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Journal of Osteopathic Medicine Mar 2024An important diagnostic tool, ultrasound (US) has been incorporated into the curriculum of medical schools for more than 20 years. In the last decade, the interest in...
CONTEXT
An important diagnostic tool, ultrasound (US) has been incorporated into the curriculum of medical schools for more than 20 years. In the last decade, the interest in US educational research has experienced exponential growth but mostly from Medical Doctor (MD)-granted schools. The extent to which US is embedded in the curricula of the colleges of osteopathic medicine (COM) still requires a comprehensive evaluation.
OBJECTIVES
This survey is designed to evaluate the current status of US teaching in COMs with an emphasis on the inclusion of the US in osteopathic manipulative medicine (OMM) training.
METHODS
An anonymous, voluntary, 22-question online survey was created and administered to all COMs to collect data about the current state of US teaching. A descriptive analysis was performed to describe and summarize the final data. Fisher's exact test was utilized for the comparison of study variables.
RESULTS
We received responses from 36 of the 43 (83.7 %) COMs invited to participate in the survey, all of which had US training within their curriculum, most commonly integrated into the year 1 curriculum (86.1 %). Focused US training is incorporated into 83.3 % of these schools (30 of 36). Focused US training is covered in 83.3 % of schools (30 of 36). US is mostly taught in the anatomy course (38.8 %). US is incorporated in the OMM course in 12 of 36 schools (33.3 %). The majority of respondents feel that US training will make osteopathic students more competitive in the job market (88.9 %) and want more US in their curriculum (86.1 %). The idea that US is useful for a better understanding of the key OMM concepts is believed by 62.9 % of respondents. The major obstacle to the implementation of US in the curriculum is having appropriately trained faculty (86.1 %). The majority of the respondents did not feel that an adequate budget is a handicap to implementing US in the curriculum.
CONCLUSIONS
US is included within the curriculum of all respondents to our survey, a third of whom included US within their OMM curriculum. US is treated as a useful and important skill for future osteopathic physicians. The majority of COMs desire more US training in the curriculum. The main barrier to implementing US in the curriculum is the lack of appropriately trained faculty.
Topics: Humans; Schools, Medical; Curriculum; Emotions; Manipulation, Osteopathic; Mesna
PubMed: 38053432
DOI: 10.1515/jom-2023-0027 -
AIDS (London, England) Jul 2023To determine immune-metabolic dysregulation in children born to women living with HIV.
OBJECTIVE
To determine immune-metabolic dysregulation in children born to women living with HIV.
METHODS
Longitudinal immune-metabolomic analyses of plasma of 32 pregnant women with HIV (WHIV) and 12 uninfected women and their children up to 1.5 years of age were performed.
RESULTS
Using liquid chromatography-mass spectrometry and a multiplex bead assay, 280 metabolites (57 amino acids, 116 positive lipids, 107 signalling lipids) and 24 immune mediators (e.g. cytokines) were quantified. combinational antiretroviral therapy (cART) exposure was categorized as cART initiation preconception (long), cART initiation postconception up to 4 weeks before birth (medium) and cART initiation within 3 weeks of birth (short). Plasma metabolite profiles differed between HIV-exposed-uninfected (HEU)-children with long cART exposure compared to HIV-unexposed-children (HUU). Specifically, higher levels of methionine-sulfone, which is associated with oxidative stress, were detected in HEU-children with long cART exposure compared to HUU-children. High infant methionine-sulfone levels were reflected by high prenatal plasma levels in the mother. Increased methionine-sulfone levels in the children were associated with decreased growth, including both weight and length.
CONCLUSION
These findings based on longitudinal data demonstrate that dysregulation of metabolite networks associated with oxidative stress in children born to WHIV is associated with restricted infant growth.
Topics: Infant; Humans; Pregnancy; Female; HIV Infections; Pregnancy Complications, Infectious; Methionine; Sulfones; Lipids
PubMed: 37070556
DOI: 10.1097/QAD.0000000000003574 -
Chemosphere Oct 2023Fluorinated chrome mist suppressants (CMSs) have been widely used in the electroplating industry globally, including China. In compliance with the Stockholm Convention... (Review)
Review
Fluorinated chrome mist suppressants (CMSs) have been widely used in the electroplating industry globally, including China. In compliance with the Stockholm Convention on Persistent Organic Pollutants, China has phased out perfluorooctane sulfonate (PFOS) as CMS, except for closed-loop systems, before March 2019. Since then, several alternatives have been introduced to replace PFOS, but many of them still belong to the per- and polyfluoroalkyl substances (PFASs) family. In this study, for the first time, we collected and analyzed CMS samples from the Chinese market in 2013, 2015, and 2021 to determine their PFAS composition. For products with relatively few PFAS targets, we performed a total fluorine (TF) screening test and suspect and non-target analysis. Our findings suggest that 6:2 fluorotelomer sulfonate (6:2 FTS) has become the primary alternative on the Chinese market. Surprisingly, we identified 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFAES) as the primary ingredient in a CMS product (F-115B), which is the longer chain modification of the classical CMS product (F-53B). Furthermore, we identified three novel PFASs as PFOS alternatives, including hydrogen-substituted perfluoroalkyl sulfonates (H-PFSAs) and perfluorinated ether sulfonates (O-PFSAs). We also screened and identified six hydrocarbon surfactants in PFAS-free products as the primary ingredients. Despite this, some PFOS-based CMSs remain on the Chinese market. To prevent the opportunistic use of PFOS for illegal purposes, it is essential to enforce regulations strictly and ensure that such CMSs are used only in closed-loop chrome plating systems.
Topics: Alkanesulfonic Acids; Fluorocarbons; Alkanesulfonates; Ether; Ethers; China
PubMed: 37419156
DOI: 10.1016/j.chemosphere.2023.139419 -
Urologia Feb 2024Indications for treating Benign Prostatic Hyperplasia include reversing signs and symptoms or preventing the progression of the disease. Alpha-blockers are the most...
INTRODUCTION
Indications for treating Benign Prostatic Hyperplasia include reversing signs and symptoms or preventing the progression of the disease. Alpha-blockers are the most effective, least costly, and best tolerated of the drugs for relieving LUTS. The aim of the study is to investigate the immediate impact of alpha-blocker medications on lower urinary tract symptoms (LUTS).
MATERIALS AND METHODOLOGY
About 100 patients were included in the study-50 patients in each of the groups A (tamsulosin) and B (silodosin). The first visit was the baseline examination before starting alpha-blockers and included history, DRE, UFM, USG KUBP with PVR, IPSS, serum PSA, serum creatinine, urine analysis, urine culture, and sensitivity. All above parameters were also at 1 week, 1 month, and 3 months following starting of alpha-blockers respectively, and compared with baseline.
RESULT
As of the first, second, third, and fourth visits, the mean Qmax in group A was 10.3 ± 3.3 s, 15.08 ± 2.80 s, 15.66 ± 3.18 s, and 15.12 ± 3.24 s, respectively, while in group B it was 10.1 ± 3.1 s, 14.88 ± 2.80 s, 15.18 ± 3.18 s, and 15.08 ± 3.24 s, respectively ( < 0.001). The mean voiding time was 40.87 ± 23.91 s, 36.41 ± 20.73 s, 34.85 ± 21.37 s, and 32.07 ± 21.81 s, respectively in group A, and 41.27 ± 15.49 s, 37.23 ± 21.34 s, 38.59 ± 20.83 s, and 33.10 ±22.08. In group A, the mean PVR and IPSS scores were improved and also improved in group B.
CONCLUSION
The first dose of tamsulosin and silodosin improves UFM and predicts the mid-term change in UFM as well as IPSS indices in the treatment of BPH-related LUTS.
Topics: Male; Humans; Tamsulosin; Prostatic Hyperplasia; Sulfonamides; Treatment Outcome; Adrenergic alpha-Antagonists; Lower Urinary Tract Symptoms
PubMed: 37606221
DOI: 10.1177/03915603231192738 -
Environmental Toxicology and Chemistry Oct 2023With the goal of aiding risk assessors conducting site-specific risk assessments at per- and polyfluoroalkyl substance (PFAS)-contaminated sites, this critical review... (Review)
Review
A Critical Review of Amphibian Per- and Polyfluoroalkyl Substance Ecotoxicity Research Studies: Identification of Screening Levels in Water and Other Useful Resources for Site-Specific Ecological Risk Assessments.
With the goal of aiding risk assessors conducting site-specific risk assessments at per- and polyfluoroalkyl substance (PFAS)-contaminated sites, this critical review synthesizes information on the ecotoxicity of PFAS to amphibians in 10 amphibian species and 16 peer-reviewed publications. The studies in this review consisted of spiked-PFAS chronic toxicity experiments with perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and 6:2 fluorotelomer sulfonate (6:2 FTS) that evaluated apical endpoints typical of ecological risk-based decision making (survival, growth, and development). Body mass was the most sensitive endpoint, showing clear and biologically meaningful population level adverse effect sizes (≥20% adverse effects). From these results, we recommend chronic no observed effect concentration (NOEC) screening levels of 590 µg/L for PFOS and 130 µg/L for PFOA. At or above recommended chronic lowest observed effect concentration screening levels of 1100 µg/L PFOS and 1400 µg/L PFOA, there is an increased chance of adverse biologically relevant chronic effects. Biologically relevant adverse effects were not observed for PFHxS and 6:2 FTS, so unbounded NOECs of 1300 µg/L PFHxS and 1800 µg/L 6:2 FTS are recommended. Screening levels are also provided for the concentration of PFAS in an amphibian diet, amphibian tissue, and moss substrate. In addition, we recommend bioconcentration factors that can be useful to predict concentrations of PFAS in amphibians using concentrations in water; these values are useful for food web modeling to understand risks to vertebrate wildlife that prey on amphibians. Overall, the present study provides a guide to the wealth of ecotoxicological research on PFAS conducted by our research group and highlights the need for additional work that would improve the understanding of chemical risks to amphibians. Environ Toxicol Chem 2023;42:2078-2090. © 2023 SETAC.
Topics: Animals; Water; Alkanesulfonic Acids; Fluorocarbons; Risk Assessment; Alkanesulfonates; Amphibians
PubMed: 37314102
DOI: 10.1002/etc.5695 -
Scientific Reports Oct 2023Tissue engineering is a promising alternative to current full thickness circumferential esophageal replacement methods. The aim of our study was to develop a clinical...
Tissue engineering is a promising alternative to current full thickness circumferential esophageal replacement methods. The aim of our study was to develop a clinical grade Decellularized Human Esophagus (DHE) for future clinical applications. After decontamination, human esophagi from deceased donors were placed in a bioreactor and decellularized with sodium dodecyl sulfate (SDS) and ethylendiaminetetraacetic acid (EDTA) for 3 days. The esophagi were then rinsed in sterile water and SDS was eliminated by filtration on an activated charcoal cartridge for 3 days. DNA was removed by a 3-hour incubation with DNase. A cryopreservation protocol was evaluated at the end of the process to create a DHE cryobank. The decellularization was efficient as no cells and nuclei were observed in the DHE. Sterility of the esophagi was obtained at the end of the process. The general structure of the DHE was preserved according to immunohistochemical and scanning electron microscopy images. SDS was efficiently removed, confirmed by a colorimetric dosage, lack of cytotoxicity on Balb/3T3 cells and mesenchymal stromal cell long term culture. Furthermore, DHE did not induce lymphocyte proliferation in-vitro. The cryopreservation protocol was safe and did not affect the tissue, preserving the biomechanical properties of the DHE. Our decellularization protocol allowed to develop the first clinical grade human decellularized and cryopreserved esophagus.
Topics: Mice; Animals; Humans; Tissue Scaffolds; Extracellular Matrix; Tissue Engineering; Cryopreservation; Sodium Dodecyl Sulfate; Esophagus
PubMed: 37880340
DOI: 10.1038/s41598-023-45610-5 -
BMC Gastroenterology Aug 2023The effectiveness of selective COX-2 inhibitors in preventing colorectal cancer recurrence has been demonstrated, however it is unknown how safe and successful they will... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effectiveness of selective COX-2 inhibitors in preventing colorectal cancer recurrence has been demonstrated, however it is unknown how safe and successful they will be over the long term. As a result, we looked at the efficacy, safety, and consequences of adding COX-2 inhibitors to the treatment plan afterward.
METHODS
In patients with advanced colorectal cancer, we compared the efficacy of celecoxib at two different doses (200 mg twice day and 400 mg twice daily) with placebo. To evaluate the impacts of post-treatment, several datasets from inception to June 2022 were searched. Response rate, illness control rate, and 3-year survival were the main results. And evaluated several safety outcomes, particularly those that were susceptible to adverse events.
RESULTS
The study comprised a total of 9 randomized controlled trials (3206 participants). Celecoxib and rofecoxib doidn't significantly improved the 1-3 year remission rate (OR, 1.57 [95% CI: 0.95-2.57]) and disease control rate (OR, 1.08 [95% CI: 0.99-1.17]). Subgroup analysis of different doses showed that 400 mg of celecoxib significantly improved the response rate (OR, 2.82 [95%CI: 1.20-6.61]). 200 mg celecoxib was not significant (OR, 1.28 [95% CI: 0.66-2.49]). Rofecoxib also did not fully improve disease response rates. Celecoxib at any dose improved 3-year survival (OR, 1.21 [95% CI: 1.02-1.45]). It is important to note that COX-2 inhibitors did not significantly enhance the likelihood of adverse events including gastrointestinal or cardiovascular side effects at any dose.
CONCLUSIONS
For patients with advanced colorectal cancer, a reasonable chemoprevention regimen can include celecoxib 400 mg twice daily.
Topics: Humans; Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Colorectal Neoplasms; Cyclooxygenase 2 Inhibitors; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Sulfones
PubMed: 37580670
DOI: 10.1186/s12876-023-02918-w -
Nature Communications Jul 2023The sulfonamides (sulfas) are the oldest class of antibacterial drugs and inhibit the bacterial dihydropteroate synthase (DHPS, encoded by folP), through chemical...
The sulfonamides (sulfas) are the oldest class of antibacterial drugs and inhibit the bacterial dihydropteroate synthase (DHPS, encoded by folP), through chemical mimicry of its co-substrate p-aminobenzoic acid (pABA). Resistance to sulfa drugs is mediated either by mutations in folP or acquisition of sul genes, which code for sulfa-insensitive, divergent DHPS enzymes. While the molecular basis of resistance through folP mutations is well understood, the mechanisms mediating sul-based resistance have not been investigated in detail. Here, we determine crystal structures of the most common Sul enzyme types (Sul1, Sul2 and Sul3) in multiple ligand-bound states, revealing a substantial reorganization of their pABA-interaction region relative to the corresponding region of DHPS. We use biochemical and biophysical assays, mutational analysis, and in trans complementation of E. coli ΔfolP to show that a Phe-Gly sequence enables the Sul enzymes to discriminate against sulfas while retaining pABA binding and is necessary for broad resistance to sulfonamides. Experimental evolution of E. coli results in a strain harboring a sulfa-resistant DHPS variant that carries a Phe-Gly insertion in its active site, recapitulating this molecular mechanism. We also show that Sul enzymes possess increased active site conformational dynamics relative to DHPS, which could contribute to substrate discrimination. Our results reveal the molecular foundation for Sul-mediated drug resistance and facilitate the potential development of new sulfas less prone to resistance.
Topics: Anti-Bacterial Agents; Escherichia coli; 4-Aminobenzoic Acid; Sulfanilamide; Sulfonamides; Plasmids
PubMed: 37419898
DOI: 10.1038/s41467-023-39778-7 -
Bioorganic & Medicinal Chemistry Aug 2023Chlamydia trachomatis is the most prevalent sexually transmitted bacterial infection in the United States and the world. This pathogen can cause health problems ranging...
Chlamydia trachomatis is the most prevalent sexually transmitted bacterial infection in the United States and the world. This pathogen can cause health problems ranging from trachoma (blindness) to damage of the fallopian tubes or ectopic pregnancy, which can be life-threatening if not treated properly. To this day, there is no chlamydia-specific drug on the market. Previously, we reported the activity and basic structure-activity relationships (SAR) of sulfonylpyridine molecules that possess antichlamydial action. Based on those results, we prepared a new series of derivatives. Our data indicate the new analogs can halt the growth of C. trachomatis. The lead compound, 22, was more active than our previous molecules and did not affect the growth of S. aureus and E. coli, suggesting bacterial selectivity. We performed docking studies on the presumed target, the cylindrical protease of Chlamydia. The in-silico studies partially explained the in vitro biological result as well as predicted a possible binding pose in the binding pocket. The top compound displayed a good cytotoxicity profile towards mammalian cell lines and was stable in both serum and stimulated gastric fluid. The presented data suggests the sulfonylpyridines are promising and selective anti-chlamydial compounds that merit further structural optimization.
Topics: Animals; Female; Humans; Cell Line; Chlamydia Infections; Chlamydia trachomatis; Escherichia coli; Mammals; Staphylococcus aureus; Sulfones; Pyridines
PubMed: 37453189
DOI: 10.1016/j.bmc.2023.117401 -
Journal of Colloid and Interface Science Oct 2023Nanoparticles (NPs) have broad application prospects in the field of biomedicine due to their excellent physicochemical properties. When entering biological fluids, NPs...
Nanoparticles (NPs) have broad application prospects in the field of biomedicine due to their excellent physicochemical properties. When entering biological fluids, NPs inevitably encountered proteins and were subsequently surrounded by them, forming the termed protein corona (PC). As PC has been evidenced to have critical roles in deciding the biological fates of NPs, how to precisely characterize PC is vital to promote the clinical translation of nanomedicine by understanding and harnessing NPs' behaviors. During the centrifugation-based separation techniques for the PC preparation, direct elution has been most widely used to strip proteins from NPs due to its simpleness and robustness, but the roles of multifarious eluents have never been systematically declared. Herein, seven eluents composed of three denaturants, sodium dodecyl sulfate (SDS), dithiothreitol (DTT), and urea (Urea), were applied to detach PC from gold nanoparticles (AuNPs) and silica nanoparticles (SiNPs), and eluted proteins in PC have been carefully characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and chromatography coupled tandem mass spectrometry (LC-MS/MS). Our results showed that SDS and DTT were the main contributors to the efficient desorption of PC on SiNPs and AuNPs, respectively. The molecular reactions between NPs and proteins were explored and verified by SDS-PAGE analysis of PC formed in the serums pretreated with protein denaturing or alkylating agents. The proteomic fingerprinting analysis indicated the difference of the eluted proteins brought by the seven eluents was the abundance rather than the species. The enrichment of some opsonins and dysopsonins in a special elution reminds us that the possibility of biased judgments on predicting NPs' biological behaviors under different elution conditions. The synergistic effects or antagonistic effects among denaturants for eluting PC were manifested in a nanoparticle-type dependent way by integrating the properties of the eluted proteins. Collectively, this study not only underlines the urgent need of choosing the appropriate eluents for identifying PC robustly and unbiasedly, but also provides an insight into the understanding of molecular interactions during PC formation.
Topics: Protein Corona; Gold; Chromatography, Liquid; Sodium Dodecyl Sulfate; Proteomics; Metal Nanoparticles; Tandem Mass Spectrometry; Proteins; Nanoparticles
PubMed: 37307606
DOI: 10.1016/j.jcis.2023.05.045