Pathological Studies Research Articles

Heart rate and oxygen saturation patterns in very low birth weight infants with early onset sepsis and histologic chorioamnionitis.

Chorioamnionitis and early onset sepsis (EOS) in very low birth weight (VLBW,< 1500 g) infants may cause a systemic inflammatory response reflected in patterns of heart rate (HR) and oxygenation measured by pulse oximetry (SpO2). Identification of these patterns might inform decisions about duration of antibiotic therapy after birth. Compare early HR and SpO2 patterns in VLBW infants with or without early onset sepsis (EOS) or histologic chorioamnionitis (HC). Retrospective study of placental pathology and HR and SpO2 in the first 72 h from birth in relation to EOS status for inborn VLBW NICU patients 2012-2019. Among 362 VLBW infants with HR and SpO2 data available, clinical, or culture-positive EOS occurred in 91/362 (25%) and HC in 81/355 (22%). In univariate analysis, EOS was associated with higher mean HR, lower mean SpO2, and less negative skewness of HR in the first 3 days after birth. HC was associated with higher standard deviation and skewness of HR but no difference in SpO2. In multivariable modeling, significant risk factors for EOS were mean HR, gestational age, HC, mean SpO2, and skewness of SpO2. HR and SpO2 patterns differ shortly after birth in VLBW infants exposed to HC or with EOS, likely reflecting a systemic inflammatory response.

ROLE OF CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY (CCTA) IN SPONTANEOUS CORONARY ARTERY DISSECTION (SCAD)

Abstract Spontaneous Coronary Artery Dissection (SCAD) is a rare but insidious cause of myocardial infarction and sudden cardiac death especially in those who lacks of traditional cardiovascular risk factors. Although the most appropriate management of patients with SCAD is not clearly defined, it‘s essential to make an early diagnosis in order to follow a conservative approach. Nowadays, the role of Coronary Computed Tomography Angiography (CCTA) is consolidated in the study of atherosclerotic coronary pathology but its contribution in the diagnosis and follow–up of patients with SCAD does not apperar to be defined. The purpose of this study was to retrospectively investigate the diagnostic performance of CCTA and its role in the follow–up of patients with diagnosis of SCAD. We examined 307 patients admitted to emergency department for acute chest pain and an ECG diagnosis of STEMI from March 2021 to July 2023. 1 patient was diagnosed with type 2 SCAD on invasive coronary angiography (ICA) and 2 patients received a suspected diagnosis of SCAD at ICA and CCTA examination was performed to confirm the suspicion. CCTA examination showed the acute presence of Intramural hematoma (IMH) of the wall of left anterior descending artery (LAD) in 2 patients, confirming the angiographic suspect of SCAD type 2. All 3 patients were treated with conservatie therapy and subsequentely underwent CCTA of follow–up. The examination performed respectively 3 months, 45 days and 1 month after the acute event demonstrated the complete resolution of IMH in all patients and the patency of the vessel lumens. CCTA seems to be a feasible and effective imaging modality to detect the main findings of SCAD. It may play a crucial role in the management of patients with acute chest pain at low–intermediate risk of ACS in order to reduce the number of misdiagnoses. Furthermore, CCTA could facilitate follow–up of patients with diagnosis of SCAD given the high recurrency rate of this pathology. However, further large prospective studies are needed to clarify the role of CCTA in the diagnosis and in the follow–up of SCAD.

The Efficacy of Noninvasive Ventilation in Patients Affected by Rett Syndrome With Hypoventilation

BackgroundRett syndrome is a progressive neurological disorder associated to several comorbidities that contribute significantly to impair lung function. Respiratory morbidity represents a major cause of death in this population. Little is known about the benefit of noninvasive ventilation. MethodsWe retrospectively enrolled patients with Rett syndrome who underwent a pneumological evaluation combined with a cardiorespiratory polygraphy and/or a pulse oximetry and capnography from 2012 to 2022. ResultsMedical records of 11 patients with Rett syndrome, mean age 13 ± 6 years, were evaluated. Most patients presented with both epilepsy and scoliosis. Five patients showed a pathologic sleep study and/or impaired night gas exchange: mean obstructive apnea-hypopnea index was 4 ± 3 events/hour; mean and minimal SpO2 were, respectively, 93% ± 2% and 83% ± 6%, while mean and maximal transcutaneous carbon dioxide monitoring (PtcCO2) were, respectively, 51 ± 5 mm Hg and 55 ± 8 mm Hg; and mean oxygen desaturation index was 13 ± 11 events/hour. These patients started noninvasive ventilation with clinical benefit and improved gas exchange mostly in terms of PtcCO2 (mean PtcCO2 51 ± 5 mm Hg before and 46 ± 6 mm Hg after noninvasive ventilation). ConclusionsNoninvasive ventilation is a suitable option for patients with Rett syndrome.

Development of a ratiometric fluorescent probe for the detection of peroxynitrite

Peroxynitrite is one of the important reactive oxygen species in the human body and is closely related to the physiological and pathological processes of many diseases. Therefore, the development of probes to detect peroxynitrite is important for diagnostic and pathologic studies of many diseases. In this work, a ratiometric probe was designed using benzopyran as the recognition site, and the sensitivity and selectivity of the probe were tuned by modification of substituents on benzopyran. Upon reaction with peroxynitrite, the color of the solution changes to the naked eye (from blue to yellow), and the fluorescence changes from red to blue. The probe SJ has the advantages of large Stokes shift (237 nm), fast response (≤10 s), wide linear range, good selectivity, low detection line (21.3 nm), and low cytotoxicity. Probe SJ has been successfully used for bioimaging of endogenous and exogenous peroxynitrite.

Modelo de cocultivo 3D in vitro de células endoteliales y vasculares de músculo liso humanas para el estudio del remodelado vascular patológico

Pathological vascular remodeling of the vessel wall refers to the structural and functional changes of the vessel wall that occur in response to injury that eventually leads to cardiovascular disease. The vessel wall is composed of two main types of cells, endothelial cells and vascular smooth muscle cells, whose communication is crucial in both the development of the vasculature and the homeostasis of mature vessels. Changes in the dialogue between endothelial cells and vascular smooth muscle cells are associated with various pathological states that triggers remodeling of the vascular wall. For many years, considerable efforts have been made to develop effective diagnoses and treatments for these pathologies by studying their mechanisms in both in vitro and in vivo models. Compared to animal models, in vitro models can provide great opportunities to obtain data in a more homogeneous, economical and massive way, providing an overview of the signaling pathways responsible for these pathologies. The implementation of three-dimensional in vitro co-culture models for the study of other pathologies has been postulated as a potentially applicable methodology, which determines the importance of its application in studies of cardiovascular diseases. In this article we present a method for culturing human endothelial cells and vascular smooth muscle cells, grown under non-adherent conditions, that generate three-dimensional spheroidal structures with greater physiological equivalence to in vivo conditions. This in vitro modeling could be used as a study tool to identify cellular and molecular mechanisms involved in the pathological processes underlying vascular remodeling.

APOE4 homozygozity represents a distinct genetic form of Alzheimer's disease.

This study aimed to evaluate the impact of APOE4 homozygosity on Alzheimer's disease (AD) by examining its clinical, pathological and biomarker changes to see whether APOE4 homozygotes constitute a distinct, genetically determined form of AD. Data from the National Alzheimer's Coordinating Center and five large cohorts with AD biomarkers were analyzed. The analysis included 3,297 individuals for the pathological study and 10,039 for the clinical study. Findings revealed that almost all APOE4 homozygotes exhibited AD pathology and had significantly higher levels of AD biomarkers from age 55 compared to APOE3 homozygotes. By age 65, nearly all had abnormal amyloid levels in cerebrospinal fluid, and 75% had positive amyloid scans, with the prevalence of these markers increasing with age, indicating near-full penetrance of AD biology in APOE4 homozygotes. The age of symptom onset was earlier in APOE4 homozygotes at 65.1, with a narrower 95% prediction interval than APOE3 homozygotes. The predictability of symptom onset and the sequence of biomarker changes in APOE4 homozygotes mirrored those in autosomal dominant AD and Down syndrome. However, in the dementia stage, there were no differences in amyloid or tau positron emission tomography across haplotypes, despite earlier clinical and biomarker changes. The study concludes that APOE4 homozygotes represent a genetic form of AD, suggesting the need for individualized prevention strategies, clinical trials and treatments.

Post Percutaneous Transluminal Coronary Angioplasty (PTCA) Coronary Aneurysm- A Case Report

Introduction Coronary aneurysm defined angiographically as luminal dilation 50% larger than that of the adjacent reference segment. (1) Drug-eluting stents (DES), which locally elute antiproliferative drugs, can dramatically inhibit neointimal growth. However, several pathological studies have indicated that DES may delay healing after vascular injury, and DES implantation may be theoretically associated with a risk of coronary artery aneurysm formation. Coronary aneurysms have been reported from 3 days to up to 4 years after DES implantation procedures, with varying clinical presentations. The incidence of coronary artery aneurysms after DES implantation is low within the first 9 months, with a reported incidence of 0.2% to 2.3%, a rate similar to that reported after bare-metal stent (BMS) implantation (0.3% to 3.9%) in the DES versus BMS randomized trials.(2) However, the true incidence of coronary aneurysms in an unselected patient population is still largely unknown. It can be congenital, or secondary to vasculitis (Kawasaki disease) or after percutaneous coronary intervention. Drug-eluting stents (DES), which locally elute antiproliferative drugs, can dramatically inhibit neointimal growth has become standard of care for routine coronary angioplasty. However, several pathological studies have indicated that DES may delay endothelial healing after vascular injury, and DES implantation may be theoretically associated with a risk of coronary artery aneurysm formation (3)

한국어교육학과 언어병리학 그리고 청각학의 학문 간 융합 연구 시론

In order to expand the research area of Korean language pedagogy, this paper attempted to explore convergence research tasks with academic fields that have the commonality of Korean, such as Speech-Language Pathology and auditory studies. Speech-Language pathology is essentially an academic field that seeks ways to solve problems for people who have communication problems. Audiology is also an academic field that focuses on how to overcome communication difficulties using speech sounds based on the perception characteristics of speech sounds. As such, the need for convergence research to solve tasks that are difficult to solve independently in each academic field is great in that they are interested in the nature of Korean and its usage patterns. In the field of Speech-Language Pathology, in order to solve problems related to language development, standards for accurately measuring the degree of language development and treating people with delayed development or disabilities are needed. Although there is a need for convergence research with the Korean Language Pedagogy on how to prepare standards and guide language functions such as reading, writing, speaking, and listening, as well as essential vocabulary and grammar dlements used in everyday life, according to age and school age, such research has not been sufficiently conducted. There is no standard for treating this because it does not clearly present clear standards for language ability development, and it is difficult to present appropriate and effective educational methods in terms of educational methodology. In this regard, it was argued that future research on the development and rehabilitation methods of language development diagnostic tools should be conducted. In the field of Audiology, research related to the development of speech perception test tools is needed. For full communication, it is necessary to develop a tool that can test the communication ability of words, phrases, sentences, and discourse units beyond the stimulation of speech sounds at the phoneme level. Although there are differences in educational methods depending on the subject of education, linguistic pathology, and audiology, the fundamental content of education is very large. In the case of researchers, there may be a tendency to think that Korean language pedagogy has conducted relatively more research related to the characteristics of the Korean language than speech-language pathology and audiology. However, it is necessary to acknowledge that the research results on the nature of the Korean language required by neighboring disciplines are insignificant, and to conduct research to identify the nature and usage patterns of the Korean language through communication and cooperation with neighboring disciplines.

Chronic inflammatory demyelinating polyradiculoneuropathy associated with neuromyelitis optica spectrum disorder: A rare case report

IntroductionChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare disease that targets the myelin sheath, while neuromyelitis optica spectrum disorder (NMOSD) with anti-aquaporin-4 antibodies (AQP4-Ab) affects astrocytes. We report a unique case of CIDP associated with NMOSD. Case presentationA 49-year-old woman presented to the emergency department with recurrent episodes of vertigo and blurred vision. Brain magnetic resonance imaging (MRI) with contrast eight months before admission showed Dawson’s finger, and follow-up brain MRI showed a new hyperintense lesion. Visual evoked potential showed bilateral pre-chiasma lesions, and somatosensory evoked potential indicated lesions between the medulla and cerebral cortex. The patient tested positive for AQP4-Ab, and had ascending lower motor neuron weakness for the past 10 weeks. Electromyography revealed multiple demyelinating lesions suggestive of CIDP. The patient was intravenously administered corticosteroids, methotrexate, and azathioprine, resulting in clinical improvement. ConclusionCIDP associated with NMOSD is a rare occurrence. In our patient, a combination of corticosteroids and immunosuppressants was effective. The mechanism of combined demyelination of the central and peripheral nervous systems is still not fully understood, and further immunological and pathological studies are needed.

Modern In Vitro Techniques for Modeling Hearing Loss.

Sensorineural hearing loss (SNHL) is a prevalent and growing global health concern, especially within operational medicine, with limited therapeutic options available. This review article explores the emerging field of in vitro otic organoids as a promising platform for modeling hearing loss and developing novel therapeutic strategies. SNHL primarily results from the irreversible loss or dysfunction of cochlear mechanosensory hair cells (HCs) and spiral ganglion neurons (SGNs), emphasizing the need for innovative solutions. Current interventions offer symptomatic relief but do not address the root causes. Otic organoids, three-dimensional multicellular constructs that mimic the inner ear's architecture, have shown immense potential in several critical areas. They enable the testing of gene therapies, drug discovery for sensory cell regeneration, and the study of inner ear development and pathology. Unlike traditional animal models, otic organoids closely replicate human inner ear pathophysiology, making them invaluable for translational research. This review discusses methodological advances in otic organoid generation, emphasizing the use of human pluripotent stem cells (hPSCs) to replicate inner ear development. Cellular and molecular characterization efforts have identified key markers and pathways essential for otic organoid development, shedding light on their potential in modeling inner ear disorders. Technological innovations, such as 3D bioprinting and microfluidics, have further enhanced the fidelity of these models. Despite challenges and limitations, including the need for standardized protocols and ethical considerations, otic organoids offer a transformative approach to understanding and treating auditory dysfunctions. As this field matures, it holds the potential to revolutionize the treatment landscape for hearing and balance disorders, moving us closer to personalized medicine for inner ear conditions.

PEARL-21: SIX ROWED, HIGH YIELDING, HEAT STRESS RESISTANT, AND EARLY MATURING BARLEY CULTIVAR

Pearl-21, an early maturing barley cultivar that was developed keeping in view the fluctuating climatic scenarios as drought stress is severely impairing the yield of crops in Pakistan. The exquisite genotypes were received from the International Center for Agricultural Research in the Dry Areas (ICARDA), Lebanon. The superior line was screened out from the international barley segregating population received from ICARDA. It was evaluated under code B-14035 in station yield trails for two years (2014-15 &amp; 2015-16). It excelled by 15.26% and 7.38% in provincial barley yield trials during 2017-18 and 18.77% and 10.18% in national barley yield trials during 2018-19 in contrast to commercial checks Haider-93 and Sultan-17, respectively over four locations. It also presented encouraging results in rainfed yield trials. Pathological studies depicted that the proposed cultivar had exceptional resistance against rust diseases. Pearl-21 has plant height ranging from 95-99 cm with semi-erect growth habit both at the seedling and booting stage. It has a high tillering trend (140 productive tillers per meter). It took only 99-101 days to head while, 123-130 days for maturity. It bears 60-70 seeds per ear and has 34-38g thousand-grain weight. The prominent features it encompasses are drought and lodging tolerance and short duration. Due to encouraging steady performance for better grain yield, resistance against rusts, and quality Punjab Seed Council approved it in 2021 with the name “Pearl-21” for general cultivation in Punjab, Pakistan.

Physiological and Therapeutic Role of Calcitonin

Homosapeins have been identified with over 50 hormones. Hormones control or regulate different biological processes. Among all, Calcitonin is one of theabandoned hormones. Calcitonin is released from the C-cell of the thyroid gland. Thyrocalcitonin is a type of neuroendocrine composed of 32 amino acids released from parafollicular cells(C-Cells) present in the thyroid gland in human beings and many other animals in the body. The utility of hormones is still under consideration. Calcitonin is physiologically involved in the maintenance of the calcium and phosphate levels in the blood. As diagnostic parameter utility is observed in the diagnosis of medullary thyroid cancer, C cell hyperplasia. Therapeutically the monoclonal antibodies derived from calcitonin are effective for the treatment of migraine. It possesses anodynic, cardioprotective, and peripheral nerve regeneration. Recent research shows the use of human analogue calcitonin as FDA approved second-line treatment for Paget’s disease. Calcitonin analogue shows its usefulness, especially in the case of bisphosphate tolerance. Calcitonin will be a research topic for future perspective. This study was conducted to the elaborate role of calcitonin in human physiologyThis study involved the utilization of standard databases like PubMed and google scholar to determine the different roles of calcitonin in pathological and physiologicalThe present study shows that calcitonin levels are not only raised in diagnosing C -cell hyperplasia and medullary thyroid cancer, but other conditions are responsible for increased calcitonin in the systemic circulation.The current study manifests the role of calcitonin as a diagnostic parameter and pharmacological treatment. It was observed that calcitonin can be helpful in another pathological disease.

Ultra-high-field 7-Tesla magnetic resonance imaging in fragile X tremor/ataxia syndrome (FXTAS).

Fragile X tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder characterized by premutation expansion of fragile X mental retardation 1 (FMR1) gene. It is a common single-gene cause of tremor, ataxia, and cognitive decline in adults. FXTAS affects the central, peripheral and autonomic nervous systems, leading to a range of neurological symptoms from dementia to dysautonomia. A characteristic imaging feature of FXTAS is symmetric T2 hyperintensity in the deep white matter of the cerebellar hemispheres and middle cerebral peduncle. However, recent studies have reported additional findings on diffusion weighted images (DWI), such as a symmetric high-intensity band-like signal at the cerebral corticomedullary junction. These findings, along with the characteristic cerebellar signal alterations, overlap with imaging findings seen in adult-onset neuronal intranuclear inclusion disease (NIID). Importantly, recent pathology studies have shown that both FXTAS and NIID can manifest intranuclear inclusion bodies, posing a diagnostic challenge and potential for misdiagnosis. We describe a 58-year-old man with FXTAS who received an erroneous diagnosis based on imaging and histopathology results. We emphasize the potential pitfalls in distinguishing NIID from FXTAS and stress the importance of genetic analysis in all cases with suspected NIID and FXTAS for confirmation. Additionally, we present the 7T MRI brain findings of FXTAS.

Metabolic difference between patient-derived xenograft model of pancreatic ductal adenocarcinoma and corresponding primary tumor

BackgroundPatients-derived xenograft (PDX) model have been widely used for tumor biological and pathological studies. However, the metabolic similarity of PDX tumor to the primary cancer (PC) is still unknown.MethodsIn present study, we established PDX model by engrafting primary tumor of pancreatic ductal adenocarcinoma (PDAC), and then compared the tumor metabolomics of PC, the first generation of PDX tumor (PDXG1), and the third generation of PDX tumor (PDXG3) by using 1H NMR spectroscopy. Then, we assessed the differences in response to chemotherapy between PDXG1 and PDXG3 and corresponding metabolomic differences in drug-resistant tumor tissues. To evaluate the metabolomic similarity of PDX to PC, we also compared the metabolomic difference of cell-derived xenograft (CDX) vs. PC and PDX vs. PC.ResultsAfter engraftment, PDXG1 tumor had a low level of lactate, pyruvate, citrate and multiple amino acids (AAs) compared with PC. Metabolite sets enrichment and metabolic pathway analyses implied that glycolysis metabolisms were suppressed in PDXG1 tumor, and tricarboxylic acid cycle (TCA)-associated anaplerosis pathways, such as amino acids metabolisms, were enhanced. Then, after multiple passages of PDX, the altered glycolysis and TCA-associated anaplerosis pathways were partially recovered. Although no significant difference was observed in the response of PDXG1 and PDXG3 to chemotherapy, the difference in glycolysis and amino acids metabolism between PDXG1 and PDXG3 could still be maintained. In addition, the metabolomic difference between PC and CDX models were much larger than that of PDX model and PC, indicating that PDX model still retain more metabolic characteristics of primary tumor which is more suitable for tumor-associated metabolism research.ConclusionsCompared with primary tumor, PDX models have obvious difference in metabolomic level. These findings can help us design in vivo tumor metabolomics research legitimately and analyze the underlying mechanism of tumor metabolic biology thoughtfully.

Next-Generation Sequencing-Based Spatial Transcriptomics: A Perspective from Barcoding Chemistry.

Gene expression profiling of tissue cells with spatial context is in high demand to reveal cell types, locations, and intercellular or molecular interactions for physiological and pathological studies. With rapid advances in barcoding chemistry and sequencing chemistry, spatially resolved transcriptome (SRT) techniques have emerged to quantify spatial gene expression in tissue samples by correlating transcripts with their spatial locations using diverse strategies. These techniques provide both physical tissue structure and molecular characteristics and are poised to revolutionize many fields, such as developmental biology, neuroscience, oncology, and histopathology. In this context, this Perspective focuses on next-generation sequencing-based SRT methods, particularly highlighting spatial barcoding chemistry. It delves into optically manipulated spatial indexing methods and DNA array-barcoded spatial indexing methods by exploring current advances, challenges, and future development directions in this nascent field.

Hospital Incidence and Treatment Outcomes of Patients with Aneurysms and Dissections of the Iliac Artery in Switzerland-A Secondary Analysis of Swiss DRG Statistics Data.

Background/Objectives: Aneurysms and dissections of the iliac artery (ADIAs) are significant vascular conditions often associated with aortic pathologies. Despite their importance, reports on isolated iliac artery pathologies are rare. This study aimed to investigate the epidemiology of ADIA in Switzerland including treatment incidence and hospital outcomes. Methods: A retrospective analysis of diagnosis-related group (DRG) statistics from 2011 to 2018 in Switzerland was conducted, identifying all cases of ADIA while excluding those with concomitant treatment of aortic pathologies. Age-standardized incidence rates and treatment outcomes were assessed, with multivariable logistic regression performed to identify factors associated with hospital mortality. Results: From 2011 to 2018, 1037 ADIA cases were hospitalized in Switzerland. Incidence rates for elective treatment were significantly higher in men than women, increasing in men from 1.5 to 2.4 cases per 100,000 men (p = 0.007), while remaining stable in women at around 0.2 cases per 100,000 women. Acute treatment incidence rates were lower but still higher in men, at 0.9 cases per 100,000 men and 0.2 cases per 100,000 women. Crude hospital mortality rates were lower for endovascular repair than open surgical repair in both elective (0.8% vs. 3.1%, p = 0.023) and emergency treatment (6.7% vs. 18.4%, p = 0.045). Multivariable analysis showed that endovascular repair was associated with significantly reduced hospital mortality compared to open repair (OR 0.27, 95%-CI: 0.10 to 0.66, p = 0.006). Conclusions: This nationwide study of iliac artery pathologies shows that the treatment incidence was about 10 times higher in men than in women for elective procedures, but only about five times higher for emergency treatment. Endovascular procedures were associated with significantly lower hospital mortality than open procedures, while hospital mortality rates were comparable for men and women.

Reduced myelin content in bipolar disorder: A study of inhomogeneous magnetization transfer

BackgroundPrevious neuroimaging and pathological studies have found myelin-related abnormalities in bipolar disorder (BD), which prompted the use of magnetic resonance (MR) imaging technology sensitive to neuropathological changes to explore its neuropathological basis. We holistically investigated alterations in myelin within BD patients by inhomogeneous magnetization transfer (ihMT), which is sensitive and specific to myelin content. MethodsThirty-one BD and 42 healthy controls (HC) were involved. Four MR metrics, i.e., ihMT ratio (ihMTR), pseudo-quantitative ihMT (qihMT), magnetization transfer ratio and pseudo-quantitative magnetization transfer (qMT), were compared between groups using analysis methods based on whole-brain voxel-level and white matter regions of interest (ROI), respectively. ResultsThe voxel-wise analysis showed significantly inter-group differences of ihMTR and qihMT in the corpus callosum. The ROI-wise analysis showed that ihMTR, qihMT, and qMT values in BD group were significantly lower than that in HC group in the genu and body of corpus callosum, left anterior limb of the internal capsule, left anterior corona radiate, and bilateral cingulum (p < 0.001). And the qihMT in genu of corpus callosum and right cingulum were negatively correlated with depressive symptoms in BD group. LimitationsThis study is based on cross-sectional data and the sample size is limited. ConclusionThese findings suggest the reduced myelin content of anterior midline structure in the bipolar patients, which might be a critical pathophysiological feature of BD.

Clinical and Pathological Features of FTDP-17 with MAPT p.K298_H299insQ Mutation.

MAPT is a causative gene in frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), a hereditary degenerative disease with various clinical manifestations, including progressive supranuclear palsy, corticobasal syndrome, Parkinson's disease, and frontotemporal dementia. To analyze genetically, biochemically, and pathologically multiple members of two families who exhibited various phenotypes of the disease. Genetic analysis included linkage analysis, homozygosity haplotyping, and exome sequencing. We conducted tau protein microtubule polymerization assay, heparin-induced tau aggregation, and western blotting with brain lysate from an autopsy case. We also evaluated abnormal tau aggregation by using anti-tau antibody and PM-PBB3. We identified a variant, c.896_897insACA, p.K298_H299insQ, in the MAPT gene of affected patients. Similar to previous reports, most patients presented with atypical parkinsonism. Biochemical analysis revealed that the mutant tau protein had a reduced ability to polymerize microtubules and formed abnormal fibrous aggregates. Pathological study revealed frontotemporal lobe atrophy, midbrain atrophy, depigmentation of the substantia nigra, and four-repeat tau-positive inclusions in the hippocampus, brainstem, and spinal cord neurons. The inclusion bodies also stained positively with PM-PBB3. This study confirmed that the insACA mutation caused FTDP-17. The affected patients showed symptoms resembling Parkinson's disease initially and symptoms of progressive supranuclear palsy later. Despite the initial clinical diagnosis of frontotemporal dementia in the autopsy case, the spread of lesions could explain the process of progressive supranuclear palsy. The study of more cases in the future will help clarify the common pathogenesis of MAPT mutations or specific pathogeneses of each mutation.

A polarity-responsive lysosomes-nucleus translocation probe for the dual-emissive visualization of cell apoptosis

Visualization of cell apoptosis is a critical task playing central roles in the fundamental studies in biology, pathology, and biomedicine. Dual-emissive fluorescent probes are desired molecular tools for study on apoptosis, which however were rarely reported. Herein, utilizing the polarity differences between lysosomes and nucleus, a translocation type of fluorescent probe (NA-S) was developed for the dual-color visualization of cell apoptosis. NA-S was designed to be polarity sensitive, bearing alkalescence group, and with DNA affinity. In living cells, NA-S targeted the lysosomes to give blue fluorescence, which translocated into the nucleus during cell apoptosis to give green emission. Thereby, the cell apoptosis could be visualized with NA-S in dual-emissive manner. With the unique probe, the cell apoptosis induced by oxidative stress, UV irradiation, rotenone, colchicine, and paclitaxel have been successfully visualized.

Comparative Study on the Effectiveness of Three Inoculation Methods for Valsa sordida in Populus alba var. pyramidalis.

A key step in the study of tree pathology is the identification of an appropriate method for inoculating pathogens of diseases in branches and trunks. Pathogens of diseases in branches and trunks are commonly inoculated through punching, burning, and toothpick inoculation. However, there is a lack of comparative analyses of the inoculation outcomes of these three methods. In this work, six-year-old P. alba var. pyramidalis were inoculated with V. sordida using punching, burning, and toothpick techniques to investigate the differences in the effectiveness of these inoculation methods. Results reveal that the incidence rate was 93.55% in the toothpick inoculation group, significantly higher than the 80.65% in the burning inoculation group (chi-square, n = 90, p = 0.007), while punching inoculation exhibited significant pathological responses in the early stages, with spontaneous healing in the later stage. Additionally, toothpick inoculation was more efficient in inducing Valsa canker when inoculating the pathogen at the bottom of the tree, with lower intra- and inter-row spacing (stand density) providing better outcomes than higher intra- and inter-row spacing. The results of this study demonstrate that toothpick inoculation is an optimal option for studying the artificial inoculation of V. sordida in six-year-old P. alba var. pyramidalis, providing technical support for research on poplar diseases and offering a theoretical basis for the inoculation of other diseases in the branch and trunk.