"Keep On Keep Up" (KOKU) is a tablet-based digital program based on the well-validated Otago and Fitness and Mobility Exercise programs for older adults to decrease the risk of falling. This substudy involved a process evaluation in order to analyze the usage patterns of the KOKU digital program, specifically training frequency, volume, and intensity among older adults over a 3-month self-managed training period. Pre-post changes in physical capacity and real-world walking were examined. This study is a nested cohort study within the three-armed randomized controlled SMART-AGE trial conducted in Germany (German Clinical Trials Register ID: DRKS00034316). Participants aged 67 years or older with basic digital literacy were included. KOKU provided guided but unsupervised progressive strength and balance training for 3 months. The data on training adherence, engagement, and progression were collected. Instrumented assessments included the Timed Up and Go Test, the 30-Second Chair Rise Test, and real-world walking monitoring using wearable sensors. A total of 113 participants (n=63, 56% female; mean age 74.02, SD 5.36 y) were included in the analysis. During the 3-month period, participants used KOKU for 24 (SD 15) days, that is, 2 to 3 times per week. Over the entire study period, no falls or other adverse events were reported due to KOKU usage. The number of exercises performed per participant ranged from 2 to 213, with a median value of 70. The instrumented Timed Up and Go Test results revealed a prolonged total duration (d=0.26; P=.009). In the instrumented 30-Second Chair Rise Test, improvements were observed in the number of completed repetitions (d=0.21; P=.04) and frequency of repetitions (d=0.23; P=.03). This was mainly due to a reduction in inactive time (d=-0.60; P<.001). Real-world walking parameters remained unchanged, except for a slower walking speed during walking bouts of less than 30 seconds (d=0.49; P<.001). All changes did not meet the criteria for minimally important differences. KOKU is a novel digital intervention for older adults, promoting balance and strength exercises. Physical capacity improvements were small. However, the use of instrumented assessments provided further insights into participants' capacity and mobility that would not have been identifiable with conventional assessments. Future improvements to the program should focus on incorporating more challenging exercises for individuals with varying levels of physical capacity.
Although many studies document advancing phenology in response to warming, it is challenging to identify which environmental drivers influence phenology and whether phenological shifts suitably track changing environmental conditions. By examining phenological trends on a climate-relevant scale (e.g., heat accumulated at flowering or days between snowmelt and flowering), we can test whether climate change outpaces phenological shifts. If these climate-relevant phenology metrics remain constant over time, that would suggest perfect phenological tracking to match the climate conditions under which plants historically flowered. We analyzed a long-term data set on timing of first flower and climate from 1995 to 2024 in 25 species in a semiarid intermontane grassland in west-central Montana, United States. We used an information theoretic approach to examine how flowering phenology shifted over time and in response to a suite of environmental variables (temperature, growing degree days [GDD], precipitation, snowmelt, drought), whether responses were nonlinear, and whether responses differed between early- vs. late-spring flowering species. We then asked whether climate-relevant measures of phenology remained constant over time, which would suggest tracking of suitable environmental conditions. Flowering phenology advanced nonlinearly over time and under warmer and drier conditions. In particular, early-spring flowering species advanced flowering under drought conditions. Plants flowered with fewer GDD accumulated and sooner post-snowmelt than historically. Phenological shifts keep pace with climate change in our system. However, nonlinear phenological responses to climate indicate that phenological shifts are slowing. Phenological shifts in spring flowering species may be limited as temperatures continue to increase.
Whom we meet shapes how infections spread. Where earlier focus of mathematical epidemiology was on incorporating age, more recent work has begun to reveal the importance of socioeconomic aspects for understanding and managing future epidemics.
This study investigated queer therapists' perceptions of police bias and attitudes toward police. We used a mixed-methods explanatory approach by administering the Perceptions of Police Scale (POPS) to mental health professionals and conducted follow-up qualitative interviews with participants who identify with a queer sexuality to explore the factors influencing their perceptions of police and the ways in which they view and utilize reliance on police when a client is experiencing a mental health crisis. Quantitative data were analyzed with SPSS using correlations and t-tests to assess the relationship between sexuality and perceptions of police scores. Sexuality significantly correlated with perceptions of the police, meaning queer therapists viewed the police less favorably compared to heterosexual participants. A qualitative analysis using reflexive thematic analysis revealed seven themes that address how queer therapists perceive police and strategies utilized to decide if calling 911 for a client in crisis would be lifesaving or life-threatening.
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Antifungal resistance (AFR), an emerging and significant threat to humanity, receives far less attention than antibacterial resistance. AFR management is plagued by rising incidence in both immunocompromised and immunocompetent populations, zoonotic infections, limited fungal diagnostics, limited antifungal armamentarium with even fewer in pipeline, cross-resistance between environmental fungicides and clinically used antifungals, lack of strong antifungal stewardship programs, limited applications of novel strategies for human AFR, to name a few. In this review, we compile available information, current advances and our perspectives on major challenges in the origin and management of AFR. We conduct systematic review of all available publications on standard databases using search terms related to AFR from the past until January 2026. We consider all major publications on key questions in AFR. We focus on the following aspects of AFR: environmental drivers, AFR and "One Health" perspective, climate change and AFR, emerging fungal zoonoses, fungal diagnostic challenges and advances, key resistant fungal pathogens, antifungal stewardship programs, summarize the use of newer antifungals and their clinical trials, and provide an overview of novel strategies for tackling AFR, like the potential use of mycoviruses and vaccines. We also briefly present our perspective on the future of AFR progression and management. Fungi are tiny germs that can cause serious infections in humans. There are only a few medicines available to cure these infections. Sometimes, these medicines cannot kill the fungi. This is called antifungal resistance (AFR). When AFR happens, the fungus keeps growing in the body, making the person sicker and the infection does not heal. This resistance can develop when these medicines are used too much or unnecessarily, either in farming (to protect crops) or in people (when a different medicine was needed as the germ was different). It is important to detect fungal infections and resistance early so that the right treatment can be given. In the future, we need to develop new medicines, improve testing methods in the laboratory for detecting this germ early in patients, use antifungal medicines carefully, and create rules to prevent their unnecessary use, especially in farming. These steps will help keep the current medicines effective and prevent antifungal resistance, so that patients are cured of such infections.
INTRODUCTION Anthropogenic climate change is reshaping where plants can live. As temperature and precipitation patterns shift, many species are moving to stay within suitable environmental conditions. Predicting how these range shifts will affect future biodiversity requires knowing both where suitable habitats will occur and whether species can reach them. The latter is challenging because dispersal abilities differ widely among species and depend on landscape structure, anthropogenic barriers, and climatic conditions. Large-scale biodiversity forecasts therefore often rely on overly simple assumptions-such as no dispersal, unlimited dispersal, or identical movement rates for all species-thus adding major uncertainty to projections and conservation planning. RATIONALE We used the largest global database of observed plant range shifts (BioShifts; 14,488 records across 6579 plant species) to build models that predict species-specific range shift velocities. Combining 6.8 million plant occurrence records, an ensemble of two top-performing habitat models, and climate projections from 10 global circulation models, we mapped current and future suitable habitats-areas with favorable climate, soil, and land use-at 8 × 8 km resolution for each species. Our analysis covers 18% of known vascular plant species under four greenhouse-gas emissions scenarios for 2081 to 2100. We then overlaid the projected future suitable habitats with species-specific range shift velocities to determine where each species is likely to persist or expand by the end of this century. From these results, we estimated global extinction risks, changes in local species richness, and temporal species turnover in community composition. RESULTS Overall, 7 to 16% of modeled plant species are projected to lose >90% of their range across emissions scenarios, placing them at high risk of extinction. Most of these losses (70 to 80%) stem from suitable habitats disappearing as a result of climate change, rather than from dispersal limitations, indicating that climate-induced habitat loss, rather than an inability to keep pace with changing climate, is the primary threat. Although range shifts are unlikely to prevent many global extinctions, they will strongly reshape local species composition. Plant movements into newly suitable habitats are expected to increase local species richness across 28% of Earth's land surface, maintain latitudinally averaged species richness in the tropics and subtropics (35°S to 35°N), and generate substantial species turnover in mid-latitudes (30° to 50° in both hemispheres). By contrast, in regions north of 50°N, warming is so rapid that most plants cannot keep pace, leading to widespread local extirpations and sharp declines in species richness. CONCLUSION Range shifts can help sustain local species richness but are unlikely to provide much relief from global extinctions. To reduce extinction risks, identifying and protecting climate change refugia to safeguard biodiversity, and expanding ex situ conservation efforts, such as global seed bank and botanic garden networks, may be more effective than facilitating migrations. At the same time, conservation strategies should anticipate changing community compositions and ecosystem functioning as new species arrive and ecosystems reorganize. In high-latitude regions where dispersal lags considerably behind the rapid warming, improving habitat connectivity, reducing human-made barriers, and where appropriate, assisting species movement could help maintain local species richness, ecosystem productivity, carbon sequestration, and ecosystem stability. [Figure: see text].
While this book's theme is proteomics and virology, this chapter on the role of proteomics in clinical virology may seem unsatisfying to the reader. The reason is simple: proteomics has not made a major impact on the diagnosing of viral infections. However, it is still important to evaluate the present role of proteomics in clinical virology as it provides a vision of what is required if it is to ever have a major impact in diagnosing viral infections. This chapter will initially provide a background on current techniques for diagnosing viral infections. Although the names may not be familiar to the casual reader, the techniques will be as most individuals have been tested using one of these techniques during their lifetime. The chapter will later switch to describe proteomic methods for the direct detection of viruses in clinical samples. While outside the scope of this book, a proteomic method for bacterial identification is included because (i) it describes a proteomic technology that has been approved by the FDA for clinical use and (ii) since viruses and bacteria are both infectious agents it demonstrates the potential of proteomics for overall pathogen detection. To keep the topic in perspective, however, the advantages and disadvantages of using proteomics in clinical virology are compared to current existing methods particularly those that target the detection of genomic features within these pathogens.
The forced-attention dichotic listening (FADL) task is used to examine how people control attention during speech processing. Younger adults can flexibly shift attention to instructed ears from the baseline right-ear advantage (REA) for consonants (cued by temporal information). However, it remains underexplored whether tonal language speakers can control their attention to tones, which are cued by spectral information and typically trigger a left-ear advantage (LEA) at baseline. Moreover, older adults sometimes fail to show these patterns, as compared to younger adults, possibly due to age-related decline. This study investigated whether these attentional controls generalize to Cantonese tones and whether younger and older Cantonese speakers show different attentional control in an FADL task of Cantonese tones. Sixty native Cantonese-speaking younger adults, aged 18-25 years (Experiment 1), and 64 older adults, aged 59-72 years (Experiment 2), completed tone training followed by an FADL test. In three conditions (i.e., nonforced, forced-left [FL], and forced-right [FR]), they identified dichotically presented Cantonese tones according to attentional instructions. Both the younger and older adults successfully modulated attention. The participants, regardless of age, enhanced the LEA in the FL condition and reversed it to an REA in the FR condition. An exploratory group comparison showed that younger adults might exhibit a significantly larger shift of ear preference in the FL condition than older adults. The findings provide evidence that auditory attentional control is a highly flexible and cue-general cognitive function, which can be generalized to Cantonese tones. Crucially, the core performance of attentional control in Cantonese processing remains largely preserved with aging. It suggests that age-related decline is not the only consequence of aging, but compensatory strategies are adopted by older adults to cope with possible decline and keep their behavioral performance intact. https://doi.org/10.23641/asha.32177577.
Descemet Membrane Endothelial Keratoplasty (DMEK) is a surgical intervention for restoring endothelial function in Fuchs endothelial corneal dystrophy (FECD). However, changes in corneal biomechanical properties assessed using dynamic Scheimpflug analyzer (DSA) remain limited. This study aimed to assess alterations in corneal biomechanical parameters before and after surgery in patients with FECD using DSA. This prospective study included 24 FECD patients. Demographic data, visual acuity, central corneal thickness (CCT), endothelial cell count, intraocular pressure (IOP), stress strain index (SSI) and others DSA parameters were evaluated. Measurements were obtained preoperatively and at 1, 3, and 6 months after surgery. Repeated measures analysis of variance and pairwise correlations were used to assess differences and associations. Significant postoperative alterations were observed in multiple corneal biomechanical parameters. CCT, ARTh, A1 length, A1 DefA and SPA showed significant reductions over time. Conversely, the DefA max, maximum inverse radius, DA ratio, integrated radius and CBI significantly increased during follow-up. While, SSI remained stable at all time points. These findings demonstrate a biomechanical transformation following DMEK from 1 to 6 months postoperatively, reflecting the transition from a swollen, thickened cornea to a thinner, clearer cornea in the postoperative state. DMEK resulted in reduced corneal thickness and significant changes in several corneal biomechanical parameters. However, the stability of SSI, which is independent of CCT and bIOP, suggests that intrinsic corneal stiffness remains unchanged despite postoperative remodeling. The observed biomechanical alterations may provide useful markers for monitoring corneal recovery following DMEK. Fuchs Endothelial Corneal Dystrophy (FECD) is a common condition that affects the back layer of the cornea. In FECD, the cells that keep the cornea healthy gradually die, causing swelling, blurred vision, and glare. Descemet Membrane Endothelial Keratoplasty (DMEK) can replace the damaged cells and restore vision. However, DMEK’s effect on cornea strength and how it responds to pressure remains unclear. In this study, we followed 24 patients with FECD who underwent DMEK surgery. We measured how their corneas responded to small air pulses using a special imaging tool called a Dynamic Scheimpflug Analyzer. We also measured corneal thickness, eye pressure, and vision before surgery and 1, 3, and 6 months afterward. We found that DMEK improved vision and reduced corneal swelling in all patients. Many of the cornea’s mechanical properties changed after surgery, mostly because the cornea became thinner and less swollen. Importantly, the stress–strain index, which reflects the cornea’s true stiffness, did not change. This means that DMEK restores corneal shape and function without altering the tissue’s natural strength. These results show that DMEK effectively improves vision and corneal health. Measuring corneal properties after surgery can help doctors monitor recovery and understand how the cornea adapts. This research also highlights which measurements reflect real tissue changes and which are influenced by swelling, guiding future studies and patient care.
Rapid pathogen evolution threatens public health by eroding the effectiveness of vaccines, therapeutics, and diagnostic tools. Although spike protein targeting monoclonal antibodies (mAbs) were developed within 10-12 months of the initial outbreak to serve as key theranostic agents, their redesign has struggled to keep pace with viral evolution, rendering many neutralizing antibodies ineffective. Here we demonstrate a novel platform that combines a random-rational hybrid library diversification with high-throughput MiSeq screening to rapidly reprogram aptamers against emerging SARS-CoV-2 spike variants. Interactions between 3 different spike proteins and 11,806 unique aptamer variant designs were profiled within a few days. Starting from a 40-nt aptamer originally selected against wild-type (WT) spike protein, our screen identified a Delta-binding mutant with a 4-fold affinity improvement and an Omicron-binding mutant that converted undetectable binding into nanomolar affinity. We also identified a WT-selective mutant with substantially reduced affinity for Delta, as well as previously unrecognized bases that critically contribute to spike recognition. Integrating high-throughput binding data with molecular dynamics simulations further revealed sequence-dependent structural features underlying variant-specific aptamer-spike interactions. Finally, we developed a sensor based on the identified WT-selective aptamer mutant, enabling highly specific detection of the WT spike protein with robust performance. Together, this work establishes a rapid and adaptable aptamer engineering platform for rapid adaptation of aptamers to evolving pathogens in future pandemics.
Effective log assessment is a cornerstone for ensuring the reliability and smooth functioning of large-scale, cloud-based infrastructures. As these environments continuously grow in scope and intricacy, traditional monitoring approaches often struggle to keep up, leading to unnecessary computational strain and diminished system performance. To address these challenges, this research introduces a hybrid framework that integrates natural language processing (NLP) with an optimized LightGBM classifier, tailored for anomaly detection in cloud-generated system logs. Central to the design is a thorough preprocessing pipeline that filters irrelevant information and minimizes bias, thereby sharpening anomaly detection accuracy. The experimental setup explored multiple NLP-based preprocessing strategies, including TF-IDF, BERT, and Word2Vec implementations (employing spaCy and Gensim). Classification relied on the LightGBM model, whose hyperparameters were refined using a customized particle swarm optimization (PSO) metaheuristic. This modified optimization routine boosted both predictive accuracy and model robustness. Results from the study reveal that the combined system significantly enhanced both the identification and classification of anomalies in cloud logs. The most effective configuration achieved up to 100% accuracy under the evaluated experimental conditions, highlighting the framework's potential to strengthen security within cloud ecosystems. To ensure statistical soundness, extensive comparative evaluations were conducted across all configurations. Additionally, model interpretability was improved through SHapley Additive exPlanations (SHAP), which provided transparent insights into the role of individual features in shaping classification outcomes.
The application of artificial intelligence (AI) is increasingly valuable as a tool and assistant in many areas of clinical and academic medicine. Generative AI (GenAI) creates new content used by large language models, which can generate language that strongly resembles or even improves on that of humans. Learners and educators in many areas of education are using GenAI for essays and assessments, raising issues regarding learning and assessment. GenAI is also raising new concerns in health professions education (HPE), an area of health professions training that sometimes has different aims and assessment methods compared to its clinical counterparts. HPE needs to assess levels of knowledge and understanding of pedagogy, and the use of GenAI presents challenges to its current assessments, which are predominantly written. The study aimed to investigate educators' and learners' perspectives on the opportunities and challenges presented by GenAI in postgraduate HPE assessments. It particularly focused on perspectives of how GenAI may influence the future of assessment and essay-based assessments in HPE. Informed by a constructivist paradigm, a qualitative approach was adopted, undertaking 8 semistructured interviews conducted via Microsoft Teams. Purposive sampling ensured a mixture of educators and learners in current HPE courses from a range of health care professions. Data were thematically analyzed. There was no difference between educator and learner perspectives. Four themes were identified: AI is here, students are at a disservice if we do not embrace it; AI as an opportunity to rethink HPE assessments; AI is a "gray area"; and AI is fallible. The findings present AI as an external catalyst, highlighting the current internal desire for assessment change within HPE. It offers opportunities for creative, authentic assessments that reflect real-life academic and clinical practice, aiming to develop competent future HPE educators and keep courses relevant. These findings contribute to the debate around the future potential and development of AI in HPE assessments.
Surgical wounds healing by secondary intention occur if a surgical wound is not closed or dehisces following primary closure. Surgical wounds healing by secondary intention are common and adversely affect patients' quality of life. Treatment is often prolonged, complex and expensive. Negative pressure wound therapy applies a controlled vacuum to the wound and is increasingly used to promote surgical wound healing by secondary intention despite limited rigorous evidence for the clinical and cost-effectiveness of negative pressure wound therapy to augment surgical wound healing by secondary intention. Assess the clinical and cost-effectiveness of negative pressure wound therapy versus usual care (no negative pressure wound therapy) in treating surgical wounds healing by secondary intention. A pragmatic, two-arm, parallel-group, randomised controlled superiority trial. Twenty-eight UK NHS Trusts randomised adult patients with a surgical wounds healing by secondary intention to receive negative pressure wound therapy or usual care (no negative pressure wound therapy). The planned sample size was 696 participants. Participants were followed up for 12 months via weekly telephone contact to collect the primary outcome (time to healing: full cover with no scab in days since randomisation) and clinical secondary outcomes: wound healing, surgical site infection, pain, hospital re-admission, current treatment and reasons for treatment change (if applicable), reoperation, amputation, antibiotic use, death. Patient-reported outcomes (pain, health-related quality of life and resource use) were collected by postal questionnaire at 3, 6 and 12 months. Validation of the Bluebelle Wound Healing Questionnaire, a patient-reported measure of surgical site infection, was also undertaken. A cost-effectiveness decision model considering all available evidence, and a within-trial cost-utility analysis, was also undertaken to evaluate the cost-effectiveness of negative pressure wound therapy against usual care. Neither participants nor the investigators were blind to treatment allocation. Between 15 May 2019 and 13 January 2023, 686 participants were recruited, randomised and included in the analysis (negative pressure wound therapy n = 349; usual care n = 337). Most participants had a single surgical wound healing by secondary intention (n = 622, 90.7%), located on the foot (n = 551, 80.3%) or leg (n = 69, 10.1%) arising following vascular surgery (n = 619, 90.2%). Most participants had comorbidities; diabetes (n = 549, 80.0%), cardiovascular disease (n = 446, 65.0%) and/or peripheral vascular disease (n = 349, 50.9%). Median time to healing was 187 days (negative pressure wound therapy) versus 195 days (usual care), with no evidence that negative pressure wound therapy reduced the time to wound healing compared to usual care (hazard ratio 1.08, 95% CI 0.88 to 1.32; p = 0.47). Odds of re-admission, reoperation, surgical site infection and antibiotic use were slightly higher, and odds of amputation or death slightly lower for negative pressure wound therapy participants. These results were not clinically or statistically significant. Bluebelle Wound Healing Questionnaire, quality of life and wound pain scores were not statistically significantly different at any time point. Serious adverse events were rare (nine negative pressure wound therapy vs. five usual-care participants). Both cost-effectiveness analyses concluded that negative pressure wound therapy generates higher costs and marginally higher quality-adjusted life-years than usual care, although findings were statistically insignificant. The probability of negative pressure wound therapy being cost-effective was under the recommended National Institute for Health and Care Excellence cost-effectiveness thresholds. The Bluebelle Wound Healing Questionnaire was acceptable to participants, had low levels of missing data and demonstrated good levels of sensitivity and specificity in the detection of surgical site infection in surgical wounds healing by secondary intention. The trial included a high proportion of diabetic participants with foot wounds, which may affect study generalisability. Negative pressure wound therapy use for 'wound management', common in certain surgical specialties, was not assessed in this study. Negative pressure wound therapy is not clinically or cost-effective in augmenting healing in patients with surgical wounds healing by secondary intention, particularly those with comorbidities. Evaluation of methods to treat or prevent infection of surgical wounds healing by secondary intention and evaluation of negative pressure wound therapy for 'wound management' are recommended. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/42/94. After an operation, most wounds are closed using stitches or staples. Some wounds cannot be closed and are left open. Some closed wounds may reopen. These ‘open’ wounds are usually left to heal slowly from the bottom up. Negative pressure wound therapy is commonly used to treat ‘open’ wounds. Negative pressure wound therapy uses a machine to apply gentle suction to a wound, which removes wound fluid, and may help keep the wound clean and perhaps aid healing. We do not know if negative pressure wound therapy is as good as, better than or worse than standard wound dressings that are also used for healing ‘open’ surgical wounds. We also do not know if negative pressure wound therapy is good value for money. There has not been enough, high quality, independent research to enable doctors and nurses to decide on the best treatment. Between May 2019 and January 2023, 686 patients with an open wound agreed to take part and were equally randomly assigned to standard dressings or negative pressure wound therapy. Most of the wounds were on patient’s feet. Most patients had diabetes, and many patients also had conditions affecting their heart and/or blood vessels. We collected wound healing data, treatment information and health outcomes for each participant for a year. We found no clear evidence that negative pressure wound therapy provided any significant benefits for patients and specifically that negative pressure wound therapy did not reduce the time it took for wounds to heal compared to standard wound care. Negative pressure wound therapy was also more expensive than standard dressings and so was not likely to be a good use of healthcare resources. Patients and doctors will be able to make more informed decisions about which dressing to use to help wounds heal. The National Health Service can save money by recommending the use of standard dressings for open wounds instead of using the more expensive negative pressure wound therapy.
Anemia is a frequent complication in cats with chronic kidney disease (CKD), mainly due to decreased erythropoietin (EPO) production resulting from a loss of renal erythropoietin-producing (REP) cells. Anemia affects both survival and quality of life by inducing clinical signs such as lethargy and anorexia. Early detection of anemia by monitoring hematocrit/packed cell volume (Htc/PCV) trends is essential to initiate treatment before progressive renal damage limits therapeutic effectiveness. Molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), is a novel oral drug stimulating endogenous erythropoietin synthesis. However, treatment has to be started when REP cells are still functional, with PCV target ranges between 30-40%. Regular monitoring following the International Renal Interest Society (IRIS) guidelines is essential to keep PCV within the target range and to determine when treatment should be started, stopped, or restarted. Moreover, monitoring the iron status is important since both functional and absolute iron deficiency might be seen in cats with CKD and can impair response to treatment. Anämie ist eine häufige Komplikation bei Katzen mit chronischer Nierenerkrankung (chronic kidney disease, CKD), hauptsächlich aufgrund einer verminderten Produktion von Erythropoetin (EPO), die aus einem Verlust von renalen Erythropoetin-produzierenden (REP) Zellen resultiert. Anämie beeinflusst sowohl das Überleben als auch die Lebensqualität, indem sie klinische Symptome wie Lethargie und Appetitlosigkeit hervorruft. Die frühzeitige und regelmäßige Hämatokrit-Bestimmung (Htk/PCV) ist für eine Behandlungsentscheidung wichtig, bevor progressive Nierenschäden die therapeutische Wirksamkeit einschränken. Molidustat, ein Hypoxie-induzierbarer Faktor (HIF)-Prolylhydroxylase-Inhibitor (PHI), ist ein neues orales Medikament, das die endogene EPO-Synthese stimuliert. Die Behandlung sollte jedoch begonnen werden, wenn die REP-Zellen noch funktionsfähig sind, mit PCV-Zielwerten zwischen 30–40%. Eine regelmäßige Überwachung gemäß den Richtlinien der International Renal Interest Society (IRIS) ist entscheidend, um den PCV-Wert innerhalb des Zielbereichs zu halten und zu bestimmen, wann die Behandlung begonnen, beendet oder wiederaufgenommen werden sollte. Darüber hinaus ist die Überwachung des Eisenstatus wichtig, da sowohl funktioneller als auch absoluter Eisenmangel bei Katzen mit CKD auftreten können und die Antwort auf die Behandlung beeinträchtigen können.
The rising demand for interventional radiology procedures (IRPs) performed under fluoroscopic guidance increases the risk of harmful radiation effects for patients and staff. Radiation dose optimisation using diagnostic reference levels (DRLs) is necessary to keep radiation 'as low as reasonably achievable (ALARA)'. Establishment of DRLs is required for radiation imaging centres; however, only a few have published them in South Africa. This study aimed to establish local diagnostic reference levels (LDRLs) for IRPs and compare them with DRLs of local and international imaging centres. A retrospective descriptive study was conducted at a single imaging centre. The IRPs performed on adults between 01 January 2023 and 31 December 2023 were considered. Ethical clearance was obtained before data collection. Data on fluoroscopy time (FT) and kerma air product (KAP) were obtained from a procedure register book. The third quartile (75th percentile) of the dataset for KAP and FT of every IRP indicated the LDRLs. A total of 375 IRPs were analysed. The most frequently performed IRP was cerebral interventions (21%, n = 80). Aortic interventions recorded the highest dose LDRL (KAP = 252.5 Gy/cm2), followed by cerebral interventions (KAP = 211.3 Gy/cm2). Cerebral interventions recorded the longest FT (56.8 min), followed by aortic interventions (36.2 min), both of which exceeded the local centres' DRL ranges. Permanent catheterisation (KAP = 10.7 Gy/cm2) also exceeded the international DRL range. Established LDRLs for IRPs were mostly within local and international DRL ranges. The study contributed to the establishment of local, national and regional DRLs, which assisted imaging centres in optimising radiation doses for IRPs.
Angiogenesis is essential for breast cancer progression and metastasis; however, the clinical impact of vascular endothelial growth factor (VEGF)-targeted therapies remains limited due to adaptive resistance and activation of compensatory angiogenic pathways. Angiogenesis-regulating microRNAs (angiomiRs) act as upstream modulators of both VEGF-dependent and VEGF-independent signaling networks contributing to vascular plasticity, immune evasion, and therapeutic escape. Dietary flavonols such as kaempferol, myricetin, and quercetin have demonstrated anti-angiogenic activity in preclinical models, yet their mechanistic interaction with angiomiR-mediated regulation in breast cancer remains poorly characterized. This narrative review critically evaluates evidence identified through structured searches of Google Scholar, PubMed, Scopus, and Web of Science (2010-2026). We synthesize mechanistic and translational findings linking flavonols to microRNA-associated regulation of hypoxia signaling, endothelial activation, extracellular vesicle communication, and vascular normalization. Available evidence indicates that flavonols may influence angiogenic pathways both directly, by inhibiting key signaling cascades, and indirectly, through modulation of non-coding RNA networks. Despite these insights, experimental validation of specific flavonol-angiomiR interactions in breast cancer remains limited. AngiomiR modulation by flavonols, therefore, represents a mechanistically grounded but predominantly preclinical concept that warrants further translational investigation to clarify its therapeutic relevance and potential applications within precision oncology in breast cancer. Blood vessels are essential for supplying breast cancer tumors with nutrients and oxygen. Tumors often rely on a molecule called vascular endothelial growth factor (VEGF) to form new blood vessels. For this reason, treatments that block VEGF have been developed to slow tumor growth. However, these treatments can lose effectiveness over time because cancer cells can find alternative ways to keep their blood supply. Blood vessel formation is controlled by signals within cells. MicroRNAs (miRNAs) are very small molecules that help turn genes on or off, influencing how blood vessels develop and how tumors respond to treatment. Flavonols are naturally occurring compounds found in certain fruits and vegetables. Some studies suggest that flavonols can affect blood vessel growth, possibly by influencing miRNAs involved in this process. Although early findings are promising, most evidence comes from laboratory and preclinical studies. Further research is needed to determine whether targeting these pathways could lead to safe and effective treatment strategies for patients with breast cancer.
Tracheobronchial tuberculosis (TBTB) is a special clinical type of pulmonary tuberculosis (MTB), belonging to lower respiratory tract tuberculosis. Due to its non-specific clinical manifestations, it is prone to misdiagnosis, underdiagnosis, mistreatment, and missed treatment in clinical practice. To enhance the early and accurate diagnosis and timely and standardized treatment of TBTB in clinical practice, the Tuberculosis Branch of the Chinese Medical Association organized experts in relevant fields, adopted evidence-based medical methods, basing on the original consensus and guidelines (trial), and mainly made the following updates: New evidence quality evaluation, recommendation strength, consensus rate, and molecular biological detection methods were added; the original term "bacteriology" was revised to "etiology"; the diagnostic methods and criteria were supplemented and improved, with emphasis on revising the original clinical classification and staging diagnosis to bronchoscopic classification and staging diagnosis; the treatment methods for TBTB were comprehensively and systematically introduced; the interventional treatment principles for different classifications and stages were recommended, especially emphasizing the emergency treatment methods for extremely severe and severe tracheal tuberculosis combined with tracheal stenosis in order to improve the diagnosis and treatment.This guideline specifically presents 31 recommendations around the following 22 common clinical issues, with the aim of improving the diagnosis and treatment level of TBTB in clinical practice and benefiting more patients.The recommendations are listed below:Recommendation 1: Definition of TBTB: Tuberculosis that occurs in the mucosa, submucosa and outer membrane of the tracheas and bronchi.Recommendation 2: Typical clinical manifestations of TBTB: Irritating cough, expectoration, hemoptysis, wheezing and varying degrees of breathing difficulties lasting more than 2 weeks, and wheezing sounds in the lungs, dry and wet rales, weakened or absent breathing sounds, tracheal deviation, etc.Recommendation 3: Typical imaging signs that should be paid special attention to: during clinical review of chest CT scans, not only the lung window, mediastinal window and soft tissue signs should be emphasized, but also the signs within the airway, on the airway wall and outside the airway should be closely observed. When TBTB is suspected, it is recommended to perform multi-dimensional airway reconstruction imaging technology with chest CT.Recommendation 4: Etiological testing of TBTB: Biopsy tissues, brush specimens, lavage fluids, lavage fluids and puncture materials can be obtained with bronchoscopy. Relevant acid-resistant staining, culture & drug sensitivity tests and molecular etiology of Mycobacterium tuberculosis should be conducted.Recommendation 5: Pathological features of TBTB: It is consistent with tuberculosis changes that the histopathology of the lesion tissue sampled by bronchoscopy indicates. Further acid-fast staining of tissue specimens and molecular pathological detection of Mycobacterium tuberculosis should be conducted.Recommendation 6: The role and status of bronchoscopy in the diagnosis of TBTB: Currently, bronchoscopy remains an indispensable interventional examination method for the confirmed diagnosis of TBTB.Recommendation 7: The value of immunological indicators in the diagnosis of TB: Serological immunological indicators are only used as an important reference basis for the clinical diagnosis of tuberculosis.Recommendation 8: Pulmonary function and blood gas analysis: For severe TBTB, it is recommended to conduct pulmonary function and blood gas analysis tests.Recommendation 9: Diagnostic methods for TBTB: Currently, it mainly relies on bronchoscopy, combining with etiological, pathological and molecular biological evidence.Recommendation 10: Diagnostic types and criteria of TBTB: Diagnostic types are divided into suspected diagnosed cases, clinically diagnosed cases and confirmed cases. The criteria for a confirmed case are typical lesions of TBTB that are directly visible under bronchoscopy, and a positive result in one of the following: etiology, pathology, or molecular biology. There are corresponding standards for clinical diagnosis and suspected diagnosis.Recommendation 11: Classification diagnosis of TBTB under bronchoscopy: Based on the main anatomical morphological changes of local airway lesions under direct bronchoscopy at that time, combined with the reactions before and after interventional therapy, it is recommended that TBTB be classified into nine bronchoscopic types: Type Ⅰ (inflammatory infiltration type), type Ⅱ (ulcer necrosis type), type Ⅲ (granulation tissue proliferation type), type Ⅳ (lymph node fistula type), type Ⅴ (wall fistula type), type Ⅵ (wall softening type), type Ⅶ (scar stenosis type), type Ⅷ (lumen occlusion type), and type Ⅸ (repeated retraction type).Recommendation 12: Staging diagnosis of TBTB under bronchoscopy: Based on the different development stages of local airway inflammation under direct bronchoscopy, TBTB can be divided into two bronchoscopic stages: active stage and inactive stage. Type I to Ⅳ & inflammatory fistulas in type V are manifestations of active stage under the bronchoscopy, while purification fistulas in type V & type Ⅳ to Ⅸ are manifestations of inactive stage under the bronchoscopy.Recommendation 13: Naming principles for TBTB: For the naming of TBTB, it is recommended to adopt a comprehensive naming method that takes into account the cause & anatomical location, and its relationship with the airway & the degree of stenosis.Recommendation 14: Differential diagnosis of TBTB: It should be differentiated diagnosis from bronchial asthma, airway fungal infections, bronchiectasis, chronic obstructive pulmonary disease, airway tumors and other rare airway diseases.Recommendation 15: The main objective and general principles of TBTB treatment: The primary objective of treatment is to prevent and cure central airway stenosis, occlusion and softening caused by tuberculosis, as well as the resulting poor airway drainage and atoptasis, and to correct poor pulmonary ventilation function and respiratory failure as soon as possible. The overall principle of treatment is to conduct bronchoscopic interventional therapy for TBTB with indications on the basis of systemic chemotherapy with anti-tuberculosis drugs.Recommendation 16: The systemic chemotherapy regimen and course of anti-tuberculosis drugs recommended against TBTB: The systemic chemotherapy regimen of anti-tuberculosis drugs is basically the same as the treatment regimen for pulmonary tuberculosis. It is recommended to formulate the chemotherapy regimen in reference to the relevant consensus and guidelines of the World Health Organization and China. It is specifically determined based on whether the patient is a sensitive or drug-resistant case, as well as the different types and stages under bronchoscopy.Recommendation 17: Implementation of local airway aerosol inhalation of anti-tuberculosis drugs for TBTB: On the basis of systemic chemotherapy with anti-tuberculosis drugs, for the active TBTB under the bronchoscopy, airway aerosol inhalation of anti-tuberculosis drugs is recommended. However, the local drugs used must be consistent with the systemic chemotherapy regimen.Recommendation 18: Application of glucocorticoids: For those with indications for glucocorticoids,on the basis of systemic chemotherapy with anti-tuberculosis drugs, it is recommended to use glucocorticoids in the local airway for a short-term.Recommendation 19: Surgical treatment: If good results cannot be achieved after systemic chemotherapy with anti-tuberculosis drugs and interventional treatment with bronchoscopy, and there are indications for surgical treatment, thoracic surgery is recommended.Recommendation 20: Purpose, principles and measures for interventional treatment of TBTB with bronchoscopy: For TBTB patients with indications for interventional treatment with bronchoscopy, based on different bronchoscopic stages and types, it is recommended to adopt a comprehensive interventional treatment combining multiple interventional methods with bronchoscopy on the basis of systemic chemotherapy with anti-tuberculosis drugs.Principles and objectives of interventional treatment for different types and stages of TBTB under the bronchoscopy:Recommendation 21: For the Type Ⅰ (inflammatory infiltration type), aspiration clearance, cryotherapy and local drug administration are recommended.Recommendation 22: For the Type Ⅱ (ulcer necrosis type), cryotherapy, argon plasma coagulation(APC) combined cryotherapy and local drug administration are recommended.Recommendation 23: For the type Ⅲ (granulation tissue proliferation type), thermal ablation combined with cryotherapy and local drug administration are recommended.Recommendation 24: For the type Ⅳ (lymph node fistula type), thermal ablation combined with cryotherapy and local drug administration are recommended.Recommendation 25: For the type Ⅴ [wall fistula type (inflammatory fistula)], ablation and local administration are recommended to promote the healing of the wall fistula.Recommendation 26: For the type Ⅴ [wall fistula type (purification fistula)], it is recommended to seal the wall fistula with bronchoscopy to restore airway integrity.Recommendation 27: For the type Ⅵ (wall softening type), patients with wall softening central airway stenosis combined with dyspnea and recurrent severe infections, airway stent implantation is recommended to support the collapsed airway, reshape the airway structure and maintain airway patency.Recommendation 28: For the type Ⅶ (scar stenosis type), balloon dilation is recommended as the first choice to expand the narrowed airway.Recommendation 29: For the type Ⅷ (lumen occlusion type), patients with lumen occlusion who have indications for recanalization, it is recommended to use ablation to open the occluded airway, and then combine balloon dilation to expand the narrowed airway after opening.Recommendation 30: For the type Ⅸ (repeated retraction type), it is necessary to keep the airway open and prevent airway retraction.Recommendation 31: Interventional treatment for tracheal tuberculosis with extremely severe or severe tracheal stenosis: When tracheal tuberculosis with extremely severe or severe tracheal stenosis poses a threat to the patient's life, it is recommended to urgently adopt measures such as balloon dilation, stent placement, T-tube placement, and tracheotomy for emergency interventional treatment. 气管支气管结核（TBTB）为肺结核特殊临床类型，属于下呼吸道结核，由于其临床表现不具有特异性，临床上极易被误诊漏诊、误治漏治。为加强临床对TBTB的早期正确诊断、及时规范治疗，中华医学会结核病学分会组织相关领域专家，采用循证医学方法，在原有共识、指南（试行）基础上，主要做了以下工作：新增了证据质量评价、推荐强度及共识率、分子生物学检测方法；将原细菌学改为病原学；补充完善了诊断方法及诊断标准，重点将原来临床分型分期诊断修改为镜下分型分期诊断；原则性地简单介绍了TBTB的治疗方法，重点推荐了针对不同镜下分型分期的介入治疗原则，尤其是强调了针对极重度及重度气管结核并气管狭窄的急救处理等。指南具体围绕22个临床常见问题形成31条推荐意见，以期提高临床TBTB的诊治水平，造福更多患者。.
Men with obesity infrequently engage with weight management services. To determine: (1) percentage weight loss at 12 and 24 months for text messages with or without financial incentives compared to control; (2) secondary outcomes; (3) cost-effectiveness; (4) moderators of effectiveness and (5) participant and stakeholder perspectives. Assessor-blinded randomised controlled trial. United Kingdom National Health Service perspective cost-effectiveness over 24 months and modelled lifetime horizon. Mixed-methods process evaluation. Five hundred and eighty-five men with body mass index ≥ 30 kg/m2 enrolled (July 2021-May 2022) in Belfast, Bristol and Glasgow; final follow-up June 2024. Random allocation to 12 months of behavioural text messages plus financial incentives (N = 196), same texts alone (N = 194) or 12-month waiting list control group offered 3 months of texts between 12 and 15 months (N = 195). A £400 financial incentive was lost if weight loss targets were not met. Weight change as a percentage of baseline weight at 12 and 24 months comparing control with (1) texts with financial incentives and (2) texts alone. Of 585 men (mean age 51 years; mean weight: 119 kg), 227 (39%) lived in lower socioeconomic areas, 146 (25%) reported a mental health condition and 253 (40%) had multiple long-term conditions. Follow-up was completed by 426 (73%) at 12 months and 377 (64%) at 24 months. At 12 months, mean percentage weight changes (standard deviation) were -4.8% (6.1) (-5.7 kg), -2.7% (6.3) (-3.0 kg), and - 1.3% (5.5) (-1.5 kg) for the incentives, text-only, and control groups, respectively. Compared to control, weight loss was significantly greater with incentives [-3.2% (97.5% confidence interval -4.6 to -1.9; p < 0.001)] but not texts alone (-1.4%; confidence interval -2.9 to 0.0; p = 0.053). At 24 months, changes were -3.9% (-4.6 kg), -2.6% (-3.1 kg), and -2.2% (-2.6 kg), no significant between-group differences. Intervention costs were £243 for texts with incentives, £110 for texts alone. There were no significant differences between 24-month costs and quality-adjusted life-years. Long-term modelling found texts with incentives versus control were: quality-adjusted life-year difference (95% confidence interval): 0.02 (0.007 to 0.029); cost difference: £176 (£43; £311); incremental cost-effectiveness ratio: £9748 (£7705 to £11,791). For texts alone versus control: quality-adjusted life-year difference: 0.03 (0.015 to 0.037); cost difference: £16.5 (-£117; £152); incremental cost-effectiveness ratio: £628 (-£5914 to £5384). There were no moderator effects for socioeconomic, health or well-being status for either comparison versus control. The texts with incentives group had a higher engagement in weight goal setting, food changes, self-weighing, confidence, satisfaction and quality of life compared to the control. Generalisability to women, diverse ethnic groups and people with low literacy is uncertain. Not generalisable to people with no mobile phone access. Retention was lowest in the text messages alone group. Texts with financial incentives have a modest but important effect to 12 months with clinically relevant weight loss maintenance to 24 months, are cost-effective and equally effective regardless of socioeconomic or health characteristics. Implementation, adapt for women, other cultures and longer-term follow-up. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme as award number NIHR129703. The Game of Stones study aimed to help men lose weight and keep it off for at least 2 years. Five hundred and eighty-five men living with obesity across the United Kingdom were split into three groups by chance: supportive text messages for 1 year and opportunity to get money for weight loss the same text messages alone for 1 year neither for 1 year, then text messages for 3 months. The first two groups received the same daily text messages about changing weight-related behaviours. Group 1 was told at the start that £400 had been put aside for them and that money would be lost if weight targets were missed. The targets were 5% weight loss at 3 months, 10% at 6 months and maintaining that 10% loss at 12 months. Money was then paid to the men after being weighed at 12 months. Every man was asked questions about their health, well-being and experiences of being in the study. After 1 year, the men in group 1 lost the most weight (5%, 5.7 kg). The men in group 2 lost some weight (3%, 3.0 kg) but not as much as the first group. The men in group 3 lost the smallest amount of weight (1%, 1.5 kg). On average, men in group 1 received £128 for meeting weight loss targets. One year after the 12-month measures, men in groups 1 and 2 had gained back some weight. Men in group 3 lost a bit more weight between year 1 and 2. Weight loss was similar whether or not men had long-term health conditions, disability, mental health issues or lived in the most deprived areas. This study showed that Game of Stones was a popular, low-cost and modestly effective way of helping men to lose weight.