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Toxics May 2024A community engaged research (CER) approach was used to provide an exposure assessment of poly- and perfluorinated (PFAS) compounds in North Carolina residential...
A community engaged research (CER) approach was used to provide an exposure assessment of poly- and perfluorinated (PFAS) compounds in North Carolina residential drinking water. Working in concert with community partners, who acted as liaisons to local residents, samples were collected by North Carolina residents from three different locations along the Cape Fear River basin: upper, middle, and lower areas of the river. Residents collected either drinking water samples from their homes or recreational water samples from near their residence that were then submitted by the community partners for PFAS analysis. All samples were processed using weak anion exchange (WAX) solid phase extraction and analyzed using a non-targeted suspect screening approach as well as a quantitative approach that included a panel of 45 PFAS analytes, several of which are specific to chemical industries near the collection site locations. The non-targeted approach, which utilized a suspect screening list (obtained from EPA CompTox database) identified several PFAS compounds at a level two confidence rating (Schymanski scale); compounds identified included a fluorinated insecticide, a fluorinated herbicide, a PFAS used in polymer chemistry, and another that is used in battery production. Notably, at several locations, PFOA (39.8 ng/L) and PFOS (205.3 ng/L) were at levels that exceeded the mandatory EPA maximum contaminant level (MCL) of 4 ng/L. Additionally, several sites had detectable levels of PFAS that are unique to a local chemical manufacturer. These findings were communicated back to the community partners who then disseminated this information to the local residents to help empower and aid in making decisions for reducing their PFAS exposure.
PubMed: 38922083
DOI: 10.3390/toxics12060403 -
Veterinary Sciences May 2024In the present case report, we describe the clinical course and postmortem findings of a 12-year-old Labrador retriever dog with a third-degree atrio-ventricular block...
In the present case report, we describe the clinical course and postmortem findings of a 12-year-old Labrador retriever dog with a third-degree atrio-ventricular block that developed a chronic cough, and later dyspnea and weakness as a result of massive pulmonary thromboembolism 3 years after implantation of a transvenous permanent pacemaker. A large soft tissue mass was seen in the right ventricular chamber around the pacing lead with echocardiography. Initially, this was thought to be caused by mural bacterial endocarditis based on hyperthermia, severe leukocytosis and the appearance of runs of ventricular tachycardia, the latter suggesting myocardial damage. While blood culture results were pending, antibiotics were administered without a positive effect. Due to clinical deterioration, the owner elected for euthanasia and a post-mortem examination confirmed a right ventricular thrombus and surrounding myocarditis, without signs of bacterial infection, and a massive pulmonary thromboembolism. We conclude that pulmonary thromboembolism should be considered in dogs with a cough that have an endocardial pacing lead implanted. Serial screening for proteinuria before and after implantation of an endocardial pacing lead would allow timely initiation of prophylactic antiplatelet therapy. Local myocarditis can develop secondary to an intracavitary thrombus, which can subsequently lead to runs of ventricular tachycardia.
PubMed: 38921984
DOI: 10.3390/vetsci11060237 -
Marine Drugs Jun 2024Bioprospecting the secondary metabolism of underexplored Actinomycetota taxa is a prolific route to uncover novel chemistry. In this work, we report the isolation,...
Bioprospecting the secondary metabolism of underexplored Actinomycetota taxa is a prolific route to uncover novel chemistry. In this work, we report the isolation, structure elucidation, and bioactivity screening of cellulamides A and B ( and ), two novel linear peptides obtained from the culture of the macroalga-associated CT-R177. The host of this microorganism, the Chlorophyta , was collected in the northern Portuguese coast and, in the scope of a bioprospecting study focused on its associated actinobacterial community, strain CT-R177 was isolated, taxonomically identified, and screened for the production of antimicrobial and anticancer compounds. Dereplication of a crude extract of this strain using LC-HRMS(/MS) analysis unveiled a putative novel natural product, cellulamide A (), that was isolated following mass spectrometry-guided fractionation. An additional analog, cellulamide B () was obtained during the chromatographic process and chemically characterized. The chemical structures of the novel linear peptides, including their absolute configurations, were elucidated using a combination of HRMS, 1D/2D NMR spectroscopy, and Marfey's analysis. Cellulamide A () was subjected to a set of bioactivity screenings, but no significant biological activity was observed. The cellulamides represent the first family of natural products reported from the Actinomycetota genus , showcasing not only the potential of less-explored taxa but also of host-associated marine strains for novel chemistry discovery.
Topics: Humans; Peptides; Actinobacteria; Antineoplastic Agents; Aquatic Organisms; Biological Products; Cell Line, Tumor; Anti-Bacterial Agents
PubMed: 38921579
DOI: 10.3390/md22060268 -
Marine Drugs May 2024Tuberculosis, a persistent illness caused by , remains a significant global public health challenge. The widespread use of anti-tuberculosis drugs has resulted in the...
Tuberculosis, a persistent illness caused by , remains a significant global public health challenge. The widespread use of anti-tuberculosis drugs has resulted in the emergence of drug-resistant strains, which complicates treatment efforts. Addressing this issue is crucial and hinges on the development of new drugs that can effectively target the disease. This involves identifying novel therapeutic targets that can disrupt the bacterium's survival mechanisms in various environments such as granulomas and lesions. Citrate lyase, essential for the survival of species at lesion sites and in granulomatous conditions, is a potential target for the treatment of tuberculosis. This manuscript aimed to construct an efficient enzyme inhibitor screening platform using ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF MS). This system can accurately identify compounds with enzyme inhibitory activity from a library of marine terpenoids and phenolic compounds. Utilizing the screened herbal enzyme inhibitors as a starting point, we analyzed their chemical structures and skillfully built a library of marine compounds based on these structures. The results showed that all of the tested compounds from the phenolics library inhibited citrate lyase by more than 50%, and a significant portion of terpenoids also demonstrated inhibition, with these active terpenoids comprising over half of the terpenoids tested. The study underscores the potential of marine-derived phenolic and terpenoid compounds as potent inhibitors of citrate lyase, indicating a promising direction for future investigations in treating tuberculosis and associated disorders.
Topics: Tandem Mass Spectrometry; Enzyme Inhibitors; Antitubercular Agents; Mycobacterium tuberculosis; Chromatography, High Pressure Liquid; ATP Citrate (pro-S)-Lyase; Aquatic Organisms; Terpenes; Humans; Phenols; Chromatography, Liquid
PubMed: 38921556
DOI: 10.3390/md22060245 -
Metabolites May 2024For either healthy or diseased organisms, lipids are key components for cellular membranes; they play important roles in numerous cellular processes including cell... (Review)
Review
For either healthy or diseased organisms, lipids are key components for cellular membranes; they play important roles in numerous cellular processes including cell growth, proliferation, differentiation, energy storage and signaling. Exercise and disease development are examples of cellular environment alterations which produce changes in these networks. There are indications that alterations in lipid metabolism contribute to the development and progression of a variety of cancers. Measuring such alterations and understanding the pathways involved is critical to fully understand cellular metabolism. The demands for this information have led to the emergence of lipidomics, which enables the large-scale study of lipids using mass spectrometry (MS) techniques. Mass spectrometry has been widely used in lipidomics and allows us to analyze detailed lipid profiles of cancers. In this article, we discuss emerging strategies for lipidomics by mass spectrometry; targeted, as opposed to global, lipid analysis provides an exciting new alternative method. Additionally, we provide an introduction to lipidomics, lipid categories and their major biological functions, along with lipidomics studies by mass spectrometry in cancer samples. Further, we summarize the importance of lipid metabolism in oncology and tumor microenvironment, some of the challenges for lipodomics, and the potential for targeted approaches for screening pharmaceutical candidates to improve the therapeutic efficacy of treatment in cancer patients.
PubMed: 38921447
DOI: 10.3390/metabo14060312 -
Healthcare (Basel, Switzerland) Jun 2024(1) Background: This study investigated the association between body mass index (BMI) categories and comorbidities in the context of a developing country, utilizing data...
(1) Background: This study investigated the association between body mass index (BMI) categories and comorbidities in the context of a developing country, utilizing data from a nationwide health screening in Mongolia. (2) Methods: The study included 181,080 individuals (mean age 47.0 ± 15.3, 42.0% male) from the population-based general health screening. We counted the number of diseases from participants' medical records based on ICD-10 codes, excluding those categorized under Z00-Z99 and codes indicating acute disorders, as well as individuals classified as underweight. (3) Results: Among study participants, the prevalence of two or more comorbidities was 4.2%. The weight distribution comprised 40.4% normal weight; 37.1% overweight; and 16.9%, 4.4%, and 1.2% in the Class I, II, and III obesity categories, respectively. Comorbidities increased with BMI: normal weight (0.222); overweight (0.255); and Class I (0.290), Class II (0.302), and Class III obesity (0.303), suggesting a dose-dependent likelihood of having multiple diseases. Adjusted linear regression (beta coefficients, 95% CIs) showed increased comorbidity risks in overweight (0.017, 0.013-0.021) and obesity (0.034, 0.030-0.039). Interaction analysis with age revealed a significant effect ( < 0.001). While comorbidities tend to increase with higher BMI categories in all age-tertile groups, this association was notably stronger among younger individuals. (4) Conclusions: Obesity is associated with a twofold increase in the prevalence of multiple comorbidities compared to normal weight. Our findings also highlight the critical role of age in the development of multiple diseases, with BMI remaining a significant factor across various age groups, encompassing both younger and older adults.
PubMed: 38921336
DOI: 10.3390/healthcare12121222 -
Insects Jun 2024, the city flower of Chengdu, is culturally significant and has nutritional and medicinal benefits. However, frequent infestations of have caused economic losses. This...
, the city flower of Chengdu, is culturally significant and has nutritional and medicinal benefits. However, frequent infestations of have caused economic losses. This study aimed to identify insect-resistant varieties. Over two years, varieties like Jinqiusong, Zuiyun, and Zuifurong showed moderate to high resistance based on reproductive indices. Assessments of antixenosis and developmental impacts revealed that adult exhibited low selectivity toward these resistant varieties, indicating a strong repellent effect. Gas chromatography-mass spectrometry analysis identified volatile organic compounds, such as alcohols, alkanes, and terpenes. Notably, 2-ethylhexanol and 6-methylheptanol exhibited repellent properties. Using nontargeted metabolomics, this study compared the metabolite profiles of the insect-resistant variety Jinqiusong (JQS), moderately resistant Bairihuacai (BRHC), and highly susceptible Chongbanbai (CBB) post infestation. Fifteen key metabolites were linked to resistance, emphasizing the phenylpropanoid biosynthesis pathway as crucial in defense. These findings offer a theoretical foundation for breeding insect-resistant varieties and developing eco-friendly strategies against infestations.
PubMed: 38921168
DOI: 10.3390/insects15060454 -
Insects May 2024Prolonged periods of host-lethal infection by entomopathogenic fungi pose challenges to the development of biological control agents. The obligate entomopathogen ,...
Transcriptomic Profiling of Bean Aphid upon Exposure to the Aphid-Obligate Entomopathogen (Entomophthoromycotina) and Screening of CytCo-Binding Aphid Proteins through a Pull-Down Assay.
Prolonged periods of host-lethal infection by entomopathogenic fungi pose challenges to the development of biological control agents. The obligate entomopathogen , however, rapidly kills aphid hosts, warranting investigation. This study investigated the interaction between and a bean aphid during the incubation period of infection, using transcriptome analysis to map host gene expression profiles. Results indicate -inoculated aphid activation of the wound healing immune responses, alongside suppression of the key molecules involved in Toll signaling, melanization, and metabolism. Furthermore, neuromotor system-related genes were upregulated, paralleling the intoxication observed in a nematode pest treated with -derived CytCo protein. To deepen interaction insights, a His-tag pull-down assay coupled with mass spectrometry analysis was conducted using CytCo as a bait to screen for potential aphid protein interactors. The proteins were identified based on the assembled transcriptome, and eleven transmembrane proteins were predicted to bind to CytCo. Notably, a protein of putatively calcium-transporting ATPase stood out with the highest confidence. This suggests that CytCo plays a vital role in killing aphid hosts, implicating calcium imbalance. In conclusion, effectively inhibits aphid immunity and exhibits neurotoxic potential, expediting the infection process. This finding facilitates our understanding of the complex host-pathogen interactions and opens new avenues for exploring biological pest management strategies in agroforestry.
PubMed: 38921103
DOI: 10.3390/insects15060388 -
Current Oncology (Toronto, Ont.) Jun 2024Diagnostic blood tests have the potential to identify lung cancer in people at high risk. We assessed the cost-effectiveness of a lung cancer screening intervention,...
BACKGROUND
Diagnostic blood tests have the potential to identify lung cancer in people at high risk. We assessed the cost-effectiveness of a lung cancer screening intervention, using the EarlyCDT-Lung Test (ECLS) with subsequent X-ray and low-dose chest CT scans (LDCT) for patients with a positive test result, compared to both usual care and LDCT screening for the target population.
METHODS
We conducted a model-based lifetime analysis from a UK NHS and personal social services perspective. We estimated incremental net monetary benefit (NMB) for the ECLS intervention compared to no screening and to LDCT screening.
RESULTS
The incremental NMB of ECLS intervention compared to no screening was GBP 33,179 (95% CI: -GBP 81,396, GBP 147,180) and GBP 140,609 (95% CI: -GBP 36,255, GBP 316,612), respectively, for a cost-effectiveness threshold of GBP 20,000 and GBP 30,000 per quality-adjusted life year. The same figures compared with LDCT screening were GBP 162,095 (95% CI: GBP 52,698, GBP 271,735) and GBP 52,185 (95% CI: -GBP 115,152, GBP 219,711).
CONCLUSIONS
The ECLS intervention is the most cost-effective screening alternative, with the highest probability of being cost-effective, when compared to no screening or LDCT screening. This result may change with modifications of the parameters, suggesting that the three alternatives considered in the main analysis are potentially cost-effective.
Topics: Humans; Lung Neoplasms; Early Detection of Cancer; Scotland; Cost-Benefit Analysis; Female; Male; Middle Aged; Tomography, X-Ray Computed; Aged; Hematologic Tests; Mass Screening
PubMed: 38920744
DOI: 10.3390/curroncol31060261 -
Annali Dell'Istituto Superiore Di Sanita 2024Maternal antenatal depression affects 21-28% of expectants globally and negatively impacts both maternal and child health in the short and long term. (Comparative Study)
Comparative Study
BACKGROUND
Maternal antenatal depression affects 21-28% of expectants globally and negatively impacts both maternal and child health in the short and long term.
OBJECTIVE
To compare the psychometric properties and clinical utility of the Edinburgh Postnatal Depression Scale (EPDS) and the Patient Health Questionnaire (PHQ-9) in pregnant individuals.
METHODS
In this cross-sectional study, 953 third-trimester pregnant Italian individuals completed both the EPDS and the PHQ-9.
RESULTS
Both scales demonstrated good internal consistency (EPDS ω=0.83, PHQ-9 ω=0.80) and a moderate correlation between their scores (r=0.59). Concordance at recommended cut-off points (≥14 for both) was moderate (k=0.55). Factor analyses indicated a bifactor solution for the EPDS (dimensions: "depression" and "anxiety") and for the PHQ-9 (dimensions: "depression", "pregnancy symptoms", "somatic"). Benchmarks for clinical change were also established.
CONCLUSIONS
The EPDS and PHQ-9 capture distinct aspects of perinatal depressive symptomatology. Clinically, these findings recommend using both scales in obstetric and gynaecologic settings to minimize false positives and negatives.
Topics: Humans; Female; Pregnancy; Adult; Cross-Sectional Studies; Pregnancy Complications; Psychometrics; Depression; Patient Health Questionnaire; Psychiatric Status Rating Scales; Depression, Postpartum; Italy; Young Adult; Surveys and Questionnaires; Reproducibility of Results; Mass Screening
PubMed: 38920259
DOI: 10.4415/ANN_24_01_08