Primary immune thrombocytopenia (ITP) is characterized by the dual pathology of peripheral immune-mediated platelet clearance and restricted platelet production by megakaryocytes. The TPO-MPL axis is a central regulator of platelet homeostasis, and ligand-induced receptor activation is associated with downstream JAK2-STAT, MAPK, and PI3K-AKT signaling. This review summarizes the structural and functional features of TPO and MPL, the major immunopathogenic mechanisms of ITP, and the current clinical use of thrombopoietin receptor agonists (TPO-RAs) in ITP. Recent structural and functional studies suggest that TPO-RAs with distinct binding sites may not engage MPL in fully identical ways and may therefore be associated with differences in receptor conformation, dimer geometry, and downstream signaling output. Within this emerging structural and functional framework, these structural and signaling differences may help explain response heterogeneity and the clinical observation that some patients may still benefit after switching agents. However, direct experimental evidence linking switching outcomes to specific alterations in MPL dimer geometry remains lacking, and the available clinical evidence regarding switching comes mainly from retrospective and observational studies, with additional support from post hoc analyses. Overall, continued investigation of the TPO-MPL pathway and its structural basis may help refine our understanding of ITP pathogenesis, treatment-response heterogeneity, and the clinical observations associated with switching, although the proposed mechanistic links still require direct experimental validation.
Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder. Although mucosal involvement is uncommon, it may indicate a more severe clinical phenotype. This study evaluated the prevalence and clinical features associated with mucosal involvement in BP. This retrospective cohort study included 265 patients with BP diagnosed at Peking Union Medical College Hospital between January 2013 and May 2022. Clinical, laboratory, immunological, and treatment-related characteristics were compared between patients with and without mucosal involvement. Logistic regression analyses were performed to identify factors associated with mucosal involvement, and model performance was assessed using receiver operating characteristic analysis. Seventy-one patients (26.8%) had mucosal involvement, most commonly affecting the oral mucosa, followed by genital and ocular sites. Compared with patients without mucosal lesions, those with mucosal involvement were younger at disease onset, more frequently had a history of malignancy, and showed a more severe clinical phenotype, including higher hospitalization rates, more infections within 1 year, higher corticosteroid requirements, higher BPDAI scores, and more frequent head/neck and hands/feet involvement. Indirect immunofluorescence seropositivity and peripheral eosinophilia were less frequent in patients with mucosal involvement. In multivariate analysis, head/neck involvement (adjusted OR 8.276, 95% CI 2.211-30.977), hands/feet involvement (adjusted OR 34.559, 95% CI 8.191-145.805), and higher BPDAI score (adjusted OR 1.055, 95% CI 1.020-1.091) were independently associated with mucosal involvement, whereas peripheral eosinophilia was inversely associated (adjusted OR 0.027, 95% CI 0.005-0.148). The model demonstrated excellent apparent discrimination (AUC 0.937). Mucosal involvement in BP is associated with a more severe clinical phenotype. Head/neck and acral involvement, higher BPDAI scores, and a lower frequency of peripheral eosinophilia may serve as practical clinical indicators for identifying patients who require closer mucosal assessment and more intensive monitoring. Bullous pemphigoid is a skin disease that mainly affects older adults and causes large blisters on the skin. In some patients, the disease also affects the mouth or other mucosal surfaces. Doctors consider this type of involvement uncommon, and they still know little about which patients are more likely to develop it. In this study, we analyzed medical records from 265 patients with bullous pemphigoid treated at a large hospital in China. We compared patients who had mucosal involvement with those who did not. We aimed to identify clinical features that may help doctors recognize patients who need closer mucosal assessment and monitoring. We found that about one in four patients had mucosal involvement. These patients tended to develop the disease at a younger age and often had more severe skin disease. They were also more likely to require hospitalization and stronger treatment. Skin lesions on the head, neck, hands, and feet were more common in these patients. In addition, these patients less often had increased eosinophils, a type of white blood cell, in their blood. Our results suggest that mucosal involvement may represent a more severe form of bullous pemphigoid. Recognizing these clinical features may help doctors identify these patients earlier and provide closer monitoring and more appropriate treatment.
Obesity is a worldwide public health issue, and it is crucial to identify individual risk factors for excessive food intake, as these may help inform obesity prevention/treatment efforts. One potential reason for which some individuals, but not others, overeat and become obese is food consumption in response to emotions, particularly in the absence of effective emotion regulation (ER) strategies. The current study used Ecological Momentary Assessment (EMA) to assess the effect of emotions and ER on eating in daily life in women with obesity (n = 46) and women with a healthy weight (n = 54). After completing a baseline questionnaire, participants responded to an EMA survey regarding momentary emotions, ER, and eating behavior five times per day for seven days. Women with obesity used less adaptive ER than women with a healthy weight in daily life. Positive emotions were prospectively associated with more unhealthy food choices in daily life. Negative emotions and ER were not prospectively associated with any eating behavior in daily life. Our findings do not support the notion that improving ER in response to negative emotions could be an effective intervention to reduce food consumption. Yet, in light of our findings regarding positive emotions, future studies could test whether improving ER in response to positive emotions could help individuals manage unhealthy food choices.
Intestinal barrier dysfunction has been implicated in the pathophysiology of irritable bowel syndrome (IBS), contributing to increased permeability, low-grade inflammation, and symptom generation. Microbial compositions are known to improve epithelial barrier function, although the underlying molecular mechanisms remain elusive. The aim was to investigate the effects of the fermented oat gruel preparation ReFerm® on colonic barrier function and tight junction protein expressions in patients with IBS. Colonic biopsies from patients with IBS were mounted in Ussing chambers to assess the direct effects of ReFerm® on epithelial permeability. In parallel, biopsies from patients treated with ReFerm® or placebo by enema were analyzed for the expression of multiple tight junction proteins using Western blotting and confocal microscopy. In vitro effects were further evaluated in Caco-2 cells. ReFerm® reduced both paracellular and transcellular permeability when added directly to biopsies mounted in Ussing chambers, compared with unstimulated biopsies. This effect was accompanied by increased expression of the tight junction protein tricellulin at tricellular junctions. In vitro experiments in Caco-2 cells supported these findings, demonstrating direct effects of ReFerm® on epithelial barrier properties. ReFerm® strengthens colonic barrier integrity in the gut mucosa of patients with IBS, potentially through modulation of the tight junction protein tricellulin. These findings provide mechanistic insight into the barrier-protective effects of fermented oat interventions such as ReFerm® and support the potential therapeutic role in IBS. Patients with irritable bowel syndrome (IBS) have an impaired gut barrier function, which may allow substances to pass more easily through the gut lining and contribute to symptoms. We investigated whether a fermented oat‐based preparation, ReFerm®, can strengthen the gut barrier in patients with IBS using two complementary approaches. In one approach, gut biopsies from patients with IBS were exposed to ReFerm® to examine its immediate effects on gut permeability. In parallel, biopsies from patients treated with ReFerm® or placebo by enema were analyzed to assess changes in tight junction proteins that help seal the spaces between the intestinal cells. We found that ReFerm® improves gut barrier function by reducing permeability and increasing levels of the tight junction protein tricellulin, important for maintaining the gut barrier. These findings suggest that fermented oat preparations such as ReFerm® may help protect the gut lining and could have therapeutic potential for patients with IBS.
When and how much plants grow under environmental constraints are fundamental questions in biology and increasingly important for predicting biomass production and carbon sequestration under climate change. While temperature and water availability directly regulate plant growth, the timing and rate of growth are also shaped by internal developmental programming, though this is rarely considered in predictions of tree growth responses to future climates. Here, we revisit a concept central to this internal programming-(in)determinacy. Focusing on woody plants, we define it as the extent to which annual shoot growth is deployed from preformed organs versus produced de novo during the current season. We argue that this trait is best understood as a continuum and that it can help explain contrasting growth responses in a changing climate. More determinate species concentrate growth within a narrow seasonal window, which may reduce exposure to late-season stress but also limit their ability to exploit longer growing seasons. More indeterminate species retain greater flexibility to extend or resume growth when conditions remain favourable, which may be advantageous under climate change, but this same flexibility may also increase exposure to frost, drought and incomplete tissue maturation. Because primary shoot growth also shapes canopy development and is linked to other growth processes, variation in (in)determinacy could help explain broader differences in whole-plant performance, carbon gain and species responses to climate change.
Polypharmacy is common in older adults and, independent of underlying multimorbidity, is associated with adverse drug events, reduced quality of life, and increased healthcare use. Deprescribing can help address these issues. Pharmacists can identify deprescribing opportunities during clinical medication reviews (CMRs), and guidelines may support this process. However, their impact depends on successful implementation. To identify determinants relevant for the implementation of this deprescribing guideline based on CPs' experiences with its use in clinical practice. Online focus groups were held with community pharmacists from the intervention group of a cluster randomized trial evaluating guideline-assisted deprescribing during CMRs in older patients with hyperpolypharmacy (≥10 medications). Pharmacists received training on the guideline and its drug-specific fact sheets. The topic guide was informed by the Tailored Implementation for Chronic Diseases (TICD) checklist. Transcripts were deductively coded and analysed thematically. Nineteen of 24 eligible pharmacists participated in three focus groups. Across seven TICD domains, 26 determinants were identified. There were few barriers related to the guideline itself, with pharmacists appreciating the layered structure and summaries and applicability of recommended interventions. At personal level, their ability to identify deprescribing opportunities and to monitor clinical outcomes was considered relevant. . At patient level, barriers included limited knowledge and ambivalent attitudes. Key influences regarding professional interaction included general practitioners' familiarity with deprescribing, clarity of task allocation, and interprofessional trust. Regarding resources insufficient reimbursement, and lack of integrated decision support were reported as barriers. Drug-specific fact sheets support deprescribing but do not fully address the complexity of decision-making in practice. Implementation is influenced by clinical uncertainty, experience, interprofessional collaboration, and organisational factors. Strengthening decision support, collaboration, and organisational conditions is essential for sustainable implementation.
Lumbar disk herniation (LDH) is an important cause of low back pain and functional impairment. For patients with severe LDH who are not immediate candidates for surgery or prefer to delay surgery, pharmacological treatment remains a major therapeutic option; however, short-term treatment responses vary substantially among individuals. At present, individualized tools for predicting short-term functional improvement after pharmacological treatment are lacking. Therefore, this study aimed to develop and internally validate a nomogram to predict 14-day improvement in the Oswestry Disability Index (ODI) in patients with severe LDH following pharmacological treatment. A total of 199 patients with MRI-confirmed severe LDH from 13 centers were included. All patients received 14 days of pharmacological treatment [Chinese patent medicine (CPM) vs. non-steroidal anti-inflammatory drugs (NSAIDs)]. The primary outcome was change in ODI at day 14. Candidate predictors were reduced using AIC-guided multivariable modeling, and a nomogram was developed from the final model. Secondary exploratory logistic analyses were performed using clinically relevant ODI improvement thresholds (>10, >20, and >30 points), with >10 points corresponding to the minimal clinically important difference (MCID). Internal validation was performed using bootstrap resampling. The optimal linear prediction model included six key variables: treatment group, sex, alkaline phosphatase (ALP), angular instability, degree of disk herniation (DDH), and hypertrophy of the ligamentum flavum (HLF). In the primary linear model, CPM treatment, female sex, higher ALP levels, and DDH-protrusion were significantly associated with lower ODI improvement (all P < 0.05). In secondary threshold-based analyses, sex, ALP, and HLF were significant negative factors when ODI improvement was >30 points, while DDH-protrusion was associated with a lower likelihood of ODI improvement > 20 points. Calibration plots suggested acceptable agreement between predicted and observed 14-day ODI improvement in internal bootstrap validation. This internally validated nomogram may help estimate short-term functional improvement after pharmacological treatment in severe LDH and may assist pre-treatment risk stratification. However, given the short follow-up, limited sample size, and absence of external validation, the model should be considered preliminary and requires further validation before routine clinical use.
Healthcare systems are struggling to keep pace with growing populations and their complex social/medical needs. Most believe that integrated care closer to home, not hospitals, is the answer, but this requires a shift in our mental models. In establishing a distributed health network for the Northern York and South Simcoe regions of Ontario, Canada, we realized the need for a measure that reflects the magnitude of the challenge ahead and the new thinking required to get there. Population avoidable days combines four commonly used measures of unnecessary hospital utilization into a single absolute value that can help achieve these objectives.
Acid sphingomyelinase deficiency (ASMD) is an inherited autosomal recessive disease caused by pathogenic variants in the sphingomyelin phosphodiesterase-1 (SMPD1) gene, which encodes acid sphingomyelinase (ASM). ASMD has 3 broad phenotypes (type A, type A/B, and type B) characterized by the age of onset, symptomatology, and the rapidity of disease progression. The diagnosis of ASMD can be delayed or missed because of the wide spectrum of severity and its variable manifestations. Analysis of genotype-phenotype correlations can help to determine ASMD disease type and inform management. Here, we describe the clinical presentation of 47 patients with ASMD referred to a single center in Iraq since 2007, whose diagnosis was confirmed by gene sequencing and ASM activity. This was a retrospective observational cohort study of patients diagnosed with ASMD in Iraq. The cohort included 47 patients with ASMD. A positive family history and consanguinity were noted in 66% and 98% of these cases, respectively. Hepatosplenomegaly, anemia, and thrombocytopenia were present in 100%, 79%, and 44% of patients, respectively. Notably, dysmorphic features were observed in 23% of cases. Thirteen SMPD1 variants were present in this cohort, the most common of which were c.1556A > G (p.Tyr519Cys), c.740delG (p.Gly247Alafs*10), c.967A > C (p.Ser323Arg), and c.1267C > T (p.His423Tyr). Three of the variants identified were novel, specifically c.967A > C (p.Ser323Arg), c.1579A > G (p.Asn527Asp), and c.905C > T (p.Thr302Ile). Physicians assessing infants and children who present with hepatosplenomegaly or anemia and dysmorphic features should have a high index of suspicion for ASMD, particularly in regions with high rates of consanguineous unions.
To describe the clinical and laboratory characteristics of third-trimester preeclampsia, summarize management patterns, and identify factors associated with adverse neonatal outcomes at a single public tertiary referral obstetrics and gynecology hospital in Vietnam. This retrospective descriptive study included 154 pregnant women diagnosed with preeclampsia and delivered at a single public tertiary referral obstetrics and gynecology hospital in Vietnam between August 1, 2022 and July 31, 2023. Clinical, laboratory, treatment, delivery, and neonatal data were analyzed using descriptive statistics and logistic regression. The composite adverse neonatal outcome was defined as the presence of one or more of the following: fetal growth restriction, preterm birth, intrauterine fetal death, low birth weight, neonatal respiratory morbidity, neonatal transfer, or perinatal death. Severe preeclampsia accounted for 57.1% of cases. Maternal age ≥35 years was associated with severe disease (OR 3.00, 95% CI 1.56-5.85), as were primigravidity (OR 1.98, 95% CI 1.03-3.78), prior stillbirth (OR 2.94, 95% CI 1.10-7.80), and assisted conception in the index pregnancy (OR 3.35, 95% CI 1.20-9.36). Elevated liver enzymes, hypoalbuminemia, hyperuricemia, and elevated urea were more frequent in severe preeclampsia. All women with severe preeclampsia underwent cesarean delivery; the overall cesarean rate was 81.2%. Preterm birth occurred in 35.7% of pregnancies and fetal growth restriction in 10.4%. In multivariable analysis, adverse neonatal outcomes were associated with maternal age >35 years (adjusted OR 2.24), gestational age <34 weeks (adjusted OR 8.77), albumin <35 g/L (adjusted OR 3.24), serum uric acid ≥400 umol/L (adjusted OR 3.93), severe hypertension (adjusted OR 2.29), and <=1 day of medical management before delivery (adjusted OR 9.34). Third-trimester preeclampsia at a public tertiary obstetrics and gynecology hospital in Vietnam was characterized by a high proportion of severe cases and a very high cesarean delivery rate. Older maternal age, primigravidity, assisted conception, severe hypertension, hyperuricemia, and hypoalbuminemia were associated with worse maternal or neonatal profiles. Earlier gestational age at birth remained the strongest predictor of adverse neonatal outcomes. Preeclampsia is a serious condition in pregnancy that causes high blood pressure and can affect the mother’s organs and the baby’s health. It can lead to problems such as preterm birth, poor fetal growth, and in severe cases, life-threatening complications for both mother and baby. This study looked at 154 pregnant women with preeclampsia in the third trimester who were treated at a major public tertiary obstetrics and gynecology hospital in Vietnam. More than half of the women had severe preeclampsia. Cesarean section was very common, especially in severe cases. Many babies were born too early, and some had growth problems. The study also found that worse neonatal outcomes were more likely when the mother was older than 35 years, the baby was delivered before 34 weeks of pregnancy, the mother had severe high blood pressure, or blood tests showed low albumin or high uric acid levels. A very short time between hospital treatment and delivery was also linked with poorer neonatal outcomes. These findings show that preeclampsia remains a major challenge in maternal care. Early detection, close monitoring, timely referral, and careful delivery planning may help reduce risks for both mothers and babies, especially in referral hospitals and lower-resource settings.
ESKAPE pathogens are a major cause of hospital-acquired colonization or infection among very preterm infants in neonatal intensive care units (NICUs). Early identification of high-risk infants can help prioritize infection-control interventions and guide targeted preventive care. A single-center retrospective cohort study was conducted among 465 very preterm infants (gestational age, GA ≤ 32 weeks) admitted to the NICU of a tertiary hospital between January 2015 and June 2025. Infants were randomly divided into training (n = 325) and internal validation (n = 140) cohorts at a 7:3 ratio. Predictors available within 24 h after birth were screened using least absolute shrinkage and selection operator (LASSO) regression. A multivariable logistic regression model was constructed and presented as a nomogram. Overall, 77 infants (16.56%) developed hospital-acquired ESKAPE colonization or infection, of which 67.5% (52/77) were first identified within 14 days after birth. Among 109 non-duplicate ESKAPE isolates, the predominant pathogens were Acinetobacter baumannii (38/109, 34.86%) and Klebsiella pneumoniae (31/109, 28.44%); respiratory specimens were the primary source (90/109, 82.57%). Four predictors were retained in the final model: GA at birth, initial invasive mechanical ventilation, vasoactive exposure within the first 24 h, and 5-minute Apgar score. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.786 (95% CI: 0.718-0.853) in the training cohort and 0.770 (95% CI: 0.673-0.866) in the internal validation cohort, indicating moderate discrimination. Calibration curves and decision curve analysis demonstrated good agreement between predicted probabilities and observed risks, with net benefit across a wide range of clinically relevant threshold probabilities. An online prediction tool was also developed (https://newborn.shinyapps.io/dynnomapp/). We developed and internally validated a nomogram for early prediction of hospital-acquired ESKAPE colonization or infection in very preterm infants using routine clinical indicators obtained within 24 h after birth. The model can support early risk stratification and infection control prioritization in the NICU. External validation and prospective implementation studies are required before routine clinical adoption.
With the rapid development of the nursing industry, the stability and professional competence of nursing personnel have become increasingly important. Professional identity, as a key factor influencing the development of nursing personnel, is crucial to the construction and development of the nursing workforce. Especially during the clinical internship phase, nursing interns face many sources of uncertainty, which may negatively affect their professional identity. However, some interns are able to maintain a high level of professional identity in uncertain environments, which may be closely related to their career resilience. This study aims to explore the mediating role of career resilience between intolerance of uncertainty and nursing interns' professional identity, providing theoretical support and intervention strategies for enhancing interns' professional identity. A convenience sampling method was used to select 298 nursing students who had completed 8 months of internship at a tertiary hospital in Zhengzhou from February to April 2025 as the study subjects. A general demographic questionnaire, the short version of the Intolerance of Uncertainty Scale (IUS-12), the Career Resilience Scale (CRS), and the Nursing Student Professional Identity Questionnaire (PIQN) were used for the survey. Descriptive statistics of all variables were conducted using SPSS 27.0 software to understand the basic characteristics of the sample. Pearson correlation analysis was used to test the correlations between intolerance of uncertainty (IU), career resilience (CRS), and professional identity (PIQN). The Process macro model 4 (developed by Hayes) was used for mediation effect analysis to test the mediating role of career resilience (CRS) between intolerance of uncertainty (IU) and professional identity (PIQN). The total score for intolerance of uncertainty in nursing interns was (38.57 ± 7.20), for career resilience (19.98 ± 2.71), and for professional identity (61.04 ± 9.30). Intolerance of uncertainty was negatively correlated with professional identity(r = -0.26, p < 0.001) and with career resilience (r = -0.31, p < 0.001), while career resilience was positively correlated with professional identity (r = 0.48, p < 0.001). Mediation analysis revealed that career resilience partially mediated the relationship between intolerance of uncertainty and professional identity [indirect effect = -0.17, 95% CI (-0.26, -0.10)], accounting for 52.64% of the total effect. Intolerance of uncertainty directly negatively affects nursing interns' professional identity, while career resilience plays a partial mediating role in buffering the negative impact of intolerance of uncertainty on professional identity. This suggests that nursing educators should specifically help nursing interns actively cope with uncertain situations and strengthen the development of career resilience, thereby enhancing their professional identity.
Despite remarkable advances in stroke management, there is a continued lack of evidence to guide care for the 1 in 3 stroke patients living with disability or dementia (PLWD). To help inform best practices, this study sought to understand how physicians approach the complex issue of determining goals of care for PLWD and what challenges they encounter. In a mixed-methods investigation, we invited physicians involved in stroke care to participate in semistructured interviews and an online survey, enquiring into perspectives on stroke management in PLWD. Interviews were analyzed using an interpretive grounded theory approach. Qualitative findings were triangulated with results from a descriptive analysis of survey items. Of 82 approached physicians, 30 participated in interviews (43% from North America, 77% with ≥10 years of experience; 60% neurologists); of 200 consenting to the survey, 132 completed it (37% from North America, 51% with ≥10 years of experience, 56% neurologists). For both prestroke disability and dementia, survey respondents most frequently indicated severity of the prior condition (87% [95% CI, 80%-91%] and 89% [95% CI, 82%-93%]) and quality of life (88% [95% CI, 82%-93%] and 87% [95% CI, 80%-91%]) as either very or extremely important in decision-making. However, interviewed physicians emphasized uncertainty in evaluating these factors and forming perceptions of patient prognosis and treatment appropriateness. This was attributed to limited reliable information regarding patients' prior well-being and wishes, and paucity of PLWD-specific evidence to guide stroke management. While these ambiguous circumstances appeared to warrant a highly individualized approach to care, physicians also recognized the consequent high risk of biases affecting equity. Physicians encounter profound, multifaceted uncertainty in determining goals of care for PLWD, which may contribute to adverse variability in stroke management. This uncertainty may be eased by routinely documenting patients' baseline well-being and advance healthcare directives in clinical practice and promoting inclusion of PLWD in stroke research, in both contexts, considering patient and family perspectives on quality of life and favorable outcomes.
Facial pain or pressure is often non-rhinogenic but is frequently misdiagnosed as sinusitis, leading to inappropriate treatment with antibiotics and surgery. The objective of this study was to develop and validate a brief self-administered questionnaire, the Sinus Headache Screener (SHS), to help differentiate chronic rhinosinusitis (CRS) from non-rhinogenic facial pain or pressure (NRFP). Patients presenting to the rhinology clinic with a chief complaint of facial pain or pressure completed an 89-item questionnaire bank developed previously through qualitative methods. A diagnosis of CRS or NRFP was given based on imaging criteria. Psychometric analysis and logistic regression were utilized to select items and create a scoring system that could reliably differentiate the two conditions. Predictive performance was evaluated through the area under the receiver operating characteristic curve (AUC) with bootstrapping. Of 251 patients enrolled, 114 had CRS and 137 had NRFP. Mean (SD) age was 50 (16), and 69.3% were women. Eight items with scoring weights were included in the SHS. Scores ranged from -4 to 9, with higher positive values predictive of NRFP. With a score cutoff of > 0, the SHS had a sensitivity/specificity of 0.87/0.64, and positive/negative predictive values of 0.74/0.80 for NRFP. The optimism-corrected AUC was 0.798 (95% CI: 0.766, 0.877). In patients presenting with sinus headache, the SHS accurately differentiated NRFP from CRS. The use of the SHS as a point-of-care clinical tool can improve diagnostic accuracy and facilitate cost-effective management.
Cognitive development during adolescence is arguably unmatched by any other period of life. Enhanced brain maturation, increased memory capacity, and the acquisition of new cognitive skills help prepare adolescents for adult social roles. Among these skills is cognitive monitoring, or the ability to reflect on one's own thinking-traditionally referred to as "metacognition." Using cross-sectional data from the first wave of a longitudinal panel cohort, we examined three facets of cognitive monitoring: decision-making (e.g., gathering information, evaluating alternatives), self-reinforcement (e.g., praise and encouragement), and affective self-regulation (e.g., emotional control) in four age groups of Czech high school students. Multiple-group confirmatory factor analysis tested primary, higher-order, age and gender-based models. Overall, model fit was acceptable, with only trivial differences in item intercepts, factor correlations, variances, and latent factor means. Primary factor models revealed gender differences favoring girls' use of decision-making strategies and older youth employing more decision-making skills. A higher-order metacognitive factor to account for correlations among the monitoring skills was supported across both age and gender groups. Results are discussed in terms of promoting cognitive monitoring as a key 21st-century skill and advancing higher-order reflective skills as a critical learning task during adolescence.
Xylopodia and woody rhizomes are highly lignified belowground bud-bearing organs (BBOs) reaching extensive depths in soil, persisting through a viable belowground bud bank over many years. In this context, maintaining hydraulic functionality and storing resources are essential secondary xylem functions for their survival in environments prone to disturbances such as fire and drought. Here, we examine how secondary xylem traits vary between roots and both BBOs (woody rhizomes and xylopodia) in resprouting woody species from Cerrado. We evaluated cross-sections of secondary xylem from two BBO types and their taproots of ten native woody species in a Cerrado area under regeneration after decades of pine cultivation. We applied linear mixed models (LMMs) to test whether secondary xylem traits differ between roots and BBOs. Xylopodium-type BBOs had narrower, dense vessels, a higher fiber fraction, and lower hydraulic potential conductivity than their roots. Woody rhizome-type BBOs had narrower vessel diameters and lower densities than their roots. Woody rhizome-type BBOs had narrower vessels and a higher density than xylopodia. Xylem fractions (vessels, rays, and axial parenchyma) were not statistically different between roots and BBOs. BBOs share similar strategies regarding storage capacity and mechanical support. Storage is a key trait for belowground bud bank resourcing during unfavorable periods and supporting resprouting after fire and drought. Fibers are essential for the mechanical stability of new branches. In addition, high lignification could help prevent wood decay and herbivory in the soil, as BBOs remain buried throughout the species' lifespan.
Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disease that not only affects motor function but is also associated with gastrointestinal and emotional disturbances. Recent research highlights the potential role of gut microbiota and diet in modulating these symptoms, suggesting a complex interaction between nutrition, intestinal health, and presence of anxiety and depression in ALS patients. This study aims to investigate the relationship between dietary intake, gut microbiota composition, and presence of anxiety and depression in patients with amyotrophic lateral sclerosis (ALS). A cross-sectional study conducted with a sample of 48 patients with bulbar-onset or spinal-onset ALS from different regions of Spain. Dietary intake was assessed through 24-h records and food frequency questionnaires, while anxiety and depression were evaluated using validated scales that formed a latent factor called emotional distress. Stool consistency was assessed following the Bristol Stool Scale and the abundance of bacterial microbiota was quantified. Confirmatory factor analysis identified a nutritional factor composed of vitamins B1, B2, B9, C, and fiber, revealing a significant inverse association with anxiety and depression levels. The predictive model revealed both direct and indirect effects of this factor on presence of anxiety and depression, mediated by Bacteroides abundance and stool consistency. This model explained 19% of the variance in psychological distress. Our findings suggest that a diet rich in B vitamins, C vitamin and fiber may help improve emotional well-being in patients with ALS, highlighting the importance of nutritional strategies, as well as the role of Bacteroides related to stool consistency in patients with ALS.
Anatomical variations in the brachial plexus can significantly affect upper-extremity surgical procedures. This report highlights a rare case where both pectoralis muscles receive accessory innervation. The pectoralis major exhibited three additional branches stemming directly from the anterior divisions of the superior and middle trunks, effectively bypassing the lateral cord. The pectoralis minor likewise demonstrated variant innervation, receiving two additional branches. One was an unexpected confluence in which a branch destined for the pectoralis major coursed through and innervated the pectoralis minor, despite the pectoralis minor typically receiving its own independent branch. The other branch originated from the anterior division of the middle trunk. Furthermore, a variant ansa pectoralis was identified, originating from the anterior division of the middle trunk and medial cord, and giving rise to the medial and lateral pectoral nerves. This unique configuration may present clinical implications for surgeons, particularly during procedures involving the proximal upper limb and supraclavicular pectoral region. Identifying these variations can help minimize the risk of iatrogenic nerve injury and enhance surgical planning.
Accurate estimation of the postmortem interval (PMI) is a crucial aspect of forensic investigations. Traditional methods rely on rectal temperature measurement, but alternative sites may provide more reliable measurements under certain conditions. The subgingival region, being a well-insulated anatomical site, has been considered for temperature-based assessments. However, no studies have explored its viability in PMI estimation. This study aims to assess subgingival temperature changes before and after euthanasia in rats and rabbits and compare them with rectal temperature variations. Understanding these temperature shifts could help clarify the forensic relevance of subgingival temperature as an alternative or complementary method for PMI estimation. To evaluate pre-euthanasia and posteuthanasia changes in subgingival and rectal temperatures in rats and rabbits. Based on a pilot study, the sample size was calculated (n = 8), comprising four rabbits and four rats. Following ethical clearance, a specialized subgingival thermometer was designed for measuring subgingival temperature, whereas rectal temperature was recorded using a commercially available digital thermometer (Omron MC-246 Digital Thermometer). Pre-euthanasia subgingival and rectal temperatures were recorded, followed by a second measurement taken 10 min posteuthanasia. The obtained temperature values (°C) were subjected to statistical analysis using the Wilcoxon signed-rank test and Spearman's rank correlation. Subgingival temperature before euthanasia was the only statistically significant finding (P = 0.010). In rats, a strong pre-euthanasia correlation between subgingival and rectal temperatures (r = 1.000, P = 0.010) weakened markedly after death (r = 0.200, P = 0.800). Conversely, rabbits exhibited a moderate correlation before euthanasia (r = 0.600, P = 0.400), which strengthened postmortem (r = 0.800, P = 0.200), indicating species-specific variations in heat retention and dissipation after death. Both subgingival and rectal temperatures decreased after euthanasia, confirming a postmortem temperature decline. However, the results were not statistically significant due to the small sample size. With further research overcoming these limitations, subgingival temperature could serve as a potential alternative for PMI estimation.
Chronic pain is increasingly recognized not merely as a physiological symptom of tissue damage, but as a multidimensional pathological state involving sensory, emotional, and cognitive components. Central to its modulation is the gut-brain axis (GBA), a bidirectional communication network linking the enteric nervous system (ENS), the active intestinal epithelium, gut microbiota, and central nervous system (CNS) through neural, endocrine, immune, and metabolic pathways. Despite growing clinical evidence linking microbial dysbiosis to conditions such as irritable bowel syndrome (IBS), migraine, and fibromyalgia (FM), important gaps remain in understanding the molecular mechanisms that govern gut microenvironmental signaling in pain regulation. This review comprehensively summarizes the current literature on GBA-mediated pain regulation, with a focus on the molecular mechanisms by which microbial metabolites, such as short-chain fatty acids (SCFAs), and brain-gut peptides (BGPs) influence peripheral and central sensitization. Available evidence suggests that microbiota-derived inflammatory mediators, including lipopolysaccharide (LPS) and pro-inflammatory cytokines, contribute to neuroinflammation by activating glial cells and increasing blood-brain barrier (BBB) permeability. In addition, host intestinal epithelial and enteroendocrine cells (EECs), particularly enterochromaffin cells (ECs), are not merely passive barriers but active signaling interfaces, capable of releasing 5-hydroxytryptamine (5-HT), glutamate derived from neuropod cells, and multiple endocrine peptides involved in gut-brain communication and nociceptive regulation. The interplay between the hypothalamic-pituitary-adrenal (HPA) axis and the endogenous cannabinoid system (ECS) may act as an important regulatory "filter" in descending pain modulation. This review also discusses how reprogramming of the gut microbiota through probiotics and dietary interventions may influence the pain matrix and help alleviate comorbid affective symptoms. Overall, this review provides an integrated perspective on chronic pain as a disorder influenced by multi-level gut-brain interactions and potentially sustained by a bidirectional pathogenic feedback loop, thereby offering a theoretical basis for the development of gut microenvironment-targeted analgesic strategies.