Search Results (349)

Continuing professional development (CPD) is an essential tool for healthcare professionals to remain up-to-date with the latest advancements in their field. In Saudi Arabia, pharmacists are officially registered healthcare professionals by the Saudi Commission for Health Specialties (SCFHS). To uphold their licensure, they must complete 40 h of CPD every two years. This qualitative study aimed to explore hospital pharmacists’ perceptions, barriers, and challenges of CPD, as well as their recommendations for improving CPD activities. A qualitative descriptive approach with semi-structured face-to-face interviews was employed. Using purposive sampling, 12 hospital pharmacists were interviewed. The recorded data were transcribed and analyzed using thematic analysis. Pharmacists generally showed positive perceptions of CPD, recognizing its importance for their professional development and the provision of high-quality patient care. However, some pharmacists expressed dissatisfaction with the current system. Several barriers to participation such as heavy workloads, lack of time, and limited financial support were highlighted. The primary motivations for engaging in CPD included fulfilling regulatory requirements. Workshops were the most beneficial CPD activities among others. Additionally, importance of more specialized, practice-oriented programs was highlighted. The study provides valuable insights into the needs and challenges faced by hospital pharmacists in Saudi Arabia regarding CPD. The insights gained can inform theory, policy, and practice relating to pharmacists’ CPD at both professional and governmental levels. Full article

Surface enhanced fluorescence (SEF) based on noble metal nanoparticles is an effective means to achieve high sensitivity in fluorescence detection. Currently, the physical mechanism behind enhanced fluorescence is not fully understood. This paper measures the fluorescence signals of Dihydroporphyrin f methyl ether (CPD4) under both single-photon and two-photon excitation based on submicrometer silver particles with rough morphologies, achieving enhancement factors of 34 and 45 times, respectively. On this basis, by combining the radiative field characteristics produced by the silver particles, a stimulated radiation model of molecules is established to elucidate the changes in the molecular photophysical process when influenced by silver particles. Moreover, the fluorescence lifetime of the molecules was measured, showing that the presence of silver particles induces an increase in the molecular radiative decay rate, causing the fluorescence lifetime to decay from 3.8 ns to 3 ns. The results indicate that the fluorescence enhancement primarily originates from the submicrometer silver particles’ enhancement effect on the excitation light. Additionally, the fluorescence signal emitted by the molecules couples with the silver particles, causing the local surface plasmon resonances generated by the silver particles to also emit light signals of the same frequency. Under the combined effect, the fluorescence of the molecules is significantly enhanced. The findings provide a theoretical foundation for understanding the fluorescence enhancement mechanism of silver particles, adjusting the enhancement effect, and developing enhanced fluorescence detection devices based on submicrometer silver particles, holding significant practical importance. Full article

This paper aims to conduct a bibliometric analysis and traditional literature review concerning collaborative project delivery (CPD) methods, with an emphasis on design-build (DB), construction management at risk (CMAR), and integrated project delivery (IPD) Methods. This article seeks to identify the most influential publications, reveal the advantages and disadvantages of CPD, and determine the most suitable CPD methods for sustainable construction. This research involves the application of bibliometric instruments in R, which is a powerful statistical computing language that can be used to perform complex data analyses and visualizations on bibliographic data to scrutinize academic journals retrieved from the Scopus database. Google Scholar is also utilized for an in-depth analysis as part of this study. Relevant articles are identified and screened for review. Our analysis is grounded on an extensive dataset of 927 journal articles collected from the year 2000 up to September 2023, providing a robust foundation for a comprehensive examination. Citation analysis identified highly cited publications that have significantly influenced the discourse on CPD. The analysis further established the advantages and disadvantages of CPD methods to suggest the most suitable CPD technique for sustainable construction. The results of this analysis offer insights into future directions and opportunities for further research through a comprehensive overview of the existing discourse on the subject. The paper classifies CPD through collaborative contracting, particularly through early contractor involvement (ECI), groups the design-build and construction manager at risk methods under CPD, and aligns their advantages with the critical success factors for sustainable construction in order to select the most suitable CPD technique. This research can serve as a guide for industry professionals, researchers, and policymakers, providing a structured path for collaborative endeavors and facilitating coordinated efforts toward collaborative project delivery methods and sustainable construction. Full article

Immune activation status determines non-small cell lung cancer (NSCLC) prognosis, with reported positive/negative associations for T helper type 2 (TH2) responses, including allergen-specific IgE and eosinophils. Our study seeks to explore the potential impact of these comorbid immune responses on the survival rates of patients with NSCLC. Our retrospective study used data from the Data Warehouse of the German Center for Lung Research (DZL) and Lung Biobank at Thoraxklinik Heidelberg. We estimated the association of blood eosinophilia and neutrophilia on survival rates in an inflammatory cohort of 3143 patients with NSCLC. We also tested sensitization to food and inhalants and high-sensitivity C-reactive protein (hs-CRP) in a comorbidity cohort of 212 patients with NSCLC. Finally, we estimated the infiltration of immune-relevant cells including eosinophils, T-cells, and mast cells in a tissue inflammatory sub-cohort of 60 patients with NSCLC. Sensitization to at least one food or inhalant (sIgE) was higher in patients with adenocarcinoma (adeno-LC) than the non-adenocarcinoma (non-adeno-LC). Furthermore, hs-CRP was higher in non-adeno-LC compared with adeno-LC. Peripheral inflammation, particularly eosinophilia and neutrophilia, was associated with poor survival outcomes in NSCLC with a clear difference between histological subgroups. Finally, blood eosinophilia was paralleled by significant eosinophil infiltration into the peritumoral tissue in the lung. This study provides novel perspectives on the crucial role of peripheral inflammation, featuring eosinophilia and neutrophilia, with overall survival, underscoring distinctions between NSCLC subgroups (adeno-LC vs. non-adeno-LC). Peripheral eosinophilia enhances eosinophil infiltration into tumors. This sheds light on the complex interplay between inflammation, eosinophil infiltration, and NSCLC prognosis among various histological subtypes. Further studies are required to underscore the role of eosinophils in NSCLC among different histological subgroups and their role in shaping the tumor microenvironment. Full article

Epilepsy is a chronic neurological disorder characterized by recurrent seizures that affects over 70 million people worldwide. Although many antiepileptic drugs that block seizures are available, they have little effect on preventing and curing epilepsy, and their side effects sometimes lead to serious morbidity. Therefore, prophylactic agents with anticonvulsant properties and no adverse effects need to be identified. Recent studies on probiotic administration have reported a variety of beneficial effects on the central nervous system via the microbiota–gut–brain axis. In this study, we investigated the effects of the oral administration of Bifidobacterium breve strain A1 [MCC1274] (B. breve A1) on tonic–clonic seizure in a pentylenetetrazole (PTZ)-induced kindling mouse (KD mouse) model. We found that the oral administration of B. breve A1 every other day for 15 days significantly reduced the seizure score, which gradually increased with repetitive injections of PTZ in KD mice. The administration of B. breve A1, but not saline, to KD mice significantly increased the level of Akt Ser⁴⁷³ phosphorylation (p-Akt) in the hippocampus; this increase was maintained for a minimum of 24 h after PTZ administration. Treatment of B. breve A1-administered KD mice with the selective inhibitor of integrin-linked kinase (ILK) Cpd22 significantly increased the seizure score and blocked the antiepileptic effect of B. breve A1. Moreover, Cpd22 blocked the B. breve A1-induced increase in hippocampal p-Akt levels. These results suggest that the ILK-induced phosphorylation of Akt Ser⁴⁷³ in the hippocampus might be involved in the antiepileptic effect of B. breve A1. Full article

(1) Background: The Portfolio Diet, a dietary pattern of cholesterol-lowering foods, is also rich in low glycemic index (GI) foods. While strong evidence supports clinically meaningful reductions in cholesterol, evidence on the relationship between the Portfolio Diet and diabetes management is lacking. (2) Objective: To evaluate the relationship between the Portfolio Diet and glycated hemoglobin (HbA1c) as a determinant of glycemic control among adults living with type 2 diabetes mellitus (T2DM). (3) Methods: Patient-level data was pooled from two randomized dietary trials of low glycemic index interventions compared to high cereal fibre control diets in adults living with T2DM where HbA1c was collected (clinicaltrials.gov identifiers: NCT00438698, NCT00438698). Dietary exposure was assessed using weighed 7-day diet records. Adherence to the Portfolio Diet and its pillars (nuts and seeds, plant protein, viscous fibre, plant sterols, monounsaturated fatty acid [MUFA] oils) was determined using the validated clinical Portfolio Diet Score (c-PDS). Multiple linear regression was used to assess the association between change in the c-PDS and change in HbA1c over 6-months with covariate adjustments. (4) Results: A total of 267 participants, predominantly White (67%) and male (63%), were included, with a mean ± standard error age of 62 ± 0.5 years, baseline BMI of 30.2 ± 0.3 kg/m², HbA1c of 7.08 ± 0.03%, and a c-PDS of 4.1 ± 0.3 points out of 25. Change in the c-PDS was significantly associated with a change in HbA1c (β: −0.04% per point, 95% CI: −0.07, −0.02, p = 0.001). A 7.5-point (30%) increase in the c-PDS was associated with a 0.3% reduction in HbA1c. Of the individual pillars, a 1-point change in nut and seeds intake (β: −0.07%, 95% CI: −0.12, −0.02, p = 0.009) or in plant protein intake (β: −0.11%, 95% CI: −0.18, −0.03, p = 0.009) was associated with a change in HbA1c. Further analysis of plant protein intake revealed that an increase in dietary pulse intake, a particularly low-GI food, was significantly associated with a reduction in HbA1c (β: −0.24% per 1-cup points cooked pulses (226 g) or 2 c-PDS points, 95% CI: −0.45, −0.03, p = 0.028). (5) Conclusions: Among adults living with T2DM, the Portfolio Diet was associated with lower HbA1c over a 6-month period, predominantly driven by two pillars: nuts and seeds and plant protein, particularly dietary pulses. These data have implications for including the Portfolio Diet in dietary recommendations for glycemic control in T2DM. A trial demonstrating the direct causal effect of the Portfolio Diet in a diverse group is warranted. Full article

Background/Objectives: Wilms tumor (WT) is the most common form of pediatric renal tumor, accounting for over 90% of cases followed by hypernephroma. Some pediatric patients with WT (10%) experience relapse or metastasis and have poor survival rates. PD-L1 assists cancer cells in escaping damage from the immune system. P53 mutations are found in relapsed WT tumor samples. We hypothesized that testing circulating PD-1 and PD-L1 and P53 expression levels could offer a simple method to predict patient relapse and explore novel treatments for pediatric WTs and hypernephroma. Methods: Flow cytometric detection of cPD-1, cPD-L1, and P53 expression in relapsed and in-remission WT and hypernephroma before and after one year of chemotherapy was performed. Results: Our data shows increased levels of cPD-L1 in relapsed pediatric patients with WT or hypernephroma before and after chemotherapy. There were also slight and significant increases in cPD-1 levels in relapsed groups before chemotherapy. Additionally, we observed significant decreases in P53 expression after one year of chemotherapy in relapsed pediatric patients. Conclusions: Our study found that circulating PD-L1 can be used as a predictor marker for WT and hypernephroma relapse. In conclusion, these circulating markers can assist in monitoring relapse in WT and hypernephroma patients without the need for several biopsies. Full article

Glucocorticoids (GCs) are widely used for treating hematological malignancies despite their multiple adverse effects. The biological response to GCs relies on glucocorticoid receptor (GR) transrepression (TR) that mediates the anticancer effects and transactivation (TA) associated with the side effects. Selective GR agonists (SEGRAs) preferentially activating GR TR could offer greater benefits in cancer treatment. One of the well-characterized SEGRAs, 2-(4-acetoxyphenyl)-2-chloro-N-methylethylammonium-chloride (CpdA), exhibited anticancer activity; however, its translational potential is limited due to chemical instability. To overcome this limitation, we obtained CpdA derivatives, CpdA-01–CpdA-08, employing two synthetic strategies and studied their anti-tumor activity: 4-(1-hydroxy-2-(piperidin-1-yl)ethyl)phenol or CpdA-03 demonstrated superior GR affinity and stability compared to CpdA. In lymphoma Granta and leukemia CEM cell lines, CpdA-03 ligand exhibited typical SEGRA properties, inducing GR TR without triggering GR TA. CpdA-03 effects on cell viability, growth, and apoptosis were similar to the reference GR ligand, dexamethasone (Dex), and the source compound CpdA. In vivo testing of CpdA-03 activity against lymphoma on the transplantable P388 murine lymphoma model showed that CpdA-03 reduced tumor volume threefold, outperforming Dex and CpdA. In conclusion, in this work, we introduce a novel SEGRA CpdA-03 as a promising agent for lymphoma treatment with fewer side effects. Full article

Plasmodium vivax causes the largest malaria burden in Brazil, and chloroquine resistance poses a challenge to eliminating malaria by 2035. Illegal mining in the Roraima Yanomami Indigenous territory can lead to the introduction of resistant parasites. This study aimed to investigate mutations in the pvcrt-o and pvmdr-1 genes to determine their potential as predictors of P. vivax chloroquine-resistant phenotypes. Samples were collected in two health centers of Boa Vista. A questionnaire was completed, and blood was drawn from each patient. Then, DNA extraction, PCR, amplicon purification, and DNA sequencing were performed. After alignment with the Sal-1, the amplified fragment was analyzed. Patients infected with the mutant parasites were queried in the Surveillance Information System. Among the patients, 98% (157/164) of participants were from illegal mining areas. The pvcrt-o was sequenced in 151 samples, and the K10 insertion was identified in 13% of them. The pvmdr1 was sequenced in 80 samples, and the MYF haplotype (958M) was detected in 92% of them and the TYF was detected in 8%, while the MYL was absent. No cases of recrudescence, hospitalization, or death were found. Mutations in the pvcrt-o and pvmdr-1 genes have no potential to predict chloroquine resistance in P. vivax. Full article

Changes in physiological and biochemical parameters are crucial for the reproductive performance and health of perinatal ewes. This study investigated the temporal variations in feed intake, nutrient digestibility, serum parameters, and ruminal fermentation on days 21, 14, and 7 before lambing (Q21, Q14, and Q7) and days 3, 7, and 14 after lambing (H3, H7, and H14). The results showed that dry matter intake (DMI) and glucose (Glu) gradually decreased (p < 0.05) before lambing and increased (p < 0.05) after lambing. The digestibility of dry matter (DMD), crude protein (CPD), and acid detergent fiber (ADFD) increased (p < 0.05) before lambing, then decreased (p < 0.05) on day H3, and then increased (p < 0.05) on day H14. The rumen pH, NH₃-N, and triglycerides (TG) gradually increased (p < 0.05) before lambing and were higher (p < 0.05) on day Q7 than after lambing. The concentrations of acetate, butyrate, and total volatile fatty acids (T-VFA) were lower (p < 0.05) on day Q7 than those on days Q21 and Q14, then increased (p < 0.05) after lambing. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) concentrations gradually decreased (p < 0.05) in perinatal ewes. BHBA and NEFA concentrations were lower (p < 0.05) on day Q21 than those from days Q14 to H14. The rumen microbiota compositions were different (p < 0.05) in perinatal ewes, and g_Anaerovibrio, g_Lachnobacterium, and g_Schwartzia were positively correlated (p < 0.05) with DMI, Glu, acetate, propionate, and T-VFA, and negatively correlated (p < 0.05) with LDL-C. g_Bacillus was negatively correlated (p < 0.05) with DMI, Glu, acetate, propionate, butyrate, and T-VFA, but positively correlated (p < 0.05) with rumen pH and LDL-C. In summary, the DMI, nutrient digestibility, rumen fermentation, and serum parameters changed during the perinatal period of ewes, and the changes in DMI, serum glucose, acetate, propionate, and T-VFA were related to the rumen bacteria. Full article

Introduction: Complicated perianal disease (cPD) may be the sole presentation of Crohn’s disease (CD). The role of small-bowel capsule endoscopy (SBCE) in the diagnostic algorithm of cPD is unclear. We aimed to evaluate the role of SBCE as a diagnostic tool, in patients with cPD, after a negative standard workup for CD. Methods: A multicenter, retrospective, cross-sectional study, in patients with cPD, and negative standard workup for CD (ileocolonoscopy and cross-sectional imaging), who underwent SBCE for suspected CD. Demographics, biomarkers, and the Lewis Score (LS) were recorded and analyzed. An LS ≥ 135 was considered a positive SBCE for diagnosing CD. Results: Ninety-one patients were included: 65 (71.4%) males; median age: 37 (29–51) years; cPD duration: 25.1 (12.5–66.1) months. Positive SBCE: 24/91 (26.4%) patients. Fecal calprotectin (FC) positively correlated with LS (r = 0.81; p < 0.001). FC levels of 100 µg/g and 50 µg/g had a sensitivity of only 40% and 55% to rule out small-bowel CD, with a negative predictive value (NPV) of only 76% and 80%, respectively. Conclusions: SBCE contributed to CD diagnosis in a quarter of patients with cPD after a negative standard workup. FC levels correlated with the degree of inflammation defined by the LS. However, the NPV of FC was low, suggesting that SBCE should be considered for patients with cPD even after a negative standard workup. Full article

Elucidation of pathways regulating parasite cell death is believed to contribute to identification of novel therapeutic targets for protozoan diseases, and in this context, apoptosis-like cell death has been reported in different groups of protozoa, in which metacaspases seem to play a role. In the genus Plasmodium, apoptotic markers have been detected in P. falciparum and P. berghei, and no study focusing on P. vivax cell death has been reported so far. In the present study, we investigated the susceptibility of P. vivax to undergo apoptotic cell death after incubating mature trophozoites with the classical apoptosis inducer staurosporine. As assessed by flow cytometry assays, staurosporine inhibited parasite intraerythrocytic development, which was accompanied by a decrease in cell viability, evidenced by reduced plasmodial mitochondrial activity. However, typical signs of apoptosis, such as DNA fragmentation, chromatin condensation, and nuclear segregation, were not detected in the parasites induced to cell death, and no significant alteration in metacaspase gene expression (PvMCA1) was observed under cell death stimulus. Interestingly, dying parasites positively modulated cell death (eryptosis) of host erythrocytes, which was marked by externalization of phosphatidylserine and cell shrinkage. Our study shows for the time that P. vivax blood stages may not be susceptible to apoptosis-like processes, while they could trigger eryptosis of parasitized cells by undergoing cell death. Further studies are required to elucidate the cellular machinery involved in cell death of P. vivax parasites as well as in the modulation of host cell death. Full article

The emergence of drug-resistance-inducing mutations in Hepatitis C virus (HCV) coupled with genotypic heterogeneity has made targeting NS3/4A serine protease difficult. In this work, we investigated the mutagenic variations in the binding pocket of Genotype 3 (G3) HCV NS3/4A and evaluated ligands for efficacious inhibition. We report mutations at 14 positions within the ligand-binding residues of HCV NS3/4A, including H57R and S139P within the catalytic triad. We then modelled each mutational variant for pharmacophore-based virtual screening (PBVS) followed by covalent docking towards identifying a potential covalent inhibitor, i.e., cpd-217. The binding stability of cpd-217 was then supported by molecular dynamic simulation followed by MM/GBSA binding free energy calculation. The free energy decomposition analysis indicated that the resistant mutants alter the HCV NS3/4A–ligand interaction, resulting in unbalanced energy distribution within the binding site, leading to drug resistance. Cpd-217 was identified as interacting with all NS3/4A G3 variants with significant covalent docking scores. In conclusion, cpd-217 emerges as a potential inhibitor of HCV NS3/4A G3 variants that warrants further in vitro and in vivo studies. This study provides a theoretical foundation for drug design and development targeting HCV G3 NS3/4A. Full article

In order to develop new feed resources, the aim of this study was to investigate the effects of moisture content, additives, and their interactions on the fermentation quality, aerobic stability, and in vitro digestibility of mixed silage of amaranth and cornmeal. The mass ratios of amaranth and cornmeal were 69:31, 76:24, and 84:16 for adjusting the moisture content of silage to 60% (W1), 65% (W2), and 70% (W3), respectively. The silage treatments included no additives (U), the addition of Lactobacillus plantarum (L), the addition of cellulase (E), and the addition of Lactobacillus plantarum + cellulase (M) mixed reagents. The results revealed that the pH and ammonia nitrogen (NH₃-N/TN) ratios were significantly lower in W1 than in W2 and W3 (3.66,19.3 g kg⁻¹ TN vs. 3.70, 3.70, 20.0 kg⁻¹ TN, 25.1 kg⁻¹ TN, p < 0.05). Moreover, dry matter (DM), organic matter (OM), in vitro dry matter digestibility (ivDMD), in vitro organic matter digestibility (ivOMD), and in vitro crude protein digestibility (ivCPD) significantly increased (p < 0.05). Meanwhile, the aerobic stability of mixed silage containing amaranth and cornmeal decreased with increasing water content. The aerobic stability of the L, E, and M treatment groups was improved by 15, 105, and 111 h, respectively, compared with that of the control group at W1. The pH and NH₃-N/TN ratios were lower with the addition of E (E and M) than with the absence of E (U and L) (3.73, 20.1 g kg⁻¹ DM vs. 3.64, 22.9 g kg⁻¹ DM, p < 0.05). NDF and ADF were significantly lower with the addition of E than without the addition of E (598 g kg⁻¹ DM, 145 g kg⁻¹ DM vs. 632 g kg⁻¹ DM, 160 g kg⁻¹ DM, p < 0.05). However, CP, ivDMD, ivOMD, and ivCPD were significantly higher (p < 0.05). AA and NH₃-N/TN were significantly lower (p < 0.05) with the addition of L (L and M) than without the addition of L (U and E). In conclusion, the best fermentation quality, in vitro digestibility, and aerobic stability of amaranth and cornmeal mixed silage treated with Lactobacillus plantarum + cellulase (M) were achieved at 60% water content. The present study confirmed the potential of amaranth as silage and its potential application for improving feed quality and animal performance. Full article

The SARS-CoV-2 helicase, non-structural protein 13 (Nsp13), plays an essential role in viral replication, translocating in the 5′ → 3′ direction as it unwinds double-stranded RNA/DNA. We investigated the impact of structurally distinct DNA lesions on DNA unwinding catalyzed by Nsp13. The selected lesions include two benzo[a]pyrene (B[a]P)-derived dG adducts, the UV-induced cyclobutane pyrimidine dimer (CPD), and the pyrimidine (6–4) pyrimidone (6–4PP) photolesion. The experimentally observed unwinding rate constants (k_obs) and processivities (P) were examined. Relative to undamaged DNA, the k_obs values were diminished by factors of up to ~15 for B[a]P adducts but only by factors of ~2–5 for photolesions. A minor-groove-oriented B[a]P adduct showed the smallest impact on P, which decreased by ~11% compared to unmodified DNA, while an intercalated one reduced P by ~67%. However, the photolesions showed a greater impact on the processivities; notably, the CPD, with the highest k_obs value, exhibited the lowest P, which was reduced by ~90%. Our findings thus show that DNA unwinding efficiencies are lesion-dependent and most strongly inhibited by the CPD, leading to the conclusion that processivity is a better measure of DNA lesions’ inhibitory effects than unwinding rate constants. Full article