The role of bacterial size, shape and surface in macrophage engulfment of uropathogenic E. coli cells.

Uropathogenic Escherichia coli (UPEC) can undergo extensive filamentation in the host during acute urinary tract infections (UTIs). It has been hypothesised that this morphological plasticity allows bacteria to avoid host immune responses such as macrophage engulfment. However, it is still unclear what properties of filaments are important in macrophage-bacteria interactions. The aim of this work was to investigate the contribution of bacterial biophysical parameters, such as cell size and shape, and physiological parameters, such as cell surface and the environment, to macrophage engulfment efficiency. Viable, reversible filaments of known lengths and volumes were produced in the UPEC strain UTI89 using a variety of methods, including exposure to cell-wall targeting antibiotics, genetic manipulation and isolation from an in vitro human bladder cell model. Quantification of the engulfment ability of macrophages using gentamicin-protection assays and fluorescence microscopy demonstrated that the ability of filaments to avoid macrophage engulfment is dependent on a combination of size (length and volume), shape, cell surface and external environmental factors. UTI89 filamentation and macrophage engulfment efficiency were also found to occur independently of the SOS-inducible filamentation genes, sulA and ymfM in both in vivo and in vitro models of infection. Compared to filaments formed via antibiotic inhibition of division, the infection-derived filaments were preferentially targeted by macrophages. With several strains of UPEC now resistant to current antibiotics, our work identifies the importance of bacterial physiological and morphological states during infection.

Education and healthcare services for children and young people with intellectual disability in Vietnam: an ecological systems analysis.

PURPOSE: This paper examines the current state of services and support for children and young people with intellectual disability in Vietnam through the perspectives and experiences of parents and professionals in the education and health systems. MATERIALS AND METHODS: We undertook 24 semi-structured interviews with parents and professionals from two Vietnamese central provinces to ask about their experiences and support needs. We draw on the networked model of ecological systems to identify contextual factors in the micro-, meso-, exo- and macro-systems. RESULTS: Access to education and healthcare services were found to be limited for children, young people, and families in central Vietnam. Barriers to provision, accessibility and quality of services were identified at multiple intersecting levels and systems. Parents reported high needs for formal services provided by trained professionals as well as information and education for themselves to provide optimum support for their children. For professionals, further training and government investment and oversight are needed to improve access and ensure quality of services. CONCLUSIONS: Services and support in education and healthcare for children and young people with intellectual disability and their families remains lacking and needs significant improvement. Further information and support for parents, capacity building for professionals, strengthened disability policies and regulations, and public awareness are required.

Despite an overall increase in the number of service providers for children with intellectual disability in Vietnam, parents and professionals describe these services as in significant need of improvement in terms of quality and accessibility.There is a lack of financial and human resources, centralised legislation, guidelines, and regulation to safeguard the quality of rehabilitation and education service provided.Capacity building for disability professionals needs to focus on evidence-based therapies and clinical skills, as well as on attitudes and skills to support and work with parents as collaborators in children's care and services.

Applying machine learning in screening for Down Syndrome in both trimesters for diverse healthcare scenarios.

Background: This paper describes the development of low-cost, effective, non-invasive machine learning-based prediction models for Down Syndrome in the first two trimesters of pregnancy in Vietnam. These models are adaptable to different situations with limited screening capacities at community-based healthcare facilities. Method: Ultrasound and biochemical testing alone and in combination, from both trimesters were employed to build prediction models based on k-Nearest Neighbor, Support Vector Machine, Random Forest, and Extreme Gradient Boosting algorithms. Results: A total of 7,076 pregnant women from a single site in Northern Vietnam were included, and 1,035 had a fetus with Down Syndrome. Combined ultrasound and biochemical testing were required to achieve the highest accuracy in trimester 2, while models based only on biochemical testing performed as well as models based on combined testing during trimester 1. In trimester 1, Extreme Gradient Boosting produced the best model with 94% accuracy and 88% AUC, while Support Vector Machine produced the best model in trimester 2 with 89% accuracy and 84% AUC. Conclusions: This study explored a range of machine learning models under different testing scenarios. Findings point to the potential feasibility of national screening, especially in settings without enough equipment and specialists, after additional model validation and fine tuning is performed.

Organophosphate esters and their metabolites in silver pomfret (Pampus argenteus) of the Vietnamese coastal areas: Spatial-temporal distribution and exposure risk.

A large number of studies on organophosphate esters (tri-OPEs) in marine organisms have not assessed the simultaneous occurrence of tri-OPEs and their metabolites (di-OPEs) in these species. This research investigated the concentration and geographical distribution of 15 tri-OPEs and 7 di-OPEs in 172 samples of Pampus argenteus that were collected annually from 2021 to 2023 at three distinct locations along the Vietnamese coast. As a result, tri-OPEs and di-OPEs were detected in numerous fish samples, indicating their widespread spatial and temporal occurrence in marine fish and pointing out the importance of monitoring their levels. The tri-OPEs and di-OPEs ranged within 2.1-38.9 ng g-1 dry weight (dw) and 3.2-263.4 ng g-1 dw, respectively. The mean concentrations of tri-OPEs ranged from 0.4 (TIPrP) to 5.4 ng g-1 dw (TBOEP), with TBOEP and TEHP having the highest mean values. In addition, the profiles of tri-OPEs in fish exhibited a descending order: Σalkyl OPEs > ΣCl-alkyl OPEs > Σaryl OPEs. The di-OPEs, namely BEHP and DMP, had the highest mean levels, measuring 33.4 ng g-1 dw and 23.8 ng g-1 dw, respectively. Furthermore, there have been significant findings of strong positive correlations between di-OPEs and tri-OPE pairs (p < 0.05). It is worth noting that there is a noticeable difference in the composition of tri-OPEs between the North and other regions. Despite these findings, the presence of OPE-contaminated fish did not pose any health risks to Vietnam's coastal population.

Mycoplasma genitalium infections among participants in a HIV pre-exposure prophylaxis program in Hanoi, Vietnam.

BACKGROUND: Mycoplasma genitalium causes a sexually transmitted infection and is also emerging as an important antimicrobial resistant pathogen. Data on M. genitalium infections among men who have sex with men (MSM) in low-resource settings are sparse. METHODS: From January to December 2022, participants in an HIV pre-exposure prophylaxis (PrEP) program in Hanoi, Vietnam were enrolled into the study. Demographic, behavioral, and clinical characteristics were collected. Self-collected urine, rectal, and pharyngeal specimens were tested for M. genitalium using the Alinity m STI Assay (Abbott Molecular, USA). Univariate and multivariate logistic regression were performed to assess for factors associated with infections. RESULTS: Among 477 participants, the median age was 25.3 years (21.7-29.6) and 92.2% (n = 440) identified as MSM; 48.6% had ≥2 sex partners and 38.1% reported condomless anal sex in the prior month. The overall prevalence of M. genitalium infection was 10.9% (52/477); 7.3% (34/464) rectal, 3.2% (15/476) urethral, and 1.9% (9/476) pharyngeal. Infections were asymptomatic in 71.2% (37/52). Among those with M. genitalium, 30.7% (16/52) were co-infected with either N. gonorrhoeae or C. trachomatis. Among those reporting rectal (n = 51) or urethral (n = 35) symptoms, but without C. trachomatis or N. gonorrhoeae co-infections, five (9.8%) had rectal infections and one (2.9%) had urethral infection. Participants with M. genitalium were more likely to be asymptomatic than participants without M. genitalium (aOR 1.93; 95% CI 1.01-3.71). CONCLUSIONS: M. genitalium infections were common among primarily MSM engaged in an HIV PrEP program in Vietnam. The prevalence was highest in rectal specimens and nearly three quarters of M. genitalium infections were asymptomatic. Testing for M. genitalium infections among those with symptoms is important to enable pathogen-directed therapy. Additional research on antimicrobial resistance and treatment strategies for M. genitalium in low-resource settings is needed.

Cementless TKA use as an alternative to cemented TKA in high BMI patients: A systematic review and meta-analysis.

Purpose: Obesity is prevalent, with nearly one-third of the world's population being classified as obese. In patients with high body mass index (BMI)/body mass undergoing total knee arthroplasty (TKA), there is an increase in strain placed on the implant fixation interfaces. As such, component fixation is a potential concern when performing TKA in the obese patient. To address the growing concerns around the longevity of implant fixation, some have advocated cementless over cemented fixation. However, there is no clear consensus on whether a cementless fixation has more favourable outcomes. The aim of this paper was to present a systematic review and meta-analysis of the existing evidence to establish if cementless TKA has a lower rate of aseptic loosening in high BMI patients when compared to cemented TKA procedures. Methods: A systematic review was performed, and the following databases Medical Literature Analysis and Retrieval System Online (1946 to date), PubMed (1966 to date) and Excerpta Medica Database (1974 to date) were searched. All studies comparing cementless to cemented TKA in patients with BMI > 30 were considered. Meta-analysis compared aseptic loosening and all-cause revision between cemented and uncemented implant use in BMI > 30 patients. Results: The search returned 91 articles in total; after duplicates were removed, the yield was 44 studies. Of the remaining studies that were assessed, three studies met the inclusion criteria for meta-analysis. The pooled odds ratio for all-cause revisions was 0.17 (95%, 0.08-0.36) in favour of uncemented implants (p < 0.01). The pooled odds ratio for aseptic loosening was 0.15 (95% confidence interval, 0.02-0.90) in favour of uncemented implants (p = 0.04). Conclusions: Meta-analysis demonstrated a significant decrease in all-cause revisions and revisions for aseptic loosening when using uncemented fixation in high BMI patients when compared to the use of cemented implants. Level of Evidence: The level of evidence is 1 for our systematic review.

Knowledge and attitudes of medical and pharmacy university students regarding monkeypox: a multicenter, cross-sectional study in Vietnam.

BACKGROUND: In May 2022, monkeypox (mpox) suddenly reappeared and rapidly spread worldwide. This global outbreak was a public health emergency of international concern. This study investigated Vietnamese medical and pharmacy university students' knowledge and attitudes towards mpox. METHODS: This online cross-section survey was administered among students in four universities using a convenience sampling method. A semi-structured questionnaire was shared among students via a Google Forms link (quick-response code) in university amphitheaters at recess. Frequency (percentage) and mean (standard division) were used for descriptive statistics. Univariate and multivariate linear regression analyses were conducted to identify factors associated with students' mpox knowledge and attitudes. A p-value < 0.001 was considered statistical significance. RESULTS: A total of 1,848 students participated in this study (including 1,030 medical students and 818 pharmacy students). Their common sources for seeking mpox/health information included the Internet (89.7%) and mass media (64.2%). Students' average knowledge and attitude scores were 11.542 ± 3.910 (range: 0-23) and 30.301 ± 3.738 (range: 9-45), respectively. The average knowledge score of pharmacy students (12.139 ± 3.545) was significantly higher than that of medical students (11.067 ± 4.118) (p < 0.001). The average attitude score of the former (30.454 ± 3.787) was comparatively higher than that of the latter (30.181 ± 3.696), but this difference was insignificant (p = 0.111). Factors significantly associated with students' mpox knowledge and/or attitudes were their sex, age, year of study, residence, major, grade point average, type of university, seeking mpox information in the past, and using reliable sources to seek health information (p < 0.001). A positive correlation existed between students' knowledge and attitude scores (p < 0.001). CONCLUSIONS: Students' knowledge about mpox was relatively poor, while their attitudes were comparatively positive. Universities and relevant authorities should focus on the above factors and use multiple platforms and channels of communication to guarantee that trustworthy information about mpox can reach as many students as possible.

Surgical complications in neuromuscular scoliosis surgery: systematic review and meta-analysis of the last ten years.

PURPOSE: Surgical correction of neuromuscular scoliosis is often a challenging and extensive procedure. Due to this complexity and the high disease burden that these patients carry, per and post-operative complications are not uncommon. The purpose of this study was to systematically review and describe the pooled rates of postoperative complications and analyze risk factors for complications in neuromuscular scoliosis surgery described in the literature in the last ten years. METHODS: A systematic review of the English literature across multiple databases was conducted using search criteria (neuromuscular scoliosis AND complications) and using PRISMA guidelines (Jan 2012-July 2022). Studies with less than 30 patients and follow-up of < 2 years were excluded. Data extraction and meta-analysis were performed using random mode effect. Statistical analysis was conducted using OpenMeta software. Meta-regression analysis was used to detect risk factors (surgical approach, intraoperative time, intraoperative blood loss, preoperative Cobb angle and patient diagnosis) associated with each complication group. Confidence interval (CI) was set at 95%. RESULTS: Twenty-two studies met the inclusion criteria involving 2155 patients. The level of evidence among studies were III (9) and IV (13). The most common primary diagnosis was cerebral palsy (43%) followed by Duchenne muscle dystrophy (20%), myelomeningocele (7.4%), spinal muscle atrophy (7.1%), Rett syndrome (< 2%) and combined other pathologies (20.2%). The pooled incidence rate of wound complications was the highest, amongst all complications, at 13.3% (CI 10.838 to 16.861); closely followed by respiratory complications (11.8%;CI 5.7 to 19.7). Implant failure occurred in 7.1% cases (CI 6.418 to 11.465), gastrointestinal complications was 5.2%; CI 2.4 to 8), pseudarthrosis in (4.6%;CI 2.2 to 6.9) and neurological deficit in 2.9% (CI 1.989 to 6.086). The pooled rate of revision surgery was (9.6%; CI 6.2 to 12.9). Heterogeneity was assessed using I2 test which results were moderately heterogeneous. Meta-regression analysis revealed that the diagnosis of myelomeningocele or Duchenne muscle dystrophy or spinal muscle atrophy were strongly associated with wound and respiratory complications (p = 0.007 and p = 0.005, respectively). CONCLUSION: Wound-related (13.3%) and respiratory complications (11.8%) remain the most common complications among studies after corrective surgery for neuromuscular scoliosis. Both are significantly associated with Duchenne muscle dystrophy, spinal muscle atrophy and myelomeningocele.

Development of an miRFP680-Based Fluorescent Calcium Ion Biosensor Using End-Optimized Transposons.

The development of new or improved single fluorescent protein (FP)-based biosensors (SFPBs), particularly those with excitation and emission at near-infrared wavelengths, is important for the continued advancement of biological imaging applications. In an effort to accelerate the development of new SFPBs, we report modified transposons for the transposase-based creation of libraries of FPs randomly inserted into analyte binding domains, or vice versa. These modified transposons feature ends that are optimized to minimize the length of the linkers that connect the FP to the analyte binding domain. We rationalized that shorter linkers between the domains should result in more effective allosteric coupling between the analyte binding-dependent conformational change in the binding domain and the fluorescence modulation of the chromophore of the FP domain. As a proof of concept, we employed end-modified Mu transposons for the discovery of SFPB prototypes based on the insertion of two circularly permuted red FPs (mApple and FusionRed) into binding proteins for l-lactate and spermidine. Using an analogous approach, we discovered calcium ion (Ca2+)-specific SFPBs by random insertion of calmodulin (CaM)-RS20 into miRFP680, a particularly bright near-infrared (NIR) FP based on a biliverdin (BV)-binding fluorescent protein. Starting from an miRFP680-based Ca2+ biosensor prototype, we performed extensive directed evolution, including under BV-deficient conditions, to create highly optimized biosensors designated the NIR-GECO3 series. We have extensively characterized the NIR-GECO3 series and explored their utility for biological Ca2+ imaging. The methods described in this work will serve to accelerate SFPB development and open avenues for further exploration and optimization of SFPBs across a spectrum of biological applications.

Obesity Induces Temporally Regulated Alterations in the Extracellular Matrix That Drive Breast Tumor Invasion and Metastasis.

Obesity is associated with increased incidence and metastasis of triple-negative breast cancer, an aggressive breast cancer subtype. The extracellular matrix (ECM) is a major component of the tumor microenvironment that drives metastasis. To characterize the temporal effects of age and high-fat diet (HFD)-driven weight gain on the ECM, we injected allograft tumor cells at 4-week intervals into mammary fat pads of mice fed a control or HFD, assessing tumor growth and metastasis and evaluating the ECM composition of the mammary fat pads, lungs, and livers. Tumor growth was increased in obese mice after 12 weeks on HFD. Liver metastasis increased in obese mice only at 4 weeks, and elevated body weight correlated with increased metastasis to the lungs but not the liver. Whole decellularized ECM coupled with proteomics indicated that early stages of obesity were sufficient to induce changes in the ECM composition. Obesity led to an increased abundance of the proinvasive ECM proteins collagen IV and collagen VI in the mammary glands and enhanced the invasive capacity of cancer cells. Cells of stromal vascular fraction and adipose stem and progenitor cells were primarily responsible for secreting collagen IV and collagen VI, not adipocytes. Longer exposure to HFD increased the invasive potential of ECM isolated from the lungs and liver, with significant changes in ECM composition found in the liver with short-term HFD exposure. Together, these data suggest that changes in the breast, lungs, and liver ECM underlie some of the effects of obesity on triple-negative breast cancer incidence and metastasis. Significance: Organ-specific extracellular matrix changes in the primary tumor and metastatic microenvironment are mechanisms by which obesity contributes to breast cancer progression.

Investigation of Urinary Metabolites of Organophosphate Esters in Hanoi, Vietnam: Assessment Exposure and Estimated Daily Intake.

In recent years, organophosphate esters (OPEs) have become one of the most common additives in various consumer products worldwide, therefore the exposure and impact of OPEs on human health are drawing a lot of attention. In this study, three metabolites of OPEs including bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPhP) and diethyl phosphate (DEP) were investigated in first-morning void urine samples taken from a population (age range: 3-76 years old) in Hanoi, Vietnam. The most dominant urinary OPE metabolite was DEP with the geometric mean of specific gravity adjust (SG-adjusted) concentration were 1960 ng mL-1 and detected frequency (DF) of 98%. Followed by DPhP (8.01 ng mL-1, DF: 100%) and BDCIPP (2.18 ng mL-1, DF: 51%). The results indicated that gender and age might have associations with the OPE metabolites variation in urine samples. The levels of OPE metabolites in urine samples from females were slightly higher than in males. An increase in age seems to have an association with a decrease in DPhP levels in urine. Exposure doses of parent OPEs were evaluated from the unadjusted urinary concentration of corresponding OPE metabolite. The estimated exposure doses of triethyl phosphate (TEP) (mean: 534,000 ng kg-1 d-1) were significantly higher than its corresponding reference dose, suggesting the high potential risk from the current exposure doses of TEP to human health. The results of this work provided the initial information on the occurrence of three OPE metabolites in urine from Hanoi, Vietnam and estimated exposure dose of corresponding parent OPEs.

High-Performance Genetically Encoded Green Fluorescent Biosensors for Intracellular l-Lactate.

l-Lactate is a monocarboxylate produced during the process of cellular glycolysis and has long generally been considered a waste product. However, studies in recent decades have provided new perspectives on the physiological roles of l-lactate as a major energy substrate and a signaling molecule. To enable further investigations of the physiological roles of l-lactate, we have developed a series of high-performance (ΔF/F = 15 to 30 in vitro), intensiometric, genetically encoded green fluorescent protein (GFP)-based intracellular l-lactate biosensors with a range of affinities. We evaluated these biosensors in cultured cells and demonstrated their application in an ex vivo preparation of Drosophila brain tissue. Using these biosensors, we were able to detect glycolytic oscillations, which we analyzed and mathematically modeled.

The impacts of telemedicine on assisted reproduction: a systematic review and meta-analysis.

Telemedicine is being applied in assisted reproduction technology (ART) to provide remote consultations, monitoring and support for patients. This study aimed to evaluate the potential advantages of telemedicine in ART treatment in the form of virtual consultations. Studies in which patients were using telemedicine during ART treatment were identified from four scientific databases (PudMed, EMBASE, Scopus, Web of Science). The success of fertility treatments was compared between telemedicine and in-office care, and patient satisfaction with ART through telemedicine was assessed. Eleven studies, comprising 4697 patients, were identified. Quality assessment (Joanna Briggs Institute Critical Appraisal and revised Cochrane risk-of-bias tools) revealed an acceptable risk of bias for both randomized controlled trials and observational studies. Using a fixed-effects model, telemedicine was comparable to in-person care regarding the pregnancy rate achieved (odds ratio 1.02, 95% confidence intervals 0.83-1.26, P = 0.83). A Q-test suggested that all the included studies were homogeneous. Patients who received telemedicine during fertility treatment reported a high level of satisfaction (91%, 95% confidence intervals 80-96%). Egger's test confirmed that no publication bias was found. Telemedicine could serve as a complementary tool during fertility treatment to facilitate patients' satisfaction and overcome some practical problems without compromising treatment outcomes. Future studies should continue exploring the potential applications of telemedicine in assisted reproduction.

Optimizing electrochemically active microorganisms as a key player in the bioelectrochemical system: Identification methods and pathways to large-scale implementation.

The rapid global economic growth driven by industrialization and population expansion has resulted in significant issues, including reliance on fossil fuels, energy scarcity, water crises, and environmental emissions. To address these issues, bioelectrochemical systems (BES) have emerged as a dual-purpose solution, harnessing electrochemical processes and the capabilities of electrochemically active microorganisms (EAM) to simultaneously recover energy and treat wastewater. This review examines critical performance factors in BES, including inoculum selection, pretreatment methods, electrodes, and operational conditions. Further, authors explore innovative approaches to suppress methanogens and simultaneously enhance the EAM in mixed cultures. Additionally, advanced techniques for detecting EAM are discussed. The rapid detection of EAM facilitates the selection of suitable inoculum sources and optimization of enrichment strategies in BESs. This optimization is essential for facilitating the successful scaling up of BES applications, contributing substantially to the realization of clean energy and sustainable wastewater treatment. This analysis introduces a novel viewpoint by amalgamating contemporary research on the selective enrichment of EAM in mixed cultures. It encompasses identification and detection techniques, along with methodologies tailored for the selective enrichment of EAM, geared explicitly toward upscaling applications in BES.

Mixed-methods needs assessment for development of school-based mental health implementation science capacity in low- and middle-income countries: Vietnam as a case example.

Worldwide, the majority of youth reside in low- and middle-income countries (LMIC). School-based mental health (SBMH) services are particularly important in LMIC, in part because of LMIC's limited mental health infrastructure. Among the challenges to developing SBMH in LMIC are limited implementation science (IS) capacity, critical for identifying barriers to evidence-based intervention (EBI) use and dissemination, etc., specific to the local country context. A key step in IS capacity development is conducting a needs assessment, to identify barriers (and their solutions) to IS development itself within the local context. The present study conducted an IS needs assessment focused on SBMH in the Southeast Asian LMIC of Vietnam. Seventy-five Vietnamese mental health professionals in SBMH-related fields participated in a mixed-methods study. Vietnamese SBMH researchers and practitioners most likely to have experience and/or interest in IS were selected for study recruitment. Professionals' formal understanding of and experience with IS as a scientific field was highly limited. However, after reading a brief but detailed description of IS, participants' interest in IS training was high, and their mean rating of its potential utility for Vietnam to develop SBMH was 4.7 on a 1-5 scale. Participants also reported on barriers and potential solutions for EBI use in SBMH in Vietnam. Contrary to expectations, the most frequent and severe barriers were not financial but related to limited stakeholder engagement. Overall, these and other study results provide some suggestions how IS capacity to support SBMH may be most efficiently developed in settings such as Vietnam. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Return to work after cancer-the impact of working conditions: A Norwegian Register-based Study.

PURPOSE: The purpose of this study is to compare a cohort of cancer survivors with a cohort of cancer-free employees (1) with respect to employment prospects over a 15-year period and (2) with respect to the differential impact of working conditions on employment over this time period. METHODS: The cancer cohort is retrieved from the Cancer Registry of Norway, while data on the non-cancer cohort are retrieved from register data managed by Statistics Norway. Job exposure matrices were used to remedy the lack of working-conditions information in the register data. We use nearest-neighbor matching to match the non-cancer cohort (the control group) to the cancer-survivor cohort (the treatment group). Cox regression analysis was applied to examine the relationships between working conditions, employment, and cancer. The results are reported separately for mechanical-job exposures and psychosocial exposures, as well as by gender. RESULTS: Cancer survivors are more likely to experience reduced employment as compared to individuals without a history of cancer. Male cancer survivors in physically demanding occupations have an increased risk of reduced employment after being diagnosed with cancer. This does not apply to female cancer survivors. Regarding the impact of psychosocial exposures on employment, we find no differences over time between cancer survivors and the non-cancer population. CONCLUSIONS: Male cancer survivors in physically demanding occupations have an increased risk of reduced employment after being diagnosed with cancer, whereas this is not the case for female cancer survivors. Psychosocial exposures do not impact the relative risk of reduced employment over time. IMPLICATIONS FOR CANCER SURVIVORS: We suggest that return to work after cancer should be considered a process rather than only the re-entry step of resuming work. Thus, it is important to provide long-term support for cancer survivors. We recommend providing more attention to working conditions, particularly in occupations that involve a high level of mechanical-job exposures.

Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging.

L-Lactate is increasingly appreciated as a key metabolite and signaling molecule in mammals. However, investigations of the inter- and intra-cellular dynamics of L-lactate are currently hampered by the limited selection and performance of L-lactate-specific genetically encoded biosensors. Here we now report a spectrally and functionally orthogonal pair of high-performance genetically encoded biosensors: a green fluorescent extracellular L-lactate biosensor, designated eLACCO2.1, and a red fluorescent intracellular L-lactate biosensor, designated R-iLACCO1. eLACCO2.1 exhibits excellent membrane localization and robust fluorescence response. To the best of our knowledge, R-iLACCO1 and its affinity variants exhibit larger fluorescence responses than any previously reported intracellular L-lactate biosensor. We demonstrate spectrally and spatially multiplexed imaging of L-lactate dynamics by coexpression of eLACCO2.1 and R-iLACCO1 in cultured cells, and in vivo imaging of extracellular and intracellular L-lactate dynamics in mice.

Age and obesity-driven changes in the extracellular matrix of the primary tumor and metastatic site influence tumor invasion and metastatic outgrowth.

Younger age and obesity increase the incidence and metastasis of triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer. The extracellular matrix (ECM) promotes tumor invasion and metastasis. We characterized the effect of age and obesity on the ECM of mammary fat pads, lungs, and liver using a diet-induced obesity (DIO) model. At 4 week intervals, we either injected the mammary fat pads with allograft tumor cells to characterize tumor growth and metastasis or isolated the mammary fat pads and livers to characterize the ECM. Age had no effect on tumor growth but increased lung and liver metastasis after 16 weeks. Obesity increased tumor growth starting at 12 weeks, increased liver metastasis only at 4 weeks, and weight gain correlated to increased lung but not liver metastasis. Utilizing whole decellularized ECM coupled with proteomics, we found that early stages of obesity were sufficient to induce changes in the ECM composition and invasive potential of mammary fat pads with increased abundance of pro-invasive ECM proteins Collagen IV and Collagen VI. We identified cells of stromal vascular fraction and adipose stem and progenitor cells as primarily responsible for secreting Collagen IV and VI, not adipocytes. We characterized the changes in ECM in the lungs and liver, and determined that older age decreases the metastatic potential of lung and liver ECM while later-stage obesity increases the metastatic potential. These data implicate ECM changes in the primary tumor and metastatic microenvironment as mechanisms by which age and obesity contribute to breast cancer progression.

Occurrence, biomagnification, and risk assessment of parabens and their metabolites in marine fish: The case study of Vietnam.

Parabens have emerged as the primary preservative of choice in numerous consumer goods, prompting growing apprehension regarding their potential for human exposure. The study employed the optimized QuEChERs sample extraction method and the UHPLC-Q-Orbitrap HRMS system to generate the initial contamination profiles of seven parabens and their four metabolites in a total of 114 fish samples found along the coastline of Vietnam. The findings of the study indicated that methylparaben was the predominant substance detected, exhibiting the highest concentration in the largehead hairtail (Trichiurus lepturus) species at 32.8 ng g-1 dry weight (dw). Additionally, the metabolites with the highest detectable concentrations in the largehead hairtail were found to be 4-HB and 3,4-DHB, with levels of 8822.0 ng g-1 dw and 3490.8 ng g-1 dw, respectively. Besides, the study reveals notable variations in paraben concentrations across three distinct regions in Vietnam, namely the Central, North, and South (Mann-Whitney U test, p < 0.05). The trophic magnification factors (TMF) for methylparaben, ethylparaben, ethyl protocatechuate, and 4-hydroxybenzoic acid exhibited values exceeding 1, indicating substantial biomagnification of these substances within the marine food web of Vietnam. Additionally, noteworthy positive associations have been observed between methylparaben and ethylparaben, as well as their respective metabolites. Based on the findings of the study, it can be concluded that there is no direct impact of seafood consumption on human health in Vietnam.