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1.
bioRxiv ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38712135

ABSTRACT

Preclinical and clinical studies suggest that lipid-induced hepatic insulin resistance is a primary defect that predisposes to dysfunction in pancreatic islets, implicating a perturbed liver-pancreas axis underlying the comorbidity of T2DM and MASLD. To investigate this hypothesis, we developed a human biomimetic microphysiological system (MPS) coupling our vascularized liver acinus MPS (vLAMPS) with primary islets on a chip (PANIS) enabling MASLD progression and islet dysfunction to be quantitatively assessed. The modular design of this system (vLAMPS-PANIS) allows intra-organ and inter-organ dysregulation to be deconvoluted. When compared to normal fasting (NF) conditions, under early metabolic syndrome (EMS) conditions, the standalone vLAMPS exhibited characteristics of early stage MASLD, while no significant differences were observed in the standalone PANIS. In contrast, with EMS, the coupled vLAMPS-PANIS exhibited a perturbed islet-specific secretome and a significantly dysregulated glucose stimulated insulin secretion (GSIS) response implicating direct signaling from the dysregulated liver acinus to the islets. Correlations between several pairs of a vLAMPS-derived and a PANIS-derived secreted factors were significantly altered under EMS, as compared to NF conditions, mechanistically connecting MASLD and T2DM associated hepatic factors with islet-derived GLP-1 synthesis and regulation. Since vLAMPS-PANIS is compatible with patient-specific iPSCs, this platform represents an important step towards addressing patient heterogeneity, identifying complex disease mechanisms, and advancing precision medicine.

2.
bioRxiv ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38712213

ABSTRACT

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a worldwide health epidemic with a global occurrence of approximately 30%. The pathogenesis of MASLD is a complex, multisystem disorder driven by multiple factors including genetics, lifestyle, and the environment. Patient heterogeneity presents challenges for developing MASLD therapeutics, creation of patient cohorts for clinical trials and optimization of therapeutic strategies for specific patient cohorts. Implementing pre-clinical experimental models for drug development creates a significant challenge as simple in vitro systems and animal models do not fully recapitulate critical steps in the pathogenesis and the complexity of MASLD progression. To address this, we implemented a precision medicine strategy that couples the use of our liver acinus microphysiology system (LAMPS) constructed with patient-derived primary cells. We investigated the MASLD-associated genetic variant PNPLA3 rs738409 (I148M variant) in primary hepatocytes, as it is associated with MASLD progression. We constructed LAMPS with genotyped wild type and variant PNPLA3 hepatocytes together with key non-parenchymal cells and quantified the reproducibility of the model. We altered media components to mimic blood chemistries, including insulin, glucose, free fatty acids, and immune activating molecules to reflect normal fasting (NF), early metabolic syndrome (EMS) and late metabolic syndrome (LMS) conditions. Finally, we investigated the response to treatment with resmetirom, an approved drug for metabolic syndrome-associated steatohepatitis (MASH), the progressive form of MASLD. This study using primary cells serves as a benchmark for studies using patient biomimetic twins constructed with patient iPSC-derived liver cells using a panel of reproducible metrics. We observed increased steatosis, immune activation, stellate cell activation and secretion of pro-fibrotic markers in the PNPLA3 GG variant compared to wild type CC LAMPS, consistent with the clinical characterization of this variant. We also observed greater resmetirom efficacy in PNPLA3 wild type CC LAMPS compared to the GG variant in multiple MASLD metrics including steatosis, stellate cell activation and the secretion of pro-fibrotic markers. In conclusion, our study demonstrates the capability of the LAMPS platform for the development of MASLD precision therapeutics, enrichment of patient cohorts for clinical trials, and optimization of therapeutic strategies for patient subgroups with different clinical traits and disease stages.

3.
Osteoarthr Cartil Open ; 6(2): 100467, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38655014

ABSTRACT

Objective: Low vagal tone is common in osteoarthritis (OA) comorbidities and results in greater peripheral inflammation. Characterizing vagal tone's role in OA pathogenesis may offer insights into OA's influences beyond the articular joint. We hypothesized that low vagal tone would accelerate onset of OA-related gait changes and worsen joint damage in a rat knee OA model. Methods: Knee OA was induced in male Sprague Dawley rats by transecting the medial collateral ligament and medial meniscus. Then, left cervical vagus nerve transection (VGX, n â€‹= â€‹9) or sham VGX (non-VGX, n â€‹= â€‹6) was performed. Gait and tactile sensitivity were assessed at baseline and across 12 weeks, with histology and systemic inflammation evaluated at endpoint. Results: At week 4, VGX animals showed limping gait characteristics through shifted stance times from their OA to non-OA limb (p â€‹= â€‹0.055; stance time imbalance â€‹= â€‹1.6 â€‹± â€‹1.6%) and shifted foot strike locations (p â€‹< â€‹0.001; spatial symmetry â€‹= â€‹48.4 â€‹± â€‹0.835%), while non-VGX animals walked with a balanced and symmetric gait. Also at week 4, while VGX animals had a mechanical sensitivity (50% withdrawal threshold) of 13.97 â€‹± â€‹7.70 compared to the non-VGX animal sensitivity of 29.74 â€‹± â€‹9.43, this difference was not statistically significant. Histologically, VGX animals showed thinner tibial cartilage and greater subchondral bone area than non-VGX animals (p â€‹= â€‹0.076; VGX: 0.80 â€‹± â€‹0.036 â€‹mm2; non-VGX: 0.736 â€‹± â€‹0.066 â€‹mm2). No group differences in systemic inflammation were observed at endpoint. Conclusions: VGX resulted in quicker onset of OA-related symptoms but remained unchanged at later timepoints. VGX also had thinner cartilage and abnormal bone remodeling than non-VGX. Overall, low vagal tone had mild effects on OA symptoms and joint remodeling, and not at the level seen in common OA comorbidities.

4.
Anal Methods ; 16(16): 2449-2455, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38563199

ABSTRACT

Carotenoids are yellow, orange, and red pigments commonly found in plants. In leaves, these molecules are essential for photosynthesis, but they also play a major role in plant growth and development. Efficiently monitoring concentrations of specific carotenoids in plant tissues could help to explain plant responses to environmental stressors, infection and disease, fertilization, and other conditions. Previously, Raman methods have been used to demonstrate a correlation between plant fitness and the carotenoid content of leaves. Due to solvatochromatic effects and structural similarities within the carotenoid family, current Raman spectroscopy techniques struggle to assign signals to specific carotenoids with certainty, complicating the determination of amounts of individual carotenoids present in a sample. In this work, we use thin layer chromatography-Raman spectroscopy, or TLC-Raman, to identify and quantify carotenoids extracted from tomato leaves. These quick and accurate methods could be applied to study the relationship between pigment content and a number of factors affecting plant health.


Subject(s)
Carotenoids , Plant Leaves , Solanum lycopersicum , Spectrum Analysis, Raman , Plant Leaves/chemistry , Spectrum Analysis, Raman/methods , Chromatography, Thin Layer/methods , Carotenoids/analysis , Carotenoids/chemistry , Solanum lycopersicum/chemistry , Solanum lycopersicum/metabolism , Pigments, Biological/analysis , Pigments, Biological/chemistry
5.
Curr Pharm Teach Learn ; 16(5): 319-326, 2024 May.
Article in English | MEDLINE | ID: mdl-38575501

ABSTRACT

OBJECTIVES: To describe the creation of podcasts for instructional delivery and evaluate strengths and areas for improvement in a post-graduate training (PGT) elective course. METHODS: After creating a podcast series, students in the PGT elective from Spring 2021 to Fall 2022 listened to the series then completed a reflection based on five open-ended questions that provoked their thoughts and feelings about use of podcasts as a method of delivering information and teaching. Responses were downloaded and a content analysis was performed. Each investigator analyzed responses from all reflections to identify major themes and subthemes. Letter of intent assignment and overall course grades were compared to assess if podcasts affected student learning. RESULTS: Ninety-one students provided reflections about the use of podcasts in the PGT elective course, which revealed three major themes with 13 subthemes, including perception of guests, learner experience, and show and episode production. Students appreciated the various perspectives, authenticity, relatability, and diversity of the guest speakers; the learning environment was described as flexible, relatable, positive, and a safe space; the podcast design was noted to be informative, organized, and easily accessible. Areas for improvement included more interaction with guests and more visuals. Letter of intent assignment and overall course grades were similar before and after podcast implementation. CONCLUSION: The use of podcasts as an educational tool in a PGT elective course had a variety of characteristics that students preferred to traditional lecture-style classes.


Subject(s)
Education, Pharmacy , Educational Measurement , Humans , Educational Measurement/methods , Students , Education, Pharmacy/methods
6.
J Control Release ; 369: 775-785, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38604386

ABSTRACT

Many areas of science and medicine would benefit from selective release of drugs in specific regions. Nanoparticle drug carriers activated by focused ultrasound-remotely applied, depth-penetrating energy-may provide such selective interventions. Here, we developed stable, ultrasound-responsive nanoparticles that can be used to release drugs effectively and safely in non-human primates. The nanoparticles were used to release propofol in deep brain visual regions. The release reversibly modulated the subjects' visual choice behavior and was specific to the targeted region and to the released drug. Gadolinium-enhanced MR imaging suggested an intact blood-brain barrier. Blood draws showed normal clinical chemistry and hematology. In summary, this study provides a safe and effective approach to release drugs on demand in selected deep brain regions at levels sufficient to modulate behavior.

7.
Article in English | MEDLINE | ID: mdl-38631877

ABSTRACT

BACKGROUND: Adolescence is a sensitive stage of oral microbial development that often coincides with the initiation and escalation of alcohol use. Thus, adolescents may be particularly susceptible to alcohol-induced alterations in the oral microbiome, though minimal research has been done in this area. Understanding the connection between the oral microbiome and alcohol use during adolescence is important to understand fully the biological consequences of alcohol use to mitigate potential adverse outcomes. METHODS: Saliva samples were collected from adolescents aged 17-19 who used alcohol heavily (n = 21, 52.4% female) and those who did not use alcohol or any other substances (n = 18, 44.4% female). We utilized 16S rRNA sequencing to examine differences in microbial diversity and composition between the groups. RESULTS: For alpha diversity, evenness was significantly lower in the drinking group than the control group as indicated by Pielou's evenness, Shannon, and Simpson indices. There were no statistically significant findings for beta diversity. Differential abundance analyses revealed higher abundances of Rothia and Corynebacterium in the alcohol-using group using both centered-log-ratio and relative abundance normalization. These genera are known for their high capacity to convert alcohol into acetaldehyde, a toxic metabolite reported to play a role in the neurobiological effects of alcohol. An unclassified Clostridia UCG-014, Streptobacillus, Comamonas, unclassified Lachnospiraceae, and Parvimonas were also identified as significantly different between groups when using only one of the normalization techniques. CONCLUSIONS: This is the first study designed specifically to compare the oral microbiome of adolescents who use alcohol with that of control participants. Our findings reveal distinct alcohol-related differences in microbial composition and taxon abundance, emphasizing the importance of understanding the impact on the oral microbiome of alcohol use during adolescence. Because the oral microbiome is malleable, this study provides foundational work for future prevention and intervention studies.

8.
Body Image ; 49: 101713, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38636387

ABSTRACT

Using an experimental posttest-only control group design, the purpose of this study was to examine the effects of self-compassionate writing exercises on transgender and non-binary participants' body satisfaction, gender identity pride, and internalized transphobia. A total of 238 transgender people participated in this study (Mage = 28.27, SD = 8.12). Participants were randomly assigned to a self-compassionate writing task focusing on their gender identity, a self-compassionate writing task focusing on their body image as a transgender person (i.e., gendered body image), and a control condition, which required them to write about a neutral day in their lives. Results demonstrated that those in the gendered body image self-compassionate condition reported higher state-level effects of body satisfaction following the intervention than those in the control condition. No significant effects were observed for condition on state-level gender identity pride or internalized transphobia. Results also demonstrated that non-binary participants reported higher levels of gender identity pride than trans femme participants. Exploratory post-hoc analyses revealed that gender identity pride moderated the effect of condition on body satisfaction. Compared to those in the control condition, participants in the gendered body self-compassionate condition with moderate and high levels of gender identity pride reported higher levels of body satisfaction. Results demonstrate potential beneficial effects of brief self-compassionate writing exercises on transgender peoples' body satisfaction.

9.
Sports Biomech ; : 1-15, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38623642

ABSTRACT

Vertical and horizontal rhythms are crucial aspects of a dynamic golf swing, and the two-step swing drills (TSSD) were specifically designed to promote rhythmic unloading and loading of the legs. The purpose of this study was to evaluate the effects of a TSSD training session on the swing rhythm and clubhead speed (CHS) among competitive junior golfers (3.1 ± 4.4 hcp). The driver swings (7 swings each) of 10 competitive junior golfers (aged 15-18) were captured before and after a TSSD session consisting of four stages (lasting less than 45 minutes). Post-TSSD training, there were significant increases in CHS (p < .001), maximum unweighting (p = .006), the trail-side push (p = .009), the horizontal motion ranges of the body and pelvis (p = .005-.031), the upward/downward motion range of the body in the backswing (p = .042/.024), and the backswing/downswing angular velocity peaks of the axle-chain system (p < .033). The stepping-like leg actions primarily facilitated horizontal motion rhythm over vertical motion and unweighting over push in terms of ground interaction. These findings suggest that TSSD can serve as an effective method for developing a rhythmic and dynamic motion pattern while increasing CHS.

10.
Lancet ; 403(10435): 1443-1444, 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38614475
11.
Rev Sci Instrum ; 95(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38557886

ABSTRACT

JET's frequency-modulated continuous wave (FMCW) reflectometers have been operating well with the current design since 2005, and density profiles have been automatically calculated intershot since then. However, the calculated profiles had long suffered from several shortcomings: poor agreement with other diagnostics, sometimes inappropriately moving radially by several centimeters, elevated levels of radial jitter, and persistent wriggles (strong unphysical oscillations). In this research, several techniques are applied to the reflectometry data analysis, and the shortcomings are significantly improved. Starting with improving the equilibrium reconstruction that estimates the background magnetic field, adding a ripple correction in the reconstructed magnetic field profile, and adding new inner-wall reflection positions estimated through ray-tracing, these changes not only improve the agreement of reconstructed profiles to other diagnostics but also solve density profile wriggles that were present during band transitions. Other smaller but also persistent wriggles were also suppressed by applying a localized correction to the measured beat frequency where persistent oscillations are present. Finally, the burst analysis method, as introduced by Varela et al. [Nucl. Fusion 46 S693 (2006)], has been implemented to extract the beat frequency from stacked spectrograms. Due to the strong suppression of spurious reflections, the radial jitter that sometimes would span several centimeters has been strongly reduced. The stacking of spectrograms has also been shown to be very useful for stacking recurring events, like small gas puff modulations, and extracting transport coefficients that would otherwise be below the noise level.

12.
Article in English | MEDLINE | ID: mdl-38680216

ABSTRACT

Although many prevention and treatment programs exist for children and families, there have been no reviews specifically examining their impact on infant mental health at the program level. Therefore, the purpose of the current review was to a) systematically examine prevention and treatment programs targeting infant mental health outcomes (i.e., internalizing problems, externalizing problems, social-emotional development, trauma) or the parent-infant relationship/ attachment in children from pregnancy to 2 years; b) classify each program by level of empirical support; and c) highlight strengths and identify gaps in the existing literature to inform future mental health intervention science. From over 121,341 publications initially identified, 60 prevention and treatment programs met inclusion criteria for this review. Each program was reviewed for level of scientific evidence. Of the 60 programs reviewed, 29 (48.33%) were classified as promising, while only six (10.0%) were classified as effective. Lastly, only two programs (3.33%; Attachment and Biobehavioral Catch-Up and Video-feedback Intervention Parenting Program) were classified as evidence-based specific to infant mental health and/or parent-infant relationship/attachment outcomes. Implications related to disseminating evidence-based prevention/treatment programs are discussed.

13.
Int J Antimicrob Agents ; 63(6): 107165, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38570019

ABSTRACT

BACKGROUND: Oritavancin and dalbavancin are long-acting lipoglycopeptide antibiotics approved for the treatment of skin and skin structure infections. Recently, they have been used for outpatient antimicrobial therapy for complicated infections. No head-to-head studies exist for this purpose. OBJECTIVE: To compare outcomes of patients treated with multiple doses of oritavancin or dalbavancin for complicated infections. PATIENTS AND METHODS: This was a single-centre, retrospective cohort study evaluating adult patients who received two or more doses of lipoglycopeptides for complicated infections from February 2019 through December 2022. Patients receiving oritavancin were compared to dalbavancin after propensity score-matching. The primary endpoint was clinical success at 90 days. Other endpoints included: 30-day re-admission, 30-day mortality, adverse drug reactions (ADRs), and changes in white blood cell count and inflammatory markers after the first dose. RESULTS: After exclusions and propensity score-matching, 131 matched pairs (N = 262) were included in the analysis. Most patients were receiving lipoglycopeptide therapy for osteomyelitis. There was no significant difference in clinical success at 90 days in patients who received oritavancin compared to those who received dalbavancin (99 [76%] vs. 103 [79%], respectively; P = 0.556). There was no significant difference in secondary endpoints, however, there was a trend towards higher incidence of ADRs oritavancin compared to dalbavancin (9 [7%] vs. 2 [2%], respectively; P = 0.060) which led to more treatment discontinuation. CONCLUSION: There was no significant difference in efficacy between multi-dose oritavancin and dalbavancin for the treatment of complicated infections. Both agents were generally well tolerated; however, dalbavancin may be better tolerated when long-term treatment is warranted.

14.
Cleft Palate Craniofac J ; : 10556656241239459, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38490221

ABSTRACT

OBJECTIVE: To investigate whether flexible nasopharyngoscopy, when performed in addition to magnetic resonance imaging (MRI), influences the type of surgery selected or success of surgery in patients with velopharyngeal insufficiency (VPI). DESIGN: Cohort study. SETTING: A metropolitan children's hospital. PATIENTS: Patients with non-syndromic, repaired cleft palate presenting for management of VPI. INTERVENTIONS: MRI and nasopharyngoscopy or MRI alone for preoperative imaging of the velopharyngeal mechanism. MAIN OUTCOME MEASURES: (1) Surgical selection and (2) resolution of hypernasality. All speech, MRI, and nasopharyngoscopy measurements were performed by raters blinded to patients' medical and surgical history. RESULTS: Of the 25 patients referred for nasopharyngoscopy, 76% completed the exam. Of the 41 patients referred for MRI, the scan was successfully completed by 98% of patients. Completion of nasopharyngoscopy was significantly (p=0.01) lower than MRI. Surgical selection did not significantly differ (p=0.73) between the group receiving MRI and nasopharyngoscopy and the group receiving MRI alone, nor was there a significant difference between these groups in the proportion of patients achieving resolution of hypernasality postoperatively (p=0.63). Percent total velopharyngeal closure assessments on nasopharyngoscopy and MRI were strongly correlated (r=0.73). CONCLUSIONS: In patients receiving MRI as part of their preoperative VPI evaluation, the addition of nasopharyngoscopy did not result in a difference in surgical selection or resolution of hypernasality. Routine inclusion of nasopharyngoscopy may not be necessary for the evaluation of velopharyngeal anatomy when MRI is available.

16.
J Orthop Trauma ; 38(3): 148-154, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38385974

ABSTRACT

OBJECTIVES: To compare outcomes in patients on direct oral anticoagulants (DOACs) treated within 48 hours of last preoperative dose with those with surgical delays >48 hours. DESIGN: Retrospective cohort study. SETTING: Three academic Level 1 trauma centers. PATIENT SELECTION CRITERIA: Patients 65 years of age or older on DOACs before hip fracture treated between 2010 and 2018. Patients were excluded if last DOAC dose was >24 hours before admission, patient suffered from polytrauma, and/or delay to surgery was not attributed to DOAC. OUTCOME MEASURES AND COMPARISONS: Primary outcome measures were the postoperative complication rate as determined by diagnosis of deep venous thrombosis or pulmonary embolus, wound breakdown, drainage, or infection. Secondary outcomes included transfusion requirement, perioperative bleeding, length of stay, reoperation rates, readmission rates, and mortality. RESULTS: Two hundred five patients were included in this study, with a mean cohort age of 81.9 years (65-100 years), 64% were (132/205) female, and a mean Charlson Comorbidity Index of 6.4 (2-20). No significant difference was observed among age, sex, Charlson Comorbidity Index, or fracture pattern between cohorts (P > 0.05 for all comparisons). Seventy-one patients had surgery <48 hours after final preoperative DOAC dose; 134 patients had surgery >48 hours after. No significant difference in complication rate between the 2 cohorts was observed (P = 0.30). Patients with delayed surgical management were more likely to require transfusion (OR 2.39, 95% CI, 1.05-5.44; P = 0.04). Patients with early surgical management had significantly shorter lengths of stay (5.9 vs. 7.6 days, P < 0.005). There was no difference in estimated blood loss, anemia, reoperations, readmissions, 90-day mortality, or 1-year mortality (P > 0.05 for all comparisons). CONCLUSIONS: Geriatric patients with hip fracture who underwent surgical management within 48 hours of their last preoperative DOAC dose required less transfusions and had decreased length of stay, with comparable mortality and complication rates with patients with surgery delayed beyond 48 hours. Providers should consider early intervention in this population rather than adherence to elective procedure guidelines. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Hip Fractures , Humans , Female , Aged , Aged, 80 and over , Retrospective Studies , Hip Fractures/complications , Hip Fractures/surgery , Reoperation , Drainage , Anticoagulants/therapeutic use
17.
Neurobiol Learn Mem ; 209: 107906, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38408534

ABSTRACT

Few studies have quantified what an individual remembers about a laboratory-controlled stressor. Here, we aimed to replicate previous work by using a modified version of the Trier Social Stress Test (TSST) to quantify participant memory for a stressful experience. We also aimed to extend this work by quantifying false and intrusive memories that ensued. One hundred and seven participants were exposed to the TSST (stress) or the friendly TSST (f-TSST; no stress). The TSST required participants to deliver a ten-minute speech in front of two laboratory panel members as part of a mock job interview; the f-TSST required participants to casually converse with the panel members about their interests. In both conditions, the panel members interacted with (central) or did not interact with (peripheral) several objects sitting on a desk in front of them. The next day, participants' memory for the objects was assessed with recall and recognition tests. We also quantified participants' intrusive memories on Days 2, 4, 6, and 8. Stressed participants recalled more central objects and exhibited greater recognition memory, particularly for central objects, than controls. Stress also led to less false recall and more intrusive memories on Days 2 and 4. Consistent with previous work, these findings suggest that participants exhibit enhanced memory for the central details of a stressful experience; they also extend prior work by showing that participants exposed to a stressor have less false memories and experience intrusive memories for several days following the event. The modified TSST paradigm used here may be useful for researchers studying not only what participants remember about a stressful event but also their susceptibility to intrusive memory formation.


Subject(s)
Hydrocortisone , Saliva , Humans , Memory , Stress, Psychological , Mental Recall
18.
Occup Med (Lond) ; 74(2): 161-166, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38381669

ABSTRACT

BACKGROUND: Typically, the fitness of UK firefighters is assessed via submaximal estimate methods due to the low demands on time, money, expertise and equipment. However, the firefighter-specific validity of such testing in relation to maximum aerobic capacity (V˙O2max) and particularly muscular strength is not well established. AIMS: To examine the validity of submaximal methods to estimate V˙O2max and maximal strength in operational firefighters. METHODS: Twenty-two full-time operational firefighters (3 female) completed same-day submaximal (Chester Step Test; CST) and maximal (treadmill) assessments of V˙O2max, with a sub-sample of 10 firefighters (1 female) also completing submaximal and maximal back-squat (i.e. one repetition maximum; 1RM) assessments. All participants then completed the Firefighter Simulation Test (FFST) within 2-4 days. RESULTS: CST underestimated actual V˙O2max by 1.4 ml·kg-1·min-1 (~3%), although V˙O2max values were positively correlated (r = 0.61, P < 0.01) and not significantly different. Estimated V˙O2max values negatively correlated with FFST performance (r = -0.42). Predicted 1RM underestimated actual 1RM by ~2%, although these values were significantly correlated (r = 0.99, P < 0.001) and did not significantly differ. The strongest predictive model of FFST performance included age, body mass index, and direct maximal measures of 1RM and V˙O2max. CONCLUSIONS: Submaximal back-squat testing offers good validity in estimating maximum firefighter strength without exposure to the fatigue associated with maximal methods. The CST provides a reasonably valid and cost-effective V˙O2max estimate which translates to firefighting task performance, although the error observed means it should be used cautiously when making operational decisions related to V˙O2max benchmarks.


Subject(s)
Firefighters , Physical Fitness , Humans , Female , Oxygen Consumption , Exercise Test/methods , Exercise Tolerance
19.
Article in English | MEDLINE | ID: mdl-38415097

ABSTRACT

Objective: This comprehensive literature scoping review outlines available infection prevention and control (IPC) methods for viral-mediated gene therapies and provides one IPC strategy for the healthcare setting based on a single-center recommendation. Methods: A team of experts in pharmacy, healthcare epidemiology, and biosafety with experience in viral-mediated gene therapy was assembled within a pediatric hospital to conduct a comprehensive literature scoping review. The comprehensive review included abstracts and full-text articles published since 2009 and utilized prespecified search terms of the five viral vectors of interest: adenovirus (AV), retrovirus (RV), adeno-associated virus (AAV), lentivirus (LV), and herpes simplex virus (HSV). Case reports, randomized controlled trials, and bench research studies were all included, while systematic reviews were excluded. Results: A total of 4473 case reports, randomized control trials, and benchtop research studies were identified using the defined search criteria. Chlorine compounds were found to inactivate AAV and AV, while alcohol-based disinfectants were ineffective. There was a relative paucity of studies investigating surface-based disinfection for HSV, however, alcohol-based disinfectants were effective in one study. Ultraviolent irradiation was also found to inactivate HSV in numerous studies. No studies investigated disinfection for LV and RV vectors. Conclusions: The need to define IPC methods is high due to the rapid emergence of viral-mediated gene therapies to treat rare diseases, but published clinical guidance remains scarce. In the absence of these data, our center recommends a 1:10 sodium hypochlorite solution in clinical and academic environments to ensure complete germicidal activity of viral-mediated gene therapies.

20.
Nat Commun ; 15(1): 1459, 2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38368421

ABSTRACT

Here, four MOFs, namely Sc-TBAPy, Al-TBAPy, Y-TBAPy, and Fe-TBAPy (TBAPy: 1,3,6,8-tetrakis(p-benzoic acid)pyrene), were characterized and evaluated for their ability to remediate glyphosate (GP) from water. Among these materials, Sc-TBAPy demonstrates superior performance in both the adsorption and degradation of GP. Upon light irradiation for 5 min, Sc-TBAPy completely degrades 100% of GP in a 1.5 mM aqueous solution. Femtosecond transient absorption spectroscopy reveals that Sc-TBAPy exhibits enhanced charge transfer character compared to the other MOFs, as well as suppressed formation of emissive excimers that could impede photocatalysis. This finding was further supported by hydrogen evolution half-reaction (HER) experiments, which demonstrated Sc-TBAPy's superior catalytic activity for water splitting. In addition to its faster adsorption and more efficient photodegradation of GP, Sc-TBAPy also followed a selective pathway towards the oxidation of GP, avoiding the formation of toxic aminomethylphosphonic acid observed with the other M3+-TBAPy MOFs. To investigate the selectivity observed with Sc-TBAPy, electron spin resonance, depleted oxygen conditions, and solvent exchange with D2O were employed to elucidate the role of different reactive oxygen species on GP photodegradation. The findings indicate that singlet oxygen (1O2) plays a critical role in the selective photodegradation pathway achieved by Sc-TBAPy.

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