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Journal of Microbiological Methods Jun 2024Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is the first-line method for the rapid identification of most cultured...
Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is the first-line method for the rapid identification of most cultured microorganisms. As for Streptomyces strains, MALDI-TOF MS identification is complicated by the characteristic incrustation of colonies in agar and the strong cell wall of Actinomycetes cells requiring the use of alternative protein extraction protocols. In this study, we developed a specific protocol to overcome these difficulties for the MALDI-TOF MS identification of Actinomycetes made on solid medium. This protocol includes incubation of colony removed from agar plate with the beta-agarase enzyme, followed by a mechanical lysis and two washes by phosphate buffer and ethanol. Twenty-four Streptomyces and two Lentzea strains isolated from Algerian desertic soils were first identified by 16S rRNA sequencing as gold standard method, rpoB gene was used as a secondary gene target when 16S rRNA did not allow species identification. In parallel the isolates were identified by using the MALDI-TOF MS protocol as reported. After the expansion of the database with the inclusion of this MSP, the strains were analyzed again in MALDI Biotyper, and all were identified. This work demonstrates that the rapid identification of Actinomycetes can be obtained without protein extraction step frequently used in MALDI-TOF mass spectrometry with this type of microorganisms.
PubMed: 38955305
DOI: 10.1016/j.mimet.2024.106984 -
Child Abuse & Neglect Jul 2024Institutionalization involving psychosocial deprivation affects child development negatively. However, there are few longitudinal studies, and no prospective study has...
BACKGROUND
Institutionalization involving psychosocial deprivation affects child development negatively. However, there are few longitudinal studies, and no prospective study has yet examined the consequences of institutionalization in late adulthood.
OBJECTIVE
Investigating effects of psychosocial deprivation on cognitive functioning 60 years later.
PARTICIPANTS AND SETTING
A population-based survey of institutionalized infants and toddlers was conducted in Switzerland from 1958 to 1961 (n = 387; M = 0.93 years, SD = 0.53, 48 % female, 48 % Swiss nationality). In parallel, a comparison group of 399 family-raised children were assessed (M = 0.85 years, SD = 0.50, 46 % female, 100 % Swiss nationality). Six decades later, data on cognitive functioning were collected for 88 of the institutionalized group (M = 62.63 years, SD = 1.32), and 148 of the comparison group (M = 65.06, SD = 1.32).
METHODS
Standardized tests were used: the Brunet-Lézine Developmental Test in early childhood and a short form of the Wechsler Adult Intelligence Scale in late adulthood.
RESULTS
Formerly institutionalized individuals scored lower on cognitive functioning (d = - 0.67, p < .001), with the greatest difference in working memory (d = -0.78, p < .001). Longer duration of institutionalization increased the risk of lower cognitive functioning, indicating a dose-response effect. Institutionalization's impact on adult cognitive functioning was mediated by early childhood developmental status but not by later educational attainment.
CONCLUSIONS
This study confirms the early experience hypothesis, indicating that early life conditions have lasting effects on human development, even into late adulthood.
PubMed: 38955051
DOI: 10.1016/j.chiabu.2024.106917 -
International Immunopharmacology Jul 2024Neuroinflammation, characterized by microglial activation and the release of multiple inflammatory mediators, is a key factor in acute glaucomatous injury leading to...
Neuroinflammation, characterized by microglial activation and the release of multiple inflammatory mediators, is a key factor in acute glaucomatous injury leading to retinal ganglion cell (RGC) death and ultimately irreversible vision loss. Irisin, a novel exercise-induced myokine, has demonstrated anti-inflammatory activity in ischemia/reperfusion injuries across multiple organs and has displayed a significant neuroprotective role in experimental stroke disease models. This study examined the protective impact of irisin and investigated its potential mechanism involved in this process utilizing an acute ocular hypertension (AOH)-induced retinal injury model in mice and a microglia inflammation model induced by lipopolysaccharide (LPS). There was a transient downregulation of irisin in the retina after AOH injury, with parallel emergence of retinal neuroinflammation and RGC death. Irisin attenuated retinal and optic nerve damage and promotes the phenotypic conversion of microglia from M1 to M2. Mechanistically, irisin significantly upregulated the expression of integrin αVβ5, p-AMPK, and autophagy-related markers. Integrin αVβ5 was highly expressed on microglia but hardly expressed on RGC. The integrin αVβ5 inhibitor cilengitide, the AMPK inhibitor dorsomorphin, and the autophagy inhibitor 3-Methyladenine (3-MA) blocked the neuroprotective effects of irisin. Our results suggest irisin attenuates acute glaucoma-induced neuroinflammation and RGC death by activating integrin αVβ5/AMPK in microglia and promoting autophagy. It should be considered a potential neuroprotective therapy for acute glaucoma.
PubMed: 38955026
DOI: 10.1016/j.intimp.2024.112545 -
Anatomical Sciences Education Jul 2024This study assesses the acceptability, appropriateness, feasibility, and efficacy of a novel asynchronous video-based intervention for teaching respiratory physiology...
This study assesses the acceptability, appropriateness, feasibility, and efficacy of a novel asynchronous video-based intervention for teaching respiratory physiology and anatomy to medical students in resource-limited settings. A series of short video lectures on pleural anatomy, pulmonary physiology, and pathophysiology was created using Lightboard and screen capture technology. These were uploaded to YouTube and Google Drive and made available to 1st-3rd year medical students at two Latin American universities for 1 week. Employing a parallel-convergent mixed methods design, we conducted surveys, focus groups, interviews, and pre/post testing for qualitative and quantitative data. Thematic Analysis was used to analyze qualitative data and McNemar's test for quantitative analysis. Seventy-six students participated. The videos' short format, interactivity, and Lightboard style were highly valued for their flexibility, time efficiency, and educational impact. Students recognized their clinical relevance and trusted their content, suggesting potential applicability in similar settings. Despite infrastructure and connectivity challenges, the use of flexible streaming and downloadable options facilitated learning. Survey results indicated high levels of feasibility (99%), appropriateness (95%), and acceptability (95%), with significant knowledge gains observed (37% correct pre-test answers vs. 56% post-test, p < 0.0001). Our findings demonstrate high acceptability, appropriateness, feasibility, and efficacy of a targeted asynchronous education centered on short-format videos in resource-limited settings, enabling robust learning despite local barriers. Flexible access is key for overcoming localized barriers. Taking an adaptive, learner-centered approach to content creation and delivery to address constraints was pivotal to success. Our modular videos could serve as versatile models for flexible education in resource-constrained settings.
PubMed: 38954744
DOI: 10.1002/ase.2474 -
PLoS Genetics Jul 2024The drug floxuridine (5-fluorodeoxyuridine, FUdR) is an active metabolite of 5-Fluorouracil (5-FU). It converts to 5-fluorodeoxyuridine monophosphate (FdUMP) and...
The drug floxuridine (5-fluorodeoxyuridine, FUdR) is an active metabolite of 5-Fluorouracil (5-FU). It converts to 5-fluorodeoxyuridine monophosphate (FdUMP) and 5-fluorodeoxyuridine triphosphate (FdUTP), which on incorporation into the genome inhibits DNA replication. Additionally, it inhibits thymidylate synthase, causing dTMP shortage while increasing dUMP availability, which induces uracil incorporation into the genome. However, the mechanisms underlying cellular tolerance to FUdR are yet to be fully elucidated. In this study, we explored the mechanisms underlying cellular resistance to FUdR by screening for FUdR hypersensitive mutants from a collection of DT40 mutants deficient in each genomic maintenance system. We identified REV3, which is involved in translesion DNA synthesis (TLS), to be a critical factor in FUdR tolerance. Replication using a FUdR-damaged template was attenuated in REV3-/- cells, indicating that the TLS function of REV3 is required to maintain replication on the FUdR-damaged template. Notably, FUdR-exposed REV3-/- cells exhibited defective cell cycle arrest in the early S phase, suggesting that REV3 is involved in intra-S checkpoint activation. Furthermore, REV3-/- cells showed defects in Chk1 phosphorylation, which is required for checkpoint activation, but the survival of FUdR-exposed REV3-/- cells was further reduced by the inhibition of Chk1 or ATR. These data indicate that REV3 mediates DNA checkpoint activation at least through Chk1 phosphorylation, but this signal acts in parallel with ATR-Chk1 DNA damage checkpoint pathway. Collectively, we reveal a previously unappreciated role of REV3 in FUdR tolerance.
PubMed: 38954736
DOI: 10.1371/journal.pgen.1011341 -
PloS One 2024Transperineal laser ablation is a minimally invasive thermo-ablative treatment for prostate cancer that requires the insertion of a needle for accurate optical fiber...
Transperineal laser ablation is a minimally invasive thermo-ablative treatment for prostate cancer that requires the insertion of a needle for accurate optical fiber positioning. Needle insertion in soft tissues may cause tissue motion and deformation, resulting in tissue damage and needle positioning errors. In this study, we present a wasp-inspired self-propelled needle that uses pneumatic actuation to move forward with zero external push force, thus avoiding large tissue motion and deformation. The needle consists of six parallel 0.25-mm diameter Nitinol rods driven by a pneumatic actuation system. The pneumatic actuation system consists of Magnetic Resonance (MR) safe 3D-printed parts and off-the-shelf plastic screws. A self-propelled motion is achieved by advancing the needle segments one by one, followed by retracting them simultaneously. The advancing needle segment has to overcome a cutting and friction force, while the stationary needle segments experience a friction force in the opposite direction. The needle self-propels through the tissue when the friction force of the five stationary needle segments overcomes the sum of the friction and cutting forces of the advancing needle segment. We evaluated the prototype's performance in 10-wt% gelatin phantoms and ex vivo porcine liver tissue inside a preclinical Magnetic Resonance Imaging (MRI) scanner in terms of the slip ratio of the needle with respect to the phantom or liver tissue. Our results demonstrated that the needle was able to self-propel through the phantom and liver tissue with slip ratios of 0.912-0.955 and 0.88, respectively. The prototype is a promising step toward the development of self-propelled needles for MRI-guided transperineal laser ablation as a method to treat prostate cancer.
Topics: Needles; Animals; Equipment Design; Male; Humans; Wasps; Printing, Three-Dimensional; Laser Therapy; Swine; Prostatic Neoplasms; Magnetic Resonance Imaging
PubMed: 38954720
DOI: 10.1371/journal.pone.0306411 -
IEEE Journal of Biomedical and Health... Jul 2024Major depressive disorder (MDD) is a chronic mental illness which affects people's well-being and is often detected at a later stage of depression with a likelihood of...
Major depressive disorder (MDD) is a chronic mental illness which affects people's well-being and is often detected at a later stage of depression with a likelihood of suicidal ideation. Early detection of MDD is thus necessary to reduce the impact, however, it requires monitoring vitals in daily living conditions. EEG is generally multi-channel and due to difficulty in signal acquisition, it is unsuitable for home-based monitoring, whereas, wearable sensors can collect single-channel ECG. Classical machine-learning based MDD detection studies commonly use various heart rate variability features. Feature generation, which requires domain knowledge, is often challenging, and requires computation power, often unsuitable for real time processing, MDDBranchNet is a proposed parallel-branch deep learning model for MDD binary classification from a single channel ECG which uses additional ECG-derived signals such as R-R signal and degree distribution time series of horizontal visibility graph. The use of derived branches was able to increase the model's accuracy by around 7%. An optimal 20-second overlapped segmentation of ECG recording was found to be beneficial with a 70% prediction threshold for maximum MDD detection with a minimum false positive rate. The proposed model evaluated MDD prediction from signal excerpts, irrespective of location (first, middle or last one-third of the recording), instead of considering the entire ECG signal with minimal performance variation stressing the idea that MDD phenomena are likely to manifest uniformly throughout the recording.
Topics: Humans; Deep Learning; Electrocardiography; Depressive Disorder, Major; Signal Processing, Computer-Assisted; Algorithms; Adult; Male
PubMed: 38954560
DOI: 10.1109/JBHI.2024.3390847 -
Radiation Research Jul 2024The concept of radiation-induced clustered damage in DNA has grown over the past several decades to become a topic of considerable interest across the scientific...
The concept of radiation-induced clustered damage in DNA has grown over the past several decades to become a topic of considerable interest across the scientific disciplines involved in studies of the biological effects of ionizing radiation. This paper, prepared for the 70th anniversary issue of Radiation Research, traces historical development of the three main threads of physics, chemistry, and biochemical/cellular responses that led to the hypothesis and demonstration that a key component of the biological effectiveness of ionizing radiation is its characteristic of producing clustered DNA damage of varying complexities. The physics thread has roots that started as early as the 1920s, grew to identify critical nanometre-scale clusterings of ionizations relevant to biological effectiveness, and then, by the turn of the century, had produced an extensive array of quantitative predictions on the complexity of clustered DNA damage from different radiations. Monte Carlo track structure simulation techniques played a key role through these developments, and they are now incorporated into many recent and ongoing studies modelling the effects of radiation. The chemistry thread was seeded by water-radiolysis descriptions of events in water as radical-containing 'spurs,' demonstration of the important role of the hydroxyl radical in radiation-inactivation of cells and the difficulty of protection by radical scavengers. This led to the concept and description of locally multiply damaged sites (LMDS) for DNA double-strand breaks and other combinations of DNA base damage and strand breakage that could arise from a spur overlapping, or created in very close proximity to, the DNA. In these ways, both the physics and the chemistry threads, largely in parallel, put out the challenge to the experimental research community to verify these predictions of clustered DNA damage from ionizing radiations and to investigate their relevance to DNA repair and subsequent cellular effects. The third thread, biochemical and cell-based research, responded strongly to the challenge by demonstrating the existence and biological importance of clustered DNA damage. Investigations have included repair of a wide variety of defined constructs of clustered damage, evaluation of mutagenic consequences, identification of clustered base-damage within irradiated cells, and identification of co-localization of repair complexes indicative of complex clustered damage after high-LET irradiation, as well as extensive studies of the repair pathways involved in repair of simple double-strand breaks. There remains, however, a great deal more to be learned because of the diversity of clustered DNA damage and of the biological responses.
PubMed: 38954537
DOI: 10.1667/RADE-24-00017.1 -
Archives of Toxicology Jul 2024Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals used in many industrial applications. Exposure to PFAS is associated with several health risks,...
Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals used in many industrial applications. Exposure to PFAS is associated with several health risks, including a decrease in infant birth weight, hepatoxicity, disruption of lipid metabolism, and decreased immune response. We used the in vitro cell models to screen six less studied PFAS [perfluorooctane sulfonamide (PFOSA), perfluoropentanoic acid (PFPeA), perfluoropropionic acid (PFPrA), 6:2 fluorotelomer alcohol (6:2 FTOH), 6:2 fluorotelomer sulfonic acid (6:2 FTSA), and 8:2 fluorotelomer sulfonic acid (8:2 FTSA)] for their capacity to activate nuclear receptors and to cause differential expression of genes involved in lipid metabolism. Cytotoxicity assays were run in parallel to exclude that observed differential gene expression was due to cytotoxicity. Based on the cytotoxicity assays and gene expression studies, PFOSA was shown to be more potent than other tested PFAS. PFOSA decreased the gene expression of crucial genes involved in bile acid synthesis and detoxification, cholesterol synthesis, bile acid and cholesterol transport, and lipid metabolism regulation. Except for 6:2 FTOH and 8:2 FTSA, all tested PFAS downregulated PPARA gene expression. The reporter gene assay also showed that 8:2 FTSA transactivated the farnesoid X receptor (FXR). Based on this study, PFOSA, 6:2 FTSA, and 8:2 FTSA were prioritized for further studies to confirm and understand their possible effects on hepatic lipid metabolism.
PubMed: 38953992
DOI: 10.1007/s00204-024-03814-2 -
Social Psychiatry and Psychiatric... Jul 2024Previous studies have reported that levels of rurality and deprivation are factors associated with suicide risk. Reports on the association between rurality, deprivation...
PURPOSE
Previous studies have reported that levels of rurality and deprivation are factors associated with suicide risk. Reports on the association between rurality, deprivation and suicide incidence during the COVID-19 pandemic are scarce. The study aims to investigate how suicide rates evolved in areas with different levels of rurality and deprivation among Japanese adults aged 20 years or older between 2009 and 2022.
METHODS
This study used population density in 2020 as an indicator of rurality and per capita prefectural income in 2019 as a proxy for deprivation in Japan's 47 prefectures. Joinpoint regression analysis was performed to analyze secular trends in suicide rates by rurality and deprivation.
RESULTS
Suicide rates for both men and women at different levels of rurality and deprivation remained roughly parallel during the research period. Suicide rates for men and women at all levels of rurality and deprivation were on a downward trend until around 2019, just before the onset of the pandemic. Following this, suicide rates in women showed a clear upward trend, while the trend in suicide rates for men also changed around 2019, with a slightly increasing or flat trend thereafter. Changes in suicide rates were greater among women and those aged 20-59 years.
CONCLUSIONS
In Japan, time trends in suicide rates for both men and women have changed before and after the pandemic, but levels of rurality and deprivation across the 47 prefectures do not appear to have contributed much to these changes.
PubMed: 38953923
DOI: 10.1007/s00127-024-02718-x