Tag: pubmed

J Am Chem Soc. 2024 Mar 13. doi: 10.1021/jacs.4c00374. Online ahead of print.

ABSTRACT

Methods to access chiral sulfur(VI) pharmacophores are of interest in medicinal and synthetic chemistry. We report the desymmetrization of unprotected sulfonimidamides via asymmetric acylation with a cinchona-phosphinate catalyst. The desired products are formed in excellent yield and enantioselectivity with no observed bis-acylation. A data-science-driven approach to substrate scope evaluation was coupled to high throughput experimentation (HTE) to facilitate statistical modeling in order to inform mechanistic studies. Reaction kinetics, catalyst structural studies, and density functional theory (DFT) transition state analysis elucidated the turnover-limiting step to be the collapse of the tetrahedral intermediate and provided key insights into the catalyst-substrate structure-activity relationships responsible for the origin of the enantioselectivity. This study offers a reliable method for accessing enantioenriched sulfonimidamides to propel their application as pharmacophores and serves as an example of the mechanistic insight that can be gleaned from integrating data science and traditional physical organic techniques.

PMID:38480482 | DOI:10.1021/jacs.4c00374

Res Synth Methods. 2024 Mar 13:e1713. doi: 10.1002/jrsm.1713. Online ahead of print.

ABSTRACT

Meta-analysis is a useful tool in clinical research, as it combines the results of multiple clinical studies to improve precision when answering a particular scientific question. While there has been a substantial increase in publications using meta-analysis in various clinical research topics, the number of published meta-analyses in metabolomics is significantly lower compared to other omics disciplines. Metabolomics is the study of small chemical compounds in living organisms, which provides important insights into an organism’s phenotype. However, the wide variety of compounds and the different experimental methods used in metabolomics make it challenging to perform a thorough meta-analysis. Additionally, there is a lack of consensus on reporting statistical estimates, and the high number of compound naming synonyms further complicates the process. Easy-Amanida is a new tool that combines two R packages, “amanida” and “webchem”, to enable meta-analysis of aggregate statistical data, like p-value and fold-change, while ensuring the compounds naming harmonization. The Easy-Amanida app is implemented in Shiny, an R package add-on for interactive web apps, and provides a workflow to optimize the naming combination. This article describes all the steps to perform the meta-analysis using Easy-Amanida, including an illustrative example for interpreting the results. The use of aggregate statistics metrics extends the use of Easy-Amanida beyond the metabolomics field.

PMID:38480474 | DOI:10.1002/jrsm.1713

Proc Inst Mech Eng H. 2024 Mar 13:9544119241232286. doi: 10.1177/09544119241232286. Online ahead of print.

ABSTRACT

In vitro studies investigating the effect of high physiological compressive loads on the intervertebral disc mechanics as well as on its recovery are rare. Moreover, the osmolarity effect on the disc viscoelastic behavior following an overloading is far from being studied. This study aims to determine whether a compressive loading-unloading cycle exceeding physiological limits could be detrimental to the cervical disc, and to examine the chemo-mechanical dependence of this overloading effect. Cervical functional spine units were subjected to a compressive loading-unloading cycle at a high physiological level (displacement of 2.5 mm). The overloading effect on the disc viscoelastic behavior was evaluated through two relaxation tests conducted before and after cyclic loading. Afterward, the disc was unloaded in a saline bath during a rest period, and its recovery response was assessed by a third relaxation test. The chemo-mechanical coupling in the disc response was further examined by repeating this protocol with three different saline concentrations in the external fluid bath. It was found that overloading significantly alters the disc viscoelastic response, with changes statistically dependent on osmolarity conditions. The applied hyper-physiological compressive cycle does not cause damage since the disc recovers its original viscoelastic behavior following a rest period. Osmotic loading only influences the loading-unloading response; specifically, increasing fluid osmolarity leads to a decrease in disc relaxation after the applied cycle. However, the disc recovery is not impacted by the osmolarity of the external fluid.

PMID:38480472 | DOI:10.1177/09544119241232286

Eur Urol. 2024 Mar 12:S0302-2838(24)02140-7. doi: 10.1016/j.eururo.2024.01.033. Online ahead of print.

NO ABSTRACT

PMID:38480110 | DOI:10.1016/j.eururo.2024.01.033

Vaccine. 2024 Mar 12:S0264-410X(24)00259-7. doi: 10.1016/j.vaccine.2024.02.083. Online ahead of print.

ABSTRACT

BACKGROUND: Following the global mpox outbreak in 2022, multiple regions in Asia have been reporting ongoing mpox cases within high-risk groups, including gay, bisexual, and other men who have sex with men (GBMSM). An optimal level of vaccination rate is essential to prevent further mpox outbreaks. However, no existing studies have examined mpox vaccine uptake among GBMSM in East Asia.

METHODS: A cross-sectional survey was conducted among a sample of 531 GBMSM in Hong Kong, China, between March and October 2023. The study used multivariable logistic regression models to investigate the associations between mpox-related disease perceptions, exposures to sources and contents of mpox-related information, and mpox vaccine uptake.

RESULTS: The prevalence of mpox vaccine uptake among GBMSM in Hong Kong was 21.7%, with 7.7% completing one dose and 13.9% completing two doses. GBMSM who were younger or earning less monthly income were less likely to have been vaccinated. After adjusting for confounding variables, participants who perceived more negative impacts on their lives if they were to contract mpox, more severe symptoms, and a more coherent understanding of mpox were positively associated with mpox vaccine uptake. In addition, more frequent exposure to information through the following sources: TV, newspaper, radio and posters, government websites, news websites or apps, other people’s social media, and communication over the phone or face-to-face was positively associated with mpox vaccine uptake. Finally, more frequent exposure to the following information contents: mpox statistics from other countries, the Hong Kong government’s responses to mpox cases, negative information about patients with mpox, and information on prevention and treatment of mpox were positively associated with mpox vaccine uptake.

CONCLUSIONS: This study provides timely and evidence-based implications to address health communication and messaging needs in promoting mpox vaccination among GBMSM in Hong Kong, relevant to regions with similar sociocultural contexts.

PMID:38480102 | DOI:10.1016/j.vaccine.2024.02.083

HPB (Oxford). 2024 Feb 13:S1365-182X(24)00027-3. doi: 10.1016/j.hpb.2024.02.008. Online ahead of print.

ABSTRACT

BACKGROUND: Optimisation of the future liver remnant (FLR) is crucial to outcomes of extended liver resections. This study aimed to assess the quality of the FLR before and after dual vein embolization (DVE) by quantitative multiparametric MRI.

METHODS: Of 100 patients with liver metastases recruited in a clinical trial (Precision1:NCT04597710), ten consecutive patients with insufficient FLR underwent quantitative multiparametric MRI pre- and post-DVE (right portal and hepatic vein). FLR volume, liver fibro-inflammation (corrected T1) scores and fat percentage (proton density fat fraction, PDFF) were determined. Patient metrics were compared by Wilcoxon signed-rank test and statistical analysis done using R software.

RESULTS: All patients underwent uncomplicated DVE with improvement in liver remnant health, median 37 days after DVE: cT1 scores reduced from median (interquartile range) 790 ms (753-833 ms) to 741 ms (708-760 ms) p = 0.014 [healthy range <795 ms], as did PDFF from 11% (4-21%), to 3% (2-12%) p = 0.017 [healthy range <5.6%]. There was a significant increase in median (interquartile range) FLR volume from 33% (30-37%)% to 49% (44-52%), p = 0.002.

CONCLUSION: This non-invasive and reproducible MRI technique showed improvement in volume and quality of the FLR after DVE. This is a significant advance in our understanding of how to prevent liver failure in patients undergoing major liver surgery.

PMID:38480098 | DOI:10.1016/j.hpb.2024.02.008

Pain Manag Nurs. 2024 Mar 12:S1524-9042(24)00019-5. doi: 10.1016/j.pmn.2024.02.009. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to investigate the effect of an educational intervention on cancer patients receiving palliative care and their caregivers concerning symptom management and family needs.

METHODS: This study involved 120 participants-60 cancer patients and their respective caregivers-divided into intervention and control groups. Over a 2-week period, the intervention group received a comprehensive educational program focusing on symptom management, while the control group did not receive any educational intervention. The Edmonton Symptom Assessment System (ESAS) and Palliative Performance Scale (PPS) were used to assess patients’ symptoms, their intensity, and performance, while the Family Need Scale (FNS) was utilized to evaluate caregivers’ needs. These assessments were conducted at the beginning and end of the study. Primary outcomes focused on symptom assessment using ESAS and PPS, along with evaluating caregivers’ needs through FNS. Secondary outcomes involved assessing participant satisfaction with the intervention.

RESULTS: At the end of the study, comparing initial and second evaluations, both ESAS and PPS scores significantly increased in the intervention and control groups (p = .003, p = .002, respectively). Additionally, a statistically significant decrease in the severity of symptoms, except for lethargy/hypokinesis, was observed in the intervention group compared to the control group. The FNS scale indicated that family needs satisfaction was higher in the intervention group compared to the control group. The data obtained demonstrated that there was a reduction the pain, fatigue, depression, anxiety, drowsiness, and shortness of breath levels in the intervention group compared to the control group, but there was no significant difference other than these symptoms.

CONCLUSIONS: The educational intervention positively impacted symptom management and family needs. Optimizing symptom control would greatly benefit palliative care patients and their caregivers.

PMID:38480085 | DOI:10.1016/j.pmn.2024.02.009

Curr Pharm Teach Learn. 2024 Mar 12:S1877-1297(24)00060-1. doi: 10.1016/j.cptl.2024.03.001. Online ahead of print.

ABSTRACT

OBJECTIVE: Adverse Childhood Experiences (ACEs) have demonstrated negative impact on physical, emotional, and cognitive health outcomes. This study aimed to assess prevalence of ACEs among Doctor of Pharmacy (PharmD) students, and their associations with mental health, substance use, academic performance, and sleep patterns.

METHODS: A cross-sectional survey was conducted on PharmD students at a private University. ACE scores, mental health history, substance use, academic performance, and sleep habits were self-reported. Descriptive statistics and chi-square tests were used for analysis.

RESULTS: From 54 participants across all cohorts of students in the curriculum (response rate: 19%), 48% reported ≥4 ACEs. A majority of students reported having been diagnosed with or sought treatment for depression (56%) or anxiety (67%), while 42.9% reported a history of contemplating suicide. Participants with ACE scores of ≥4 were more likely to have sought treatment for depression, any mental health condition, contemplated suicide, or used alcohol for mental health purposes. No differences in academic performance based on ACE scores were found.

CONCLUSION: High numbers of ACEs were common and linked to mental illness, suicidality, and use of alcohol for mental health purposes. While no direct academic impact was found in this small sample size, adopting a trauma-informed approach is crucial to supporting student well-being. Further research in this area is needed to optimize interventions to support academic and professional success among students with ≥4 ACEs.

PMID:38480066 | DOI:10.1016/j.cptl.2024.03.001

Am J Surg. 2024 Mar 5:S0002-9610(24)00167-3. doi: 10.1016/j.amjsurg.2024.03.007. Online ahead of print.

ABSTRACT

BACKGROUND: We aimed to investigate the prevalence, characteristics, and management of nephrolithiasis in primary hyperparathyroidism (PHPT) patients.

METHODS: Medical records of patients who underwent parathyroidectomy at a tertiary care hospital in British Columbia from January 2016 to April 2023 were retrospectively reviewed. Demographic data, laboratory results, imaging reports, and urologic consultations were examined. Descriptive statistics and relevant statistical tests, including logistic regressions, were utilized for data analysis.

RESULT: Of the 413 PHPT patients included in the study population, 41.9% harbored renal stones, and nearly half (48.6%) required urological interventions. Male sex, elevated preoperative serum ionized calcium (iCa) and 24-h urinary calcium (24 ​h urine Ca) levels were independent risk factors for stone formation. Additionally, male sex, younger age, and lower preoperative serum 25-hydroxyvitamin D (25(OH)D) level were associated with higher odds of requiring urological intervention for stones.

CONCLUSIONS: This study identified significant prevalence of asymptomatic renal calcifications in PHPT patients, with a substantial proportion necessitating urological intervention. These findings emphasize the importance of incorporating screening and treatment of renal stones into the management of PHPT patients.

PMID:38480062 | DOI:10.1016/j.amjsurg.2024.03.007

Curr Probl Diagn Radiol. 2024 Mar 7:S0363-0188(24)00048-3. doi: 10.1067/j.cpradiol.2024.03.005. Online ahead of print.

ABSTRACT

OBJECTIVE: Adhesive capsulitis (AC) has traditionally been a clinical diagnosis characterized by progressive shoulder pain and decreased range of motion. Our aim is to examine the role of shoulder MRI in making the diagnosis of AC, and to identify the frequency of cases where MRI was the primary method in diagnosing AC amongst medical providers.

METHODS: This was an anonymized retrospective analysis. Patients with positive MRI features suggestive for AC from 2015 to 2018 were included. Pre and post MRI clinical notes were assessed in order to ascertain the clinical suspicion of AC. A total of 117 cases were included for this study.

RESULTS: Our results demonstrated the number of patients whose management were influenced by shoulder MRI. When all of the imaging parameters by MRI are taken into account by aggregate, there is a statistically significant difference (p-value < 0.01) with regards to orthopedists having their working diagnosis of AC confirmed by the MRI results as compared to the primary care physicians.

CONCLUSION: This study supports the role of shoulder MRI in the evaluation of AC. Not only does shoulder MRI assist ordering clinicians with providing additional evidence to support a suspected diagnosis of AC, but also plays a primary role in making the diagnosis of AC in cases in which it was not initially suspected, ultimately impacting management.

PMID:38480061 | DOI:10.1067/j.cpradiol.2024.03.005