Rational use of medicine

Antimicrobial resistance (AMR) is a pressing global issue exacerbated by the abuse of antibiotics and the formation of bacterial biofilms, which cause up to 80% of human bacterial infections. This study presents a computational strategy to address AMR by developing three novel quantitative structure-activity relationship (QSAR) models based on molecular topology to identify potential anti-biofilm and antibacterial agents. The models aim to determine the chemo-topological pattern of Gram (+) antibacterial, Gram (-) antibacterial, and biofilm formation inhibition activity...

Developing in vitro models that accurately mimic the microenvironment of biological structures or processes holds substantial promise for gaining insights into specific biological functions. In the field of tissue engineering and regenerative medicine, in vitro models able to capture the precise structural, topographical, and functional complexity of living tissues, prove to be valuable tools for comprehending disease mechanisms, assessing drug responses, and serving as alternatives or complements to animal testing...

Benzoheteroles are promising structural scaffolds in the realm of medicinal chemistry, but sustainable synthesis of 2,3-difunctionalized benzoheterole derivatives is still in high demand. Indeed, we have conceptually rationalized the intrinsic reactivity of propargylic-enyne systems for the flexible construction of 2,3-disubstituted benzoheteroles through radical sulfonylative-cyclization cascade under organophotoredox catalysis. We hereby report an efficient visible-light-induced sulfonyl radical-triggered cyclization of 1,6-enynols with sulfinic acids under the dual catalytic influence of 4CzIPN and NiBr2...

BACKGROUND: Despite being a major advancement in modern medicine, vaccines face widespread hesitancy and refusal, posing challenges to immunization campaigns. The COVID-19 pandemic accentuated vaccine hesitancy, emphasizing the pivotal role of beliefs in efficacy and safety on vaccine acceptance rates. This study explores the influence of efficacy and safety perceptions on vaccine uptake in Italy during the pandemic. METHODS: We administered a 70-item questionnaire to a representative sample of 600 Italian speakers...

Tauopathy, neuronal atrophy, and psychological impairments are hallmarks of neurodegenerative diseases, such as Alzheimer's disease, that currently lack efficacious clinical treatments capable of rectifying these issues. To address these unmet needs, we used rational drug design to combine the pharmacophores of DYRK1A inhibitors and isoDMTs to develop psychoplastogenic DYRK1A inhibitors. Using this approach, we discovered a nonhallucinogenic compound capable of promoting cortical neuron growth and suppressing tau hyperphosphorylation while also having the potential to mitigate the biological and psychological symptoms of dementia...

OBJECTIVE: To investigate the prevalence and influencing factors of isolated diastolic hypertension (IDH) in the Tibetan population in Tibet and to provide some evidence for the prevention and control of hypertension and other related diseases in high-altitude areas. METHODS: A multistage stratified whole-group random sampling method was used to enroll participants from Ngari Prefecture, Nagqu City, Shannan City, and Lhasa City, Tibet. A total of 3918 native Tibetans with complete data were enrolled in the survey between June 2020 and August 2023...

INTRODUCTION: Antimicrobial resistance (AMR) poses a threat to animal and human health, as well as food security and nutrition. Development of AMR is accelerated by over- and misuse of antimicrobials as seen in many livestock systems, including poultry production. In Vietnam, high AMR levels have been reported previously within poultry production, a sector which is dominated by small-scale farming, even though it is intensifying. This study focuses on understanding small- and medium-scale chicken farmers' knowledge and practices related to AMR by applying an item response theory (IRT) approach, which has several advantages over simpler statistical methods...

The bioactive extracts of traditional medicinal plants are rich in polyphenols and help to rejuvenate skin. The study was designed to assess the skin rejuvenating effects of a stable cream enriched with 4% I. argentea (IaMe) extract. The quantity of polyphenols by spectrophotometric methods was TPC, 101.55 ± 0.03 mg GAE/g and total flavonoid content; 77.14 ± 0.13 mg QE/g, while HPLC-PDA revealed gallic acid; 4.91, chlorogenic acid 48.12, p-coumaric acid 0.43, and rutin 14.23 μg/g...

BACKGROUND: The emergence of drug-resistant strains of Klebsiella pneumoniae (K. pneumoniae) has become a significant challenge in the field of infectious diseases, posing an urgent need for the development of highly protective vaccines against this pathogen. METHODS AND RESULTS: In this study, we identified three immunogenic extracellular loops based on the structure of five candidate antigens using sera from K. pneumoniae infected mice. The sequences of these loops were linked to the C-terminal of an alpha-hemolysin mutant (mHla) from Staphylococcus aureus to generate a heptamer, termed mHla-EpiVac...

The aim of this study was to evaluate the growth performance, fermentation indices and meat quality of Sussex steers fed totally mixed rations that composed of graded inclusion levels of Napier grass (NP). Three experimental diets designated as diet 1 (0.0 g kg-1 NP: Control), diet 2 (300 g kg-1 NP grass) and diet 3 (600 g kg-1 NP) were formulated. Twenty-four male steers aged 8 months with an average body weight of 185.0 ± 30 kg were used. In a completely randomized design, the animals were allocated to the diets and fed for 120 days...

BACKGROUND: Patients with inflammatory bowel disease (IBD), dysbiosis, and immunosuppression who receive fecal microbiota transplantation (FMT) from healthy donors are at an increased risk of developing bacteremia. This study investigates the efficacy of a mixture of seven short-chain fatty acid (SCFA)-producing bacterial strains (7-mix), the resulting culture supernatant mixture (mix-sup), and FMT for treating experimental ulcerative colitis (UC) and evaluates underlying mechanisms. METHODS: Utilizing culturomics, we isolated and cultured SCFA-producing bacteria from the stool of healthy donors...

Inadequate health literacy is a risk factor for poor health outcomes and health-related quality of life (HRQoL). So far, the impact of health literacy on HRQoL has been examined for only a few chronic conditions. In this contribution, the relationship between health literacy and HRQoL in Korean adults with chronic conditions is examined using data of the cross-sectional Korea Health Panel Survey from 2021. Health literacy was measured with the 16-item European Health Literacy Survey Questionnaire (HLS-EU-Q16) and HRQoL with the European Quality of Life-5 Dimensions (EQ-5D)...

Curcuminoids and their complexes continue to attract attention in medicinal chemistry, but little attention has been given to their metabolic derivatives. Here, the first examples of (arene)Ru(II) complexes with curcuminoid metabolites, tetrahydrocurcumin (THcurcH), and tetrahydrobisdesmethoxycurcumin (THbdcurcH) were prepared and characterized. The neutral complexes [Ru(arene)(THcurc)Cl] and [Ru(arene)(THbdcurc)Cl] (arene = cymene, benzene, or hexamethylbenzene) were characterized by NMR spectroscopy and ESI mass spectrometry, and the crystal structures of the three complexes were determined by X-ray diffraction analysis...

DNA-encoded library (DEL) technology is gaining attention for its rapid construction and deconvolution capabilities. Our study explored a novel strategy using rational DELs tailored for the SARS-CoV-2 papain-like protease, which revealed new fragments. Structural changes post-DEL screening mimic traditional medicinal chemistry lead optimization. We unveiled unique aromatic structures offering an alternative optimization path. Notably, we identified superior binding fragments targeting the BL2 groove. Derivative 16 emerged as the most promising by exhibiting IC50 values of 0...

5-Aminolevulinic acid (ALA) and its derivatives, serving as the endogenous precursor of the photosensitizer (PS) protoporphyrin IX (PpIX), successfully applied in tumor imaging and photodynamic therapy (PDT). ALA and its derivatives have been used to treat actinic keratosis (AK), basal cell carcinoma (BCC), and improve the detection of superficial bladder cancer. However, the high hydrophilicity of ALA and the conversion of PpIX to heme have limited the accumulation of PpIX, hindering the efficiency and potential application of ALA-PDT...

This research paper focuses on the study of the (3+1)-dimensional negative order KdV-Calogero-Bogoyavlenskii-Schiff (KdV-CBS) equation, an important nonlinear partial differential equation in oceanography. The primary objective is to explore various solution techniques and analyze their graphical representations. Initially, two wave, three wave, and multi-wave solutions of the negative order KdV CBS equation are derived using its bilinear form. This analysis shed light on the behavior and characteristics of the equation's wave solutions...

To investigate the quality differences between the seeds and husks of Amomum villosum and explore the rationality of using the seeds without husks, this study determined the content of protocatechuic acid, vanillic acid, epicatechin, quercitrin, volatile oil, water extract, and ethanol extract. The 2,2-diphenyl-1-picrylhydrazyl(DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), and hydroxyl radical scavenging activities were determined to evaluate the antioxidant activities of seeds and husks...

The activation of Homo sapiens Casein lysing protease P (HsClpP) by a chemical or genetic strategy has been proved to be a new potential therapy in acute myeloid leukemia (AML). However, limited efficacy has been achieved with classic agonist imipridone ONC201 . Here, a novel class of HsClpP agonists is designed and synthesized using a ring-opening strategy based on the lead compound 1 reported in our previous study. Among these novel scaffold agonists, compound 7k exhibited remarkably enhanced proteolytic activity of HsClpP (EC50 = 0...

IMPORTANCE: Delayed diagnosis of a dislocated hip in infants can lead to complex childhood surgery, interruption to family life, and premature osteoarthritis. OBJECTIVE: To evaluate the diagnostic accuracy of clinical examination in identifying dislocated hips in infants. DATA SOURCES: Systematic search of CINAHL, Embase, MEDLINE, and the Cochrane Library from the inception of each database until October 31, 2023. STUDY SELECTION: The 9 included studies reported the diagnostic accuracy of the clinical examination (index test) in infants aged 3 months or younger and a diagnostic hip ultrasound (reference test)...

BACKGROUND: Exposure to pesticides is of concern to public health officials worldwide. Deltamethrin is a synthetic pyrethroid pesticide which is widely used in agriculture and veterinary medicine. Deltamethrin poisoning is always one of the concerns in medical centers due to the deltamethrin induced hepatotoxicity. This study evaluated the hepato-protective effects of N-acetylcysteine (NAC) against deltamethrin induced hepatotoxicity in mice. METHODS: A total of 40 BALB/c male mice were randomly divided into four groups; the first group was used as a control (0...