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Bile acids (BA) are among the most abundant metabolites produced by the gut microbiome. Primary BAs produced in the liver are converted by gut bacterial 7-α-dehydroxylation into secondary BAs, which can differentially regulate host health via signaling based on their varying affinity for BA receptors. Despite the importance of secondary BAs in host health, the regulation of 7-α-dehydroxylation and the role of diet in modulating this process is incompletely defined. Understanding this process could lead to dietary guidelines that beneficially shift BA metabolism. Dietary fiber regulates gut microbial composition and metabolite production. We tested the hypothesis that feeding mice a diet rich in a fermentable dietary fiber, resistant starch (RS), would alter gut bacterial BA metabolism. Male and female wild-type mice were fed a diet supplemented with RS or an isocaloric control diet (IC). Metabolic parameters were similar between groups. RS supplementation increased gut luminal deoxycholic acid (DCA) abundance. However, gut luminal cholic acid (CA) abundance, the substrate for 7-α-dehydroxylation in DCA production, was unaltered by RS. Further, RS supplementation did not change the mRNA expression of hepatic BA producing enzymes or ileal BA transporters. Metagenomic assessment of gut bacterial composition revealed no change in the relative abundance of bacteria known to perform 7-α-dehydroxylation. P. ginsenosidimutans and P. multiformis were positively correlated with gut luminal DCA abundance and increased in response to RS supplementation. These data demonstrate that RS supplementation enriches gut luminal DCA abundance without increasing the relative abundance of bacteria known to perform 7-α-dehydroxylation.

Papiliotrema laurentii 5307AH was isolated from an aircraft polymer-coated surface. The genome size is 19,510,785 bp with a G + C content of 56%. The genome harbors genes encoding oxygenases, cutinases, lipases, and enzymes for styrene degradation, all of which could play a critical role in survival on xenobiotic surfaces.

Given the multitude of extracellular enzymes at their disposal, many of which are designed to degrade natures polymers (lignin, cutin, cellulose, etc.), fungi are adept at targeting synthetic polyesters with similar chemical composition. Microbial-influenced deterioration of xenobiotic polymeric surfaces is an area of interest for material scientists as these are important for the conservation of the underlying structural materials. Here, we describe the isolation and characterization of the Papiliotrema laurentii 5307AH (P. laurentii) cutinase, Plcut1. P. laurentii is basidiomycete yeast with the ability to disperse Impranil-DLN (Impranil), a colloidal polyester polyurethane, in agar plates. To test whether the fungal factor involved in this clearing was a secreted enzyme, we screened the ability of P. laurentii culture supernatants to disperse Impranil. Using size exclusion chromatography (SEC), we isolated fractions that contained Impranil-clearing activity. These fractions harbored a single ~22 kD band, which was excised and subjected to peptide sequencing. Homology searches using the peptide sequences identified, revealed that the protein Papla1 543643 (Plcut1) displays similarities to serine esterase and cutinase family of proteins. Biochemical assays using recombinant Plcut1 confirmed that this enzyme has the capability to hydrolyze Impranil, soluble esterase substrates, and apple cutin. Finally, we confirmed the presence of the Plcut1 in culture supernatants using a custom antibody that specifically recognizes this protein. The work shown here supports a major role for the Plcut1 in the fungal degradation of natural polyesters and xenobiotic polymer surfaces.IMPORTANCEFungi play a vital role in the execution of a broad range of biological processes that drive ecosystem function through production of a diverse arsenal of enzymes. However, the universal reactivity of these enzymes is a current problem for the built environment and the undesired degradation of polymeric materials in protective coatings. Here, we report the identification and characterization of a hydrolase from Papiliotrema laurentii 5307AH, an aircraft-derived fungal isolate found colonizing a biodeteriorated polymer-coated surface. We show that P. laurentii secretes a cutinase capable of hydrolyzing soluble esters as well as ester-based compounds forming solid surface coatings. These findings indicate that this fungus plays a significant role in biodeterioration through the production of a cutinase adept at degrading ester-based polymers, some of which form the backbone of protective surface coatings. The work shown here provides insights into the mechanisms employed by fungi to degrade xenobiotic polymers.

The design of protein-protein interfaces using physics-based design methods such as Rosetta requires substantial computational resources and manual refinement by expert structural biologists. Deep learning methods promise to simplify protein-protein interface design and enable its application to a wide variety of problems by researchers from various scientific disciplines. Here, we test the ability of a deep learning method for protein sequence design, ProteinMPNN, to design two-component tetrahedral protein nanomaterials and benchmark its performance against Rosetta. ProteinMPNN had a similar success rate to Rosetta, yielding 13 new experimentally confirmed assemblies, but required orders of magnitude less computation and no manual refinement. The interfaces designed by ProteinMPNN were substantially more polar than those designed by Rosetta, which facilitated in vitro assembly of the designed nanomaterials from independently purified components. Crystal structures of several of the assemblies confirmed the accuracy of the design method at high resolution. Our results showcase the potential of deep learning-based methods to unlock the widespread application of designed protein-protein interfaces and self-assembling protein nanomaterials in biotechnology.

Short-chain fatty acids (SCFAs) comprise the largest group of gut microbial fermentation products. While absorption of most nutrients occurs in the small intestine, indigestible dietary components, such as fiber, reach the colon and are processed by the gut microbiome to produce a wide array of metabolites that influence host physiology. Numerous studies have implicated SCFAs as key modulators of host health, such as in regulating irritable bowel syndrome (IBS). However, robust methods are still required for their detection and quantitation to meet the demands of biological studies probing the complex interplay of the gut-host-health paradigm. In this study, a sensitive, rapid-throughput, and readily expandible UHPLC-QqQ-MS platform using 2-PA derivatization was developed for the quantitation of gut-microbially derived SCFAs, related metabolites, and isotopically labeled homologues. The utility of this platform was then demonstrated by investigating the production of SCFAs in cecal contents from mice feeding studies, human fecal bioreactors, and fecal/bacterial fermentations of isotopically labeled dietary carbohydrates. Overall, the workflow proposed in this study serves as an invaluable tool for the rapidly expanding gut-microbiome and precision nutrition research field.

Abstract The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among DoD organizations and to facilitate resource, material and information sharing among consortium members, which includes collaborators in academia and industry. The 2023 annual symposium was a hybrid meeting held in Washington DC on 26–27 September 2023 concurrent with the virtual attendance, with oral and poster presentations and discussions centered on microbiome-related topics within five broad thematic areas: 1) Environmental Microbiome Characterization; 2) Microbiome Analysis; 3) Human Microbiome Characterization; 4) Microbiome Engineering; and 5) In Vitro and In Vivo Microbiome Models. Collectively, the symposium provided an update on the scope of current DoD and DoD-affiliated microbiome research efforts and fostered collaborative opportunities. This report summarizes the presentations and outcomes of the 7th annual TSMC symposium.

Introduction: This study compares online and in-person delivery of a weekly clinical reasoning seminar for fourth-year medical students at a Malaysian medical school. During the easing of COVID-19 pandemic restrictions, the initial eight seminars took place online, followed by eleven in-person seminars. This study looks at student preference for online or in-person delivery and how these reasons differ due to gender. Methods: An online questionnaire was sent to fourth-year medical students after returning to in-person seminars. The response rate was 60/128 (46.88%) and the data was analysed using SPSS software. Results: 65% of students preferred in-person seminars and a larger proportion of female students (71.43%) preferred in-person sessions compared to male students (50.00%), although this was not statistically significant (p=0.11). A significantly larger proportion of female students preferred in-person seminars for the following reasons compared to male students: enjoyment (p=0.041), developing history-taking skills (55.56%) and for formulating differential diagnoses (p=0.046). Students were asked whether online or in-person seminars were most appropriate for eighteen reasons, they felt in-person seminars were most appropriate for 16/18 of these reasons. Conclusions: More students preferred in-person clinical reasoning seminars and a higher proportion of these students were female. A significantly larger proportion of female students felt in-person seminars were better for; enjoyment and for developing history-taking skills and formulating differential diagnoses, compared to male students. The students preferred online seminars for home comforts and ease of travel, but they preferred in-person seminars for the other 16/18 reasons listed including all reasons linked to learning skills and interreacting with others.

Abstract Research into the disequilibrium of microglial phenotypes has become an area of intense focus in neurodegenerative disease as a potential mechanism that contributes to chronic neuroinflammation and neuronal loss in Parkinson’s disease (PD). There is growing evidence that neuroinflammation accompanies and may promote progression of alpha-synuclein (Asyn)-induced nigral dopaminergic (DA) degeneration. From a therapeutic perspective, development of immunomodulatory strategies that dampen overproduction of pro-inflammatory cytokines from chronically activated immune cells and induce a pro-phagocytic phenotype is expected to promote Asyn removal and protect vulnerable neurons. Cannabinoid receptor-2 (CB2) is highly expressed on activated microglia and peripheral immune cells, is upregulated in the substantia nigra of individuals with PD and in mouse models of nigral degeneration. Furthermore, modulation of CB2 protects against rotenone-induced nigral degeneration; however, CB2 has not been pharmacologically and selectively targeted in an Asyn model of PD. Here, we report that 7 weeks of peripheral administration of CB2 inverse agonist SMM-189 reduced phosphorylated (pSer129) Asyn in the substantia nigra compared to vehicle treatment. Additionally, SMM-189 delayed Asyn-induced immune cell infiltration into the brain as determined by flow cytometry, increased CD68 protein expression, and elevated wound-healing-immune-mediator gene expression. Additionally, peripheral immune cells increased wound-healing non-classical monocytes and decreased pro-inflammatory classical monocytes. In vitro analysis of RAW264.7 macrophages treated with lipopolysaccharide (LPS) and SMM-189 revealed increased phagocytosis as measured by the uptake of fluorescence of pHrodo E. coli bioparticles. Together, results suggest that targeting CB2 with SMM-189 skews immune cell function toward a phagocytic phenotype and reduces toxic aggregated species of Asyn. Our novel findings demonstrate that CB2 may be a target to modulate inflammatory and immune responses in proteinopathies.

Abstract Background In Ethiopia, 79 million people live in soil transmitted helminths endemic areas. The Ethiopia established a National goal to eradicate STH transmission by 2025. To meet that goal, it is imperative that data is acquired on community helminth infection risk. This study examined the prevalence of STH and risk factors for infection in vegetable farmers working on Akaki River Bank, Addis Ababa, Ethiopia. Methods A cross-sectional study was conducted between November 7, 2022, and June 2023. A stratified random sampling was used to select farming households. Two hundred and sixteen farmers were enrolled in the study. Data on socio-demographic, WASH, wastewater irrigation related factors were collected by trained data collectors using a structured questionnaire. Kato-Katz concentration was utilized to detect STH. The data were entered using EpiData 3.1 and analyzed with Stata 14.0, using p-values less than 0.05 to identify significant factors. Logistic regression was used to identify independent risk factors for infection. Results The prevalence of STH was 22.2% (95% CI = 13.6-27.9%), with Ascaris lumbricoides being the most common (11.1%), followed by hookworm (7.4%), and Trichuris trichiura (3.7%). Low income levels (AOR = 1.85, 95% CI = 1.25–5.99), lack of handwashing before eating (AOR = 2.25, 95% CI = 1.58 − 11.3), absence of fingernails cleanliness (AOR = 1.97, 95% CI = 1.74–39.5), not wearing shoes at work (AOR = 3.4, 95% CI = 2.98–82.2), touching the face with dirty hands (AOR = 2.9, 95% CI = 0.68–28.2), washing vegetables with irrigation wastewater (AOR = 2.1, 95% CI = 1.95–45.2), and not wearing protective clothing during farming activities (AOR = 2.99, 95% CI = 1.58 − 22.4) were the significant risk factors for infection with STH. Conclusion Of the farming communities examined in this study, one of the five was found to be infected with soil transmitted helminth. This research has shown clear risk factors for STH infection including: lack of personal hygiene practices, insufficient sanitation access, and limited use of protective equipment. To achieve the national goal, there is a need for farming communities to understand preventative risks of infection, improve WASH (Water access, sanitation and hygine) practices, WASH access, protective equipment, and health education.

Neuropilin-1 (Nrp1), a transmembrane protein expressed on CD4 + T cells, is mostly studied in the context of regulatory T cell (Treg) function. More recently, there is increasing evidence that Nrp1 is also highly expressed on activated effector T cells and that increases in these Nrp1-expressing CD4 + T cells correspond with immunopathology across several T cell-dependent disease models. Thus, Nrp1 may be implicated in the identification and function of immunopathologic T cells. Nrp1 downregulation in CD4 + T cells is one of the strongest transcriptional changes in response to immunoregulatory compounds that act though the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. To better understand the link between AhR and Nrp1 expression on CD4 + T cells, Nrp1 expression was assessed in vivo and in vitro following AhR ligand treatment. In the current study, we identified that the percentage of Nrp1 expressing CD4 + T cells increases over the course of activation and proliferation in vivo . The actively dividing Nrp1 + Foxp3 - cells express the classic effector phenotype of CD44 hi CD45RB lo , and the increase in Nrp1 + Foxp3 - cells is prevented by AhR activation. In contrast, Nrp1 expression is not modulated by AhR activation in non-proliferating CD4 + T cells. The downregulation of Nrp1 on CD4 + T cells was recapitulated in vitro in cells isolated from C57BL/6 and NOD (non-obese diabetic) mice. CD4 + Foxp3 - cells expressing CD25, stimulated with IL-2, or differentiated into Th1 cells, were particularly sensitive to AhR-mediated inhibition of Nrp1 upregulation. IL-2 was necessary for AhR-dependent downregulation of Nrp1 expression both in vitro and in vivo . Collectively, the data demonstrate that Nrp1 is a CD4 + T cell activation marker and that regulation of Nrp1 could be a previously undescribed mechanism by which AhR ligands modulate effector CD4 + T cell responses.

Abstract The development of Zambia has brought increased large-scale infrastructure construction that has necessitated the need for improved foundation techniques that are both economical and adequate in capacity. Clay and soft soils with low bearing capacities and high compressibility could render structural foundations to perform poorly and shorten the design life of the bridges and structures. This study used a bridge case study in Northern Province, Zambia to investigate the use of geosynthetic encased columns (GECs) to support the bridge embankments to reduce differential settlements. End bearing fully encased columns were compared to floating columns of varying lengths by numerical modelling in PLAXIS 3D. The Hardening Soil and Mohr–Coulomb soil models were used for the column surrounding soil and the GECs in the finite element analysis. The results showed that the end bearing columns had the least differential settlements at the soil surface, whilst the reduction in floating column length increased the punching settlements. Moreover, the shear stress along the interface of the GECs and surrounding soil varied from 20 kN/m2 to 142 kN/m2, where the end bearing GEC had the least shear stress.

Abstract Background Untreated or inadequately treated wastewater carrying human feces can host helminth eggs and larvae, contaminating the soil and plants that are irrigated with it. In Addis Ababa, farmers use untreated wastewater to grow vegetables; however, there are little data currently available published on vegetables' contribution to the prevalence of helminth among female farmers along the Akaki River, in Addis Ababa, Ethiopia. Methods A cross-sectional study was conducted in Addis Ababa City in February 2022. A stratified random sampling method was used to sample farming households. The sample size for each district was determined by a proportional allocation to the total number of households in the area. Two hundred and fifty-two composite vegetable samples and 101 farmers’ stool samples were collected and analyzed for helminth prevalence. Data on socio-demographics were collected by trained data collators using a structured questionnaire. Kato-Katz concentration was used to detect STH from a stool sample. Stata version 14.0 was used to process the data. Poisson regression was used to identify the association between STH prevalence in the vegetable and the farm's stool. Results Helminths were found in 67.5% of vegetables sampled and 20.8% of female farmers' stools. Ascaris lumbricoides eggs (vegetable 48.4% and stool 9.9%) were identified in all analyzed samples. Hookworm eggs (vegetable 13.1% and stool 8.9%) and Trichuris trichiura eggs (vegetable 5.9% and stool 2%) were also isolated. The total number of helminth eggs present in wastewater-irrigated vegetables and female farmers’ stool had a positive association (p

Background African American women bear a disproportionate burden of cardiovascular diseases, potentially due to altered central hemodynamics. Racism and sexism often lead to African American women taking on numerous caretaking roles and overall increases their use of the Strong Black Woman (ie, Superwoman) mindset, which may have negative health consequences. We hypothesized that endorsing the Superwoman role and its Obligation to Help Others dimension would be associated with a deleterious central hemodynamics profile in African American women. Methods and Results Using cross‐sectional data, we examined central systolic blood pressure (mm Hg; n=408), augmentation index (percentage, adjusted for height and heart rate; n=408), and pulse wave velocity (m/s; n=368) in African American women aged 30 to 46 years. The Giscombe Superwoman Schema (SWS) questionnaire assessed endorsement of Overall SWS (range, 0–105) and SWS–Obligation to Help Others (range, 0–3). Multiple linear regression modeled associations between Overall SWS (10‐unit increments) and SWS–Obligation to Help Others (1‐unit increments) and central hemodynamics while adjusting for pertinent sociodemographic, clinical, and psychosocial factors. In fully adjusted models, central systolic blood pressure was significantly associated with Overall SWS (β=0.83 [95% CI, 0.19–1.47]) and SWS–Obligation to Help Others (β=2.03 [95% CI, 0.39–3.67]). Augmentation index was associated with Overall SWS (β=0.66 [95% CI, 0.02–1.30]) and SWS–Obligation to Help Others (β=2.21 [95% CI, 0.58–3.84]). Significant associations were not observed between pulse wave velocity and SWS. Conclusions Greater endorsement of the Superwoman role and prioritizing caregiving over self‐care were associated with higher central systolic blood pressure and augmentation index, which may contribute to adverse cardiovascular health among African American women.

Abstract BackgroundThe COVID-19 pandemic highlighted the need for pathogen surveillance systems to augment both early warning and outbreak monitoring/control efforts. Community wastewater samples provide a rapid and accurate source of environmental surveillance data to complement direct patient sampling. Due to its global presence and critical missions, the US military is a leader in global pandemic preparedness efforts. Clinical testing for COVID-19 on US Air Force (USAF) bases (AFBs) was effective but costly with respect to direct monetary costs and indirect costs due to lost time. To remain operating at peak capacity, such bases sought a more passive surveillance option and piloted wastewater surveillance (WWS) at 17 AFBs to demonstrate feasibility, safety, utility, and cost-effectiveness from May 2021 to January 2022. ObjectiveWe model the costs of a wastewater program for pathogens of public health concern within the specific context of US military installations using assumptions based on the results of the USAF and Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense pilot program. The objective was to determine the cost of deploying WWS to all AFBs relative to clinical swab testing surveillance regimes. MethodsA WWS cost projection model was built based on subject matter expert input and actual costs incurred during the WWS pilot program at USAF AFBs. Several SARS-CoV-2 circulation scenarios were considered, and the costs of both WWS and clinical swab testing were projected. Analysis was conducted to determine the break-even point and how a reduction in swab testing could unlock funds to enable WWS to occur in parallel. ResultsOur model confirmed that WWS is complementary and highly cost-effective when compared to existing alternative forms of biosurveillance. We found that the cost of WWS was between US $10.5-$18.5 million less expensive annually in direct costs as compared to clinical swab testing surveillance. When the indirect cost of lost work was incorporated, including lost work associated with required clinical swab testing, we estimated that over two-thirds of clinical swab testing could be maintained with no additional costs upon implementation of WWS. ConclusionsOur results support the adoption of WWS across US military installations as part of a more comprehensive and early warning system that will enable adaptive monitoring during disease outbreaks in a more cost-effective manner than swab testing alone.

Telehealth services, specifically telemedicine audio-video and audio-only patient encounters, expanded dramatically during the COVID-19 pandemic through temporary waivers and flexibilities tied to the public health emergency. Early studies demonstrate significant potential to advance the quintuple aim (patient experience, health outcomes, cost, clinician well-being, and equity). Supported well, telemedicine can particularly improve patient satisfaction, health outcomes, and equity. Implemented poorly, telemedicine can facilitate unsafe care, worsen disparities, and waste resources. Without further action from lawmakers and agencies, payment will end for many telemedicine services currently used by millions of Americans at the end of 2024. Policymakers, health systems, clinicians, and educators must decide how to support, implement, and sustain telemedicine, and long-term studies and clinical practice guidelines are emerging to provide direction. In this position statement, we use clinical vignettes to review relevant literature and highlight where key actions are needed. These include areas where telemedicine must be expanded (e.g., to support chronic disease management) and where guidelines are needed (e.g., to prevent inequitable offering of telemedicine services and prevent unsafe or low-value care). We provide policy, clinical practice, and education recommendations for telemedicine on behalf of the Society of General Internal Medicine. Policy recommendations include ending geographic and site restrictions, expanding the definition of telemedicine to include audio-only services, establishing appropriate telemedicine service codes, and expanding broadband access to all Americans. Clinical practice recommendations include ensuring appropriate telemedicine use (for limited acute care situations or in conjunction with in-person services to extend longitudinal care relationships), that the choice of modality be done through patient-clinician shared decision-making, and that health systems design telemedicine services through community partnerships to ensure equitable implementation. Education recommendations include developing telemedicine-specific educational strategies for trainees that align with accreditation body competencies and providing educators with protected time and faculty development resources.

ABSTRACTBile acids (BA) are among the most abundant metabolites produced by the gut microbiome. Primary BAs produced in the liver are converted by gut bacterial 7-α-dehydroxylation into secondary BAs, which can differentially regulate host health via signaling based on their varying affinity for BA receptors. Despite the importance of secondary BAs in host health, the regulation of 7-α-dehydroxylation and the role of diet in modulating this process is incompletely defined. Understanding this process could lead to dietary guidelines that beneficially shift BA metabolism. Dietary fiber regulates gut microbial composition and metabolite production. We tested the hypothesis that feeding mice a diet rich in a fermentable dietary fiber, resistant starch (RS), would alter gut bacterial BA metabolism. Male and female wild-type mice were fed a diet supplemented with RS or an isocaloric control diet (IC). Metabolic parameters were similar between groups. RS supplementation increased gut luminal deoxycholic acid (DCA) abundance. However, gut luminal cholic acid (CA) abundance, the substrate for 7-α-dehydroxylation in DCA production, was unaltered by RS. Further, RS supplementation did not change the mRNA expression of hepatic BA producing enzymes or ileal BA transporters. Metagenomic assessment of gut bacterial composition revealed no change in the relative abundance of bacteria known to perform 7-α-dehydroxylation. P. ginsenosidimutans and P. multiformis were positively correlated with gut luminal DCA abundance and increased in response to RS supplementation. These data demonstrate that RS supplementation enriches gut luminal DCA abundance without increasing the relative abundance of bacteria known to perform 7-α-dehydroxylation.

Rationale & objectiveRecent studies evaluated and proposed new race-neutral, creatinine-based glomerular filtration rate (GFR) estimation equations. The performance of these equations in diverse potential living kidney donors requires study.Study designCross-sectional study.Setting & participants637 potential living kidney donors from one tertiary hospital with serum creatinine concentration measurement and GFR measurement by iohexol plasma clearance between October 2016 and December 2020.ExposureCreatinine-based estimation of GFR by Chronic Kidney Disease Epidemiology Collaboration (2009, CKDEPI09; 2021, CKDEPI21) and Modification of Diet in Renal Disease equations with and without inclusion of race coefficient, where applicable.OutcomesEquation bias, precision, accuracy, and accurate classification of GFR as equal to and above or below 80 mL/min/1.73 m2.Analytical approachGFR estimation equation performance compared to measured GFR (mGFR) by iohexol clearance.ResultsThe median bias of the CKDEPI21 equation underestimated mGFR by 2.8 mL/min/1.73 m2. The bias in the Black subgroup underestimated mGFR by 9.0 mL/min/1.73 m2. Compared to CKDEPI09 with and without race adjustment, the accuracy of CKDEPI21 increased across all subgroups. On average, 3.9% of individuals were misclassified by CKDEPI21 as having a GFR greater than, and 8.9% misclassified less than, 80 mL/min/1.73 m2, compared to 3.1% and 13.2% for CKDEPI09 with race adjustment, respectively. Total misclassification (either above or below 80 mL/min/1.73 m2) was 16.3% for CKDEPI21 and 16.0% for CKDEPI09 (with race adjustment).LimitationsLimited sample of individuals identifying as Black. Lack of cystatin C data.ConclusionsIn our potential living donor sample, GFR estimation by creatinine-based CKDEPI21 is less biased and more accurate than previous creatinine-based estimated GFR equations. When evaluated by race, this summative improvement remains in individuals identifying as Asian, Hispanic, or White. More external validation is needed to assess whether the new equation is an improvement over the previous CKDEPI equation with a race coefficient.

Over the past 20 years, significant effort has been devoted to advancing the modular approach to teaching chemistry laboratory courses. The development and implementation of two modules are presented here for teaching a second-semester physical chemistry laboratory course using the modular approach: an inquiry-based module concerning proteins and a project-based module concerning organic small molecules. Each module focuses on a molecular system in question and allows participating students to choose and apply various methods to study the system in different ways, according to the advantages and disadvantages of each method. The common thrust of all of the modules is to develop students' critical thinking skills, provide them a conduit to apply their knowledge to real applications, encourage them to model the approaches and behavior of practicing scientists, and excite them to initiate and pursue research opportunities. Details of implementation of this modular approach in teaching the second-semester physical chemistry laboratory for the past 11 years are provided. The assessment results indicate encouraging evidence that this two-level modular approach has achieved its goals and assisted students in choosing more research-based careers.

The liver regulates energy partitioning and use in a sex-dependent manner, coupling hepatic substrate availability to female reproductive status. Fibroblast growth factor 21 (FGF21) is a hepatokine produced in response to metabolic stress that adaptively directs systemic metabolism and substrate use to reduce hepatic lipid storage. Here we report that FGF21 altered hepatic transcriptional and metabolic responses, and reduced liver triglycerides, in a sex-dependent manner. FGF21 decreased hepatic triglycerides in obese male mice in a weight loss-independent manner; this was abrogated among female littermates. The effect of FGF21 on hepatosteatosis is thought to derive, in part, from increased adiponectin secretion. Accordingly, plasma adiponectin and its upstream adrenergic receptor → cAMP → exchange protein directly activated by cAMP signaling pathway was stimulated by FGF21 in males and inhibited in females. Both ovariectomized and reproductively senescent old females responded to FGF21 treatment by decreasing body weight, but liver triglycerides and adiponectin remained unchanged. Thus, the benefit of FGF21 treatment for improving hepatosteatosis depends on sex but not on a functional female reproductive system. Because FGF21 provides a downstream mechanism contributing to several metabolic interventions, and given its direct clinical importance, these findings may have broad implications for the targeted application of nutritional and pharmacological treatments for metabolic disease.

Abstract A proportion of people with fibromyalgia demonstrate small fibre pathology (SFP). However, it is unclear how SFP directly relates to pain phenomenology. Thirty-three individuals with FMS and ten healthy volunteers underwent assessment of SFP and sensory phenotyping using corneal confocal microscopy, validated questionnaires and quantitative sensory testing (QST). Corneal nerve fibre length was used to stratify participants with fibromyalgia into with SFP [SFP+] and without SFP [SFP−]. SFP was detected in 50% of the fibromyalgia cohort. Current pain score and QST parameters did not differ between SFP+ and SFP−. Mechanical pain sensitivity (MPS) demonstrated a significant gain-of-function in the SFP− cohort compared to healthy-volunteers (p = 0.014, F = 4.806, η2 = 0.22). Further stratification revealed a cohort without structural SFP but with symptoms compatible with small fibre neuropathy symptoms and a significant gain in function in MPS (p = 0.020 Chi-square). Additionally, this cohort reported higher scores for both depression (p = 0.039, H = 8.483, η2 = 0.312) and anxiety (p = 0.022, F = 3.587, η2 = 0.293). This study confirms that SFP is present in a proportion of people with fibromyalgia. We also show that in a proportion of people with fibromyalgia, small fibre neuropathy symptoms are present in the absence of structural SFP. Greater mechanical pain sensitivity, depression and anxiety are seen in these individuals.

The Manhattan-Ogden USD 383 public school system and Kansas State University's College of Education view the Professional Development School Network as central to the work of simultaneous renewal across institutions and within the professional lives of teachers, teacher candidates, and K-12 students. In this article, the authors share the pride of their nearly 40 years of PDS partnership work and their work with Manhattan/Ogden USD 383 from their collective inception as well as being the only PDS partnership to receive the Exemplary Achievement Award twice, first in 2011 and again in 2022. Herein, they highlight how they have evolved their practice in innovative ways including: the addition of two new pathways toward licensure--a Master of Arts in Teaching (MAT) program and Bachelor of Science Online (BSO); expanding their signature on-campus summer STEM camp to include Virtual STEAM serving rural schools in the state and middle school participants worldwide; and starting an annual Rural Summit event to bring together leaders from rural schools across the state.

Thirty years after the demise of the Soviet bloc, there still persists a rhetoric of differentiation and a discursive polarisation between the Western and the non-Western educational thinking and practices. This rhetoric overshadows a potential similarity, or homogeneity, between the dominant and several marginalised contexts. Regional, local and personal variations are prematurely attributed to fundamental, if often poorly argued, cultural differences. We seek to introduce and to preliminarily summarise the existing understandings of refraction in education and social research. Sporadically used but seldom defined, the refraction metaphor appears to feature: (a) a multiplicity of viewpoints as an incentive for social research, (b) non-relativistic, scientific progress as an end value for understanding social reality, (c) a balanced approach towards homogeneity and heterogeneity in social research, and (d) a substantially historical orientation towards analysing homogeneity and heterogeneity. Education in the former socialist European countries demonstrates how heterogeneity is rhetorically overstated and how variations can be more adequately addressed by analysing refractions.