Early Phase Research Articles

Effect of prudent use of antimicrobials in the early phase of infection in pigs on the performance and meat quality of fattening pigs

The presented study was a part of the ThermoEye project. The study examined the effect of prudent antibiotic treatment in response to illness on the fattening performance, slaughter traits, and meat quality of the pig fatteners. Pigs were divided into an experimental group – EXP and a control – CON. In both groups, the body temperature was monitored, and diseases were confirmed by a veterinarian. In the EXP group, metaphylaxis was used in each case of confirmed disease. The EXP fatteners had greater slaughter weight (by 4.7 kg) and meatiness (by 2.1 percentage points) compared to the CON pigs. The pH in pork was lower in EXP compared to CON pigs. The longissimus thoracis et lumborum of EXP pigs was characterised by a lower cooking loss (28.30 vs. 30.45%) and yellower colour compared to the CON group. Among the amino acids, only the content of histidine (by 5.2%; P < 0.01) and tyrosine (by 7.2%; P < 0.01) was significantly greater in the meat of the CON group compared to EXP, with no effect of sex noted. The content of SFA (by 14.6%; P < 0.05), UFA (by 15.6%; P < 0.05), MUFA (by 17.8%; P < 0.05), MCFA (by 14.1%; P < 0.05), and LCFA (by 15.6%; P < 0.05) was also greater in CON compared to EXP meat. In conclusion, automated monitoring of pig body temperature during the fattening period enables more precise, prudent treatment and effective animal health control while reducing costs due to disease losses and pharmacotherapy. It allows optimal production and affects meat quality.

Early thrombus formation including hypo-attenuated leaflet thrombosis after surgical bioprosthetic aortic valve replacement.

To assess the occurrence, predictors, and outcomes of hypo-attenuated leaflet thickening (HALT) and thrombus outside the prosthetic valve following surgical aortic valve replacement. A total of 118 patients underwent surgical aortic valve replacement with bioprosthetic valves between July 2020 and June 2022. Sixty-two (52.5%) patients, which is a fairly high number of patients, underwent cardiac computed tomography and transthoracic echocardiography one week after surgery. Patients were divided into two groups, those with HALT (n = 14) and those without HALT (n = 48). Of the 62 patients who underwent cardiac computed tomography, HALT was observed in 14 (22.5%) patients during the very early postoperative phase. Reduced leaflet motion was observed in two of the 14 patients. The low-attenuation areas were located outside the prosthetic valve in 10 cases (71.4%) in the HALT group and in 14 cases (29.2%) in the non-HALT group. More than 50% of patients (57.1%) with HALT and 79.2% without HALT were administered warfarin. Neither in-hospital deaths nor postoperative thromboembolic events were observed during hospitalization. No patient had a mean pressure gradient > 20mmHg in either group. HALT was observed in one-fifth of the cases after surgical aortic valve replacement during the very early postoperative phase in an institution wherein administration of continuous heparin infusion after surgery is a standard practice. HALT did not affect the early prognosis or incidence of cerebral infarction.

Influence of Power-Weighted Center of Echo Signal Within Window Function on Local Strain Rate Distribution in Left Ventricular Wall

ObjectiveThe deviation of the power-weighted center of the echo signal from the geometric center within the velocity estimation window for calculating strain rate (SR) causes an estimation error. This study aimed to confirm whether an erroneous multilayer pattern in the SR distribution of the left ventricular wall could be corrected by considering the power-weighted center of the echo signal. MethodsThe SR distributions were measured locally in the transmural direction around the pre-ejection and early diastolic phases in healthy volunteers. The estimation error related to the power-weighted center of the echo signal was corrected using a previously proposed method, and the effectiveness of the correction was confirmed based on the accuracy of the estimated myocardial displacement. ResultsThe SR distribution in early diastole was observed as multilayers of low- and high-amplitude negative SRs. However, this multilayer pattern disappeared after correction. In the pre-ejection phase, multilayers of positive and negative SRs were observed in the SR distributions with and without correction. This correction was sufficiently effective in accurately tracking the local peak of the echo signal. ConclusionThe multilayer pattern of low- and high-amplitude positive or negative SRs is caused by estimation errors related to the power-weighted center of the echo signal. The multilayer pattern of positive and negative SRs might not be caused by these errors and might relate to the actual change in myocardial thickness because the estimation errors do not convert the negative (positive) SR to positive (negative) in a homogeneous negative (positive) SR distribution.

Time-shifted expression of acetoclastic and methylotrophic methanogenesis by a single Methanosarcina genomospecies predominates the methanogen dynamics in Philippine rice field soil

BackgroundThe final step in the anaerobic decomposition of biopolymers is methanogenesis. Rice field soils are a major anthropogenic source of methane, with straw commonly used as a fertilizer in rice farming. Here, we aimed to decipher the structural and functional responses of the methanogenic community to rice straw addition during an extended anoxic incubation (120 days) of Philippine paddy soil. The research combined process measurements, quantitative real-time PCR and RT-PCR of particular biomarkers (16S rRNA, mcrA), and meta-omics (environmental genomics and transcriptomics).ResultsThe analysis methods collectively revealed two major bacterial and methanogenic activity phases: early (days 7 to 21) and late (days 28 to 60) community responses, separated by a significant transient decline in microbial gene and transcript abundances and CH4 production rate. The two methanogenic activity phases corresponded to the greatest rRNA and mRNA abundances of the Methanosarcinaceae but differed in the methanogenic pathways expressed. While three genetically distinct Methanosarcina populations contributed to acetoclastic methanogenesis during the early activity phase, the late activity phase was defined by methylotrophic methanogenesis performed by a single Methanosarcina genomospecies. Closely related to Methanosarcina sp. MSH10X1, mapping of environmental transcripts onto metagenome-assembled genomes (MAGs) and population-specific reference genomes revealed this genomospecies as the key player in acetoclastic and methylotrophic methanogenesis. The anaerobic food web was driven by a complex bacterial community, with Geobacteraceae and Peptococcaceae being putative candidates for a functional interplay with Methanosarcina. Members of the Methanocellaceae were the key players in hydrogenotrophic methanogenesis, while the acetoclastic activity of Methanotrichaceae members was detectable only during the very late community response.ConclusionsThe predominant but time-shifted expression of acetoclastic and methylotrophic methanogenesis by a single Methanosarcina genomospecies represents a novel finding that expands our hitherto knowledge of the methanogenic pathways being highly expressed in paddy soils.7k5euw-hvBknz_jds4sXXfVideo

Long-term lymphocyte subset number reconstitution is unique but comparable between umbilical cord blood and unrelated bone marrow transplantation.

The number of umbilical cord blood transplantation (U-CBT) procedures has been growing annually, but little research has been done on long-term immune recovery after U-CBT. Infection risk is high in U-CBT recipients, and this can be partially attributed to immature immunocompetent cells in umbilical cord blood. In this study, we analyzed lymphocyte subset (LST) number to determine the long-term recovery timeline. We included 36 U-CBT and 10 unrelated bone marrow transplantation (U-BMT) recipients who survived more than 2years after transplantation, and followed them for up to 10years post-transplant. Recovery kinetics in the early phase post-transplant was different for each LST. Recovery of CD19+ B cells was faster after U-CBT than after U-BMT in the first 5years after transplantation. Although CD4+ T cells increased in the first several months after U-CBT, long-term cell count recovery was impaired in approximately 20% of patients. Thus, although the LST recovery pattern after U-CBT was unique, LST number recovery was statistically comparable between U-CBT and U-BMT past 5years post-transplantation.

Evaluation of fendiline treatment in VP40 system with nucleation-elongation process: a computational model of Ebola virus matrix protein assembly.

Ebola virus (EBOV) infection can cause deadly hemorrhagic fever, which has a mortality rate of ~50%-90% without treatment. The recent outbreaks in Uganda and the Democratic Republic of the Congo illustrate its threat to human health. Though two antibody-based treatments were approved, mortality rates in the last outbreak were still higher than 30%. This can partly be due to the requirement of advanced medical facilities for current treatments. As a result, it is very important to develop and evaluate new therapies for EBOV infection, especially those that can be easily applied in the developing world. The significance of our research is that we evaluate the potential of lipid-targeted treatments in reducing EBOV assembly and egress. We achieved this goal using the VP40 system combined with a computational approach, which both saves time and lowers cost compared to traditional experimental studies and provides innovative new tools to study viral protein dynamics.

Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical study

BackgroundVenous thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is based on complex imaging exams due to the lack of biomarkers. Recent multi-omics based research has contributed to the development of novel biomarkers in cardiovascular diseases. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile compared to non-acute VTE.MethodsThis observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis or pulmonary embolism, admitted to the emergency room. There were 50 patients diagnosed with acute VTE and 12 with non-acute VTE conditions and no significant differences were found between the two groups for clinical and demographic characteristics. Metabolomics assays identified and quantified a final number of 91 metabolites in plasma and 55 metabolites in red blood cells (RBCs). Plasma from acute VTE patients expressed tendency to a specific metabolomic signature, with univariate analyses revealing 23 significantly different molecules between acute VTE patients and controls (p < 0.05). The most relevant metabolic pathway with the strongest impact on the acute VTE phenotype was d-glutamine and d-glutamate (p = 0.001, false discovery rate = 0.06). RBCs revealed a specific metabolomic signature in patients with a confirmed diagnosis of DVT or PE that distinguished them from other acutely diseased patients, represented by 20 significantly higher metabolites and four lower metabolites. Three of those metabolites revealed high performant ROC curves, including adenosine 3′,5′-diphosphate (AUC 0.983), glutathione (AUC 0.923), and adenine (AUC 0.91). Overall, the metabolic pathway most impacting to the differences observed in the RBCs was the purine metabolism (p = 0.000354, false discovery rate = 0.68).ConclusionsOur findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.

The Variability of the Components of Fitness along the Menstrual Cycle.

This study aims to determine the variability of the components of fitness along the menstrual cycle (MC) of physically active eumenorrheic women. Fifteen subjects were monitored along two consecutive MCs through the calendar-based counting method in combination with a urine luteinizing hormone surge kit. Subjects were tested at the early follicular phase (EFP), pre-ovulatory or late follicular phase (LFP), and post-ovulatory or mid-luteal phase (MLP). In each session, the back squat one-repetition maximum (1-RM), maximum fat oxidation (MFO), maximum oxygen uptake (VO2max) and acute recovery capacity were determined. The results revealed a wide variability among components of fitness and a low to high variability among subjects (acute recovery: 3.6% [range 1.5 to 9.5%]; back squat 1-RM: 6.1% [range 2.2 to 11%]; VO2max: 6.6% [range 1.1 to 15%]; MFO: 23% [range 4.6 to 35%]). Despite the individual nature, considering the number and magnitude of the responses in each MC phase, VO2max and acute recovery capacity tended to be enhanced at the LFP, the MFO at the MLP, and the back squat 1-RM remained stable along the MC. Thus, practitioners are aware of which components are susceptible to change along the MC phase, but an individual monitoring is recommended.

Reply to the comment on Sanz-Pérez et al., “Paleoenvironment and paleoecology associated with the early phases of the Great American Biotic Interchange based on stable isotope analysis of fossil mammals and new U[sbnd]Pb ages from the Pampas of Argentina” [Palaeogeography, Palaeoclimatology, Palaeoecology 634 (2024), 111917

In the comment on our paper, Prevosti et al. (2024) make a series of criticisms regarding the alleged lack of information provided on the dated samples and their geographic and stratigraphic provenance. In this contribution, we will give a reply to their comments. Our new zircon dating achieves the objective of the original study and provides valuable insights into the paleoecological dynamics of the period. It was out of the scope for our work to undertake a high resolution stratigraphical/sedimentological and dating analysis of each of the selected outcrops/sites.

Surviving the Storm: Exploring Lives Through Personal Stories of Childhood Trauma

Background: Traumatic experiences in an early phase of an individual’s life stand out as a highly influential risk factor for poor developmental outcomes. Studies examining poor childhood experiences revealed childhood trauma linked to a negative impact on mental health. Therefore, the objective of this study is to comprehend and investigate the subjective childhood experiences of the affected children. Methods: A qualitative approach was adopted to explore the lived experiences with their consequences. The study employed a purposeful sampling technique to choose adolescents who had encountered abuse and were capable of articulating their experiences with clarity. In-depth interviews were carried out with 18 adolescents aged 13–18 years, all from childcare homes (mean = 16, SD = 1.46). The transcriptions of these interviews were analyzed using a thematic approach. Results: The analysis indicated that the children experienced physical abuse, sexual abuse, rape, abandonment, and neglected home environment. The children took responsibility for the abuse directed toward them and were also engaged in substance use. They further reported experiencing negative effects on their behavioral functions (anger, isolation), cognitive function (difficulty in concentration, low academic performances), emotional function (fear, helplessness), social function (withdrawal, mutism), and biological function (sleeplessness, lack of appetite) due to the adverse events in their life. Perceived needs, for instance, emotional, social, and educational support and positive relationship, as well as growth from traumatic experiences were stated by the children. Conclusion: The findings of the study could have practical implications for clinicians, aiding in the understanding of low emotional expression and unexplained behavior among individuals and assisting in addressing the underlying vulnerability to facilitate their overcoming of these challenges. Additionally, it is suggested that a comprehensive strategy be used that addresses stigma, cultural values, and social norms in addition to legal issues to address the problem.

Achievement of adequate nutrition contributes to maintaining the skeletal muscle area in patients with sepsis undergoing early mobilization: a retrospective observational study

BackgroundThe onset of muscle loss in critically ill patients, known as intensive care unit-acquired weakness (ICU-AW), worsens their outcomes. Preventing muscle loss, which begins in the early phase of critical illness, is crucial in patient care. Adequate nutrition management may contribute to maintaining muscles; however, its evidence in patients with sepsis is insufficient. This study aimed to analyze the association between energy achievement rate in the first 7-days of critical care and muscle area changes evaluated by computed tomography (CT).MethodsThis was a retrospective observational study. Patients with sepsis admitted to the intensive care (ICU) of a tertiary care hospital in Japan were included. They were divided into three groups according to tertiles of the first 7-day energy achievement rate calculated using administered energy doses and basement energy expenditure. Skeletal muscle area (SMA) and changes in SMA were determined by CT on ICU admission and within days 7–10 of ICU admission. SMA maintenance was defined as SMA change ≥ 100%. Logistic regression analyses were performed to analyze the association of energy achievement rate with SMA changes (primary outcome) and in-hospital 28-day mortality (secondary outcome).ResultsPatients (n = 93) were classified into low, middle, and high groups according to their 7-day energy achievement rate (median rates, 16.8%, 38.8%, and 73.4%, respectively). The CT scans showed that SMA decreased between the CT scans in the low and middle groups, whereas it was maintained in the high group (median changes, -8.5%, -11.7%, and 2.8%, respectively). Univariate and multivariate logistic regression analyses showed that high energy achievement rate was significantly associated with SMA maintenance (reference, middle energy achieved group; univariate, odds ratio [95% confidence interval] 6.23 [2.04–19.10], P = 0.0013; multivariate, odds ratio [95% confidence interval] 5.92 [1.90–18.40], P = 0.0021). There was no significant difference in the association between energy achievement rate and mortality among the three groups.ConclusionsOur study found that a fulfillment of energy achievement in the first 7 days of hospitalization was associated with maintenance of muscle area. Thus, satisfying adequate energy should be considered even in patients with sepsis.

Comment on “Paleoenvironment and paleoecology associated with the early phases of the Great American Biotic Interchange based on stable isotope analysis of fossil mammals and new U[sbnd]Pb ages from the Pampas of Argentina” by Sanz-Pérez et al. [Palaeogeography, Palaeoclimatology, Palaeoecology, 634 (2024), 111917

Sanz-Pérez et al. (2024) recently, based on detrital zircon, presented new maximum depositional ages for several sites of the Neogene of central Argentina to constraint the age of the faunas studied with stable isotopes. Unfortunately, the precise provenance of the dated samples is not clear. In this comment, we discuss the absence of key basic information to replicate their (geochronological) study, or even to evaluate their inferences and conclusions. Without more information about the precise geographic provenance of the dated detrital zircons, and their stratigraphic position in the geological profile/schema of each locality the interpretation of the authors is not supported by the presented information.

A Swine Burn Model for Investigating the Healing Process in Multiple Depth Burn Wounds.

Burn wound healing is a complex and long process. Despite extensive experience, plastic surgeons and specialized teams in burn centers still face significant challenges. Among these challenges, the extent of the burned soft tissue can evolve in the early phase, creating a delicate balance between conservative treatments and necrosing tissue removal. Thermal burns are the most common type, and burn depth varies depending on multiple parameters, such as temperature and exposure time. Burn depth also varies in time, and the secondary aggravation of the "shadow zone" remains a poorly understood phenomenon. In response to these challenges, several innovative treatments have been studied, and more are in the early development phase. Nanoparticles in modern wound dressings and artificial skin are examples of these modern therapies still under evaluation. Taken together, both burn diagnosis and burn treatments need substantial advancements, and research teams need a reliable and relevant model to test new tools and therapies. Among animal models, swine are the most relevant because of their strong similarities in skin structure with humans. More specifically, Yucatan minipigs show interesting features such as melanin pigmentation and slow growth, allowing for studying high phototypes and long-term healing. This article aims to describe a reliable and reproducible protocol to study multi-depth burn wounds in Yucatan minipigs, enabling long-term follow-up and providing a relevant model for diagnosis and therapeutic studies.

A Free Streamline Model for Fully Separated Turbomachine Flows

Abstract This paper describes the use of the free streamline approach to determine flows in fully separated cascades, and to thereby provide a rational basis for estimating the performance of axial turbomachinery at severely off-design conditions. On the assumption of two-dimensional, incompressible flow, the free streamlines that bound the separated region are determined using the hodograph method, in which the methods of complex analysis are used to define a tractable numerical problem. The resulting jet-wake flow profile at cascade exit is then presumed to undergo mixing at constant-area, from which performance parameters for the cascade can be determined. The proposed method is verified by comparison against flat plate cascade solutions and by checks against momentum conservation. Validation of the free streamline approach is carried out by comparison against several cascade configurations for which experimental data and simulation results are available. In general, the predictions based upon the present theoretical model are found to be good, especially for negative incidences such as those that occur in the compressor section of an engine operating at sub-idle conditions. This suggests that the present approach can be used in the estimation of turbomachinery performance maps far from the design point, especially during early design phases.

Chronic heart failure induces early defenestration of liver sinusoidal endothelial cells (LSECs) in mice.

Chronic heart failure (CHF) is often linked to liver malfunction and systemic endothelial dysfunction. However, whether cardio-hepatic interactions in heart failure involve dysfunction of liver sinusoidal endothelial cells (LSECs) is not known. Here we characterize LSECs phenotype in early and end stages of chronic heart failure in a murine model. Right ventricle (RV) function, features of congestive hepatopathy, and the phenotype of primary LSECs were characterized in Tgαq*44 mice, with cardiomyocyte-specific overexpression of the Gαq protein, at the age of 4- and 12-month representative for early and end-stage phases of CHF, respectively. 4- and 12-month-old Tgαq*44 mice displayed progressive impairment of RV function and alterations in hepatic blood flow velocity resulting in hepatic congestion with elevated GGT and bilirubin plasma levels and decreased albumin concentration without gross liver pathology. LSECs isolated from 4- and 12-month-old Tgαq*44 mice displayed significant loss of fenestrae with impaired functional response to cytochalasin B, significant changes in proteome related to cytoskeleton remodeling, and altered vasoprotective function. However, LSECs barrier function and bioenergetics were largely preserved. In 4- and 12-month-old Tgαq*44 mice, LSECs defenestration was associated with prolonged postprandial hypertriglyceridemia and in 12-month-old Tgαq*44 mice with proteomic changes of hepatocytes indicative of altered lipid metabolism. Tgαq*44 mice displayed right-sided HF and altered hepatic blood flow leading to LSECs dysfunction involving defenestration, shift in eicosanoid profile, and proteomic changes. LSECs dysfunction appears as an early and persistent event in CHF, preceding congestive hepatopathy and contributing to alterations in lipoprotein transport and CHF pathophysiology.

Exploring the nigrostriatal and digestive interplays in Parkinson's disease using dynamic total-body [11C]CFT PET/CT.

Dynamic total-body imaging enables new perspectives to investigate the potential relationship between the central and peripheral regions. Employing uEXPLORER dynamic [11C]CFT PET/CT imaging with voxel-wise simplified reference tissue model (SRTM) kinetic modeling and semi-quantitative measures, we explored how the correlation pattern between nigrostriatal and digestive regions differed between the healthy participants as controls (HC) and patients with Parkinson's disease (PD). Eleven participants (six HCs and five PDs) underwent 75-min dynamic [11C]CFT scans on a total-body PET/CT scanner (uEXPLORER, United Imaging Healthcare) were retrospectively enrolled. Time activity curves for four nigrostriatal nuclei (caudate, putamen, pallidum, and substantia nigra) and three digestive organs (pancreas, stomach, and duodenum) were obtained. Total-body parametric images of relative transporter rate constant (R1) and distribution volume ratio (DVR) were generated using the SRTM with occipital lobe as the reference tissue and a linear regression with spatial-constraint algorithm. Standardized uptake value ratio (SUVR) at early (1-3min, SUVREP) and late (60-75min, SUVRLP) phases were calculated as the semi-quantitative substitutes for R1 and DVR, respectively. Significant differences in estimates between the HC and PD groups were identified in DVR and SUVRLP of putamen (DVR: 4.82 ± 1.58 vs. 2.58 ± 0.53; SUVRLP: 4.65 ± 1.36 vs. 2.84 ± 0.67; for HC and PD, respectively, both p < 0.05) and SUVREP of stomach (1.12 ± 0.27 vs. 2.27 ± 0.65 for HC and PD, respectively; p < 0.01). In the HC group, negative correlations were observed between stomach and substantia nigra in both the R1 and SUVREP values (r=-0.83, p < 0.05 for R1; r=-0.94, p < 0.01 for SUVREP). Positive correlations were identified between pancreas and putamen in both DVR and SUVRLP values (r = 0.94, p < 0.01 for DVR; r = 1.00, p < 0.001 for SUVRLP). By contrast, in the PD group, no correlations were found between the aforementioned target nigrostriatal and digestive areas. The parametric images of R1 and DVR generated from the SRTM model, along with SUVREP and SUVRLP, were proposed to quantify dynamic total-body [11C]CFT PET/CT in HC and PD groups. The distinction in correlation patterns of nigrostriatal and digestive regions between HC and PD groups identified by R1 and DVR, or SUVRs, may provide new insights into the disease mechanism.

The Effect of Oxidative Stress on the Human Voice.

The vocal fold vibrates in high frequency to create voice sound. The vocal fold has a sophisticated histological "layered structure" that enables such vibration. As the vibration causes fricative damage to the mucosa, excessive voicing can cause inflammation or injury to the mucosa. Chronic inflammation or repeated injury to the vocal fold occasionally induces scar formation in the mucosa, which can result in severe dysphonia, which is difficult to treat. Oxidative stress has been proven to be an important factor in aggravating the injury, which can lead to scarring. It is important to avoid excessive oxidative stress during the wound healing period. Excessive accumulation of reactive oxygen species (ROS) has been found in the injured vocal folds of rats during the early phase of wound healing. Antioxidants proved to be useful in preventing the accumulation of ROS during the period with less scar formation in the long-term results. Oxidative stress is also revealed to contribute to aging of the vocal fold, in which the mucosa becomes thin and stiff with a reduction in vibratory capacity. The aged voice can be characterized as weak and breathy. It has been confirmed that ROS gradually increases in rat vocal fold mucosa with age, which may cause further damage to the vocal fold. Antioxidants have also proved effective in avoiding aging of the vocal fold in rat models. Recently, human trials have shown significant effects of the antioxidant Twendee X for maintaining the voice of professional opera singers. In conclusion, it is suggested that oxidative stress has a great impact on the damage or deterioration of the vocal folds, and the use of antioxidants is effective for preventing damage of the vocal fold and maintaining the voice.

Pain in axial spondyloarthritis: role of the JAK/STAT pathway.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that is characterized by new bone formation in the axial musculoskeletal system, with X-ray discriminating between radiographic and non-radiographic forms. Current therapeutic options include non-steroidal anti-inflammatory drugs in addition to biological disease-modifying anti-rheumatic drugs that specifically target tumor necrosis factor-alpha (TNFα) or interleukin (IL)-17. Pain is the most critical symptom for axSpA patients, significantly contributing to the burden of disease and impacting daily life. While the inflammatory process exerts a major role in determining pain in the early phases of the disease, the symptom may also result from mechanical and neuromuscular causes that require complex, multi-faceted pharmacologic and non-pharmacologic treatment, especially in the later phases. In clinical practice, pain often persists and does not respond further despite the absence of inflammatory disease activity. Cytokines involved in axSpA pathogenesis interact directly/indirectly with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling cascade, a fundamental component in the origin and development of spondyloarthropathies. The JAK/STAT pathway also plays an important role in nociception, and new-generation JAK inhibitors have demonstrated rapid pain relief. We provide a comprehensive review of the different pain types observed in axSpA and the potential role of JAK/STAT signaling in this context, with specific focus on data from preclinical studies and data from clinical trials with JAK inhibitors.

A framework for evaluating the diversity of clinical trials

ObjectivesThe topic of diversity in clinical trials is rising to the forefront of many conversations in evidence-based medicine, and efforts are being made to improve the diversity of clinical trials. However, there is little uniformity in the methods used to evaluate these efforts. In this article, we describe our Clinical trial Diversity Rating (CDR) framework and the development process, including the broader considerations for evaluating the demographic diversity of clinical trials and their implications, and demonstrate its use through an illustrative example. Study Design and SettingThe development of the framework was a four-step process, including a scoping review, a cross-sectional study, creation of the tool, and integration of feedback from an advisory group. ResultsOur scoping review identified 110 publications that examined clinical trial diversity. Race/ethnicity, sex, and age were the most common characteristics evaluated. About 85% clearly defined the benchmark used for evaluation, but less than half (48%) used disease prevalence as the benchmark. Only 64% of studies defined what would be considered adequate representation. The cross-sectional study, which applied some of the approaches identified in the literature, helped to identify the complexities of evaluating multinational trials and certain demographic characteristics. Key decisions for the CDR framework, such as the demographic characteristics to be evaluated, the benchmark and thresholds for evaluation, and how these factors contribute to the overall rating of clinical trial diversity, were informed by the two earlier phases and feedback from an advisory group. ConclusionThe CDR framework provides an objective and transparent approach to evaluating clinical trial diversity. Groups such as Health Technology Assessment bodies, clinical trial regulators, policymakers, journal editors, and individual researchers can use this tool to examine, monitor, and improve diversity in clinical trials.

Association of multi-phase rates of force development during an isometric leg press with vertical jump performances.

This study aimed to elucidate characteristics of explosive force-production capabilities represented by multi-phase rate of force developments (IRFDs) during isometric single-leg press (ISLP) through investigating relationships with countermovement (CMJ) and rebound continuous jump (RJ) performances. Two-hundred-and-thirty male athletes performed ISLP, CMJ with an arm swing (CMJAS), and RJ with an arm swing (RJAS). IRFDs were measured during ISLP using a custom-built dynamometer, while CMJAS and RJAS were measured on force platforms. The IRFDs were obtained as rates of increase in force across 50 ms in the interval from the onset to 250 ms. Jump height (JH) was obtained from CMJAS, while RJAS provided JH, contact time (CT), and reactive strength index (RSI) values. All IRFDs were correlated with CMJAS-JH (ρ = 0.20-0.45, p ≤ 0.003), RJAS-JH (ρ = 0.22-0.46, p ≤ 0.001), RJAS-RSI (ρ = 0.29-0.48, p < 0.001) and RJAS-CT (ρ = -0.29 to -0.25, p ≤ 0.025). When an influence of peak force was considered using partial rank correlation analysis, IRFDs during onset to 150 ms were correlated with CMJAS-JH (ρxy/z = 0.19-0.36, p ≤ 0.004), IRFDs during onset to 100 ms were correlated with RJAS-JH and RJAS-RSI (ρxy/z = 0.33-0.36, p < 0.001), and IRFD during onset to 50 ms was only correlated with RJAS-CT (ρxy/z = -0.23, p < 0.001). The early phase (onset to 150 ms) IRFDs measured using ISLP enabled the assessment of multiple aspects of leg-extension strength characteristics that differ from maximal strength; these insights might be useful in the assessment of the athletes' leg-extension strength capabilities.