 as a promiscuous lysolipid transporter in the lysosomes and link its physiological functions with lysosomal storage diseases.

MFSD7c functions as a transporter of choline at the blood-brain barrier.

Mutations in the orphan transporter MFSD7c (also known as Flvcr2), are linked to Fowler syndrome. Here, we used Mfsd7c knockout (Mfsd7c-/-) mice and cell-based assays to reveal that MFSD7c is a choline transporter at the blood-brain barrier (BBB). We performed comprehensive metabolomics analysis and detected differential changes of metabolites in the brains and livers of Mfsd7c-/-embryos. Particularly, we found that choline-related metabolites were altered in the brains but not in the livers of Mfsd7c-/- embryos. Thus, we hypothesized that MFSD7c regulates the level of choline in the brain. Indeed, expression of human MFSD7c in cells significantly increased choline uptake. Interestingly, we showed that choline uptake by MFSD7c is greatly increased by choline-metabolizing enzymes, leading us to demonstrate that MFSD7c is a facilitative transporter of choline. Furthermore, single-cell patch clamp analysis showed that the import of choline by MFSD7c is electrogenic. Choline transport function of MFSD7c was shown to be conserved in vertebrates, but not in yeasts. We demonstrated that human MFSD7c is a functional ortholog of HNM1, the yeast choline importer. We also showed that several missense mutations identified in patients exhibiting Fowler syndrome had abolished or reduced choline transport activity. Mice lacking Mfsd7c in endothelial cells of the central nervous system suppressed the import of exogenous choline from blood but unexpectedly had increased choline levels in the brain. Stable-isotope tracing study revealed that MFSD7c was required for exporting choline derived from lysophosphatidylcholine in the brain. Collectively, our work identifies MFSD7c as a choline exporter at the BBB and provides a foundation for future work to reveal the disease mechanisms of Fowler syndrome.

Biallelic variation in the choline and ethanolamine transporter FLVCR1 underlies a pleiotropic disease spectrum from adult neurodegeneration to severe developmental disorders.

FLVCR1 encodes Feline leukemia virus subgroup C receptor 1 (FLVCR1), a solute carrier (SLC) transporter within the Major Facilitator Superfamily. FLVCR1 is a widely expressed transmembrane protein with plasma membrane and mitochondrial isoforms implicated in heme, choline, and ethanolamine transport. While Flvcr1 knockout mice die in utero with skeletal malformations and defective erythropoiesis reminiscent of Diamond-Blackfan anemia, rare biallelic pathogenic FLVCR1 variants are linked to childhood or adult-onset neurodegeneration of the retina, spinal cord, and peripheral nervous system. We ascertained from research and clinical exome sequencing 27 individuals from 20 unrelated families with biallelic ultra-rare missense and predicted loss-of-function (pLoF) FLVCR1 variant alleles. We characterize an expansive FLVCR1 phenotypic spectrum ranging from adult-onset retinitis pigmentosa to severe developmental disorders with microcephaly, reduced brain volume, epilepsy, spasticity, and premature death. The most severely affected individuals, including three individuals with homozygous pLoF variants, share traits with Flvcr1 knockout mice and Diamond-Blackfan anemia including macrocytic anemia and congenital skeletal malformations. Pathogenic FLVCR1 missense variants primarily lie within transmembrane domains and reduce choline and ethanolamine transport activity compared with wild-type FLVCR1 with minimal impact on FLVCR1 stability or subcellular localization. Several variants disrupt splicing in a mini-gene assay which may contribute to genotype-phenotype correlations. Taken together, these data support an allele-specific gene dosage model in which phenotypic severity reflects residual FLVCR1 activity. This study expands our understanding of Mendelian disorders of choline and ethanolamine transport and demonstrates the importance of choline and ethanolamine in neurodevelopment and neuronal homeostasis.

Steric control of Mg-Mg bond formation vs. N2 activation in the reduction of bulky magnesium diamide complexes.

Reduction of the magnesium(II) diamide [Mg(TripNON)] (TripNON = 4,5-bis(2,4,6-triisopropylanilido)-2,7-diethyl-9,9-dimethyl-xanthene) with 5% w/w K/KI leads to a good yield of a dianionic dimagnesium(I) species, as its potassium salt, [{K(TripNON)Mg}2]. An X-ray crystallographic analysis shows the molecule to contain a very long Mg-Mg bond (3.137(2) Å). The formation of [{K(TripNON)Mg}2] contrasts with a previously reported reduction of a magnesium(II) complex incorporating a bulkier diamide ligand, which instead afforded a magnesium-dinitrogen complex. In the current study, [{K(TripNON)Mg}2] has been shown to be a viable reagent for the reductive activation of CO, H2 and N2O.

Ambient health sensing on passive surfaces using metamaterials.

Ambient sensors can continuously and unobtrusively monitor a person's health and well-being in everyday settings. Among various sensing modalities, wireless radio-frequency sensors offer exceptional sensitivity, immunity to lighting conditions, and privacy advantages. However, existing wireless sensors are susceptible to environmental interference and unable to capture detailed information from multiple body sites. Here, we present a technique to transform passive surfaces in the environment into highly sensitive and localized health sensors using metamaterials. Leveraging textiles' ubiquity, we engineer metamaterial textiles that mediate near-field interactions between wireless signals and the body for contactless and interference-free sensing. We demonstrate that passive surfaces functionalized by these metamaterials can provide hours-long cardiopulmonary monitoring with accuracy comparable to gold standards. We also show the potential of distributed sensors and machine learning for continuous blood pressure monitoring. Our approach enables passive environmental surfaces to be harnessed for ambient sensing and digital health applications.

The Bjøntegaard Bible Why Your Way of Comparing Video Codecs May Be Wrong.

In this paper, we provide an in-depth assessment on the Bjøntegaard Delta. We construct a large data set of video compression performance comparisons using a diverse set of metrics including PSNR, VMAF, bitrate, and processing energies. These metrics are evaluated for visual data types such as classic perspective video, 360° video, point clouds, and screen content. As compression technology, we consider multiple hybrid video codecs as well as state-of-the-art neural network based compression methods. Using additional supporting points in-between standard points defined by parameters such as the quantization parameter, we assess the interpolation error of the Bjøntegaard-Delta (BD) calculus and its impact on the final BD value. From the analysis, we find that the BD calculus is most accurate in the standard application of rate-distortion comparisons with mean errors below 0.5 percentage points. For other applications and special cases, e.g., VMAF quality, energy considerations, or inter-codec comparisons, the errors are higher (up to 5 percentage points), but can be halved by using a higher number of supporting points. We finally come up with recommendations on how to use the BD calculus such that the validity of the resulting BD-values is maximized. Main recommendations are as follows: First, relative curve differences should be plotted and analyzed. Second, the logarithmic domain should be used for saturating metrics such as SSIM and VMAF. Third, BD values below a certain threshold indicated by the subset error should not be used to draw recommendations. Fourth, using two supporting points is sufficient to obtain rough performance estimates.

Pediatric Profound Dengue Shock Syndrome and Use of Point-of-Care Ultrasound During Mechanical Ventilation to Guide Treatment: Single-Center Retrospective Study, 2013-2021.

OBJECTIVES: Profound dengue shock syndrome (DSS) complicated by severe respiratory failure necessitating mechanical ventilation (MV) accounts for high case fatality rates among PICU-admitted patients. A major challenge to management is the assessment of intravascular volume, which can be hampered by severe plasma leakage and the use of MV. DESIGN: Retrospective cohort, from 2013 to 2021. PATIENTS: Sixty-seven children with profound DSS supported by MV, some of whom underwent bedside point-of-care ultrasound (POCUS) for assessment and monitoring of hemodynamics and fluid administration. SETTING: PICU of the tertiary Children's Hospital No. 2 in Vietnam. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed data clinical and laboratory data during PICU stay. In particular, during use of MV (i.e., at times 0-, 6-, and 24-hr after commencement) and fluid resuscitation. The primary study outcome was 28-day in-hospital mortality, and the secondary outcomes were associations with changes in hemodynamics, blood lactate, and vasoactive-inotrope score (VIS). Patients had a median age of 7 years (interquartile range, 4-9). Use of POCUS during fluid management (39/67), as opposed to not using (28/67), was associated with lower mortality (6/39 [15%] vs. 18/28 [64%]; difference 49 % [95% CI, 28-70%], p < 0.001). Use of POCUS was associated with lower odds of death (adjusted odds ratio 0.17 [95% CI, 0.04-0.76], p = 0.02). The utilization of POCUS, versus not, was associated with greater use of resuscitation fluid, and reductions in VIS and pediatric logistic organ dysfunction (PELOD-2) score at 24 hours after MV and PICU discharge. CONCLUSIONS: In our experience of pediatric patients with profound DSS and undergoing MV (2013-2021), POCUS use was associated with lower odds of death, a higher volume of resuscitation fluid, and improvements in the blood lactate levels, VIS, and PELOD-2 score.

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.

Precocious infant fecal microbiome promotes enterocyte barrier dysfuction, altered neuroendocrine signaling and associates with increased childhood obesity risk.

Early life gut microbiome composition has been correlated with childhood obesity, though microbial functional contributions to disease origins remain unclear. Here, using an infant birth cohort (n = 349) we identify a distinct fecal microbiota composition in 1-month-old infants with the lowest rate of exclusive breastfeeding, that relates with higher relative risk for obesity and overweight phenotypes at two years. Higher-risk infant fecal microbiomes exhibited accelerated taxonomic and functional maturation and broad-ranging metabolic reprogramming, including reduced concentrations of neuro-endocrine signals. In vitro, exposure of enterocytes to fecal extracts from higher-risk infants led to upregulation of genes associated with obesity and with expansion of nutrient sensing enteroendocrine progenitor cells. Fecal extracts from higher-risk infants also promoted enterocyte barrier dysfunction. These data implicate dysregulation of infant microbiome functional development, and more specifically promotion of enteroendocrine signaling and epithelial barrier impairment in the early-life developmental origins of childhood obesity.

Prevalence of stress and related factors among healthcare students: a cross - sectional study in Can Tho City, Vietnam.

Background: Stress is a major public health issue that can impact both physical and mental well-being. It is prevalent in many areas of modern life, including education. Healthcare students are at a high risk of experiencing stress due to the unique demands of their fields of study. Study design and methods: An online survey was conducted on 2,515 undergraduate students pursuing degrees in medicine, preventive medicine, pharmacy, and nursing at Can Tho University of Medicine and Pharmacy in Can Tho City, Vietnam. Results: Using the Perceived Stress Scale-10 (PSS-10), it was found that 35.2% of students reported mild stress, 62.7% had moderate stress, and only 2.1% experienced severe stress. Multivariable logistic regression analysis revealed nine significant factors associated with students' stress levels (p ≤ 0.05). Particularly, medicine students exhibited a significantly higher level of moderate and severe stress (95% CI = 1.22-2.01), 1.57 times higher than preventive medicine students. Sixth-year students had a stress level 1.58 times higher (95% CI = 1.11-2.26) than first-year students. Students achieving excellent and very good academic performances in the last semester had a stress level 1.60 times higher (95% CI = 1.16-2.22) than students with average and lower academic performance. Students living at home had a stress level 1.73 times higher (95% CI = 1.05-2.84) than students living in their relatives' houses. Students who rarely or never had a part-time job during academic years had a stress level 1.70 times higher (95% CI = 1.31-2.20) than those who often or sometimes had a part-time job. Students with a family history of smoking addiction had a stress level 1.69 times higher (95% CI = 1.28-2.22) than students without such a family history. Students who rarely or never received concern and sharing from family had a stress level 7.41 times higher (95% CI = 5.07-10.84) than students who often or sometimes received concern and sharing from family. Students who were often or sometimes cursed by family had a stress level 2.04 times higher (95% CI = 1.09-3.81) than students who were rarely or never cursed by family. Students without close friends had a stress level 1.46 times higher (95% CI = 1.11-1.91) than students with close friends. Conclusions: The rates of mild and moderate stress levels were significantly higher than severe stress level among healthcare students. Research has provided scientific findings as the basis for determining risk factors and imposing solutions that aim to reduce the rate of stress in students. Therefore, it helps students overcome difficulties and enhance their physical and mental health.

Ambient Cardiovascular Monitoring with Metamaterial Textile Sensors.

Contactless sensors embedded in the ambient environment have broad applications in unobtrusive, long-term health monitoring for preventative and personalized healthcare. Microwave radar sensors are an attractive candidate for ambient sensing due to their high sensitivity to physiological motions, ability to penetrate through obstacles and privacy-preserving properties, but practical applications in complex real-world environments have been limited because of challenges associated with background clutter and interference. In this work, we propose a thin and soft textile sensor based on microwave metamaterials that can be easily integrated into ordinary furniture for contactless ambient monitoring of multiple cardiovascular signals in a localized manner. Evaluations of our sensor's performance in human subjects show high accuracy of heartbeat and arterial pulse detection, with ≥ 96.5% sensitivity and < 5% mean absolute relative error (MARE) across all subjects. We demonstrate our sensor's utility for cuffless blood pressure monitoring on a human subject over a continuous 10-minute period. Our results highlight the potential of metamaterial textile sensors in ambient health and wellness monitoring applications.Clinical relevance-The contactless metamaterial textile sensors demonstrated in this paper provide unobtrusive, convenient and long-term monitoring of multiple cardiovascular health metrics, including heart rate, pulse rate and cuffless blood pressure, which can facilitate preventative and personalized healthcare.

Mfsd7b facilitates choline transport and missense mutations affect choline transport function.

MFSD7b belongs to the Major Facilitator Superfamily of transporters that transport small molecules. Two isoforms of MFSD7b have been identified and they are reported to be heme exporters that play a crucial role in maintaining the cytosolic and mitochondrial heme levels, respectively. Mutations of MFSD7b (also known as FLVCR1) have been linked to retinitis pigmentosa, posterior column ataxia, and hereditary sensory and autonomic neuropathy. Although MFSD7b functions have been linked to heme detoxification by exporting excess heme from erythroid cells, it is ubiquitously expressed with a high level in the kidney, gastrointestinal tract, lungs, liver, and brain. Here, we showed that MFSD7b functions as a facilitative choline transporter. Expression of MFSD7b slightly but significantly increased choline import, while its knockdown reduced choline influx in mammalian cells. The influx of choline transported by MFSD7b is dependent on the expression of choline metabolizing enzymes such as choline kinase (CHKA) and intracellular choline levels, but it is independent of gradient of cations. Additionally, we showed that choline transport function of Mfsd7b is conserved from fly to man. Employing our transport assays, we showed that missense mutations of MFSD7b caused reduced choline transport functions. Our results show that MFSD7b functions as a facilitative choline transporter in mammalian cells.