Teaching chemistry without access to a traditional laboratory space is an ongoing challenge that has become especially relevant because of the SARS-CoV-2 pandemic. While several remote learning ...options exist for covering general chemistry concepts (including kitchen-based experiments, online modules, and virtual reality), few options provide opportunities for hands-on learning about the chemistry of synthetic polymer materials. Here, we offer remote learning modules that use household adhesives as a platform for teaching polymer chemistry outside of the laboratory. These modules are designed for students who have taken at least one semester of organic chemistry and have varied hands-on time commitments, ranging from 2 to 10 total hours each. Concepts covered include polymer synthesis, intermolecular interactions, thermomechanical properties, structure–function relationships, and molecular design. The experiments described in these modules also give students a chance to practice research-relevant skills such as searching for primary literature sources, fabricating test samples, explaining unexpected experimental results, and revising experimental procedures to improve methodologies. Ultimately, these modules provide educators with an additional tool for teaching experimental chemistry outside of the laboratory.
An abstract of an article that assesses and compares physician order forms for appropriateness to geriatric hospice care by C. Chau et al is presented. Preprinted hospice orders are not sensitive to ...the needs of geriatric patients with advanced dementia or failure to thrive. Results support the need for systematic survey of geriatric sensitization in hospice care.
Background and purpose
Recent findings document a blunted humoral response to SARS‐CoV‐2 vaccination in patients on anti‐CD20 treatment. Although most patients develop a cellular response, it is ...still important to identify predictors of seroconversion to optimize vaccine responses.
Methods
We determined antibody responses after SARS‐CoV‐2 vaccination in a real‐world cohort of multiple sclerosis patients (n = 94) treated with anti‐CD20, mainly rituximab, with variable treatment duration (median = 2.9, range = 0.4–9.6 years) and time from last anti‐CD20 infusion to vaccination (median = 190, range = 60–1032 days).
Results
We find that presence of B cells and/or rituximab in blood predict seroconversion better than time since last infusion. Using multiple logistic regression, presence of >0.5% B cells increased probability of seroconversion with an odds ratio (OR) of 5.0 (95% confidence interval CI = 1.0–28.1, p = 0.055), whereas the corresponding OR for ≥6 months since last infusion was 1.45 (95% CI = 0.20–10.15, p = 0.705). In contrast, detectable rituximab levels were negatively associated with seroconversion (OR = 0.05, 95% CI = 0.002–0.392, p = 0.012). Furthermore, naïve and memory IgG+ B cells correlated with antibody levels. Although retreatment with rituximab at 4 weeks or more after booster depleted spike‐specific B cells, it did not noticeably affect the rate of decline in antibody titers. Interferon‐γ and/or interleukin‐13 T‐cell responses to the spike S1 domain were observed in most patients, but with no correlation to spike antibody levels.
Conclusions
These findings are relevant for providing individualized guidance to patients and planning of vaccination schemes, in turn optimizing benefit–risk with anti‐CD20.
A blunted humoral response to SARS‐CoV‐2 vaccination has been reported in patients on anti‐CD20 treatment; thus, it is important to identify predictors of seroconversion to optimize vaccine responses. In this study, B‐cell and plasma rituximab levels are shown to be better predictors of seroconversion than time between treatment dose and vaccination.
Antimicrobial (AM) resistance is largely acknowledged as one of the biggest global health and food safety challenges and the overuse of AMs is known to generate resistance in bacteria that may affect ...both animals and humans. Poultry meat is the second most-produced meat in the European Union and in recent years consumers are becoming more concerned about food safety, traceability, and animal welfare in poultry rearing system, increasingly requiring meats from broilers reared without AMs. In the present study, we performed RNA sequencing to analyze 64 liver and 54 muscle transcriptomic profiles in broilers reared without treatment or treated with different classes of AMs. Moreover, we validated the most differentially expressed genes among the treated groups to detect putative novel biomarkers able to discriminate meats of broilers reared without AMs. The PDK4, IGFBP1, and RHOB genes were identified as putative novel hepatic biomarkers, discriminating broilers treated with AMs compared to broilers reared without treatments. The whole transcriptome changes revealed the liver as a valuable target organ for AM administration screening. In addition, our results suggest a leading effect of the coccidiostat when associated with AMs, influencing several biological processes. Our study showed that RNA sequencing is a powerful and valuable method to detect aberrant regulated genes and to identify biomarker candidates for AM misuse detection in farm animals. Further validation on larger sample size and a wider spectrum of AMs are needed to confirm the viability of the aforementioned biomarkers in poultry population.
The action of glucocorticoids on target tissues is regulated by the glucocorticoid and mineralocorticoid receptors (codified by the NR3C1 and NR3C2 gene, respectively). Moreover, the prereceptor ...system, represented by the hydroxysteroid 11-beta dehydrogenases (HSD11Bs), catalyzes the interconversion from active glucocorticoids into inactive compounds. This study aimed to determine whether the expression of the prereceptor system, the corticosteroid receptors, and the molecules regulating their intracellular trafficking (FKBP prolyl isomerase 4 and FKBP prolyl isomerase 5) could be regulated in the hypothalamic-pituitary-adrenal axis and in different type of adipose tissue of calves by the administration of dexamethasone in combination with estradiol or prednisolone. Research about the glucocorticoid effects on bovine target tissues may allow development of new diagnostic methods that use potential molecular biomarkers of glucocorticoid treatment. The administration of dexamethasone in combination with estradiol increased the gene expression of HSD11B1 (P < 0.01), HSD11B2 (P < 0.05), NR3C1 (P < 0.01), and NR3C2 (P < 0.01) in the adrenal glands; NR3C2 in the intramuscular adipose tissue (P < 0.01), and HSD11B1 in the subcutaneous adipose tissue (P < 0.01). Prednisolone administration increased the gene expression of HSD11B1 (P < 0.01), NR3C1 (P < 0.05), and NR3C2 (P < 0.05) in the adrenal glands and HSD11B1 (P < 0.01) in the subcutaneous adipose tissue. Interestingly, most of the examined tissues/organs showed a significant variation of FKBP5 gene expression after the administration of dexamethasone in combination with estradiol. So, these changes suggest that the FKBP5 gene expression could be a possible biomarker of the illegal dexamethasone administration in calves.
•Glucocorticoid decrease the FKBP5 gene expression in the adipose tissue.•The response to glucocorticoids administration appears to be organ/tissue specific.•FKBP5 gene expression is used as an indirect biomarker of glucocorticoids treatment in calves.
B cell-depleting therapies are highly effective in relapsing-remitting multiple sclerosis (RRMS) but are associated with increased infection risk and blunted humoral vaccination responses. Extension ...of dosing intervals may mitigate such negative effects, but its consequences on MS disease activity are yet to be ascertained. The objective of this study was to determine clinical and neuroradiologic disease activity, as well as B-cell repopulation dynamics, after implementation of extended rituximab dosing in RRMS.
We conducted a prospective observational study in a specialized-care, single-center setting, including patients with RRMS participating in the COMBAT-MS and MultipleMS observational drug trials, who had received at least 2 courses of rituximab (median follow-up 4.2 years, range 0.1-8.9 years). Using Cox regression, hazard ratios (HRs) of clinical relapse and/or contrast-enhancing lesions on MRI were calculated in relation to time since last dose of rituximab.
A total of 3,904 dose intervals were accumulated in 718 patients and stratified into 4 intervals: <8, ≥8 to 12, ≥12 to 18, and ≥18 months. We identified 24 relapses of which 20 occurred within 8 months since previous infusion and 4 with intervals over 8 months. HRs for relapse when comparing ≥8 to 12, ≥12 to 18, and ≥18 months with <8 months since last dose were 0.28 (95% CI 0.04-2.10), 0.38 (95% CI 0.05-2.94), and 0.89 (95% CI 0.20-4.04), respectively, and thus nonsignificant. Neuroradiologic outcomes mirrored relapse rates. Dynamics of total B-cell reconstitution varied considerably, but median total B-cell counts reached lower level of normal after 12 months and median memory B-cell counts after 16 months.
In this prospective cohort of rituximab-treated patients with RRMS exposed to extended dosing intervals, we could not detect a relation between clinical or neuroradiologic disease activity and time since last infusion. Total B- and memory B-cell repopulation kinetics varied considerably. These findings, relevant for assessing risk-mitigation strategies with anti-CD20 therapies in RRMS, suggest that relapse risk remains low with extended infusion intervals. Further studies are needed to investigate the relation between B-cell repopulation dynamics and adverse event risks associated with B-cell depletion.
Evidence of the effects of the built environment on children has mainly focused on disease outcomes; however, quality of life (QoL) has gained increasing attention as an important health and policy ...endpoint itself. Research on built environment effects on children's QoL could inform public health programs and urban planning and design.
We aimed to review and synthesize the evidence of the relationship between built environment features and children's QoL.
Five research databases were searched for quantitative peer-reviewed studies on children between 2 and 18 years, published in English or German between January 2010 and August 2023. Only primary research was considered. Included studies (n = 17) were coded and methodologically assessed with the Joanna Briggs Critical Appraisal Checklists, and relevant data were extracted, analyzed, and synthesized, using the following built environment framework: (1) neighborhood green and blue space, (2) neighborhood infrastructure, and (3) neighborhood perception.
Green space was positively associated with children's QoL. Infrastructure yielded inconclusive results across all measured aspects. Overall neighborhood satisfaction was positively correlated with higher QoL but results on perceived environmental safety were mixed.
Most studies are correlational, making it difficult to infer causality. While the positive findings of green space on QoL are consistent, specific features of the built environment show inconsistent results. Overall perception of the built environment, such as neighborhood satisfaction, also shows more robust results compared to perceptions of specific features of the built environment. Due to the heterogeneity of both built environment and QoL measures, consistent measures of both concepts will help advance this area of research.
The aim of this work was to study the transcriptional effects of glucocorticoids on corticosteroid hormone receptors, prereceptors (11β-hydroxysteroid dehydrogenase 1 and 2, 11β-HSD1 and 2), and ...chaperones molecules regulating intracellular trafficking of the receptors (FKBP51 and FKBP52) in thymus of veal calves. Moreover, the expression of FKBP51 and FKBP52 gene were investigated in beef cattle thymus. In the cervical thymus of veal calves, dexamethasone administration in combination with estradiol decreased FKBP51 expression (P < 0.01). The same treatment increased mineralocorticoid receptor (MR) (P < 0.01) and 11β-HSD1 expression (P < 0.05) compared to control group in the cervical thymus of veal calves. The thoracic thymus of veal calves treated with dexamethasone and estradiol showed a decrease of FKBP51 (P < 0.05), FKBP52 (P < 0.05), glucocorticoid receptor (P < 0.05), and MR expression (P < 0.05) compared to control group in the thoracic thymus of veal calves. The gene expression of FKBP51 decreased both in cervical (P < 0.01) and thoracic thymus (P < 0.01) of beef cattle treated with dexamethasone and estradiol. In addition, also prednisolone administration reduced FKBP51 expression in the cervical thymus (P < 0.01) and in the thoracic thymus of beef cattle (P < 0.01). The gene expression of FKBP52 increased only in the cervical thymus following dexamethasone administration (P < 0.01). The decrease of FKBP51 gene expression in thymus could be a possible biomarker of illicit dexamethasone administration in bovine husbandry. Moreover, so far, an effective biomarker of prednisolone administration is not identified. In this context, the decrease of FKBP51 gene expression in thymus of beef cattle following prednisolone administration could play an important role in the indirect identification of animals illegally treated with prednisolone.
•Glucocorticoids induce a decrease of the FKBP51 messenger RNA levels in the thymus.•New valid marker to detect the illicit glucocorticoid abuse in bovine husbandry.•FKBP51 expression may be employed as a novel diagnostic screening tool.
Nurse-directed pain protocols for intranasal fentanyl administration are not widely implemented in European (EU) pediatric emergency departments (PED). Barriers include perceived safety concerns for ...intranasal (IN) fentanyl. The aim of this study is to describe our experience with a nurse-directed triage IN fentanyl protocol with a focus on safety in a tertiary EU PED.
We conducted a retrospective analysis of patient records of children aged 0-16 years who received nurse-directed IN fentanyl between January 2019 and December 2021 at the PED of the University Children's Hospital of Bern, Switzerland. Extracted data points included demographics, presenting complaint, pain score, IN fentanyl dosage, concomitant pain medication use, and adverse events.
A total of 314 patients were identified with ages ranging from 9 months to 15 years. The main indication for nurse-directed fentanyl administration was musculoskeletal pain due to trauma (
= 284, 90%). Mild adverse events (vertigo) were reported in two patients (0.6%), without a correlation to concomitant pain medication or protocol violation. The only reported severe adverse event of syncope and hypoxia in a 14-year-old adolescent occurred in a setting where the institutional nurse-directed protocol was violated.
In accordance with previous studies outside of Europe, our data support the case that when appropriately used, nurse-directed IN fentanyl is a safe potent opioid analgesic for pediatric acute pain management. We strongly encourage the introduction of nurse-directed triage fentanyl protocols Europe-wide in order to provide effective and adequate acute pain management in children.
Background
Neurofilament light (NfL) levels reflect inflammatory disease activity in multiple sclerosis (MS), but it is less clear if NfL also can serve as a biomarker for MS progression in treated ...patients without relapses and focal lesion accrual. In addition, it has not been well established if clinically effective treatment re‐establishes an age and sex pattern for cerebrospinal fluid NfL (cNfL) as seen in controls, and to what degree levels are affected by disability level and magnetic resonance imaging (MRI) atrophy metrics.
Methods
We included subjects for whom cNfL levels had been determined as per clinical routine or in clinical research, classified as healthy controls (HCs, n = 89), MS‐free disease controls (DCs, n = 251), untreated MS patients (uMS; n = 296), relapse‐free treated MS patients (tMS; n = 78), and ProTEct‐MS clinical trial participants (pMS; n = 41).
Results
Using linear regression, we found a positive association between cNfL and age, as well as lower concentrations among women, in all groups, except for uMS patients. In contrast, disability level in the entire MS cohort, or T1 and T2 lesion volumes, brain parenchymal fraction, thalamic fraction, and cortical thickness in the pMS trial cohort, did not correlate with cNfL concentrations. Furthermore, the cNfL levels in tMS and pMS groups did not differ.
Conclusions
In participants with MS lacking signs of inflammatory disease activity, disease modulatory therapy reinstates an age and sex cNfL pattern similar to that of control subjects. No significant association was found between cNfL levels and clinical worsening, disability level, or MRI metrics.
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