Dopamine D1 receptors activation rescues hippocampal synaptic plasticity and cognitive impairments in the MK-801 neonatal schizophrenia model.

Schizophrenia is a disorder with a higher cognitive decline in early adulthood, causing impaired retention of episodic memories. However, the physiological and behavioral functions that underlie cognitive deficits with a potential mechanism to ameliorate and improve cognitive performance are unknown. In this study, we used the MK-801 neurodevelopmental schizophrenia-like model. Rats were divided into two groups: one received MK-801, and the other received saline for five consecutive days (7-11 postnatal days, PND). We evaluated synaptic plasticity late-LTP and spatial memory consolidation in early adolescence and young adulthood using extracellular field recordings in acute hippocampal slices and the Barnes maze task. Next, we examined D1 receptor (D1R) activation as a mechanism to ameliorate cognitive impairments. Our results suggest that MK-801 neonatal treatment induces impairment in late-LTP expression and deficits in spatial memory retrieval in early adolescence that is maintained until young adulthood. Furthermore, we found that activation of dopamine D1R ameliorates the impairments and promotes a robust expression of late-LTP and an improved performance in the Barnes maze task, suggesting a novel and potential therapeutic role in treating cognitive impairments in schizophrenia.

Thrombectomy Outcomes for Anterior Circulation Stroke in the 6-24 h Time Window Solely Based On NCCT and CTA: A Single Center Study.

PURPOSE: Since perfusion imaging may be unavailable in smaller hospitals, alternative imaging selection methods for acute ischemic stroke can improve outcomes and optimize resources. This study assessed the safety and effectiveness of using imaging criteria other than DEFUSE 3 and DAWN for thrombectomy beyond 6 h from symptom onset in patients stroke in the anterior circulation. METHODS: This is a retrospective, single-center analysis of consecutive patients with large vessel occlusion in the anterior circulation undergoing thrombectomy. Patients were categorized into two groups based on the collateral status (moderate collaterals and good collaterals). RESULTS: Among 198 patients, 106 (54%) met the inclusion criteria and were analyzed. Good collateral status was observed in 78 (74%) patients. Patients with good collaterals showed significantly lower mRS scores at discharge and at 90 days compared to their counterparts with moderate collateral status (4 (3-4) vs. 4 (4-5); p = 0.001 and 2 (0-4) vs. 6 (3-6); p < 0.001, respectively). More patients with good collateral status achieved favorable outcomes at 90 days compared to those with moderate status (48 (61.5%) vs. 5 (17.9%); p < 0.001). Good collaterals were an independent predictor of good clinical outcomes at 90 days (OR = 1.31, 95% CI: 1.13-1.53, p < 0.001). CONCLUSION: Selecting patients for endovascular treatment of acute ischemic stroke using non-contrast CT and CT angiography shows 90-day outcomes similar to the DAWN and DEFUSE-3 trials. Using collateral status on CT angiography can predict favorable outcomes after mechanical thrombectomy in resource-limited settings where perfusion imaging is unavailable.

Flavonoid-Rich Fruit Intake in Midlife and Late-Life and Associations with Risk of Dementia: The Framingham Heart Study.

BACKGROUND: Fruits are an important source of flavonoids, and greater intake of dietary flavonoids in older adults has been shown to be associated with decreased risk of dementia. It is unclear whether this relationship is similar or different between younger adults and older adults. OBJECTIVES: We examined for associations between midlife and late-life intake of flavonoid-rich fruits and incident dementia. We hypothesized that greater total cumulative intake of flavonoid-rich fruits in midlife and late-life adults would be associated with reduced risk of all-cause dementia. DESIGN: Longitudinal, cohort study design. SETTING: Framingham Heart Study, which is a longitudinal, multi-generational community-based cohort based in Framingham, Massachusetts, USA. PARTICIPANTS: Participants from the Framingham Heart Study Offspring cohort were included (n = 2,790) who attended the fifth core exam between 1991 to 1995, and were dementia-free and at least 45 years of age at that time, as well as had valid food frequency questionnaires from the fifth to ninth core exams. MEASUREMENTS: Consumption of fruits with high flavonoid content or are important contributors to overall flavonoid intake was collected via food frequency questionnaire. Flavonoid-rich fruits from the food frequency questionnaire included raisins or grapes, prunes, bananas, fresh apples or pears, apple juice or cider, oranges, orange juice, grapefruit, grapefruit juice, strawberries, blueberries, and peaches, apricots, or plums. Dementia ascertainment was based on a multidisciplinary consensus committee, and included all-cause dementia and Alzheimer's disease dementia diagnoses based on research criteria. Cox models were used to examine associations between cumulative fruit intake and incident dementia, stratified by midlife (45-59 years; n = 1,642) and late-life (60-82 years; n = 1,148). RESULTS: Greater cumulative total fruit intake in midlife, but not late-life, was significantly associated with a 44% decreased risk of all-cause dementia (HR = 0.56; 95% CI = 0.32 - 0.98; p = 0.044). Decreased risk of all-cause dementia was also associated with higher intake of apples or pears in midlife and late-life, as well as higher intake of raisins or grapes in midlife only, and higher intake of oranges, grapefruit, blueberries, and peaches, apricots, or plums in late-life only. CONCLUSIONS: Among participants from the Framingham Heart Study, greater overall consumption of flavonoid-rich fruits in midlife was associated with reduced risk of dementia, though intake of specific fruits in midlife and late-life may have a protective role against developing dementia. These findings may help to inform future recommendations on when dietary interventions may be most beneficial to healthy brain aging across the life course.

Unveiling trends in late diagnosis among 22,504 people living with HIV in Hunan, China.

This study examined the prevalence of HIV late diagnosis (LD) and identified associated factors with LD among people living with HIV (PLWH). We extracted sociodemographic, epidemiological, and immunological information between 2018 and 2021 in Hunan, China from the HIV/AIDS Comprehensive Response Information Management System of China. The chi-squared test and multivariable logistic regression model were used to identify the factors associated with LD. Among 22,504 PLWH, 14,988 (66.6%) were diagnosed late. PLWH aged 50 and older had a higher proportion of LD (71.2%) than the younger group (60.0%). Older age, being male, Han ethnicity, being registered in Western Hunan, being transferred from health facilities, and being infected through heterosexual intercourse were associated with LD. Among PLWH younger than 50 years, apart from the factors mentioned above, individuals who had primary school or lower education, were non-student, and were divorced or widowed were more likely to be diagnosed late. Unlike younger PLWH, these factors were not associated with LD in the older group. But regional disparities in LD were more significant among them. LD in PLWH remains a severe issue, especially among older people. The study findings provided valuable insights into designing programs targeting groups at higher risk of LD to reduce its prevalence.

Significance of early diagnosis and treatment of adult late-onset Pompe disease on the effectiveness of enzyme replacement therapy in improving muscle strength and respiratory function: a case report.

BACKGROUND: Pompe disease, a rare autosomal recessive disorder, is caused by mutations in the acid α-glucosidase gene. Pompe disease is a congenital metabolic disorder that affects all organs, particularly the striated muscle and nerve cells. Diagnosis is typically confirmed through enzyme assays that reveal reduced acid α-glucosidase activity. Enzyme replacement therapy utilizing human α-glucosidase is an available treatment option. Timely diagnosis and treatment in the early stages of the disease significantly impact the effectiveness of enzyme replacement therapy in enhancing patient condition. Here, we present a case of a patient with Pompe disease diagnosed 20 years after the onset of clinical symptoms. CASE PRESENTATION: A 38-year-old Iranian Baloch woman referred to our rheumatology clinic with progressive muscle weakness presents with a complex medical history. On mechanical ventilation for 12 years, she has endured fatigue and limb weakness since the age of 16, exacerbated following an abortion at 19. Despite undergoing corticosteroid and azathioprine therapies, the suspected diagnosis of inflammatory myopathy did not yield improvement. Hospitalization at 23 due to respiratory failure post-pregnancy led to her continued reliance on a ventilator. A dried blood spot test indicated reduced GAA enzyme activity, confirming a diagnosis of Pompe disease through genetic testing. Treatment with myozyme for 2 years demonstrated limited efficacy, as the patient experienced improved breathing but no significant overall improvement in limb-girdle muscular weakness. This case underscores the challenges and complexities involved in diagnosing and managing rare neuromuscular disorders like Pompe disease. CONCLUSION: Early intervention with enzyme replacement therapy plays a crucial role in halting further muscle loss and disease progression in Pompe disease patients. It is important to note that treatment during advanced stages of the disease may not yield substantial benefits. Nevertheless, enzyme instability and denaturation due to temperature and neutral pH levels, along with limited delivery to disease-relevant tissues, can pose challenges in treatment. However, timely diagnosis of Pompe disease is paramount for its effective management and improved outcomes.

Unusual presentation of PYGM gene mutation as late-onset McArdle disease with camptocormia: a case report.

BACKGROUND: Glycogen storage disease type 5 (McArdle disease) leads to a deficiency in the activity of myophosphorylase resulting in an impaired glucose utilization. The disease can be caused by a variety of mutations in the PYGM gene, and its typical clinical manifestation is muscles weakness within the first three decades of life. CASE PRESENTATION: In this case report we present the diagnostic work-up of a physically active 78-year-old Caucasian patient suffering from a 2-year history of progressive camptocormia including clinical, radiologic, histological, and genetic tests. There was no history of neuro-muscular diseases in the family. Serum CK levels were moderately increased while other blood/urine parameters were normal. Magnetic resonance imaging showed fatty remodeling of the muscles of the back. Histochemical examination of a muscle biopsy revealed the absence of myophosphorylase activity, while gene analysis identified a known early-onset McArdle mutation in the PYGM gene. CONCLUSION: This case highlights that the clinical spectrum of PYGM gene mutation typically manifest during adolescence, but it is also a differential diagnosis in late onset muscle disorders and emphases the investigation of the role of ACE inhibitors in this disease.

Alasemenia, the earliest ovule with three wings and without cupule.

The ovules or seeds (fertilized ovules) with wings are widespread and especially important for wind dispersal. However, the earliest ovules in the Famennian of the Late Devonian are rarely known about the dispersal syndrome and usually surrounded by a cupule. From Xinhang, Anhui, China, we now report a new taxon of Famennian ovules, Alasemenia tria gen. et sp. nov. Each ovule of this taxon possesses three integumentary wings evidently extending outwards, folding inwards along abaxial side and enclosing most part of nucellus. The ovule is borne terminally on smooth dichotomous branches and lacks a cupule. Alasemenia suggests that the integuments of the earliest ovules without a cupule evolved functions in probable photosynthetic nutrition and wind dispersal. It indicates that the seed wing originated earlier than other wind dispersal mechanisms such as seed plume and pappus, and that three- or four-winged seeds were followed by seeds with less wings. Mathematical analysis shows that three-winged seeds are more adapted to wind dispersal than seeds with one, two or four wings under the same condition.

Many plants need seeds to reproduce. Seeds come in all shapes and sizes and often have extra features that help them disperse in the environment. For example, some seeds develop wings from seed coat as an outer layer, similar to fruits of sycamore trees that have two wings to help them glide in the wind. The first seeds are thought to have evolved around 372-359 million years ago in a period known as the Famennian (belonging to the Late Devonian). Fossil records indicate that almost all these seeds were surrounded by an additional protective structure known as the cupule and did not have wings. To date, only two groups of Famennian seeds have been reported to bear wings or wing-like structures, and one of these groups did not have cupules. These Famennian seeds all had four wings. Wang et al. examined fossils of seed plants collected in Anhui province, China, which date to the Famennian period. The team identified a new group of seed plants named the Alasemenia genus. The seeds of these plants each had three wings but no cupules. The seeds formed on branches that did not have any leaves, which indicates the seeds may have performed photosynthesis (the process by which plants generate energy from sunlight). Mathematical modelling suggested that these three-winged seeds were better adapted to being dispersed by the wind than other seeds with one, two or four wings. These findings suggest that during the Famennian the outer layer of some seeds that lacked cupules evolved wings to help the seeds disperse in the wind. It also indicates that seeds with four or three wings evolved first, followed by other groups of seed plants with fewer seed wings. Future studies may find more winged seeds and further our understanding of their evolutionary roles in the early history of seed plants.

Isolated central nervous system (CNS) relapse of multiple myeloma 11 years after autologous stem cell transplantation: a case report.

Background: Multiple myeloma (MM) relapse in the central nervous system (CNS) confers an adverse prognosis, usually occurring in a short period after stem cell transplant and with a short overall survival. Isolated CNS relapse is so rare that there is no current standard treatment. Case Description: We present a 59-year-old male with an isolated CNS MM relapse, who had received autologous stem-cell transplant (ASCT) and thalidomide maintenance 11 years prior. He returned to our clinic with cauda equina syndrome and a nuclear magnetic resonance (NMR) identified a spinal lesion, a lumbar puncture was performed and plasma cells were identified in his cerebrospinal fluid (CSF). He was initially treated with intrathecal (IT) chemotherapy with methotrexate and steroid + radiotherapy and plasma cells disappeared after a few bi-weekly doses. Later on, treatment with pomalidomide/dexamethasone was given for 12 cycles with good clinical response with 80% recovery of his motor function. Conclusions: In this rare case of a very late CNS MM relapse, we demonstrate that IT chemotherapy complemented with a systemic pomalidomide-based treatment is safe and effective. This is particularly important in contexts where newer therapies such as bispecifics, chimeric antigen receptor-T (CAR-T) cells or even daratumumab or selinexor are not widely available. Further clinical experience in this particular scenario will be required to confirm this observation and define overall the best strategy for this rare group of patients.

Integrating and Dividing in a Late Bronze Age Society: Internal Organization of Settlements of the Tisza Site Group in the Southern Carpathian Basin, 1600-1200 b.c.

Recent research in the later Bronze Age of the southern Carpathian Basin has revealed an extensive network of large, often-enclosed settlements. Within this network, a particularly dense group of sites has recently been characterized: the Tisza Site Group (TSG). Building on advances in inter-site relations in recent research, we explore social organization within settlements using five case studies from different parts of this network. Using a multi-proxy approach of satellite imagery, systematic surface survey, and geophysical prospection, we studied the distribution of archaeological features and surface traces of activity within the enclosed space. Results indicate that sites in the TSG shared a common ethos regarding the use of space and the role of the built environment that was specific to LBA occupation of this landscape. Activity areas with domestic assemblages distributed in low-density relative to the enclosed space indicates settlement and specialist subsistence activities took place in parallel.

Alteration of cardiac structure and function and its prognostic value in patients with Takayasu arteritis: a cardiac magnetic resonance study.

Purpose: To investigate the prevalence and characteristics of late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) and its prognostic value in patients with Takayasu arteritis (TA). Materials and methods: Sixty TA patients with a CMR examination were retrospectively included. All TA patients were divided into with LGE-positive and LGE-negative groups. Bi-ventricular function and location, distribution, and pattern of left ventricular (LV) LGE were evaluated in both LGE-positive and LGE-negative groups. Primary outcome was defined as a composite of cardiovascular death, hospitalization for heart failure, coronary artery revascularization, and stroke. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the association between variables and primary outcomes. Results: Sixty consecutive TA patients were enrolled in this study. The mean age was 38.2 ± 13.8 years and 54 patients (54/60, 90.0%) were female. LGE-positive was observed in twenty-one (21/60, 35%) patients in the total patients with TA. LGE was predominantly distributed in the middle wall and subendocardial. The patchy and infarcted LGE patterns were the most common. Compared with the LGE-negative group, the LGE-positive group had reduced LV ejection fraction (P = 0.033), elevated LV end-diastolic volume index (P = 0.008), LV end-systolic volume index (P = 0.012), and LV mass (P = 0.008). During a median follow-up period of 1,892 days (interquartile range: 1,764-1,988 days), the primary outcomes occurred in thirteen patients. In the univariate analysis, LGE-positive (hazard ratio [HR] = 4.478, 95% confidence interval [CI]: 1.376-14.570; P = 0.013) were independently associated with the primary outcomes. However, LGE-positive did not retain its value as an independent predictor of primary outcomes in the multivariate analysis. Instead, LVMI (HR = 1.030, 95%CI: 1.013-1.048; P = 0.001) was the strongest independent predictor of primary outcomes in patients with TA. The Kaplan-Meier plot revealed that patients with LVMI ≥ 57.5 g/m2 have a worse prognosis. Conclusion: LGE-positive detected by CMR was observed in 35% of total TA patients with different distributions and patterns. LGE is associated with adverse LV remodeling and worsen cardiac function. However, LVMI rather than LGE can provide independent prognostic information in patients with TA.

Risk factors associated with late-onset hearing loss in children with congenital cytomegalovirus: a systematic review.

PURPOSE: To search for existing evidence of prognostic factors related to the development of late-onset hearing loss (LOHL) in infants with congenital cytomegalovirus (cCMV). METHODS: A PRISMA systematic review was performed, with the PubMed, Embase, and Web of Science databases searched from inception through to December 2023; after the application of inclusion and exclusion criteria a total of 9 papers were included in this review. PROSPERO registration number CRD42024492244. RESULTS: 9 studies encompassing a total of 292 children with late-onset hearing loss were included. A total of 12 risk factors were identified in the literature, with 6 found to be statistically significant. Late-onset hearing loss was more frequently reported in children with symptomatic than asymptomatic cCMV. Moreover, in asymptomatic cCMV cases, elevated DNAemia and salivary viral load were associated with late-onset hearing loss. Additionally, first-trimester seroconversion was identified as a risk factor for late- onset hearing loss. Further, gestational age < 37 weeks and low birth weight were found to correlate with late-onset hearing loss. Remarkably, only one study documented a relationship between late-onset hearing loss and ultrasonographic abnormalities. CONCLUSIONS: Although six statistically significant risk factors have been identified, the available evidence is limited and inconsistent, preventing the establishment of reliable neonatal and maternal parameters to predict the development of LOHL in patients with CMV. There are few studies addressing this topic, and those available exhibit a low level of evidence and heterogeneous designs. More studies should be done.

Placental Tissue Calcification and Its Molecular Pathways in Female Patients with Late-Onset Preeclampsia.

Preeclampsia (PE) is a complex multisystem disease characterized by hypertension of sudden onset (>20 weeks' gestation) coupled with the presence of at least one additional complication, such as proteinuria, maternal organ dysfunction, or uteroplacental dysfunction. Hypertensive states during pregnancy carry life-threatening risks for both mother and baby. The pathogenesis of PE develops due to a dysfunctional placenta with aberrant architecture that releases factors contributing to endothelial dysfunction, an antiangiogenic state, increased oxidative stress, and maternal inflammatory responses. Previous studies have shown a correlation between grade 3 placental calcifications and an elevated risk of developing PE at term. However, little is known about the molecular pathways leading to placental calcification. In this work, we studied the gene and protein expression of c-Jun N-terminal kinase (JNK), Runt-related transcription factor 2 (RUNX2), osteocalcin (OSC), osteopontin (OSP), pigment epithelium-derived factor (PEDF), MSX-2/HOX8, SOX-9, WNT-1, and ß-catenin in placental tissue from women with late-onset PE (LO-PE). In addition, we employed von Kossa staining to detect mineral deposits in placental tissues. Our results show a significant increase of all these components in placentas from women with LO-PE. Therefore, our study suggests that LO-PE may be associated with the activation of molecular pathways of placental calcification. These results could be the starting point for future research to describe the molecular mechanisms that promote placental calcification in PE and the development of therapeutic strategies directed against it.

Detection of Fibroadipose Tissue Infiltration with Cardiac Computed Tomography: A Case of Arrhythmogenic Cardiomyopathy.

In the evaluation of cardiomyopathies, cardiac computed tomography (CCT) is predominantly used for assessing congenital or acquired coronary artery diseases as a potential etiology underlying the observed myocardial abnormalities. However, its utility is expected to expand. We present a case of an asymptomatic patient with claustrophobia who sought medical attention due to frequent ventricular beats. The resting electrocardiogram revealed repolarization abnormalities characterized by flattened T-waves in the lateral leads and low QRS voltages in the peripheral leads, whereas transthoracic echocardiography was normal. CCT accurately identified hypodense areas indicative of fibrofatty infiltration within the inferolateral and anterior walls of the left ventricle. Furthermore, late iodine contrast-phase imaging revealed subepicardial late enhancement striae in the same regions. These imaging findings were pivotal in establishing a diagnosis of left-dominant arrhythmogenic cardiomyopathy. This clinical vignette underscores the potential of CCT in tissue characterization, particularly when cardiac magnetic resonance imaging is contraindicated or unavailable.

Brooding, reflection, and anger rumination in late life suicidal behavior.

BACKGROUND: Current literature on age-specific risk factors for suicide in older adulthood is lacking. One risk factor for younger-life suicide, rumination, has not been extensively studied in older adults, but from prior research, may be more relevant to late-life vs. early life suicide. The current study investigated how multiple subtypes of rumination (i.e., brooding, reflection, and anger rumination) relate to suicidal ideation and recent suicidal behavior in late life. METHODS: 378 participants aged 50-90 (mean age 63.4, SD 7.5) were recruited into a case-control study examining suicide in older adults. Participants were recruited into three groups: 1) depressed adults who had made a recent (past two years) suicide attempt, 2) those with depression but no suicide attempt, and 3) a healthy comparison group. Among depressed groups, we examined relationships between rumination types, trait anger, depression, and suicidal ideation. Then, we conducted logistic regression to test which variables were related to having made a suicide attempt in the past two years among those with current suicidal ideation. RESULTS: All forms of rumination were related to depression. Brooding was related to ideation severity, but only depression severity related to presence of ideation. Anger rumination and ideation severity each contributed unique variance in their prediction of recent suicide attempts. LIMITATIONS: Our cross-section design does not allow for causal claims; future studies should consider using ecological momentary assessment approaches. CONCLUSIONS: Treatments to decrease rumination without an intense cognitive component should be considered for late-life patients.

Interpersonal distance affects advisors' responses to feedback on their advice: Evidence from event-related potentials.

Advisors typically receive two types of feedback: whether their advice is accepted and benefits the advisee. However, the effect of interpersonal distance on advisors' feedback responses remains unexplored. Therefore, to examine this association, we used an advice-giving task in which participants acted as advisors to either friends or strangers through event-related potentials (ERP). Participants received feedback reflecting whether their advice was accepted or rejected and the advisee's outcome (gains or losses). Participants' electroencephalograms were recorded when receiving feedback. Results revealed that rejections from friends elicited stronger feedback-related negativity (FRN) than acceptances from friends. Furthermore, acceptances from friends triggered larger late positive components (LPCs) than rejections from friends. No such effects were observed when the advisee was a stranger. Moreover, a stronger FRN was observed for losses than gains when strangers accepted the advice; however, this difference was not observed when strangers rejected the advice. In addition, friends' gains elicited a larger P300 than losses, regardless of whether friends accepted the advice; however, for strangers, this P300 difference was observed only when the advice was accepted. When strangers accepted the advice, gains elicited larger LPCs than losses; however, this difference was not observed when strangers rejected the advice. These results revealed that the interpersonal distance between people affected how they responded to feedback on advice. This was demonstrated by the neural responses related to expectations, motivational significance, and emotional arousal. It also suggests that the psychological processes by which interpersonal distance influences feedback processing change over the stages.

Long-term quality of survival after pediatric low-grade glioma.

BACKGROUND: Low-grade glioma is the most common brain tumor in children with different modes of treatment and a high overall survival. Low-grade glioma is considered a chronic disease, since residual tumor is present in many children. The tumor and its treatment lead to acquired brain injury with diverse consequences for later life based on factors like the diverse tumor locations, treatment(s) applied, neurofibromatosis type 1, and age at diagnosis. METHODS: An overview of affected domains is provided based upon cohort studies from literature and partially based on clinical experience with a practical approach regarding each domain of functioning in order to provide insight in the requirements for long-term care assistance after childhood low-grade glioma. RESULTS: The diverse domains that can potentially be affected are described as follows: motor function, speech, eating and swallowing, sensory functions, seizures, neuropathy, organ function after systemic treatment, late effects due to cranial radiation (vascular changes and secondary tumors, endocrine and hypothalamic function, sleep and energy, neuro-cognition and education, psychosocial effects, and quality of life. CONCLUSION: Insight in affected domains guides advices for medical follow-up, diagnostics, supportive instructions, and assistive measures per domain of functioning and provide insight in the requirements for long-term care assistance after childhood low-grade glioma.

Healthcare providers' expected barriers and facilitators to the implementation of person-centered long-term follow-up care for childhood cancer survivors: A PanCareFollowUp study.

BACKGROUND: Childhood cancer survivors face high risks of adverse late health effects. Long-term follow-up care for childhood cancer survivors is crucial to improve their health and quality of life. However, implementation remains a challenge. To support implementation of high-quality long-term follow-up care, we explored expected barriers and facilitators for establishing this follow-up care among healthcare providers from four European clinics. METHODS: A qualitative study was conducted using four focus groups comprising 30 healthcare providers in total. The semi-structured interview guide was developed based on the Grol and Wensing framework. Data was analyzed following a thematic analysis, combining both inductive and deductive approaches to identify barriers and facilitators across the six levels of Grol and Wensing: innovation, professional, patient, social, organizational and economic and political. RESULTS: Most barriers were identified on the organizational level, including insufficient staff, time, capacity and psychosocial support. Other main barriers included limited knowledge of late effects among healthcare providers outside the long-term follow-up care team, inability of some survivors to complete the survivor questionnaire and financial resources. Main facilitators included motivated healthcare providers and survivors, a skilled hospital team, collaborations with important stakeholders like general practitioners, and psychosocial care facilities, utilization of the international collaboration and reporting long-term follow-up care results to convince hospital managers. CONCLUSION: This study identified several factors for successful implementation of long-term follow-up care for childhood cancer survivors. Our findings showed that specific attention should be given to knowledge, capacity, and financial issues, along with addressing psychosocial issues of survivors.

Actin dynamics switches two distinct modes of endosomal fusion in yolk sac visceral endoderm cells.

Membranes undergo various patterns of deformation during vesicle fusion, but how this membrane deformation is regulated and contributes to fusion remains unknown. In this study, we developed a new method of observing the fusion of individual late endosomes and lysosomes by using mouse yolk sac visceral endoderm cells that have huge endocytic vesicles. We found that there were two distinct fusion modes that were differently regulated. In homotypic fusion, two late endosomes fused quickly, whereas in heterotypic fusion they fused to lysosomes slowly. Mathematical modeling showed that vesicle size is a critical determinant of these fusion types and that membrane fluctuation forces can overcome the vesicle size effects. We found that actin filaments were bound to late endosomes and forces derived from dynamic actin remodeling were necessary for quick fusion during homotypic fusion. Furthermore, cofilin played a role in endocytic fusion by regulating actin turnover. These data suggest that actin promotes vesicle fusion for efficient membrane trafficking in visceral endoderm cells.

Comparison of intestinal and pharyngeal microbiota in preterm infants on the first day of life and the characteristics of pharyngeal microbiota in infants delivered by cesarean section or vaginally.

Background: This study aimed to explore the distribution of intestinal and pharyngeal microbiota on the first day of life in preterm infants and compare the composition of microbiota in infants delivered by cesarean section or vaginally. Methods: This study included 44 late preterm infants with a gestational age of 34-36 + 6 weeks. Stool and throat swab samples were collected from the preterm infants on the first day of life. The infants were divided into cesarean section and vaginal delivery groups. Illumina NovaSeq high-throughput sequencing technology was used to sequence the V3-V4 hypervariable region of the 16S rRNA gene of all bacteria in the samples. Venn diagram was used to identify shared operational taxonomic units (OTUs) in the intestines and pharynges. Microbial analysis was conducted at the phylum and genus levels, and α and ß diversity comparisons were performed. Results: (1) Gestational age may have significantly affected the microbial colonization of the intestines and pharynges of preterm infants on the first day after birth (p ≤ 0.001). (2) More OTUs were detected in the pharynx than in the intestines, both have a total of 819 shared OTUs. Proteobacteria, Firmicutes, and Bacteroidota were the dominant phyla in both. At the genus level, Streptococcus had a lower relative abundance in stool samples (0.5%) compared to throat samples (0.5% vs. 22.2%, p = 0.003). 3) The relative abundance of Streptococcus in pharyngeal samples was 26.2% in the cesarean section group much higher than the 3.8% in the vaginal delivery group (p = 0.01). Conclusion: The early postnatal period is a critical time for the establishment of an infant's microbiota. Gestational age at birth may influence microbial colonization, while birth weight, gender, and mode of delivery do not. The intestinal and pharyngeal microbiota composition of preterm infants on the first day after birth showed high similarity, but larger samples are needed for further validation.

Cardiac sarcoidosis: diagnosis and management.

Non-caseating granulomatous infiltration of the myocardium is the hallmark of cardiac sarcoidosis (CS). CS manifests clinically as conduction disturbance, ventricular arrhythmia, sudden cardiac death and/or heart failure with reduced ejection fraction. Other than confirmation through endomyocardial biopsy, a diagnosis of probable CS can be established by histological evidence of systemic sarcoidosis in addition to characteristic clinical or advanced imaging findings. Cardiac Magnetic Resonance imaging (CMR) and 18F-flurodeoxyglycose positron emission tomography (FDG-PET) are imaging modalities indispensable in the diagnosis and monitoring of CS. FDG-PET is the method of choice for identifying the active inflammatory phase of CS and in the monitoring and modifying of immunosuppressive treatment. CMR is better suited for assessing cardiac morphology and function. Both modalities are more effective in detecting CS when used in combination than either is alone. Management of CS is primarily based upon observational data of low quality due to a paucity of randomized controlled trials. Corticosteroid therapy and/or tiered-immunosuppression are the mainstays of treatment in reducing myocardial inflammation. Steroid-sparing agents aim to limit the unfavorable side-effects of a significant steroid burden. Antiarrhythmics and guideline-directed medical therapies are utilized for control of ventricular arrhythmia and left ventricular dysfunction respectively. CS necessitates multidisciplinary care in specialized centers to most effectively diagnose and manage the disease. Additional randomized trials are warranted to further our understanding of medical optimization in CS.