7-day Period Research Articles

From molecular to physiological responses: Improved stress tolerance and longevity in Drosophila melanogaster under fluctuating thermal regimes.

Climate change introduces greater thermal variability, profoundly affecting ectothermic species whose body temperatures rely heavily on the environment. Understanding the physiological and metabolic responses to such variability is crucial for predicting how these species will cope with changing climates. This study investigates how chronic thermal stress impacts mitochondrial metabolism and physiological parameters in Drosophila melanogaster, hypothesizing that a fluctuating thermal regime (FTR) activates protective mechanisms enhancing stress tolerance and longevity. To test this, Drosophila were exposed to constant 24°C or to an FTR of 24°C/15°C day/night cycle following an initial 5-day period at 24°C. The FTR group exhibited rapid transcript level changes after the first day of FTR, particularly those related to heat shock proteins, mitophagy and regulatory factors, which returned to initial levels after 5 days. Mitochondrial respiration rates initially decreased after 1 and 2 days of FTR, then recovered by Day 5, indicating rapid acclimation. Enhanced antioxidant enzyme activities were observed early in the FTR group, after 1 day for mtSOD and SODcyt+ext and 3 days for both SOD and catalase, followed by a decline by Day 5, suggesting efficient oxidative stress management. The FTR group showed lower CTmax on Day 3, reflecting possible physiological strain at that time point, and complete recovery by Day 5. Longevity increased under FTR, highlighting the activation of protective mechanisms with beneficial long-term effects. These suggest that FTR prompts a temporal succession of rapid physiological adjustments at different levels of organisation, enhancing long-term survival in D. melanogaster.

In Vitro Assessment of the Extended 21-Day Microbial Barrier Provided by the Exofin Fusion Surgical Incision Closure System.

Background: Tissue adhesives are increasingly being used as alternatives to traditional sutures and staples in surgical incision closure applications. Exofin Fusion, a novel cyanoacrylate-based adhesive with a mesh, has been developed to enhance surgical incision closure. This study investigates the microbial barrier effectiveness of Exofin Fusion. Methods: An in vitro assessment of 35 plates, including challenge organisms, negative controls, and positive controls, was conducted by an independent research organization, North American Science Associates, Inc (NAMSA), USA. Exofin Fusion was applied to the plates aseptically. Each plate was then inoculated with specific challenge organisms. Observations for visible growth or color changes in the media were made over a 21-day period. Results: The results demonstrated no growth or color changes on test plates for common pathogens such as Staphylococcus aureus, Staphylococcus epidermidis, Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Aspergillus brasiliensis throughout the 21-day period. Candida albicans showed no growth or color changes up to day 20; however, two out of five replicates exhibited growth on day 21. Conclusions: The study confirms the microbial barrier properties of Exofin Fusion, as it effectively prevents the penetration of challenge organisms for the entire test period. Despite the growth of C. albicans in two replicates on day 21, the adhesive demonstrates remarkable efficacy in protecting against microbial infiltration. These findings suggest the potential clinical utility of Exofin Fusion in surgical incision closure applications, highlighting its significance in healthcare settings.

Three-Dimensional Printing of Hydrogel Blend Tissue Engineering Scaffolds with In Situ Delivery of Anticancer Drug for Treating Melanoma Resection-Induced Tissue Defects

Surgery is considered the gold standard for treating melanoma, but the high recurrence rate after surgery still remains as a major challenge. Therefore, using doxorubicin (DOX) as a model drug, this study investigated the 3D printing of anticancer drug-loaded hydrogel blend scaffolds for inhibiting post-operation melanoma recurrence and for promoting tissue regeneration. Three-dimensional printing could successfully produce methacrylate-modified chitosan (CSMA) and methylcellulose (MC) hydrogel blend scaffolds. Polymer blend inks exhibited satisfactory printability, and the printed porous scaffolds showed good biocompatibility and mechanical properties. Three-dimensionally printed DOX-loaded hydrogel scaffolds displayed controlled drug release, which may effectively prevent/impede tumor recurrence after surgery. Furthermore, combining 3D printing and bioprinting, DOX-loaded and rat bone marrow mesenchymal stem cell (rBMSC)-laden scaffolds were created for assessing local DOX delivery on healthy tissues. Within the 14-day culture period, rBMSCs encapsulated in multilayered scaffolds that were incorporated with DOX displayed rejuvenated cell viability. The 3D printed and bioprinted dual purpose hydrogel scaffolds have the promise of combating tumor recurrence and providing structural support for tissue regeneration.

Active cytomegalovirus infection in mechanically ventilated patients with sepsis

BackgroundActive cytomegalovirus (CMV) infection is associated with poor prognosis in septic patients with critical illness. Patients of septic category are highly likely to benefit from prophylactic antiviral therapy. Nevertheless, the clinical characteristics for CMV reactivation are lacking among septic patients requiring mechanical ventilation. The aim of this study was to investigate the incidence, risk factors, and clinical outcomes regarding active CMV infection in mechanically ventilated patients with sepsis.MethodsA single-center, retrospective cohort study conducted from January 2021 to December 2023 that included septic patients on mechanical ventilation at the intensive care unit (ICU) of a national hospital. Study participants were divided into active and non-active CMV infection groups based on CMV DNAemia within a 28-day hospitalization period in ICU. Clinical features, laboratory findings, treatment measures, and clinical outcomes were compared between the two groups.ResultsAmong 118 septic patients, 21 (17.8%) exhibited active CMV infection within 28-day ICU admission. Hemoglobin served as an independent risk factor and predictor for active CMV infection (P < 0.05). Moreover, the duration of mechanical ventilation and ICU stay in active CMV infection patients were significantly higher than in the comparison group (P < 0.05).ConclusionsActive CMV infection is common and associated with adverse clinical outcomes in mechanically ventilated patients with sepsis. A low level of hemoglobin is an independent risk factor for active CMV infection. Further prospective studies are warranted to assess the efficacy of initiating prophylactic and preemptive antiviral therapies among patients with sepsis disorders.

Long-term adaptation to dietary shifts of gut microbiota in gilthead seabream (Sparus aurata)

In many meta-analyses and literature reviews on fish microbiota, the provenance of the animals (farmed vs. wild) is often overlooked. Given the well-established role of diet as a key factor in shaping gut microbiota, this study investigates the impact of dietary nature by comparing the microbiota of gilthead seabream (Sparus aurata) fed a commercial diet versus a wild-type diet, all reared within a recirculating aquaculture system. Over a 60-day period, we tracked changes in gut bacterial diversity, structure, and composition following a shift from a commercial feed to a diet exclusively based on pink shrimp (Parapenaeus longirostris). Gut bacterial communities were assessed using 16S rRNA gene sequencing (Illumina MiSeq platform) with primers targeting the V3-V4 hypervariable regions. Twenty days after the dietary change, microbial diversity (Shannon index) increased in fish fed the shrimp diet compared to those fed the commercial diet, while Dominance index values decreased. Additionally, inter-individual (beta-) diversity based on Bray-Curtis distances also differed between dietary treatments. These results support further that microbiota comparisons between farmed/captive and wild fish are challenging due to the unpredictable feeding regimes and dietary variations in wild fish. However, the diet impact on microbiota diminished over time, with the differences in intra- and inter-individual diversity being reduced after 40 days, which suggests an adaptation of microbial communities to dietary changes. At this point, gut microbial communities also showed a similar taxonomical composition. Moreover, a core microbiota consisting of species belonging to the genera Ralstonia, Paraburkholderia, Fulvimonas, Pseudomonas, and Cutibacterium was maintained in all sampling times under both dietary treatments. Overall, this study serves as a conceptual approach that shows a long-term adaptation of the gut microbiota after a radical dietary change, probably driven by host-inherent factors. Furthermore, these results may be a valuable insight for feed manufacturers aiming to develop sustainable and cost-effective ingredients since they suggest that some alternative feeds and ingredients do not have adverse long-term effects on fish gut microbiota.

Maternal investment, body condition and calf growth in humpback whales.

Given recent declines in North Pacific humpback whale (Megaptera novaeangliae) reproductive output and calf survival, there is additional urgency to better understand how mother-calf pairs allocate energy resources across their migratory cycle. Here, unoccupied aerial system (UAS; or drone) photogrammetry was used to quantify the body size and condition (BC) of humpback whales on their Hawai'i (HI) breeding and Southeast Alaska (SEAK) feeding grounds. Between 2018 and 2022, we collected 2410 measurements of 1659 individuals. Rates of change in body volume (BV) and length (BL) were quantified using 803 repeat measurements of 275 individuals. On average, HI mothers lost 0.106m3 or 96.84kgday-1 while fasting, equivalent to 2641MJday-1 or 830kg of krill and 424kg of Pacific herring daily. HI calf BV and BL increased by 0.035m3 and 2.6cmday-1, respectively. In SEAK, maternal BV increased by 0.015m3 or 14.54kgday-1 (367MJday-1), while calf BV and BL increased by 0.039m3 and 0.93cmday-1, respectively. Maternal investment in calf growth correlated with both female BL and BC, with larger females producing larger, faster-growing calves. Finally, using 330 measurements from 156 females, we quantified differences in BC increase over four feeding seasons. Lactating females exhibited an average BC increase of 6.10%, half that of unclassified females (13.51%) and six times lower than pregnant females (37%). These findings represent novel insights into the life history of humpback whales across their migratory cycle, providing key baseline data for bioenergetic models elucidating the effects of anthropogenic disturbance and rapidly changing ocean ecosystems. KEY POINTS: On average, Hawai'i (HI) mothers lost 0.106m3 or 96.84kgday-1, equivalent to 2641MJday-1. Over a 60day period, this corresponded to an estimated mean energetic cost of 158GJ, or ≈50tons of krill or ≈25tons of Pacific herring, surpassing the total energetic cost of gestation estimated for humpback whales of similar length. In Southeast Alaska (SEAK), maternal body volume (BV) increased by just 0.015m3 or 14.54kgday-1 (367MJday-1). Further, SEAK lactating females showed the slowest rates of growth in body width and condition over a 150day period compared to non-lactating females. Maternal investment in calf growth correlated with both maternal length and body condition, with larger females producing larger, faster-growing calves. In HI, however, the ratio between maternal BV lost and calf BV gained (conversion efficiency) was relatively low compared to other mammals.

Stratification and internal temperature oscillations near a coastal inlet

ABSTRACT A vertical array of fast-response temperature sensors was deployed to investigate interior ocean temperature and thermal stratification variability during Spring, 2018 near an inlet entrance on the Otago inner continental shelf (15 m water depth). Over the 24-day observation period, the background water column structure evolved from supporting a near-surface pycnocline, to being characterised by a deep surface mixed layer. Periods of mostly low stratification due to atmospheric- and surface wave-driven mixing are also observed. Time-varying normal-mode projection demonstrates that the vertical structure of semi-diurnal temperature oscillations evolves in response to this background stratification in a manner consistent with the interpretation of internal waves. At higher frequencies (supratidal) the projection is less consistent as vertically coherent oscillations from non-linear internal solitons co-exist with non-coherent oscillations, a potential signature of stratified mixing. Although both processes are likely important contributors to the transport of coastal tracers and inlet-ocean exchange, further measurements are needed to determine the origin and fate of internal waves on the Otago continental shelf.

PRISMA-7 is a predictor of intensive care unit admission and mortality in older patients in an emergency department.

To compare the performance of the Programme of Research on the Integration of Services for the Maintenance of Autonomy (PRISMA-7), which is used to assess the frailty of older patients visiting emergency departments, with the quick Sepsis Related Organ Failure Assessment (qSOFA) and Emergency Severity Index (ESI) in terms of 28-day mortality and intensive care unit (ICU) admission. This study was prospective and observational. All patients above the age of 65 who were admitted to the Sivas Republic University Medical Faculty Hospital from March 1 to April 30 in the year 2024 were included in the study. Patients' all-cause mortality values and ICU acceptance rates were evaluated for a 28-day period following their applications. The area under the receiver operating characteristic curve stood for the 28-day mortality, while the values for PRISMA-7, ESI, and qSOFA were, respectively, 0.81 (95% confidence interval [CI]: 0.78-0.84), 0.78 (95% CI: 0.72-0.83), and 0.71 (95% CI: 0.65-0.77). Our findings have demonstrated PRISMA-7 to be more effective than ESI and qSOFA in terms of hospitalization predictions. However, while it was found to be more effective than qSOFA in mortality predictions, it was determined that, despite PRISMA-7 having a larger AUC than ESI, no meaningful difference existed between PRISMA-7 and ESI. In conclusion, PRISMA-7, which is thought of as a reliable and valid tool for the determination of frailty in emergency departments, has predictive value for individuals' 28-day mortality risk as well as for their acceptance to the ICU. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2024; ••: ••-••.

Early Stages of Bacterial Colonization Development After Xanthomonas campestris Seed Inoculation in Selected Brassica Species

This study investigates Xanthomonas campestris pv. campestris (Xcc) incidence rates in cabbage, kale, and kohlrabi, focusing on the roots and stems over a 15-day period after sowing. Seeds were inoculated with Xcc, and infection levels were monitored using confocal microscopy combined with fluorescence in situ hybridization. Significant differences in incidence rates were observed across the 15 days using a scale from 0 to 5 (0–100% incidence). Kale exhibited the highest mean incidence rates in roots (3.64), while cabbage and kohlrabi showed greater variability (3.4–3.44). Stem infections were more severe, with kale showing the highest mean levels (4.16), followed by kohlrabi (4.0), and cabbage (3.68). In cabbage roots, incidence rates increased until day 11, after which a significant decline was noted, whereas stem Xcc incidence rates remained stable. Kale roots peaked on day 9, with significant fluctuations on days 13 and 15. Kohlrabi displayed moderate, stable root incidence rates over the 15-day period. In stems, kohlrabi showed a significant increase on day 11, followed by a drop on day 15. Regression analysis revealed a significant positive linear correlation between incidence rate and days of observation in kohlrabi roots. However, no significant trends were observed in stem infections across all species, where incidence rates were high and stable from day 7 onwards. Newly acquired data indicate that the incidence rate of Xcc development depends on the type of vegetable. However, the bacterial occurrence in the root parts does not always correspond with the intensity of Xcc colonization in the stem section of the plants. Even at lower levels of Xcc occurrence in the roots, damage to the vascular bundles can be fatal. These findings offer valuable insights into Xcc infection dynamics, contributing to improved disease management strategies for Brassica crops.

The Impact of Emotion Network Density on Psychological Distress in Chinese Parents of Children with Autism: A Daily Diary Study.

Parents of children with autism often experience a wide range of emotions in their daily lives. However, previous research has primarily focused on average levels of emotional challenges, neglecting the significance of daily emotion dynamics that may underlie parental psychological functioning. This study adopted a dynamic network approach to examine the strength of temporal connections within and between various emotions-referred to as emotion network density-and further explore its impacts on parental psychological distress. Participants included 76 Chinese parents (M = 36.36 years, SD = 3.95 years; 58 mothers) of children with autism. Parents reported their psychological distress at baseline and then completed measures of daily emotions over a 14-day period. The densities of overall, positive, and negative emotion networks were estimated using the Multilevel Vector Auto-Regression model. The results indicated that higher densities of the overall and negative emotion networks were associated with increased stress, anxiety, and depressive symptoms in parents. Further analysis of network components showed that the in-strength of fear and guilt (i.e., their likelihood of being affected by other emotions) and the out-strength of anger and guilt (i.e., their capacity to influence other emotions) were positively related to parental psychological distress. However, neither the overall density of the positive emotion network nor its specific components showed a significant relationship with parental psychological distress. These findings highlight the importance of considering the daily dynamics of emotions, particularly negative emotions, from a network perspective to better understand the development of psychological distress in parents of children with autism.

A revolutionary temporary immersion bioreactor method for commercialscale Musa sp. (Tanduk and Berangan) multiplication

Large-scale clonal banana production is required to supply current industry demand. Conventional tissue culture technique needs to be improvised to overcome the high-cost manufacturing and laborious work involved. Therefore, this study aimed to develop an efficient protocol in clonal banana production by using temporary immersion bioreactor (TIB) technology which uses intermittent immersion in liquid nutrients. This study evaluated the optimum protocol pathway for efficient Musa acuminata cv. Berangan and Musa paradisiaca cv. Tanduk propagation with the application of TIB system. M. acuminata and M. paradisiaca optimum initiation medium were developed in MS (Murashige and Skoog) media supplemented with 3 mg/L 6-Benzylaminopurine (BAP) and 0.2 mg/L Thiamine and 0.3 mg/L Thidiazuron (TDZ) respectively. The optimum proliferation medium in TIB developed in MS media supplemented with 3 mg/L BAP for both varieties. The highest number of shoots was achieved in TIB with 20 initial plantlets and a 15-minute immersion with a 6-hour gap along with a 14-day incubation period. Micropropagation of Musa sp. in Temporary Immersion Bioreactor System (RITA ®) has successfully shown significant growth as compared to MS media agar-conventional technique with reduced phenolic content released in both varieties. In conclusion, the production of Musa acuminata cv Berangan and Musa paradisiaca cv. Tanduk by using a temporary immersion bioreactor (TIB) system has huge potential to improve the scale production output with lower-cost plantlets

Evaluating sorbents for reducing per- and polyfluoroalkyl substance mobility in biosolids-amended soil columns.

Sustainable reuse of biosolids as fertilizers is being threatened by the presence of per- and polyfluoroalkyl substances (PFAS) in our waste stream warranting research on strategies that will minimize PFAS mobility from land-applied biosolids. Here, we evaluated the ability of waste-derived sorbents aluminum chlorohydrate water treatment residuals (ACH-WTRs, 1wt%) and biosolids-based biochar (1.5wt%) to reduce mobility of PFAS in columns with 3wt% biosolids-amended soils with and without sorbent layered on top of soil only and operated under transient unsaturated conditions. Cycles of simulated rain events of approximately three pore volumes distributed over a 4-day period followed by 3 days of drying were imposed for 6 months. Total PFAS concentrations in collected leachates were lower in the sorbent-treated columns compared to the control columns. Biochar outperformed the ACH-WTR with 41% versus 32% lower total PFAS in leachate, respectively, compared to the control. The most significant mitigation effect was observed with PFOS (perfluorooctane sulfonate) with 68% and 62% less PFOS in the leachates from the columns treated with ACH-WTR or biochar compared to the control, respectively. These results provide a first-of-its-kind assessment of the potential benefit of co-applying WTRs or biochar with biosolids to reduce PFAS mobility in biosolids-amended soils.

Double-blind, placebo-controlled trial of the efficacy and safety of azelastine hydrochloride in children with perennial allergic rhinitis.

Allergic rhinitis (AR) affects up to 40% of the pediatric population. The US practice parameter recommends the use of INAH or INCS as first-line therapy for the treatment of AR. Although not directly targeted to children, the recent US Practice Parameters proposed intranasal antihistamines as first-line therapy whereas the ARIA guidelines did not. This was a randomized, double-blind, parallel-group study with a duration of 28 days. It compared Azelastine hydrochloride 0.10% and 0.15% to placebo of one spray per nostril twice daily in pediatric subjects with moderate-to-severe symptomatic perennial allergic rhinitis (PAR). A total of 486 subjects were included in the study. The change from baseline rTNSS was statistically significant for 0.15% AZE (P = .005) and 0.10% AZE (P = .015) vs. placebo. 0.15% AZE showed an LS mean change of -3.45 (20.2%) over the 28-day treatment period from a baseline value of 16.60 in rTNSS. 0.10% AZE showed an LS mean change of -3.37 (20.5%) over the 28-day treatment period from a baseline value of 16.35 in rTNSS. Somnolence was reported by one patient in the 0.1% group and one placebo patient (both of mild severity and unlikely to be related to treatment). None of the patients reported fatigue. 0.15% AZE significantly improved the overall rTNSS compared with placebo over the 28-day study period. 0.15% AZE was well tolerated in this study.

Evaluation of Selected Folk Herbs on the Fertility of Sprague Dawley Male Rats: Biochemical, Histological, and Molecular Investigations

Scientists have shown great interest in traditional plant extracts, particularly Lepidium sativum (LS), Origanum majorana (OM), Ferula hermonis (FH), and Eruca sativa (ES), which are frequ ently used to improve health. Recently, attention has been directed toward their influence on spermatogenesis and male fertility. Hence, the objective of this study was to explore their impact on male rats’ fertility. Antioxidant activity and total phenolic content (TPC) were determined, along with the identification and quantification of phenolic compounds. Oral administration of aqueous extracts was performed individually or as a mixture (MIX) at a dose of 100 mg/kg in 28 male Sprague Dawley rats over a 60-day period. Organ weight, sex hormone concentrations, sperm parameters, oxidative stress markers, histological and morphometric analysis, and protein expression levels were investigated. OM and MIX showed the highest TPC and antioxidant activities, and MIX possessed the highest polyphenolic constituents. Elevated serum testosterone, epididymal sperm concentration, testes glutathione levels, and histomorphometric parameters were manifested in all groups, especially in MIX. MIX group also displayed elevated levels of vimentin, protein kinase B, and mTOR expression in the testes, complemented by declined expression of Phosphatase and Tensin Homolog (PTEN). In conclusion, these findings propose that these extracts, especially MIX followed by OM, enhance fertility by stimulating spermatogenesis.

Application of a Multi-Component Composite Edible Coating for the Preservation of Strawberry Fruit

The rapid perishability of strawberries due to factors such as fungal decay, mechanical damage, and respiration significantly limits their shelf life. In this study, a novel multi-component edible coating composed of bacterial cellulose, chitosan, and gellan gum (BChG) was developed to enhance the postharvest quality and extend the shelf life of strawberries. The coated fruits were evaluated over a 15-day storage period for key parameters such as weight loss, total soluble solids (TSS), titratable acidity (TA), enzymatic activity, color retention, antioxidant activity, and microbiological analysis. The results demonstrated that coated strawberries exhibited significantly lower weight loss, reduced cellulase activity, and higher retention of TSS and TA compared to uncoated controls. The evaluation of microbial quality indicated that coatings, particularly those with higher concentrations of chitosan, control the growth of total mesophilic aerobic bacteria (TMAB) and molds and yeasts (MY), due to the antimicrobial properties of chitosan. This contributed to extending the shelf life of the fruit by preventing spoilage and reducing the risk of toxic compound formation. Additionally, the BChG coatings also preserved the characteristic red color of the fruit and maintained higher antioxidant activity, with BChG-4 being the most effective formulation. The inclusion of chitosan in the coatings was found to play a crucial role in reducing respiration, delaying ripening, and enhancing the fruit’s resistance to oxidative damage. Overall, multi-component coatings, particularly those with higher chitosan concentrations, offer a promising method for extending the shelf life of strawberries, reducing postharvest losses, and preserving fruit quality under ambient storage conditions.

Effect of Malvaviscus arboreus Flower and Leaf Extract on the Functional, Antioxidant, Rheological, Textural, and Sensory Properties of Goat Yogurt

The present study aimed to evaluate the effects of incorporating different concentrations (1% and 2%) of Malvaviscus arboreus flower (FE) and leaf (LE) extracts as functional ingredients in goat milk yogurt. This study analyzed the impact of these formulations (YFE1%, YFE2%, YLE1%, and YLE2%) on the physicochemical, bioactive, antioxidant, rheological, textural, and sensory properties of goat yogurt over a 28-day storage period. Including FE and LE extracts significantly enhanced the yogurt’s antioxidant activity, reaching up to 10.17 µmol TEAC/g, and strengthened its ability to inhibit lipid oxidation during storage. This study also observed a reduction in the viability of lactic acid bacteria, particularly L. delbrueckii subsp. bulgaricus, suggesting that the extracts may have antimicrobial properties. Notably, using FE, especially at a concentration of 2% (YFE2%), improved both antioxidant and textural properties while reducing syneresis by the end of the storage period. Sensory evaluations showed positive results for YFE1% and YFE2% formulations. These findings suggest that FE has significant potential as a functional food ingredient. This research lays the groundwork for future studies exploring the integration of Malvaviscus arboreus-based ingredients into functional food products, opening new possibilities for innovation in this field.

A microcycle of high-intensity short-interval sessions induces improvements in indicators of endurance performance compared to regular training.

The purpose of this study was to evaluate the effects of a microcycle of high-intensity interval training (HIT) sessions with multiple short work intervals followed by an active recovery period, compared to a similar duration of regular training, on determinants and indicators of endurance performance in well-trained cyclists. The participants in the BLOCK group performed a 6-day HIT microcycle including five HIT sessions (5×8.75-min 30/15s short intervals) followed by a 6-day active recovery period with reduced training load, while the regular training group (REG) performed 12days of their regular training, including four HIT sessions. Physiological testing was performed before and after the training periods. From pre- to post- intervention, BLOCK demonstrated significantly larger improvements than REG in mean power output (PO) during the last min of the maximal oxygen uptake (VO2max) test (POVO2max) (3.7 vs. 0.7%, p=0.009, and effect size (ES)=1.00) and mean PO during the 10-s sprint (2.8 vs. 1.9%, p=0.028, and ES=0.63). No significant differences between BLOCK and REG were observed for VO2max, PO at 4mmol·L-1 [blood lactate] (PO4mmol), 15-min maximal mean power output (PO15-min), and gross efficiency (p=0.156-0.919). However, there was a tendency for larger improvements in the performance index (calculated from the main performance indicators POVO2max, PO4mmol, and PO15-min) in BLOCK compared to REG (2.9% vs. 1.2%, p=0.079, and ES=0.71). A 6-day high-intensity short-interval microcycle followed by a 6-day active recovery period induces improvements in endurance performance indicators compared to regular training, demonstrating its potential as an efficient strategy for endurance training in well-trained cyclists.

Pharmacokinetics, Pharmacodynamics, Bioavailability, and Immunogenicity of Obexelimab Following Subcutaneous Administration in Healthy Japanese and Non-Japanese Volunteers.

Obexelimab is an investigational, bifunctional, non-depleting, humanized monoclonal antibody that binds CD19 and FcγRIIb to inhibit B cells, plasmablasts, and CD19-expressing plasma cells. In clinical trials, intravenous (IV) administration of obexelimab has been well-tolerated, and demonstrated clinical activity in patients with rheumatoid arthritis, systemic lupus erythematosus, and immunoglobulin G4-related disease. This study was performed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of obexelimab following subcutaneous (SC) administration, and compare PK/PD profiles between healthy Japanese and non-Japanese volunteers. This was a Phase I, open-label, parallel group, multiple-dose study. Participants were randomized to five cohorts to receive three doses of obexelimab as 125mg SC every 14days (q14d), 250mg SC q14d, 375mg SC q14d, 250mg IV q14d, and 125mg SC every 7days, then monitored during a 28-day safety follow-up period. PK/PD assessments were performed after the first and third doses. A total of 50 healthy volunteers (25 Japanese and 25 non-Japanese) were enrolled and distributed evenly between dose cohorts. All SC dosing regimens were well-tolerated. Dose-proportional PK was observed following SC doses with a bioavailability of approximately 60%. No clinically meaningful differences in PK parameters were found between healthy Japanese and non-Japanese participants. Antidrug antibodies (ADA) were detected in 6/50 (12%) participants after dosing. ADA had no or minimal impact on PK in all six ADA positive participants. Near-complete CD19 receptor occupancy and an absolute B-cell count nadir of approximately 50% baseline levels were maintained for the duration of the study in both populations. Obexelimab SC administration demonstrated favorable bioavailability, was well-tolerated, and showed no clinically meaningful ethnic differences in PK/PD. These results support further clinical development of SC obexelimab to treat B-cell mediated autoimmune diseases. NCT02867098.

Recalling what we thought we knew about recall periods: a qualitative descriptive study of how adults diagnosed with cancer use recall periods for patient-reported outcome items about physical function.

In cancer studies, assessment of patients' physical function can provide insight into cancer-related symptoms and the side effects of treatment. Physical function can be assessed using patient-reported outcome measures (PROMs), which may or may not include a recall period-the amount of time the questionnaire asks the respondent to think back to answer the questions. More understanding is needed about how patients interpret and respond to items posed with different recall periods, and which recall period they actually use. We conducted a qualitative study with 72 adults diagnosed with cancer to describe response processes when answering PROM items about physical function. When describing their physical function during concept elicitation interviews, most participants recalled their functioning over 1month or more. When presented with PROM items with no recall period, the most used period was more than 4weeks. When presented with a 7-day recall, the most used period was 7days. However, almost 30% of responses used recall periods greater than 1week. Including a 7-day recall period improves recall consistency for patients when answering physical function PROM items, but there is still room for improvement. The inaccuracy of recall for PROMs in clinical trials influences the ability to calculate the change in treatment outcomes over time and may conceal or emphasize actual treatment effects.

Behavior of PGS/apatite foam scaffolds during incubation in SBF, PBS, Ringer's solution, artificial saliva, and distilled water.

Poly(glycerol sebacate) is a polymeric material with potential biomedical application in the field of tissue engineering. In order to act as a biodegradable scaffold, its incubation study is vital to simulate its behavior. This study explores the degradation of porous poly(glycerol sebacate)/hydroxyapatite scaffolds subjected to incubation in various physiological solutions. The research involved monitoring pH and conductivity values over a 14-day period, as well as analyzing the swelling capacity and mass alterations of the scaffolds. In simulated body fluid (SBF) and phosphate-buffered saline (PBS), the pH levels remained relatively stable, whereas Ringer's solution caused a pH decrease. Conversely, artificial saliva demonstrated an increase in pH, and distilled water caused a slight decrease. The conductivity values remained stable in SBF and Ringer's solution, slightly decreased in PBS, increased in artificial saliva, and significantly increased in distilled water. The swelling capacity of the scaffolds varied depending on the solution used, with the lowest equilibrium swelling observed in SBF and PBS. The effect of the presence of ceramics on this parameter was also observed. The mass changes of the scaffolds indicated deposition of particles or salts from the incubation solutions, and subsequent rinsing in distilled water led to a decrease in mass. Scanning electron microscopy (SEM) imaging and elemental analysis confirmed the presence of crystallized salts on the scaffold surfaces after incubation in SBF. Surface roughness measurements revealed changes in roughness depending on the solution, with deposition of additional layers in SBF and degradation in artificial saliva. In summary, the scaffolds exhibited biodegradation in physiological solutions, with variations in pH, conductivity, swelling capacity, mass changes, and surface morphology depending on the specific solution and scaffold composition.