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Chemistry (Weinheim An Der Bergstrasse,... Jul 2024Considering the broad use of the trifluoromethyl functional group (-CF3) in medicinal chemistry and taking into account the recent concerns on the negative environmental...
Considering the broad use of the trifluoromethyl functional group (-CF3) in medicinal chemistry and taking into account the recent concerns on the negative environmental effects of CF3 containing compounds, we are searching for "greener" alternatives. Thus, different chemical groups (i.e. iodide, fluoride, cyclopropyl, isopropyl, cyclobutyl, 3-oxetyl, 2-oxetyl, methylsulfide, pentafluorosulfide, methylsulfonyl and sulfonamide) have been considered as potential bioequivalents of -CF3 aiming to use them in compounds with therapeutic interest instead of the polyfluoride functionality. Different structural (molecular surface and volume) and physicochemical (electronic and lipophilic) aspects of the bioequivalent functionalities proposed have been theoretically calculated and compared to those of -CF3. Additionally, the corresponding phenyl derivatives carrying these functionalities have been purchased or prepared and their experimental lipophilicity (i.e. LogP) measured using shake-flask experiments and UV-vis spectroscopy.
PubMed: 38958040
DOI: 10.1002/chem.202401954 -
Gut Microbes 2024The juxtaposition of well-oxygenated intestinal colonic tissue with an anerobic luminal environment supports a fundamentally important relationship that is altered in...
The juxtaposition of well-oxygenated intestinal colonic tissue with an anerobic luminal environment supports a fundamentally important relationship that is altered in the setting of intestinal injury, a process likely to be relevant to diseases such as inflammatory bowel disease. Herein, using two-color phosphorometry to non-invasively quantify both intestinal tissue and luminal oxygenation in real time, we show that intestinal injury induced by DSS colitis reduces intestinal tissue oxygenation in a spatially defined manner and increases the flux of oxygen from the tissue into the gut lumen. By characterizing the composition of the microbiome in both DSS colitis-affected gut and in a bioreactor containing a stable human fecal community exposed to microaerobic conditions, we provide evidence that the increased flux of oxygen into the gut lumen augments glycan degrading bacterial taxa rich in glycoside hydrolases which are known to inhabit gut mucosal surface. Continued disruption of the intestinal mucus barrier through such a mechanism may play a role in the perpetuation of the intestinal inflammatory process.
Topics: Gastrointestinal Microbiome; Colitis; Animals; Humans; Oxygen; Bacteria; Mice; Intestinal Mucosa; Feces; Mice, Inbred C57BL; Dextran Sulfate; Colon; Male
PubMed: 38958039
DOI: 10.1080/19490976.2024.2361493 -
Acta Psychiatrica Scandinavica Jul 2024This systematic review aimed to summarise and synthesise research conducted in psychiatric mother-baby units (MBUs) in relation to patients, their families, or staff,... (Review)
Review
OBJECTIVE
This systematic review aimed to summarise and synthesise research conducted in psychiatric mother-baby units (MBUs) in relation to patients, their families, or staff, published from 1st January 2016 to 1st May 2024.
METHOD
Quantitative, qualitative, and mixed-method studies were included for review if they were published in peer-review journals in English and reported research on MBUs between January 2016 and May 2024. From the initial yield of 10,007 unique studies, 53 studies were included for review.
RESULTS
MBU research was found to more frequently investigate maternal characteristics rather than the benefits of MBU treatment compared to studies conducted prior to 2016. Most studies that did investigate impact of admission showed favourable results, however few follow-up studies and studies comparing MBU outcomes to other clinical settings were undertaken. Little research has been conducted to investigate the differential impacts of MBU admission on different diagnoses and long-term (>1 year) patient outcomes. There was a dearth of research investigating partners of women in MBUs and few studies conducted on infant outcomes.
CONCLUSIONS
MBUs were consistently found to improve mental health systems and mother-infant attachment in patients after admission. More research investigating patient support networks and child health, impact of diagnosis on outcomes, and studies with adequate follow-up are required.
PubMed: 38958035
DOI: 10.1111/acps.13727 -
Chinese Medical Journal Jul 2024Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for...
BACKGROUND
Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.
METHODS
A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson's correlation, multiple linear regression, and analyses of covariance.
RESULTS
All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex.
CONCLUSIONS
The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.
PubMed: 38958034
DOI: 10.1097/CM9.0000000000003156 -
Faraday Discussions Jul 2024Biocatalysis is a rapidly evolving field with increasing impact in organic synthesis, chemical manufacturing and medicine. The reflected the current state of...
Biocatalysis is a rapidly evolving field with increasing impact in organic synthesis, chemical manufacturing and medicine. The reflected the current state of biocatalysis, covering the design of enzymatic activities, but especially methods for the improvement of enzymes targeting a broad range of applications (, hydroxylations by P450 monooxygenases, enzymatic deprotection of organic compounds under mild conditions, synthesis of chiral intermediates, plastic degradation, silicone polymer synthesis, and peptide synthesis). Central themes have been how to improve an enzyme using methods of rational design and directed evolution, informed by computer modelling and machine learning, and the incorporation of new catalytic functionalities to create hybrid and artificial enzymes.
PubMed: 38958033
DOI: 10.1039/d4fd00127c -
Dalton Transactions (Cambridge, England... Jul 2024Currently, there are many uses of metal complexes, especially in the fields of medicinal chemistry and catalysis. Thus, fabrication of new complexes which perform as a...
Fabrication of thiosemicarbazone-based Pd(II) complexes: structural elucidations, catalytic activity towards Suzuki-Miyaura coupling reaction and antitumor activity against TNBC cells.
Currently, there are many uses of metal complexes, especially in the fields of medicinal chemistry and catalysis. Thus, fabrication of new complexes which perform as a catalyst and chemotherapeutic drug is always a beneficial addition to the literature. Herein, we report three heterocyclic thiosemicarbazone-based Pd(II) complexes [Pd(HL1)Cl] (C1), [Pd(L2)(PPh)] (C2) and [Pd(L3)(PPh)]Cl (C3) having coligands Cl and PPh. Thiosemicarbazone ligands (H2L1, H2L2 and HL3) and the complexes (C1-C3) were characterized methodically using several spectroscopic techniques. Single-crystal X-ray diffraction methods reveal that the structural environment around the metal center of C2 is square planar, while for C1 and C3 it is a slighty distorted square plane. The supramolecular network of compounds was built hydrogen bonds, C-H⋯π and π⋯π interactions. Density functional theory (DFT) study of the structure of the complexes supports experimental findings. The application of these complexes as catalysts toward Suzuki-Miyaura coupling reactions has been examined with various aryl halides and phenyl boronic acid in PEG 400 solvent. The complexes displayed good biomolecular interactions with DNA/protein, with a binding constant value of the order of 10 M. C3 showed greater binding efficacy toward these biomolecules than the other complexes, which might be due to the cationic nature of C3. Furthermore, antitumor activity of the complexes was studied against the human triple-negative breast cancer (TNBC) cell line MDA-MB-231. It was found that C3 was more toxic (IC = 10 ± 2.90 μM) toward MDA-MB-231 cells than the other complexes. A known chemotherapeutic drug, 5-fluorouracil, was included as positive control. The programmed cell death mechanism of C3 was confirmed. Additionally, complex-induced apoptosis was confirmed and occurred a mitochondria-dependent (intrinsic) pathway.
PubMed: 38958025
DOI: 10.1039/d4dt00950a -
Journal of the American Heart... Jul 2024Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim...
BACKGROUND
Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis.
METHODS AND RESULTS
We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, <0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly.
CONCLUSIONS
We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.
PubMed: 38958022
DOI: 10.1161/JAHA.124.034603 -
Initiation of lipid-lowering therapy as primary prevention of cardiovascular disease in the elderly.British Journal of Clinical Pharmacology Jul 2024This study aimed to analyse the initiation adherence phase to lipid-lowering therapy for primary prevention of cardiovascular disease in a Spanish population aged...
AIMS
This study aimed to analyse the initiation adherence phase to lipid-lowering therapy for primary prevention of cardiovascular disease in a Spanish population aged 70 years or older. The secondary objective was to identify the determinants of initiation and early discontinuation.
METHODS
This was an observational study conducted in the CArdiovascular Risk factors for HEalth Service research (CARhES) cohort. People aged 70 and older with a first prescription of a lipid-lowering drug and without a previous major adverse cardiovascular event (MACE) were selected (2018-2021). Data on sociodemographics, clinical conditions, drugs and use of health services were collected from clinical and administrative electronic databases. The study population was classified into: non-initiation, early discontinuation (i.e., discontinuation after the first dispensing) and initiation with more than one dispensing. Their characteristics were compared. Determinants of initiation and early discontinuation were explored.
RESULTS
Among the 15 019 people studied, 80.2% initiated the medication, 11.2% showed an early discontinuation and 8.6% were non-initiators. An older age or conditions such as dementia, diabetes or depression reduced the likelihood of initiation, while obesity and a high pharmacological burden increased it. People over 90 years of age or those prescribed a statin in combination were more likely to have an early discontinuation.
CONCLUSIONS
Non-initiation and early discontinuation are common among older people prescribed lipid-lowering drugs as primary prevention of cardiovascular disease for the first time. The presence of chronic pathologies other than cardiovascular ones should be considered when assessing whether or not to prescribe these drugs in the elderly.
PubMed: 38958019
DOI: 10.1111/bcp.16157 -
Journal of Applied Animal Welfare... Jul 2024In this cross-sectional study, we aimed to describe differences between India and the United States in public perceptions of free-roaming dogs and cats, concerns related...
In this cross-sectional study, we aimed to describe differences between India and the United States in public perceptions of free-roaming dogs and cats, concerns related to free-roaming animals, and preferred strategies for veterinary medical interventions and population management. Between August 2021 and February 2022, 498 individuals completed an online survey including 210 Indian respondents and 288 American respondents. Free-roaming dogs and cats were largely perceived as community animals among Indian respondents, with significantly more respondents indicating they should be allowed to roam freely compared with American respondents. Respondents from both countries were concerned about animal welfare, although Americans were significantly more likely to list animal welfare, public health and wildlife risks as significant concerns related to free-roaming cats and dogs. American respondents were also more likely to support adoption for sociable animals and euthanasia for unsociable animals, whereas Indian respondents were more likely to support spay/neuter, vaccinate and release strategies for both dogs and cats. Our findings speak to the importance of implementing tailored strategies for free-roaming cat and dog management based on local cultures and community perceptions of free-roaming animals.
PubMed: 38958018
DOI: 10.1080/10888705.2024.2374078 -
Chemical Society Reviews Jul 2024Nanomaterials exhibit significant potential for stimulating immune responses, offering both local and systemic modulation across a variety of diseases. The lymphoid... (Review)
Review
Nanomaterials exhibit significant potential for stimulating immune responses, offering both local and systemic modulation across a variety of diseases. The lymphoid organs, such as the spleen and lymph nodes, are home to various immune cells, including monocytes and dendritic cells, which contribute to both the progression and prevention/treatment of diseases. Consequently, many nanomaterial formulations are being rationally designed to target these organs and engage with specific cell types, thereby inducing therapeutic and protective effects. In this review, we explore crucial cellular interactions and processes involved in immune regulation and highlight innovative nano-based immunomodulatory approaches. We outline essential considerations in nanomaterial design with an emphasis on their impact on biological interactions, targeting capabilities, and treatment efficacy. Through selected examples, we illustrate the strategic targeting of therapeutically active nanomaterials to lymphoid organs and the subsequent immunomodulation for infection resistance, inflammation suppression, self-antigen tolerance, and cancer immunotherapy. Additionally, we address current challenges, discuss emerging topics, and share our outlook on future developments in the field.
PubMed: 38958009
DOI: 10.1039/d4cs00421c