Article Gate
Not a member yet
471 research outputs found
Sort by
Enterococcus faecalis alters endo-lysosomal trafficking to replicate and persist within mammalian cells
Full text linkEnterococcus faecalis is a frequent opportunistic pathogen of wounds, whose infections are associated with biofilm formation, persistence, and recalcitrance toward treatment. We have previously shown that E. faecalis wound infection persists for at least 7 days. Here we report that viable E. faecalis are present within both immune and non-immune cells at the wound site up to 5 days after infection, raising the prospect that intracellular persistence contributes to chronic E. faecalis infection. Using in vitro keratinocyte and macrophage infection models, we show that E. faecalis becomes internalized and a subpopulation of bacteria can survive and replicate intracellularly. E. faecalis are internalized into keratinocytes primarily via macropinocytosis into single membrane-bound compartments and can persist in late endosomes up to 24 h after infection in the absence of colocalization with the lysosomal protease Cathepsin D or apparent fusion with the lysosome, suggesting that E. faecalis blocks endosomal maturation. Indeed, intracellular E. faecalis infection results in heterotypic intracellular trafficking with partial or absent labelling of E. faecalis-containing compartments with Rab5 and Rab7, small GTPases required for the endosome-lysosome trafficking. In addition, E. faecalis infection results in marked reduction of Rab5 and Rab7 protein levels which may also contribute to attenuated Rab incorporation into E. faecalis-containing compartments. Finally, we demonstrate that intracellular E. faecalis derived from infected keratinocytes are significantly more efficient in reinfecting new keratinocytes. Together, these data suggest that intracellular proliferation of E. faecalis may contribute to its persistence in the face of a robust immune response, providing a primed reservoir of bacteria for subsequent reinfection
A systematic review of federated learning applications for biomedical data
Full text linkFederated learning (FL) allows multiple institutions to collaboratively develop a machine learning algorithm without sharing their data. Organizations instead share model parameters only, allowing them to benefit from a model built with a larger dataset while maintaining the privacy of their own data. We conducted a systematic review to evaluate the current state of FL in healthcare and discuss the limitations and promise of this technology.
Methods
We conducted a literature search using PRISMA guidelines. At least two reviewers assessed each study for eligibility and extracted a predetermined set of data. The quality of each study was determined using the TRIPOD guideline and PROBAST tool.
Results
13 studies were included in the full systematic review. Most were in the field of oncology (6 of 13; 46.1%), followed by radiology (5 of 13; 38.5%). The majority evaluated imaging results, performed a binary classification prediction task via offline learning (n = 12; 92.3%), and used a centralized topology, aggregation server workflow (n = 10; 76.9%). Most studies were compliant with the major reporting requirements of the TRIPOD guidelines. In all, 6 of 13 (46.2%) of studies were judged at high risk of bias using the PROBAST tool and only 5 studies used publicly available data
Effectiveness of a tailored web app on sun protection intentions and its implications for skin cancer prevention: A randomized controlled trial
Full text linkSkin cancers related to sunexposure are rising globally, yet largely preventable. Digital solutions enable individually tailored prevention and may play a crucial role in reducing disease burden. We developed SUNsitive, a theory-guided web app to facilitate sun protection and skin cancer prevention. The app collected relevant information through a questionnaire and provided tailored feedback on personal risk, adequate sun protection, skin cancer prevention, and overall skin health. SUNsitive’s effect on sun protection intentions and a set of secondary outcomes was evaluated with a two-arm randomized controlled trial (n = 244). At 2 weeks post-intervention, we did not find any statistical evidence for the intervention’s effect on the primary outcome or any of the secondary outcomes. However, both groups reported improved intentions to sun protect compared to their baseline values. Furthermore, our process outcomes suggest that approaching sun protection and skin cancer prevention with a digital tailored “questionnaire–feedback” format is feasible, well-perceived, and well accepted
Pelagic Bacteria and Viruses in a High Arctic Region: Environmental Control in the Autumn Period
Full text linkIn the marine environment, bacteria and viruses play a significant role in carbon fluxes, remineralization processes, and the infection of various organisms. We performed a survey in the northeastern Barents Sea, a region adjacent to the Arctic Ocean, to investigate spatial patterns of microbial plankton, after the main productive period, in October 2020. Two main water masses occurred in the study region—colder Arctic Water and warmer Barents Sea Water, representing transformed Atlantic Water. Multivariate analyses detected patchiness in the horizontal distribution of bacteria and viruses, and their abundances showed no clear association with the water masses. There was an obvious vertical pattern in microbial concentration, with the highest estimates in the upper layers. Surface viral and bacterial abundance varied in a wide range (2.20 × 105–10.7 × 105 cells·mL−1 and 0.86 × 106–14.98 × 106 particles·mL−1, respectively) and were correlated with each other. Bacterioplankton was dominated by small-sized cells (<2 μm, 0.04–0.06 µm3), and the average volume of bacterial cells tended to increase toward the seafloor. The ratio of viral to bacterial abundance (VBR) was 11 ± 1 and did not differ between water masses and depth layers. VBR were higher, compared to summer values, suggesting a strong impact of viruses on bacterioplankton, after the main productive season. Redundancy and correlation analyses showed that inorganic nutrients (nitrate and phosphate) and organic carbon from zooplankton were most responsible for the total variability in the microbial parameters. Water temperature and salinity, also, had a measurable impact, but their influence was lower. Bacterial abundance was lower than in other seasons and regions of the Barents Sea, while viral abundance was comparable, suggesting a stronger viral impact on Arctic marine bacteria in the autum
Aerosol Nutrients and Their Biological Influence on the Northwest Pacific Ocean (NWPO) and Its Marginal Seas
Full text linkAtmospheric deposition is recognized as a significant source of nutrients in the surface ocean. The East Asia region is among the largest sources of aerosol emissions in the world, due to its large industrial, agricultural, and energy production. Thus, East Asian aerosols contain a large proportion of anthropogenic particles that are characterized by small size, complex composition, and high nutrient dissolution, resulting in important influences on marine microbes and biogeochemical cycles in the downwind areas of the northwest Pacific Ocean (NWPO). By using remote sensing, modeling, and incubation experimental methods, enhanced primary production due to the East Asian aerosol input has been observed in the NWPO, with subsequent promotion and inhibition impacts on different phytoplankton taxa. Changes of bacterial activity and diversity also occur in response to aerosol input. The impact of East Asian aerosol loadings is closely related to the amount and composition of the aerosol deposition as well as the hydrological condition of the receiving seawater. Here, we review the current state of knowledge on the atmospheric nutrients and the effects of the East Asian aerosols on microbes in the NWPO region. Future research perspectives are also proposed
Burden of treatment as a measure of healthcare quality: An innovative approach to addressing global inequities in multimorbidity
Full text linkGlobal evidence shows that system quality failures are responsible for more deaths than those caused by HIV, tuberculosis, and malaria combined [1]. In low- and middle-income countries (LMICs), the effects of poor quality care are particularly profound. Nearly 60% of the 8 million preventable deaths that occur yearly in LMICs are due to quality deficits [2]. These span many sectors of healthcare, including primary care, where deficiencies in disease prevention, care coordination, and continuity of care result in inadequate management of both communicable and non-communicable diseases (NCDs) [2]. As the burden of NCDs rises, the push for quality is imperative [3]. The presence of multimorbidity, defined as the occurrence of two or more chronic conditions including those of infectious etiology, compounds this need. In this commentary, we argue that novel methods to evaluate the quality of primary healthcare, such as burden of treatment, must be developed and tailored for use in order for LMICs to achieve equitable outcomes in patients with multimorbidity.
Ideal tools to measure healthcare quality respond to patient expectations in ways that are meaningful to them while also improving their health. The use of patient-reported outcome measures (PROMs) is one way to do this. PROMs reflect patients’ experiences of care and can serve as footprints of patient-centered healthcare reforms. In high-income countries (HICs), their use has been shown to improve quality of care in a patient-centered fashion, and they are even included in some national registries [4, 5].
Despite their successful application in HICs, few PROMS have been effectively used in LMICs, preventing systematic improvement in primary healthcare delivery and perpetuating poor-quality management of chronic conditions. This pattern has led to increased strain on already resource-limited healthcare systems. The presence of both infectious and non-infectious chronic diseases only increases demands by further augmenting the need for long-term, integrated care amongst various specialties and necessitating prevention efforts addressing shared risk factors [6]. Moreover, because LMIC primary healthcare systems evolved to provide short-term, curative programs to treat acute illnesses, they do not contain the infrastructure or organization necessary to provide the multidisciplinary, integrated, and longitudinal care that is required for chronic disease management [3].
Unique epidemiological patterns in the development and distribution of NCDs has created only further challenges for LMIC healthcare systems [7]. This has resulted in NCD onset and mortality at a younger age than in HICs, meaning that healthcare systems must expend more resources over a longer period of time managing the complications of chronic conditions. NCDs also tend to cluster in those with lower socioeconomic status and less education, groups whose capacity to manage extra expenses incurred by chronic diseases is limited [8, 9]. When quality of care is poor, they must deal with the prolonged consequences of their uncontrolled chronic conditions, such as less time spent working or prohibitively high medication costs. This compounds financial losses, driving them, their households, and their communities deeper into poverty and augmenting strain on the healthcare system
Timely Attendance of the First Antenatal Care among Pregnant Women Aged 15–49 Living with HIV in Juba, South Sudan
Full text linkTimely attendance of the first antenatal care (ANC) is the period in which pregnant women visit ANC less than four months of pregnancy. There is a paucity of data on timely first ANC attendance and its associated factors among pregnant women living with human immunodeficiency virus (HIV) in Juba. The aim of this study was to investigate timely attendance of the first ANC visit among pregnant women living with HIV. Institutional cross-sectional study was conducted in three public health facilities in Juba by convenience sampling from January 2019 to December 2019. Pearson’s chi-squared test was conducted for bivariate analysis and variables with probability values ( values) less than 5% were considered as statistically significant for multivariable analyses using Fisher’s exact test. At the multivariate level, binary logistic regression analysis was conducted. Out of the 192 participants studied, 27 (14.1%) had timely first ANC attendance as recommended and 165 (85.9%) attended first ANC at four months and above. Distances (adjusted risk ratio [aOR], 7.14; 95% confidence interval [CI], 1.40–36.68), ANC card (aOR, 3.48; 95% CI, 1.17–10.40), waiting time ([aOR], 0.04; 95% CI, 0.01–0.75), and prevention of mother-to-child transmission (PMTCT) services (aOR, 0.12; 95% CI, 0.03–0.56) were the factors associated with timely first ANC attendance. Health education interventions targeting pregnant women attending ANC at health facilities should focus on increasing knowledge and awareness of the importance of timely first ANC attendance
Measles-Rubella Positivity Rate and Associated Factors in Pre-Mass and Post-Mass Vaccination Periods: Analysis of Uganda Routine Surveillance Laboratory Data
Full text linkToward 2019, Uganda experienced an extensive outbreak of measles and rubella. The Uganda National Expanded Programme on Immunization implemented a mass measles-rubella vaccination campaign aimed at halting the ongoing transmission. This study determined the changes in the disease burden thereafter. We conducted a retrospective cross-sectional study on measles-rubella positivity and its associated factors in Uganda using 1697 case-based surveillance data for 2019 and 2020 stratified into two dispensations: prevaccination and postvaccination campaigns. Statistical tests employed in STATA 15 included chi-square, Fisher’s exact, and binomial tests. Measles positivity rates in the period before and after the mass immunization campaign were 41.88% (95% CI: 39.30–44.51) and 37.96% (95% CI: 32.81–43.40), respectively. For rubella, the positivity rate in the precampaign season was 21.73% (95% CI: 19.61–23.99) and in the postvaccination season was 6.65% (95% CI: 4.36–10.00). Binomial tests indicated that postcampaign positivity rates were significantly lower than the precampaign rate for measles () and rubella (). Generally, age (χ2 = 58.94, /χ2 = 51.91, ) and vaccination status (χ2 = 60.48, /χ2 = 16.90, ) were associated with the measles positivity rate in both pre/postcampaign periods. Rubella positivity rate was associated with vaccination status (χ2 = 32.97, /) in both periods and age in the precampaign season (). The measles-rubella mass campaign lessened rubella burden remarkably, but barely adequate change was observed in the extent of spread of measles. Children aged less than 9 months are at higher chances of testing positive amidst low vaccination levels among the eligible. The immunization programme must attain and maintain routine immunization coverage at 95% or more and roll out a second-dose measles-rubella vaccination to sustain the reduced disease burden
Use of Glycoproteins—Prostate-Specific Membrane Antigen and Galectin-3 as Primary Tumor Markers and Therapeutic Targets in the Management of Metastatic Prostate Cancer
Full text linkGalectins and prostate specific membrane antigen (PSMA) are glycoproteins that are functionally implicated in prostate cancer (CaP). We undertook this study to analyze the “PSMA-galectin pattern” of the human CaP microenvironment with the overarching goal of selecting novel-molecular targets for prognostic and therapeutic purposes. We examined CaP cells and biopsy samples representing different stages of the disease and found that PSMA, Gal-1, Gal-3, and Gal-8 are the most abundantly expressed glycoproteins. In contrast, other galectins such as Gal-2, 4–7, 9–13, were uniformly expressed at lower levels across all cell lines. However, biopsy samples showed markedly higher expression of PSMA, Gal-1 and Gal-3. Independently PSA and Gleason score at diagnosis correlated with the expression of PSMA, Gal-3. Additionally, the combined index of PSMA and Gal-3 expression positively correlated with Gleason score and was a better predictor of tumor aggressiveness. Together, our results recognize a tightly regulated “PSMA-galectin- pattern” that accompanies disease in CaP and highlight a major role for the combined PSMA and Gal-3 inhibitors along with standard chemotherapy for prostate cancer treatment. Inhibitor combination studies show enzalutamide (ENZ), 2-phosphonomethyl pentanedioic acid (2-PMPA), and GB1107 as highly cytotoxic for LNCaP and LNCaP-KD cells, while Docetaxel (DOC) + GB1107 show greater efficacy in PC-3 cells. Overall, 2-PMPA and GB1107 demonstrate synergistic cytotoxic effects with ENZ and DOC in various CaP cell lines
Prophylactic NAC promoted hematopoietic reconstitution by improving endothelial cells after haploidentical HSCT: a phase 3, open-label randomized trial
Full text linkPoor graft function (PGF) or prolonged isolated thrombocytopenia (PT), which are characterized by pancytopenia or thrombocytopenia, have become serious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our previous single-arm trial suggests that N-acetyl-L-cysteine (NAC) prophylaxis reduced PGF or PT after allo-HSCT. Therefore, an open-label, randomized, phase 3 trial was performed to investigate the efficacy and tolerability of NAC prophylaxis to reduce PGF or PT after allo-HSCT.
Methods
A phase 3, open-label randomized trial was performed. Based on the percentage of CD34+VEGFR2 (CD309)+ endothelial cells (ECs) in bone marrow (BM) detected by flow cytometry at 14 days before conditioning, patients aged 15 to 60 years with acute leukemia undergoing haploidentical HSCT were categorized as low-risk (EC ≥ 0.1%) or high-risk (EC < 0.1%); patients at high risk were randomly assigned (2:1) to receive NAC prophylaxis or nonprophylaxis. The primary endpoint was PGF and PT incidence at +60 days post-HSCT.
Results
Between April 18, 2019, and June 24, 2021, 120 patients with BM EC <0.1% were randomly assigned for NAC (group A, N = 80) or nonprophylaxis (group B, N = 40), and 105 patients with EC≥0.1% (group C) were also analyzed. The +60 days incidence of PGF and PT was 7.5% (95% CI, 1.7 to 13.3%) and 22.5% (95% CI, 9.1 to 35.9%) in group A and group B (hazard ratio, 0.317; 95% CI, 0.113 to 0.890; P = 0.021) and 11.4% (95% CI, 5.2 to 17.6%) in group C (hazard ratio, 0.643; 95% CI, 0.242 to 1.715; P = 0.373). Consistently, NAC prophylaxis gradually improved BM ECs and CD34+ cells in group A, whereas reduced their reactive oxygen species (ROS) levels post-HSCT. Within 60 days post-HSCT, the most common grade 3 to 5 adverse events for the NAC and control groups were infections (19/80 [24%] vs. 10/40 [25%]) and gastrointestinal adverse events (16/80 [20%] vs. 7/40 [18%]). There were no treatment-related deaths.
Conclusions
N-Acetyl-L-cysteine prophylaxis can prevent the occurrence of poor hematopoietic function and is well tolerated in haploidentical HSCT. It may offer a potential pathogenesis-oriented therapeutic approach for patients with poor hematopoietic function