Neurologic sequelae occur after cerebral malaria (CM) but are less well described after non-cerebral severe malaria (NCSM). In a prospective cohort study, we determined the presence, type and outcomes of neurologic sequelae (persistent neurologic deficits and/or development of epilepsy over 12-month follow-up) in Ugandan children admitted with CM (n = 54) or NCSM (severe malarial anemia, respiratory distress, malaria with multiple seizures, or prostration, n = 495). At hospital discharge, neurologic deficits were more frequent in children with CM (21/54 [38.9%]) than children with NCSM (45/495 [9.1%], P < 0.001). At 12-month follow-up, persistent neurologic deficits did not differ significantly between children with CM or NCSM (1/47 (2.1%) vs. 2/449 (0.4%), OR [95% CI], 5.8 [0.8, 44.7]). However, development of epilepsy, and consequently presence of neurologic sequelae, at 12-month follow-up were more frequent in children with CM than NCSM (3/47 (6.4%) vs. 3/449 (0.7%), OR [95% CI] 10.0 [2.2, 45.6], and 3/47 (6.4%) vs. 5/449 (1.1%), OR [95% CI] 6.4 [1.6, 25.1], respectively). Seven children with no neurologic deficits at discharge had new deficits at 12 months. Neurologic sequelae, particularly epilepsy, are more common in CM than other forms of severe malaria, but occur rarely in non-cerebral severe malaria. Long-term neurologic sequelae in children after forms of severe malaria other than cerebral malaria (e.g., severe malarial anemia, respiratory distress, malaria with multiple seizures, and prostration) are not well-characterized. In the present study, long-term neurologic sequelae (persistent neurological deficits and/or development of epilepsy after discharge over 12- month follow-up) were more common in children with cerebral malaria (6%) than in children with non-cerebral severe malaria (1%). Epilepsy was the primary driver of the differences between groups (cerebral malaria, 6%, non-cerebral severe malaria 0.7%). Long-term neurologic sequelae are rare in children with non-cerebral severe malaria.
STAT3 is a promising therapeutic target for human cancers and other diseases. Herein, we report our development of novel STAT3 proteolysis-targeting chimera degraders using high-affinity STAT3 and Von Hippel-Lindau 1 ligands, which led to the discovery of SD-2301 as a highly potent, selective, and efficacious STAT3 degrader. SD-2301 achieved DC50 = 4 nM and Dmax of >95% and is >100 times more potent than SD-36 and SD-91. SD-2301 is highly selective for inducing STAT3 degradation over other Signal Transducer and Activator of Transcription members. SD-2301 inhibited cell growth with IC50 = 5-11 nM in the SU-DHL-1 and SUP-M2 lymphoma cell lines. SD-2301 displayed an excellent pharmacokinetic profile in mice and achieved rapid and persistent depletion of STAT3 protein in native and xenograft tumor tissues in mice. SD-2301 was capable of achieving complete and long-lasting tumor regression in vivo and is a promising STAT3 degrader for the treatment of human cancers and other human diseases.
A decision coach (DC) is a trained healthcare professional who provides non-directive support to patients in health-related decision-making. The decision coach role can be integrated into shared decision-making (SDM) processes, but is not an inherent component of SDM, as both may be applied independently depending on the clinical context. Numerous trained DCs are nurses who have transitioned from their roles as patient educators to knowledgeable, skilled decision facilitators. Thus, developing core competencies has become increasingly crucial for DC training, especially patient-centered care in nursing education. This study aimed to evaluate DC competencies in SDM by examining accessibility, performance, and perceived directional relationships among competency domains. This mixed-methods study combined a narrative literature review and expert consultations to identify key DC competency criteria. Subsequently, a cross-sectional questionnaire survey was administered to healthcare professionals at two hospitals in Taiwan between April 2023 and February 2024. Accessibility-performance analysis (APA) and the decision-making trial and evaluation laboratory (DEMATEL)-based network relation map (NRM) approach were applied to evaluate competency accessibility, performance, and perceived directional relationships across domains. A total of 149 healthcare professionals, including physicians, nurses, and other clinical staff, completed the valid questionnaires. The reliability of the overall criteria was measured at 0.965. The findings suggest that the professional knowledge (PK) aspect demonstrated perceived directional associations with the outcome evaluation (OE), process management (PM), and guidance skills (GS) aspects within the network structure, whereas the GS aspect was more likely to be associated with other competency domains. Each of the four aspects has a criterion critical to improving DCs' competencies: value (PK1), listening skill (GS2), shared decision-making resources (PM3), and practical decision-making results (OE3). From healthcare professionals' perspectives, professional knowledge was the competency domain most closely associated with perceived directional relationships among other competency aspects within the network structure. The integrated APA-NRM approach delivers evidence-based prioritization and practical pathways for developing DC competencies and guiding training strategies. Not applicable.
E-cigarette use has been linked to respiratory mucosal inflammation and other markers of toxicity. Dual use, or the use of e-cigarettes in combination with conventional cigarettes or other inhaled products has increased in prevalence, but there is limited understanding of the health effects associated with dual use. The aim of this study was to establish whether nasal mucosal cytokine profiles among people who never use tobacco, people who exclusively use electronic cigarettes, and people who dual tobacco product use change over time and whether dual use significantly differs from exclusive e-cigarette use. This study utilized a repeated sampling study design, collecting nasal epithelial lining fluid from young adult participants (n=64) who never used tobacco, exclusively used electronic cigarettes, and used dual tobacco products, once weekly for four weeks using a remote, non-invasive sampling technique. Nasal mucosal immune mediators and salivary cotinine were then analyzed by ELISA. Differences in mucosal immune mediators were identified between e-cigarette, dual tobacco product and never tobacco product participant groups; however, these markers did not vary across time within group. People who exclusively use e-cigs or dual tobacco products exhibited increased proinflammatory markers compared to people who never use. Chemokine profiles were uniquely altered in the dual tobacco product group. Sex differences were identified in cytokine and chemokine production across groups. Conclusions: These results suggest that remote, non-invasive nasal sampling is adequate for assessing immune profiles from people who use tobacco products and cross-sectional sampling is likely representative of consistent respiratory immune profiles across multiple weeks. Dual product use results in distinct respiratory immune profiles, which suggests that long term disease outcomes may differ from people who exclusively use e-cigs.
Parkinson's disease (PD) is a neurodegenerative disease marked by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and formation of misfolded protein aggregates. A growing body of research has implicated glial cell dysfunction in PD etiology, including the concentration of activated glial cells around protein aggregates in post-mortem tissue. A disruption in the balance of pro- and anti-inflammatory immune response functions of microglia and astrocytes is believed to contribute towards neuronal degeneration as the disease progresses. However, the molecular mechanisms remain unclear. To shed light on the role of microglia and astrocytes in PD, this study analyzes three public single nuclear RNA sequencing datasets of the SNpc from patient and control post-mortem brains to identify altered molecular pathways in PD. Both astrocytes and microglia show significant upregulation of heat shock binding and misfolded protein response pathways, likely reflecting a response to accumulating protein aggregates. Additionally, both cell types show decreased expression of genes associated with receptor functions; for microglia this included cytokine receptor genes such as IL21R, IL4R, and IFI44L. Genes associated with resting state microglia and non-inflammatory reactive state microglia were downregulated in PD microglia, including P2RY13, RSAD2, CSF2RA, CSF3R, and CX3CR1. Concurrently, astrocytes and microglia both show decreased expression of genes associated with neurotransmitter receptor functions that include glutamate and other ion channel receptors, suggesting a loss of neuron-glia communication in later disease stages. Taken together, our findings imply that astrocytes and microglia respond to protein misfolding pathology in PD by upregulating chaperone protein folding functions. Additionally, the profile of upregulated functions implies that both cell types are under increased energetic demand. The downregulation of neurotransmitter and channel receptor functions in both cell types indicates that neuron-glia communication and other supportive functions may be lost in favour of autophagic, protein-clearance mechanisms in PD microglia and astrocytes.
Dysmenorrhea is a common gynaecological condition among young women, with non-steroidal anti-inflammatory drugs (NSAIDs) recommended as first-line therapy. However, a substantial proportion of women experience inadequate pain relief despite NSAID use. This study aimed to determine the prevalence of NSAID-resistant dysmenorrhea and to identify predictors as well as alternative pain management strategies among female undergraduate students at Afe Babalola University, Ado-Ekiti, Nigeria (ABUAD). A descriptive cross-sectional study was conducted among 271 female undergraduate students of ABUAD. Data were collected using a structured, self-administered electronic questionnaire that assessed socio-demographic characteristics, menstrual history, dysmenorrhea severity, NSAID use, perceived effectiveness, and alternative pain management strategies. NSAID-resistant dysmenorrhea was operationally defined as persistent menstrual pain despite reported use of recommended NSAID dosages. Descriptive statistics were used to summarize data. Bivariate analyses were conducted using Chi-square, Fisher's exact, and Mann-Whitney U tests, as appropriate. Multivariate logistic regression was performed to identify independent predictors of NSAID resistance. Statistical significance was set at p ≤ 0.05. The prevalence of dysmenorrhea among participants was 70.8% (192/271). Of those with dysmenorrhea, 62.5% (120/192) reported NSAID use for pain management. Among NSAID users, 63 students were classified as having NSAID-resistant dysmenorrhea, representing 52.5% of NSAID users and 32.8% of all students with dysmenorrhea. Perceived delayed onset of NSAID action (adjusted odds ratio [AOR] = 16.91; 95% CI: 2.00-141.60; p = 0.009) and lower NSAID effectiveness scores (AOR = 0.72; 95% CI: 0.57-0.90; p = 0.004) were significant predictors of NSAID resistance. Common coping strategies among NSAID-resistant students included activities such as use of alternative medications (25.4%), NSAID dose escalation (23.8%), rest or sleep (6.3%), as well as medications including antispasmodics (31.7%), and herbal remedies (11.2%). NSAID-resistant dysmenorrhea is common among undergraduate students. Perceived delayed onset and reduced effectiveness of NSAIDs are key predictors of resistance and contribute to reliance on alternative and potentially unsafe coping strategies. These findings highlight the need for improved education on appropriate dysmenorrhea management, early identification of NSAID non-responders, and access to evidence-based alternative treatment options. Painful menstruation (dysmenorrhea) is common among young women and can affect daily activities and academic performance. Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and diclofenac, are commonly used to treat menstrual pain. However, some women do not experience adequate relief even when these medicines are taken correctly.This study investigated how often menstrual pain does not respond to NSAIDs, the predictors of poor response, and the alternative ways students manage their pain. The study included 271 female undergraduate students at Afe Babalola University in Nigeria.Most participants reported experiencing menstrual pain, and many used NSAIDs for relief. However, more than half of NSAID users reported that the medicines did not adequately relieve their pain, even when taken at the recommended doses. Overall, nearly one in three students with menstrual pain was classified as having NSAID-resistant dysmenorrhea. Many students reported that NSAIDs worked too slowly or were ineffective. When NSAIDs did not relieve pain, students often used other strategies such as increasing NSAID doses without medical advice, taking other pain medicines, resting, using heat therapy, herbal remedies, or visiting the hospital. Students who perceived NSAIDs as slow or ineffective were more likely to have NSAID-resistant menstrual pain, while factors such as age and menstrual characteristics were not strongly associated.These findings highlight the need for better education on safe pain management, early identification of students who do not respond to NSAIDs, and improved access to effective treatment options for menstrual pain.
Penguins, as distinctive marine birds, play important roles in polar and sub-Antarctic ecosystems, yet the diversity and species-specific distribution of their gut viromes remain insufficiently understood. Here, we used viral metagenomics to characterize the cloacal viromes of four penguin species-Spheniscus humboldti (S. humboldti), Pygoscelis papua (P. papua), Pygoscelis adeliae (P. adeliae), and Aptenodytes forsteri (A. forsteri)-collected at Chimelong Ocean Kingdom. A total of 219 viral sequences representing potentially novel lineages were identified, with more than 94% sharing <80% amino acid similarity with previously known viruses. These sequences were assigned to several viral families, including Parvoviridae, Caliciviridae, Anelloviridae, Circoviridae, and Microviridae, among others. Marked interspecies differences in virome composition were observed: Parvoviridae dominated in S. humboldti, Microviridae were enriched in P. papua, Caliciviridae accounted for a substantial proportion in A. forsteri, and P. adeliae displayed the greatest overall virome diversity. Multiple-virus co-detections, particularly involving Parvoviridae, were frequent in S. humboldti. Phylogenetic analyses showed that many penguin-associated viruses clustered with viruses infecting other avian and fish hosts, suggesting possible dietary or environmental origins of some detected viral sequences. These findings expand current knowledge of penguin gut virome diversity and host-associated differences and provide a valuable foundation for evaluating the ecological roles, health implications, and transmission risks of penguin-associated viruses.IMPORTANCEThis study uncovers significant diversity in the gut viromes of four penguin species, revealing over 219 viral sequences representing potentially novel lineages, many of which showed host-associated distribution patterns. Using viral metagenomics, we identified notable interspecies differences, with Parvoviridae predominating in Spheniscus humboldti and Microviridae being enriched in Pygoscelis papua. These findings highlight the complexity of viral community structures in penguins, including frequent viral co-detections, which could impact host health and ecological adaptation. Additionally, novel bacteriophage communities were identified, emphasizing their potential role in shaping the gut microbiome and influencing viral dynamics. This work provides new insights into viral diversity in wildlife and lays the groundwork for future studies on viral transmission risks and ecological conservation.
The relevance of the study is as follows. Traditional methods of pedagogy do not allow objective and continuous monitoring of the emotional state of each student. The teacher usually relies on subjective observations - facial expressions behavior in a group - which may be inaccurate. At the same time modern technologies provide new opportunities: cameras and sensors backed by AI algorithms are able to automatically recognize facial expressions voice intonations and other signs of an emotional state. There are already commercial solutions for facial emotion recognition which have been used in marketing and security. Their potential application in education is an important topic as automated emotion analysis could provide educators with objective data on how engaged a group is whether students are overworked and who is experiencing difficulties or stress. It is the problem of mass learning fatigue and emotional burnout according to empirical studies that makes the introduction of such systems modern and practically significant and is the topic of this article. The article notes that the introduction of AI systems that can monitor both behavioral and physiological indicators opens up new opportunities for objective registration of cognitive states. For example sensors and wearable devices can measure heart rate heart rate variability brain activity and other parameters related to the level of concentration and mental stress. Computer vision can track eye gaze direction blinking frequency and posture which indirectly indicates the level of attention or fatigue. The study presents the results of a psychometric testing study using validated tools for emotional involvement in the educational process and a study of the factors of burnout and knowledge fatigue among full-time students at the Novorossiysk branch of the Financial University under the Government of the Russian Federation. The sample consisted of 125 respondents. Традиционные методы педагогики не позволяют объективно и непрерывно отслеживать эмоциональное состояние каждого студента. Преподаватель обычно опирается на субъективные наблюдения — выражения лиц поведение в группе — которые могут быть неточными. Современные технологии дают новые возможности: камеры и датчики подкреплённые алгоритмами ИИ способны автоматически распознавать мимику голосовые интонации и другие признаки эмоционального состояния. Уже существуют коммерческие решения для распознавания эмоций по лицу которые применяются в маркетинге и безопасности. Проблема массовой учебной усталости и эмоционального выгорания делает внедрение подобных систем современным и практически значимым и является темой данной статьи. В статье отмечено что внедрение ИИ-систем способных проводить мониторинг как поведенческих так и физиологических индикаторов открывает новые возможности для объективной регистрации когнитивных состояний. Например датчики и носимые устройства могут измерять частоту сердечных сокращений вариабельность сердечного ритма активность мозга и другие параметры связанные с уровнем концентрации и умственного напряжения. Компьютерное зрение способно отслеживать направление взгляда частоту миганий позу что косвенно свидетельствует об уровне внимания или утомления. В исследовании приведены результаты проведённого исследования психометрического тестирования с использованием валидизированных инструментов эмоциональной включённости в образовательный процесс и исследование факторов выгорания усталости от знаний студентов очной формы обучения Новороссийского филиала Финансового университета при Правительстве РФ. Выборка составила 125 респондентов.
Sjögren's disease is an autoimmune condition that may have neurological involvement. Rituximab is a monoclonal antibody against CD20 that has shown potential in the management of central and peripheral neuropathy in lymphomas and some autoimmune disease. There is limited data on the efficacy of rituximab on central nervous system (CNS) involvement in Sjögren's disease. The aim of this systematic review was to assess the effects of rituximab on CNS involvement among adults with Sjögren's disease. The PubMed, Scopus, and Web of Science medical databases were searched and the related articles were included in the review based on the inclusion and exclusion criteria. All articles published in English language that reported the effect of rituximab in the management of CNS involvement in Sjögren's disease were included and reviewed. Of the primary retrieved 173 articles, three (N = 62) were included in the review. All the studies were cohort studies and reported the effects of rituximab on CNS involvement as secondary analysis. Rituximab was administered in combination of other medications. Data synthesis revealed that rituximab, especially in combination with other medications, might have beneficial effects in severe and refractory CNS involvement in Sjögren's disease. Rituximab administration should be limited to severe and refractory CNS involvements in Sjögren's disease. However, due to the scarcity of articles and low level of confidence, further studies should be conducted to reach a definite conclusion.
Cyberchondria may influence women's health-related behaviors by shaping how they search for and interpret online health information. This study aimed to examine the effect of cyberchondria levels on genital hygiene behaviors in women of reproductive age. This cross-sectional study was conducted with 366 women aged 15-49 years registered at a family health center. Data were collected using a Demographic Information Form, the Genital Hygiene Behaviors Scale (GHBS), and the Cyberchondria Severity Scale Short Form (CSS-12). Descriptive statistics, Student's t-test, ANOVA, Pearson correlation, and multiple linear regression analysis were used in the analysis of the data. The mean total GHBS score of the participants was 87.28 ± 10.20; the CSS-12 score was 32.19 ± 9.35. Regression analysis showed that the excessiveness and reassurance-seeking subdimensions of cyberchondria were significant positive predictors of genital hygiene behaviors, while the anxiety subdimension was a significant negative predictor (p < 0.001). Although the overall cyberchondria score showed a weak positive correlation with genital hygiene behaviors, it was determined that age may play a more significant role in explaining genital hygiene behaviors. Our findings indicate a limited association between cyberchondria and genital hygiene behaviors. However, they suggest that age and related life experiences may be more significant determinants of these behaviors. Genital hygiene behaviors are more influenced by sociodemographic factors such as education, income level, and access to hygiene education. Cyberchondria is not a strong predictor on its own and should be evaluated in conjunction with other individual factors.
Students from low-income and underrepresented backgrounds face structural barriers to entering medicine, including limited access to early clinical exposure, physician guidance, and professional networks. To address these disparities, medical students at the Warren Alpert Medical School of Brown University created a year-long Clinical Mentorship Program (CMP) for high school students in Woonsocket, Rhode Island. The intervention combined monthly after-school instruction on basic science content and clinical skills by medical students with structured hospital-based shadowing and guided discussion with resident physicians. Using a mixed-methods pre-post design, the intervention evaluated changes in educational motivation, clinical self-efficacy, medical knowledge, awareness of other academic enrichment programs, and physician access and comfort. High school students demonstrated significant gains in motivation to attend college, understanding of cardiopulmonary anatomy and physiology, understanding of physician roles, comfort interacting with physicians, self-reported physician access, and awareness of local educational opportunities. Qualitative findings highlighted the importance of experiential learning, guided shadowing, a clearer understanding of medical careers, and persistent structural barriers. These findings suggest that community-based programs that leverage local resources, networks, and infrastructure to combine medical education with guided clinical exposure may be feasible entry points into the medical pipeline for students confronting complex socioeconomic disadvantages.
Testicular malakoplakia (MP) is an extremely rare chronic granulomatous inflammatory lesion. It lacks specific clinical or imaging features and is highly prone to misdiagnosis as a testicular tumor. To our knowledge, no reports have described the contrast-enhanced ultrasound (CEUS) manifestations of this condition. Herein, we present a case with the aim of improving the understanding of testicular MP and reducing unnecessary misdiagnosis and oversight. A 41-year-old Han Chinese male presented with unexplained right scrotal swelling for more than 20 days, accompanied by intermittent fever, chills, and dysuria, along with mild distending pain in the enlarged testicle. CEUS revealed that the right affected testicle had rapid high enhancement and slow washout. Computed tomography (CT) and magnetic resonance imaging (MRI) showed marked enlargement of the right testicle and altered parenchymal density, suggestive of a neoplastic lesion. Urine culture confirmed a bacterial infection with Escherichia coli (E. coli). Treatment with ceftriaxone and other antimicrobial agents yielded no significant improvement. Subsequently, a right orchiectomy was performed, and pathological examination confirmed the diagnosis of testicular MP. The patient's urinary symptoms gradually resolved postoperatively. During the 3-month follow-up, no recurrence was observed, and inflammatory markers remained within the normal range. The clinical and imaging presentations of testicular MP are nonspecific, posing a significant challenge for preoperative diagnosis. Definitive diagnosis still relies on pathological examination. Therefore, clinicians should increase their awareness of this rare disease to avoid misdiagnosis. To our knowledge, this report represents the first description and analysis of CEUS manifestations in a case of testicular MP.
Median palatine cysts (MPCs) and nasopalatine duct cysts (NPDCs) are rare non-odontogenic cystic lesions in the pediatric population. Due to their low incidence and often asymptomatic nature in children, these cysts are frequently overlooked or misdiagnosed. To the best of our knowledge, few comparative pediatric cases have been reported. The novelty lies in the detailed histopathological differentiation and the analysis of their impact on maxillofacial development, providing a crucial clinical reference for early intervention. In this report, two pediatric patients presented with similar clinical manifestations and obvious dental malalignment. Initial imaging suggested NPDCs in both cases. Both patients underwent complete cyst removal via endoscopic nasal surgery. Postoperative histopathological examination confirmed the distinct diagnoses: one as an MPC and the other as an NPDC. The primary histopathological differentiator was the composition of the fibrous cyst wall; the NPDC contained specialized structures (blood vessels, nerves, and mucous glands), which were absent in the MPC. At the two-year follow-up, both patients showed favorable maxillofacial development and no signs of recurrence. These cases illustrate that while MPCs and NPDCs may share clinical similarities, they possess distinct histopathological characteristics. The endoscopic approach appears to be a feasible surgical option in these cases. Early and accurate differential diagnosis can aid in surgical planning and may help mitigate potential impacts on pediatric maxillofacial development, offering useful insights for otolaryngologists and pediatric dentists.
Chronic lymphocytic leukemia (CLL) progression critically depends on bidirectional communication between malignant B cells and non-malignant bystander cells within the tumor microenvironment, including stromal cells, macrophages, and T lymphocytes. Among the key regulators of this cross talk is the Src-family kinase Lyn, whose activity in stromal cells controls extracellular matrix remodeling, fibrotic niche formation, and the release of tumor-supportive extracellular vesicles (EVs). This chapter presents a comprehensive proteomics-based strategy to identify Lyn-dependent effector molecules conveyed by stromal-cell-derived EVs and to evaluate their functional relevance for leukemic cell survival. State-of-the-art EV purification methods compliant with the Minimal information for studies of extracellular vesicles (MISEV) guidelines, nanoparticle tracking analysis, and high-resolution Orbitrap mass spectrometry are integrated with CRISPR-mediated Lyn knockout models and functional co-culture assays using primary CLL cells. Comparative metaproteomic profiling of EVs from Lyn-proficient and Lyn-deficient stromal cells reveals profound alterations in extracellular matrix proteins, adhesion molecules, redox regulators, and signaling mediators, highlighting downstream pathways through which Lyn programs a tumor-supportive microenvironment. Bioinformatic network analysis and pathway enrichment further identify druggable candidate proteins, including matricellular components and integrin-associated anchors such as CD248, as potential therapeutic nodes. Collectively, this chapter illustrates how EV-focused proteomics enables the systematic dissection of microenvironment-driven oncogenic signaling and provides a translational framework for discovering actionable stromal targets in CLL and other Lyn-dependent malignancies.
Peripherally inserted central catheters (PICCs) are widely used in oncology but are associated with higher rates of catheter-related thrombosis compared to other central venous access devices. Tunnelled non-cuffed centrally inserted central catheters (tnc-CICC) may offer a safer alternative in patient at high risk of thrombosis. This retrospective cohort study evaluated 193 tnc-CICCs placed in 182 cancer patients at a tertiary oncology unit between January 2021 and December 2022. Primary outcomes is catheter-related thrombosis; secondary outcomes are procedural duration and complication rates. Data were analysed using non-parametric statistical methods. The overall thrombosis rate was 1% (0.18 per 1,000 catheter days), significantly lower than reported PICC-associated thrombosis rates. No major intraoperative complications occurred. The overall complication rate was 19.7%, with catheter malfunction (9.3%), migration (5.2%) and bloodstream infections (4.1%) being the most common. Median procedural time was 34 min, with no significant difference based on operator experience. Off label use of PICCs as tnc-CICCs seems safe and effective. It provides an alternative to PICCs in oncology patients at high risk of thrombosis, even when placed by operators with low experience levels. These findings support the inclusion of tnc-CICCs in vascular access algorithms for cancer patient at high risk of thrombosis and suggest feasibility for nurse-led insertion programs.
The article explores the current issue of medical support for merchant ship crews working in conditions of prolonged professional isolation, limited access to qualified medical care, and specific risk factors of the maritime environment. The author conducts a systematic analysis of modern digital healthcare technologies, such as wearable biometric devices, telemedicine platforms, mobile medical applications, and cloud-based data storage systems, in terms of their applicability for continuous monitoring of seafarers health during voyages. The paper presents an original methodology for assessing the comprehensive effectiveness of the implementation of digital monitoring systems, based on a multi-criteria weighted matrix, where the components correspond to medical, technical, ergonomic (household), economic, and compliance with standards. A target efficiency threshold of 0.85 has been established, which provides for a 15% reserve for possible technical failures, human factors, and unforeseen circumstances. Based on the analysis, a set of practical recommendations has been formulated for shipping companies and regulatory authorities. The results of the study allow for the optimization of health-saving strategies in the maritime industry, reducing occupational risks, improving the availability of medical care, and minimizing economic losses associated with crew illnesses during voyages. The proposed methodology can be adapted for other industries with similar working conditions. В статье исследуется актуальная проблема медицинского обеспечения экипажей судов торгового флота, работающих в условиях длительной профессиональной изоляции, ограниченного доступа к квалифицированной медицинской помощи и специфических факторов риска морской среды. Автор проводит системный анализ современных цифровых технологий здравоохранения — носимых биометрических устройств, платформ телемедицины, мобильных медицинских приложений и облачных систем хранения данных — с точки зрения их применимости для непрерывного мониторинга состояния здоровья моряков в рейсовых условиях. В работе представлена оригинальная методология оценки комплексной эффективности внедрения цифровых систем мониторинга, основанная на многокритериальной взвешенной матрице, где компоненты соответствуют медицинской, технической, эргономической (бытовой), экономической эффективности и соответствию стандартам. Установлен целевой пороговый показатель эффективности 0,85, что предусматривает 15% резерв на возможные технические сбои, человеческий фактор и непредвиденные обстоятельства. На основе проведённого анализа сформулирован комплекс практических рекомендаций для судоходных компаний и регуляторных органов. Результаты исследования позволяют оптимизировать стратегии здоровьесбережения в морской отрасли, снижая профессиональные риски, улучшая доступность медицинской помощи и минимизируя экономические потери, связанные с заболеваниями экипажей в рейсах. Предложенная методология может быть адаптирована для других отраслей с аналогичными условиями труда.
Viral arthritis accounts for approximately 1% of acute arthritis cases and may be caused by several viruses, particularly parvovirus B19 (B19V). Diagnosis relies on clinical presentation, B19V immunoglobulin M (IgM) and/or immunoglobulin G (IgG) seropositivity, and the exclusion of other infectious and non-infectious etiologies. Following a European outbreak of B19V between March and May 2024, we conducted a multicenter retrospective study. The primary outcomes were the clinical and laboratory manifestations of B19V-associated arthritis; secondary outcomes included progression to chronic inflammatory disease and the need for escalation to disease-modifying antirheumatic drugs (DMARDs). A total of 28 patients (25 women and 3 men) were included, with a mean age of 44±11.4 years; 16 patients (57.1%) reported epidemiological risk factors. Acute, additive, symmetrical inflammatory polyarthralgia was the predominant clinical feature (26 patients, 92.9%), while axial inflammatory pain was reported by four patients (14.3%). Laboratory evaluation revealed positivity for antinuclear antibody (ANA) in 32.1%, rheumatoid factor (RF) in 19.7%, and HLA-B27 in 7.1% of patients. Anti-double-stranded DNA (dsDNA) and anti-cyclic citrullinated peptide antibodies (ACPA) were negative in all cases. Complement consumption was observed in a minority of patients, with low C3 levels in four (14.3%) and low C4 levels in three patients (10.7%). Regarding treatment, 39.3% of patients received nonsteroidal anti-inflammatory drugs (NSAIDs), while 60.7% were treated with systemic corticosteroids (prednisolone 10-40 mg/day); one patient required intravenous methylprednisolone (125 mg). Clinical remission was achieved in 24 patients (85.7%) after a mean duration of 34±47.0 days. However, four patients experienced relapse during corticosteroid tapering, suggesting potential progression to a chronic inflammatory condition. Among these, one patient achieved adequate symptom control with intermittent courses of NSAID alone, whereas the remaining three required initiation of DMARD therapy. This study provides one of the most comprehensive characterizations of B19V-associated arthritis in immunocompetent adults. Our findings emphasizes B19V infection as a significant viral mimic of early inflammatory rheumatic diseases and suggests considering it in the differential diagnosis of acute polyarthritis. Moreover, our study highlights the uncommon but notable potential of B19V infection to induce persistent inflammatory responses requiring immunosuppressive therapy.
SlBBX17 positively regulates tomato defense by modulating JA-mediated signaling. Jasmonic acid (JA) is a key plant defense metabolite, particularly against herbivory and necrotrophic pathogens. The MYC2 transcription factor (TF), a core TF of the JA response, is repressed by its interaction with JAZ proteins, members of the TIFY/JAZ protein family. Biotic stress stimuli trigger the accumulation of the bioactive JA-Ile conjugate, which binds to the SCFCOI1-JAZ co-receptor complex, promoting the ubiquitination and subsequent degradation of JAZ proteins, thereby releasing MYC2 to activate downstream target genes. JAZ proteins also regulate other signaling pathways through protein-protein interactions with TFs. However, interactions between JAZs and BBX TFs, emerging regulators of several physiological and developmental processes in plants, remain underexplored. In this study, we revisited the SlTIFY/JAZ family in the tomato (Solanum lycopersicum) genome, examining their diversity, domain topology, and conserved motifs. Transcriptional profiling of SlTIFY/JAZs and SlBBXs in tomato leaves revealed three distinct gene groups based on their response to JA, with some being intensely upregulated, displaying SlMYC2-like expression, or downregulated. Further investigation of differentially expressed SlJAZs and SlBBXs in different genotypes of tomato hairy root cultures underscored the dependency of SlCOI1, and, at least partially, of SlMYC1 and/or SlMYC2 for their JA-mediated transcriptional modulation. The expression patterns pinpointed SlBBX17 as a SlMYC2-dependent JA-responsive gene. Transactivation assays further indicate that SlMYC2 upregulates SlBBX17 expression. Functional analyses revealed that SlBBX17 positively contributes to plant defense, because loss-of-function genotypes displayed increased susceptibility to Spodoptera frugiperda herbivory, whereas overexpression enhanced resistance. Together, our results point to SlBBX17 as a JA-responsive regulator that modulates defense responses.
Pho4 is a fungal transcription factor essential for the response to phosphate (Pi) starvation in many fungi and is usually encoded by a single gene. However, we recently reported that the methylotrophic yeast Komagataella phaffii encodes two functional Pho4 proteins, named Pho4(A) and Pho4(B), and that only Pho4(B) was required for the transcriptional response to Pi limitation. Pho4 is also important in many yeasts for adaptation to an alkaline environment. We evaluate here the participation of Pho4(A) and Pho4(B) in the transcriptional response to alkaline pH. We show that the expression of nearly one-hundred genes is altered in a pho4(A) pho(B) mutant. In contrast to Pi starvation, Pho4(A) becomes important under high pH stress for the short-time expression of genes required for Pi homeostasis, such as PHO89, VTC1, VTC2, VTC4 and PHO4(B), suggesting that both transcription factors respond to different signals. Integration of the transcriptional data with that obtained from crz1 or rim101 mutants shows that nearly 80 genes are regulated by at least two of these transcription factors. Thus, we show that induction of PHO89 by Pi starvation or high pH is fully abolished in both double pho4(A) pho4(B) and single rim101 mutants, and that mutation of CRZ1 and RIM101 partially eliminates the sensitivity to high pH of the pho4(A) pho4(B) strain, revealing unexpected genetic interactions between these mutations. Finally, we identify an alkali-sensitive region in the PHO89 promoter and demonstrate that its duplication further increases the promoter's response to alkalinization. The transcription factor Pho4(A) is not required for the transcriptional response to Pi starvation, but it contributes to the response to alkalinization. Gene expression remodeling upon alkalinization in K. phaffii is controlled by diverse signaling pathways, including Pho4, Crz1 and Rim101 as well as other components still to uncover. Detailed knowledge of the signaling mechanisms triggered upon alkalinization and promoter mapping of the genes responsive to high pH will be useful tools for the generation of alkaline pH-regulated hybrid synthetic promoters in K. phaffii with improved features.
As the two main variety groups in improved rice, IND (indica) and JAP (temperate japonica and tropical japonica), extensive studies have utilized (single-nucleotide polymorphisms) SNPs on 233 selected improved rice cultivars to analyze the genetic basis of agronomic traits during their improvement and to compare their similarities and differences. However, the roles of other types of variations, such as insertions and deletions (INDELs) and structural variations (SVs), remain relatively underexplored. Here, using resequencing data from 233 improved rice accessions (IND: 142, JAP: 91), we identified 811,646 INDELs and 16,231 SVs in IND, and 652,793 INDELs and 10,533 SVs in JAP. The abundance of INDELs and SVs decreased as their length increased in both variety groups. INDELs and SVs also showed an uneven distribution across the chromosomes of the two variety groups. In IND, 38.92% of INDELs and 44.1% of SVs were located within the 2 kb upstream and downstream of genes; in JAP, this proportion was 38.49% for INDELs and 43.22% for SVs. By performing genome wide association studies (GWAS) using phenotypic data of six agronomic traits (heading date, flag leaf length, flag leaf width, panicle number, plant height, and thousand grain weight) along with INDELs and SVs, we identified 3,222 significant IND-INDELs, 537 significant IND-SVs, 1,996 significant JAP-INDELs, and 286 significant JAP-SVs. Comparison of significant loci revealed that IND and JAP shared only one INDEL associated with flag leaf length and one SV associated with panicle number, suggesting distinct genetic architectures determined by INDELs and SVs for these traits in the two groups. Furthermore, haplotype analysis of candidate genes demonstrated that INDELs and SVs influence key functional genes, such as the gene TAD1 (IND-INDELs) in flag leaf length, RCN2 (IND-SVs) in heading date, PLS2 (JAP-INDELs) in plant height, and OsYLC2 (JAP-SVs) in leaf development. This study analyzed the variation patterns of INDELs and SVs during the improvement of IND and JAP varieties, and identified INDELs and SVs associated with agronomic traits. These findings will provide valuable genetic and material resources for rice breeding.