Early Changes Research Articles

Sex Differences in Strength During Development: Implications for Inclusivity and Fairness in Sport.

Males, on average, are bigger and stronger than females. Hormonal differences during puberty are one reason given for this performance advantage. However, not all evidence supports that thesis. Our aim was to further this discussion by measuring early life changes between sexes (when hormones would be similar) in components of muscle function. Fifty-one children (29 boys, 22 girls) completed this study. Forearm muscle size and strength were assessed three times with each time point being separated by approximately a year (2021-2023). There was no sex*time interaction for handgrip strength (p = 0.637). There was, however, a time (p < 0.001) and sex (p < 0.001) effect. Strength increased each year and boys were stronger than girls (difference of 1.5 [95% 0.7, 2.3] kg). There was no sex*time interaction for ulnar muscle thickness (p = 0.714) but there was a time (p < 0.001) effect. Muscle size increased each year but there was no evidence of a sex effect (p = 0.12; difference of 0.81 [95% -0.21, 1.8] mm). A strong positive within-participant correlation between muscle size and strength (r = 0.803 95% CI: [0.72, 0.86], p < 0.0001) was found across time. Muscle size and strength increased together but this increase did not differ based on sex and boys were stronger than girls. Future work is needed to determine the reason for this difference in maximal strength. Any effect was seemingly present at the initial measurement (at the age of 4 years), since muscle size and strength did not change differently between boys and girls over time.

The anti-inflammatory effects of Fuzapladib in an endotoxemic porcine model.

Endotoxemia is a systemic inflammatory condition caused by lipopolysaccharide (LPS) stimulation, which produces inflammatory cytokines. Fuzapladib (FZP) inhibits the activation of adhesion molecules found on the surface of inflammatory cells, mitigating inflammation. In this study, we evaluated the therapeutic effects of fuzapladib on inflammatory cytokines and cardio-respiratory function using an LPS-induced endotoxemic porcine model. Fifteen pigs were separated into three groups: low-FZP (n=5), high-FZP (n=5), and control (n=5). Pigs were administered LPS under general anesthesia, and complete blood cell count, blood biochemistry, inflammatory cytokines, and cardio-respiratory function were evaluated. Statistical analysis was performed using a linear mixed-effects model and the Steel-Dwass test, with a significance threshold of P<0.05. During the 4 hr experimental period, one pig in the control group and two pigs in the low-FZP group died due to hypoxemia and hypotension. In the early acute changes following LPS administration, the high-FZP group maintained significantly higher arterial oxygen partial pressure and normal blood pressure compared to the control group. Although interleukin-6 levels increased in all groups during the experiment, they were significantly lower in the high-FZP group compared to the control group. Other parameters showed no clinically significant differences. In conclusion, while high-dose fuzapladib did not reduce organ damage in the porcine endotoxemia model, it suppressed interleukin-6 production, delayed the progression of deterioration, and contributed to a reduction in mortality during the observation period.

The treatment effect across ASPECTS in acute ischemic stroke: Analysis from the AcT trial.

Early ischemic changes on baseline imaging are commonly evaluated for acute stroke decision-making and prognostication. We assess the association of early ischemic changes on clinical outcomes and whether it differs between intravenous tenecteplase and Alteplase. Data are from the phase 3, Alteplase compared to Tenecteplase (AcT) trial. Subjects with anterior circulation stroke were included. Early ischemic changes were assessed using the Alberta Stroke Program Early CT score (ASPECTS). Efficacy outcomes included modified Rankin scale (mRS) 0-1, mRS 0-2, and ordinal mRS at 90 days. Safety outcomes included 24-h symptomatic intracerebral hemorrhage (sICH), any hemorrhage on follow-up scan, and 90-day mortality rate. Mixed-effects logistic regression was used to assess the association of ASPECTS (continuous and categorical (0-4 vs 5-7 vs 8-10)) with outcomes and if these associations were modified by thrombolytic type after adjusting for age, sex, and baseline stroke severity. Of the 1577 patients in the trial, 901 patients (56.3%; median age 75 years (IQR 65-84), 50.8% females, median National Institute of Health Stroke Scale (NIHSS) 14 (IQR 17-19)) with anterior circulation stroke were included. mRS 0-1 at 90 days was achieved in 1/14 (0.3%), 43/160 (14.7%), and 252/726 (85.1%) in the ASPECTS 0-4, 5-7, and 8-10 groups respectively. Every one-point decrease in ASPECTS was associated with 2.7% and 1.9% decrease in chances of mRS 0-1 and mRS 0-2 at 90 days, respectively, and 1.9% chances of increase in mortality at 90 days. Subgroup analysis in endovascular thrombectomy (EVT)-treated population showed similar results. Thrombolytic type did not modify this association between ASPECTS and 90-day mRS 0-1 (P-interaction 0.75). There was no significant interaction by thrombolytic type with any other outcomes. Similar to prior studies, we found that every one-point decrease in ASPECTS was associated with poorer clinical and safety outcomes. This effect did not differ between alteplase and tenecteplase. Data shall made available on reasonable request from the PI (BMM).

Ultrasonographic assessment of the fetal heart in intrahepatic cholestasis of pregnancy: Pulsed wave Doppler, M-mode, and tissue Doppler imaging prospective study.

To investigate the fetal heart using pulsed wave Doppler, M-mode, and tissue Doppler imaging (TDI) in cases of intrahepatic cholestasis of pregnancy (ICP). This prospective study was conducted at a single tertiary center and included 35 patients with ICP and 70 healthy pregnant women at 28-36 weeks of pregnancy. Among the patients with ICP, 26 had serum bile acid (SBA) levels less than 40 μmol/L and nine had SBA levels of 40 μmol/L or greater. Pulsed wave Doppler, M-mode, and TDI evaluations were performed on the patients to assess fetal cardiac function. The ICP group exhibited significantly higher myocardial performance index (MPI) and isovolumetric relaxation time (IRT), but similar isovolumetric contraction time (ICT). The tricuspid and mitral valve E, A, and E/A ratios were significantly reduced in the ICP group. The TDI parameters showed significantly reduced tricuspid and mitral valve E'/A' ratios in the ICP group compared with the control group (P < 0.001). The E/E' ratio was significantly increased in the ICP group (P < 0.001). According to the M-mode Doppler findings, tricuspid and mitral annular plane systolic excursion values were significantly decreased in the ICP group (P = 0.005 and P = 0.001, respectively). In the subgroup analysis, MPI and IRT were significantly higher in the severe ICP group. ICP might induce changes in the fetal heart during the early systolic and diastolic phases. The detection of these early changes using M-mode and TDI during the antenatal period can provide valuable insights into the condition of the fetus.

Early and gland-specific changes in gene expression in response to LPS-induced mastitis in a single quarter of Holstein cows

Early and gland-specific changes in gene expression in response to LPS-induced mastitis in a single quarter of Holstein cows

Twenty-Four-Hour Post-Thrombolysis NIHSS Score As the Strongest Prognostic Predictor After Acute Ischemic Stroke: ENCHANTED Study.

This study was conducted to determine optimal predictive ability of National Institutes of Health Stroke Scale (NIHSS) measurements at baseline, 24 hours, and change from baseline to 24 hours after thrombolysis on functional recovery in patients with acute ischemic stroke who participated in the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). ENCHANTED was an international, multicenter, 2×2 quasifactorial, prospective, randomized open trial of low-dose versus standard-dose intravenous alteplase and intensive versus guideline-recommended blood pressure lowering in thrombolysis-eligible patients with acute ischemic stroke. Absolute (baseline minus 24 hours) and percentage (absolute change/baseline × 100) changes in NIHSS scores were calculated. Receiver operating characteristic curve analyses assessed performance of different NIHSS measurements on 90-day favorable functional recovery (modified Rankin Scale [mRS] score 0-2) and excellent functional recovery (mRS score 0-1). Youden index was used to identify optimal predictor cutoff points. A total of 4410 patients in the ENCHANTED trial were enrolled. The 24-hour NIHSS score had the highest discriminative ability for predicting favorable 90-day functional recovery (mRS score 0-2; area under the curve 0.866 versus 0.755, 0.689, 0.764; P<0.001) than baseline, absolute, and percentage change of NIHSS score, respectively. The optimal cutoff point of 24-hour NIHSS score for predicting favorable functional recovery was ≤4 (sensitivity 66.5%, specificity 87.1%, adjusted odds ratio, 9.44 [95% CI, 7.77-11.48]). The 24-hour NIHSS score (≤3) was the best predictor of 90-day excellent functional recovery (mRS score 0-1). Findings were consistent across subgroups, including sex, race, baseline NIHSS score, stroke subtype, and age. In thrombolysis-eligible patients with acute ischemic stroke, 24-hour NIHSS score (optimal cutpoint of 4) is the strongest predictor of 90-day functional recovery over baseline and early change of NIHSS score. URL: https://clinicaltrials.gov. Unique Identifier: NCT01422616.

Deep Learning-Based ASPECTS Algorithm Enhances Reader Performance and Reduces Interpretation Time.

ASPECTS is a long-standing and well documented selection criteria for acute ischemic stroke treatment, however, the interpretation of ASPECTS is a challenging and time-consuming task for physicians with significant interobserver variabilities. We conducted a multi-reader, multi-case study in which readers assessed ASPECTS without and with the support of a deep learning (DL)-based algorithm in order to analyze the impact of the software on clinicians' performance and interpretation time. A total of 200 NCCT scans from 5 clinical sites (27 scanner models, 4 different vendors) were retrospectively collected. Reference standard was established through the consensus of three expert neuroradiologists who had access to baseline CTA and CTP data. Subsequently, eight additional clinicians (four typical ASPECTS reader and four senior neuroradiologists) analyzed the NCCT scans without and with the assistance of CINA-ASPECTS (Avicenna.AI, La Ciotat, France), a DLbased FDA-cleared and CE-marked algorithm designed to automatically compute ASPECTS. Differences were evaluated in both performance and interpretation time between the assisted and unassisted assessments. With software aid, readers demonstrated increased region-based accuracy from 72.4% to 76.5% (p<0.05), and increased ROC AUC from 0.749 to 0.788 (p<0.05). Notably, all readers exhibited an improved ROC AUC when utilizing the software. Moreover, use of the algorithm improved the score-based inter-observer reliability and correlation coefficient of ASPECTS evaluation by 0.222 and 0.087 (p<0.0001), respectively. Additionally, the readers' mean time spent analyzing a case was significantly reduced by 6% (p<0.05) when aided by the algorithm. With the assistance of the algorithm, readers' analyses were not only more accurate but also faster. Additionally, the overall ASPECTS evaluation exhibited greater consistency, less variabilities and higher precision compared to the reference standard. This novel tool has the potential to enhance patient selection for appropriate treatment by enabling physicians to deliver accurate and timely diagnosis of acute ischemic stroke. ASPECTS = Alberta Stroke Program Early Computed Tomography Score; DL = Deep Learning; EIC = Early Ischemic Changes; ICC = Intraclass Correlation Coefficient; IS = Ischemic Stroke; ROC AUC = Receiver Operating Characteristics Area Under the Curve.

Slipped capital femoral epiphysis: emphasis on early recognition and potential pitfalls.

Slipped capital femoral epiphysis is a shearing injury through the growth plate of the proximal femur and is the most common hip disorder in adolescence. Delays in diagnosis persist across practice settings despite ongoing innovations in imaging. Recent insights into pathomechanics highlight the importance of femoral head surface morphology and rotational microinstability centered at the epiphyseal tubercle in causing early physeal changes, which can be detected on imaging prior to frank slip. Scrutiny of physeal morphology and comparison to the contralateral hip is critical at all stages of disease progression, and improper technique may result in undue diagnostic delay. Selective use of cross-sectional imaging can be helpful for troubleshooting equivocal early slips and can inform operative technique and adjuvant therapy candidacy in more severe cases. This review provides a comprehensive approach to imaging suspected slipped capital femoral epiphysis, with an emphasis on early detection and potential pitfalls.

BJS 1 - Endoscopic histopathology results in patients undergoing oesophageal cell collection device and biomarker testing for Barrett’s oesophagus surveillance

Abstract Aims Barrett’s oesophagus surveillance places significant burden on endoscopy services, yet is fundamental to detect early cancerous change. Oesophageal cell collection device (OCCD) testing was introduced across Scotland for Barrett’s surveillance in response to the COVID-19 pandemic. This national retrospective study presents the CytoSCOT programme results and evaluates whether OCCD testing is successfully identifying high-risk Barrett’s patients requiring urgent endoscopy. Methods All patients undergoing OCCD testing using Cytosponge(TM) for Barrett’s surveillance across 11 Scottish health boards over a 32-month period were identified. Patients who underwent endoscopy within 12 months of OCCD test were included. Individual patient records were interrogated to record clinical information and OCCD test result to categorise patients into risk groups: endoscopic histopathology results were analysed according to risk group and segment length. Patients were deemed high-risk if the OCCD test demonstrated atypia and/or p53 positivity. Results 4204 Barrett’s OCCD tests were performed in 3745 patients: 608 patients had an endoscopy within 12 months and were included in this analysis. Patients with longer Barrett’s segments were significantly more likely to have an abnormal OCCD test (p&amp;lt;0.001). 50/608 patients (8.2%) had high grade dysplasia or cancer on endoscopic biopsies: this relays to 1.3% of the total group (50/3745). 46/50 patients (92.0%) were deemed high-risk, triggering urgent endoscopy: this rose to 100% with insufficient tests removed. There were no missed cancers within 12 months of OCCD test in our cohort. Conclusions OCCD testing is an effective triage tool to identify high-risk Barrett’s surveillance patients requiring further investigation with urgent UGI endoscopy within the real-world setting.

A new method of intraoperative assessment of the dynamics of cortical blood flow using imaging photoplethysmography

Background. Intraoperative assessment of changes in cerebral blood flow is an important component of objective quality control of surgical treatment of cerebral artery aneurysms. Various techniques have been tried to solve this task, but they all have their drawbacks, which forces us to look for new ways of blood flow monitoring. We propose to use the technology of imaging photoplethysmography (IPPG) – a technically simple, contactless, safe and cheap optical method for assessing the perfusion of biological tissues.Aim. To demonstrate the possibility of using IPPG to assess the dynamics of cerebral blood flow parameters during aneurysm clipping surgery, as well as to identify early changes in blood supply to the cerebral cortex.Materials and methods. The study was carried out during six surgeries of clipping aneurysms of the anterior part of the Willis’s circle, both in the acute stage of rupture (n = 1) and in a planned manner (n = 5). The IPPG system, which is an LED illuminator in a single unit with a digital video camera, was located on a tripod 25 cm from the intervention zone. During each operation, two one-minute recordings of the illuminated surface of the cerebral cortex were performed: after dissection of the dura mater and before its suturing at the end of the main stage of the intervention. To improve the measurement accuracy, video frames of the studied area were recorded synchronously with the registration of an electrocardiogram. After recording, two IPPG parameters were calculated and compared: the amplitude of the pulsatile component and the pulse wave transit time. Thereafter, the obtained data were compared with the results of computed tomography. Statistical analysis was performed using pairwise comparison tests in the GraphPad Prism software package.Results. Clipping of cerebral vessel aneurysms are accompanied by significant changes in the parameters of cerebral blood flow. Analysis of the data for all patients revealed significant differences in IPPG parameters before and after surgery, namely, statistically significant increase in amplitude of the pulsatile component (n = 3) and decrease in pulse wave transit time (n = 5). The absence of significant changes in both parameters was found only in one patient who had mechanical damage in the cortex in the region of video recording.Conclusion. The IPPG system is capable to quantify changes in blood supply to the cortex during surgical treatment of cerebral artery aneurysms and to identify areas with either increased or decreased blood supply. In-depth studies are required to obtain additional markers of the postoperative state of cerebral blood flow.

Oral donor site evaluation in the early and late postoperative periods for augmentation and replacement urethroplasty

Introduction. The use of oral mucosa in augmentation and replacement urethroplasty is the gold standard for several reasons. Most commonly, the mucous membrane of the cheek, the underside of the tongue or lip is employed. Assessing postoperative complications in the donor area is crucial as it impacts patients' quality of life.Objective. To evaluate early and late postoperative changes in the donor area after oral graft extraction for urethroplastyMaterials &amp; methods. A retrospective analysis of the results of surgical treatment using oral mucosa from 2017 to 2022 was carried out. The study included 65 patients. The intensity of pain syndrome in the graft sampling area was assessed by patients on a visual analog scale (VAS). The donor area was sutured only in the case of tongue and lip mucosa sampling.Results. The mucous membrane of the oral cavity was harvested from different sites in 65 patients. Specifically, it was taken from the inside of the cheek in 49 patients (75.38%), from both inner sides of the cheeks in 13 (20.0%), the lower lip in two (3.07%) and the lower surface of the tongue in one (1.54%) patient, respectively. On the first day after surgery, the median pain level according to VAS was 4 points (range: 2 – 7), at the time of discharge — 3 points (1 – 6). After 120 days, a follow-up examination showed a regression of pain symptoms: the median was 0 points (0–1). In the late postoperative period, incomplete opening of the mouth was recorded in two patients (3.07%), cosmetic defect in the donor area in two (3.07%), discomfort during meals in six (9.23%), impaired sensitivity in the donor area in two (3.07%), exacerbation of chronic stomatitis and hypersalivation in two (3.07%) patients, respectively.Conclusion. The incidence of complications in the donor area is low, but for some patients this can result in a reduced quality of life. Using proper technique when extracting oral mucosa grafts reduces pain and the likelihood of early- and late-stage postoperative complications in this area.

How position in the network determines the fate of lexical innovations on Twitter

This study analyzes the diffusion of lexical innovations on Twitter to understand how the social network position of adopters impacts their success. Looking at both successful and failed neologisms, we categorize them into "changes" which become established and "buzzes" which decline over time. Using a corpus of 650 million French tweets, we reconstruct user networks and characterize adopters of innovations during different diffusion phases based on prestige, centrality, clustering, and external ties. In the early innovation phase, change and buzz adopters have similar peripheral profiles. During propagation, changes spread to prestigious, central individuals while buzzes do not, which predicts their eventual success or failure. By the establishment phase, changes reach highly central users with closer external ties. The results align with sociolinguistic theories about weak ties for innovation and strong ties for establishment. Additionally, logistic regression models based on early adopter profiles can predict the fate of innovations. This work sheds light on the diffusion dynamics of online lexical innovations and the crucial role of user network factors.

Differences in Grey Matter Concentrations and Functional Connectivity between Young Carriers and Non-Carriers of the APOE ε4 Genotype.

Background: The pathophysiology of Alzheimer's disease (AD) may begin developing years or even decades prior to the manifestation of its first symptoms. The APOE ε4 genotype is a prominent genetic risk for AD that has been found to be associated with brain changes across the lifespan since early adulthood. Thus, studying brain changes that may occur in young adults with an APOE ε4 status is highly relevant. Objective: Examine potential differences in grey matter (GM) and functional connectivity (FC) in brains of cognitively healthy young APOE ε4 carriers and non-carriers, denoted here as ε4(+) and ε4(-), respectively. Methods: Three Tesla magnetic resonance imaging (MRI) brain scans were acquired from cognitively healthy young participants aged approximately 20 years (n = 151). Voxel-based morphometry (VBM) analysis was employed to identify potential structural differences in GM between ε4(+) and ε4(-). In a subsequent seed-based connectivity (SBC) analysis, brain regions that structurally differed in the VBM analysis were considered as seeds and correlated with all the remaining voxels across the brains to then measure the differences in FC between groups. Results: The VBM analysis suggested that ε4(+) (n = 28) had greater GM densities relative to ε4(-) (n = 123) in the left hippocampus and the left posterior insula (puncorr < 0.001). However, the effect did not survive the correction for multiple comparisons, suggesting minimal structural differences in this age range. In contrast, the SBC analysis indicated that ε4(+) exhibited significantly decreased FC between the left hippocampus and areas of the left middle temporal gyrus (n = 27) compared to ε4(-) (n = 102). These results remained significant after multiple comparisons (pFDR < 0.05). Lastly, no statistically significant differences in FC between groups were observed for the left insular seed (pFDR > 0.05). Discussion: These results suggest early structural and functional brain changes associated with the APOE ε4 genotype on young adults. Yet, they must be cautiously interpreted and contrasted with both older adults with genetic risk for AD and patients diagnosed with AD.

COPD: Prävention und Früherkennung statt Therapie ist der Schlüssel zur Elimination

Despite substantial progress in reducing the global impact of many non-communicable diseases, including heart disease and cancer, morbidity and mortality due to chronic respiratory disease continues to increase. This increase is driven primarily by the growing burden of chronic obstructive pulmonary disease (COPD), and has occurred despite the identification of cigarette smoking as the major risk factor for the disease more than 50 years ago. Many factors have contributed to what must now be considered a public health emergency: failure to limit the sale and consumption of tobacco products, unchecked exposure to environmental pollutants across the life course, and the ageing of the global population (partly as a result of improved outcomes for other conditions). Additionally, despite the heterogeneity of COPD, diagnostic approaches have not changed in decades and rely almost exclusively on post-bronchodilator spirometry, which is insensitive for early pathological changes, underused, often misinterpreted, and not predictive of symptoms. Furthermore, guidelines recommend only simplistic disease classification strategies, resulting in the same therapeutic approach for patients with widely differing conditions that are almost certainly driven by variable pathophysiological mechanisms. And, compared with other diseases with similar or less morbidity and mortality, the investment of financial and intellectual resources from both the public and private sector to advance understanding of COPD, reduce exposure to known risks, and develop new therapeutics has been woefully inadequate.

Salivary Short-chain Fatty Acids (SCFAs) Are Viable Predictors of Early Changes in Systemic Health.

Short-chain fatty acids (SCFAs) are the metabolites identified in both the oral cavity and the gut. They play an important role in the triggering, development and progression of systemic diseases. SCFAs can alter the gut microbial components, intestinal epithelium and host immune system, and are also associated with cancer incidence. Salivary SCFAs, produced by the oral microbiome, are correlated with some oral diseases. The occurrence of systemic diseases associated with gut SCFAs is more clearly defined than oral SCFAs. Salivary SCFAs can enter the bloodstream directly via inflamed gingiva to cause continuous low-grade systemic inflammation. Hence, salivary SCFAs could be an indicator for the early diagnosis of systemic diseases. Furthermore, they provide a basis for understanding the oral-systemic axis driven through salivary SCFAs in the pathogenesis of several diseases.

Association of FGF23 Levels and Development of Anemia in Patients with Non Dialysis Chronic Kidney Disease

Background: Anemia is one of the common complication of Chronic Kidney Disease that intensifies in grade and severity as eGFR decline which also increases the risks for cardiovascular mortality. The development of anemia and elevated fibroblast growth factor 23 levels are the earliest changes observed in chronic kidney disease. Objective: This study aims to understand the association of FGF23 levels development of anemia in chronic kidney disease patients prior to renal replacement therapy. Methods: This is an analytical type of cross sectional study carried out among 95 respondent'1ged between 18 and 75 years with CKD stage 1-5 before dialysis, divided into two groups- Group I­ comprised of 68 patients and Group 11- included 27 age and sex matched respondents not having CKD, enrolled from two te1tiary-care hospitals, namely- Sir Salimullah Medical College &amp; Mitford Hospital and National Institute of Kidney Diseases &amp; Urology (NIKDU). Socio-demographic status, disease profile and laboratory findings including serum iron, iron binding capacity, ferritin, transferrin saturation, calcium, phosphorus, intact parathormone, vitamin D, eGFR and FGF-23 levels were studied. Result: Mean age of the respondents was 50.1±10.74 (SD) years, mean estimated glomerular filtration rate was 35.92± 22.61 in group I and 91.66± 14.2 in group II. The mean FGF23 level in group I and II were 85.76± 207.54, 21.99± 12.12 pg/mL respectively, serum iron level was 81.61± 39.24 mcg/dL and 95.0± 32.38 mcg/dL in group I and II respectively, serum ferritin level was 225.59± 2 I 2.5 ng/mL and 157.85± 220.89 ng/ml. TIBC was 312.65± 95.83 mcg/dL and 418.85± 118.25 mcg/dL in group I and II respectively. In Group I and II, iron deficiency was found in 23% and 25%respectively when stratified according to serum ferritin level and 26.5% and 22.22% respectively, when stratified according to serum transferrin saturation level. This difference was significant among the group. Serum iron, ferritin, TIBC and TSAT were significantly associated with serum FGF23 levels. Conclusion: Disrupted iron metabolism and high FGF23 levels is commonly found in chronic kidney disease. Clinical laboratory findings have revealed the relation between FGF23 and anemia in no dialysis chronic kidney disease patients.

Providing a localised cervical cancer screening course for general practice nurses.

Cervical cancer screening programs in Australia have been developed to detect early precancerous changes in women with a cervix aged between 25 and 74. Yet, many barriers remain to the uptake of cervical screening. Barriers include a lack of culturally appropriate service provision, physical access, poor health literacy, emotional difficulties, socio-economic disadvantage and not having access to a female service provider. In remote and very remote areas of Australia, additional barriers experienced by Aboriginal or Torres Strait Islander peoples include a distrust of healthcare providers and a lack of services, resulting in a much higher rate of diagnosis and death from cervical cancer. General practice nurses (GPNs) are well placed to conduct cervical screening tests (CSTs) after they have undertaken additional education and practical training. GPNs' increase in scope of practice is beneficial to general practice as it helps to remove some barriers to cervical screening. In addition, GPNs conducting CSTs reduce GP workload and burnout and increase teamwork. GPNs working in metropolitan clinics have greater access to training facilities, whereas those working in rural and remote clinics are required to travel potentially long distances to complete practical assessments. This highlights the need for training to be made available in rural and remote areas. The aim of this forum paper is therefore to generate further discussion on the need for training programs to be made available in rural and remote areas to aid the upskilling of GPNs.

Early length changes and microscopic phase analysis of phosphorus hemihydrate gypsum fireproof mortar

Abstract Coating the surface of steel structures with phosphohemihydrate gypsum fireproof mortar can improve the fire resistance of steel structures. The hydration curve of phosphorus hemihydrate gypsum (PHG) showed a monotonic increasing trend, and the hydration time was about 1 day. In order to study the hydration process of phosphorus hemihydrate gypsum fireproof mortar, its length change in the early hardening stage was experimentally investigated. The results showed that compared with the hydration time of phosphohemihydrate gypsum, the duration of early length changes in phosphohemihydrate gypsum fireproof mortar was significantly prolonged to about 4 days, and four intervals were clearly observed during this process. Hydroxypropyl methyl cellulose (HPMC) as a water retaining agent, hydroxypropyl starch ether (HPS) as a thixotropic agent, and dispersed latex powder (LP) can all make the four intervals of length changes of fireproof mortar more significant. After adding HPMC, HPS, and LP, it can promote the formation of dihydrate gypsum mainly in fireproof mortar, but dihydrate gypsum crystals were more likely to grow along the [021] direction. The addition of additives can also effectively improve the pore structure of phosphogypsum fireproof mortar.

Cardiac biomarkers and effects of aficamten in obstructive hypertrophic cardiomyopathy: the SEQUOIA-HCM trial.

The role of biomarker testing in the management of obstructive hypertrophic cardiomyopathy (oHCM) is not well defined. This pre-specified analysis of SEQUOIA-HCM (NCT05186818) sought to define the associations between clinical characteristics and baseline concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI), and to evaluate effect of treatment with aficamten on biomarker concentrations. Cardiac biomarkers were measured at baseline and serially throughout the study. Regression analyses determined predictors of baseline NT-proBNP and hs-cTnI concentrations, and to evaluate whether early changes in these biomarkers relate to later changes in left ventricular outflow tract gradient (LVOT-G), other echocardiographic measures, health status, and functional capacity. Baseline concentration of NT-proBNP was associated with LVOT-G and measures of diastolic function, while hs-cTnI was associated with left ventricular thickness. Within 8 weeks of treatment with aficamten, NT-proBNP was reduced by 79% (95% CI 83%-76%, P < .001) and hs-cTnI by 41% (95% CI 49%-32%, P < .001); both biomarkers reverted to baseline after washout. Reductions in NT-proBNP and hs-cTnI by 24 weeks were strongly associated with a lowering of LVOT-G, improvement in health status, and increased peak oxygen uptake. NT-proBNP reduction strongly correlated with the majority of improvements in exercise capacity. Furthermore, the change in NT-proBNP by Week 2 was associated with the 24-week change in key endpoints. NT-proBNP and hs-cTnI concentrations are associated with key variables in oHCM. Serial measurement of NT-proBNP and hs-cTnI appears to reflect clinical response to aficamten therapy.

Cellular and Molecular Mechanisms of Neuronal Degeneration in Early-Stage Diabetic Retinopathy.

Studies on the early retinal changes in Diabetic Retinopathy (DR) have demonstrated that neurodegeneration precedes vascular abnormalities like microaneurysms or intraretinal hemorrhages. Therefore, there is a growing field of study to analyze the cellular and molecular pathways involved to allow for the development of novel therapeutics to prevent the onset or delay the progression of DR. Molecular Mechanisms: Oxidative stress and mitochondrial dysfunction contribute to neurodegeneration through pathways involving polyol, hexosamine, advanced glycation end products, and protein kinase C. Potential interventions targeting these pathways include aldose reductase inhibitors and protein kinase C inhibitors. Neurotrophic factor imbalances, notably brain-derived neurotrophic factor and nerve growth factor, also play a role in early neurodegeneration, and supplementation of these neurotrophic factors show promise in mitigating neurodegeneration. Cellular Mechanisms: Major cellular mechanisms of neurodegeneration include caspase-mediated apoptosis, glial cell reactivity, and glutamate excitotoxicity. Therefore, inhibitors of these pathways are potential therapeutic avenues. Vascular Component: The nitric oxide pathway, critical for neurovascular coupling, is disrupted in DR due to increased reactive oxygen species. Vascular Endothelial Growth Factor (VEGF), a long-known angiogenic factor, has demonstrated both damaging and neuroprotective effects, prompting a careful consideration of long-term anti-VEGF therapy. Current DR treatments primarily address vascular symptoms but fall short of preventing or halting the disease. Insights into the mechanisms of retinal neurodegeneration in the setting of diabetes mellitus not only enhance our understanding of DR but also pave the way for future therapeutic interventions aimed at preventing disease progression and preserving vision.