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1.
Oxf Med Case Reports ; 2024(7): omae047, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38989503

RESUMO

Introduction: Foreign body ingestion can lead to esophageal complications, including perforation and impaction, in up to 20% of cases, making it a critical situation. Misdiagnosis or delayed diagnosis can cause severe complications. Case presentation: We present the case of a 78-year-old female who swallowed an acrylic partial denture leading to progressive dysphagia and a vegetative ulcerative lesion on endoscopy. The lesion was initially misdiagnosed as a neoplasm of the esophagus. CT scan and a repeat endoscopy revealed the presence of a denture in the esophagus. The denture was successfully removed with a rigid esophagoscope, and no evidence of complications was reported in follow-up visits. Discussion: Diagnosis of esophageal foreign bodies involves imaging studies and endoscopy, which is the gold standard for diagnosis and management. CT scans also have an important role in diagnosing controversial cases. Treatment depends on the size, shape, and location of the object.

2.
Immunol Rev ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38989642

RESUMO

Alzheimer's disease (AD) is a degenerative brain disorder and the most common form of dementia. AD pathology is characterized by senile plaques and neurofibrillary tangles (NFTs) composed of amyloid-ß (Aß) and hyperphosphorylated tau, respectively. Neuroinflammation has been shown to drive Aß and tau pathology, with evidence suggesting the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome as a key pathway in AD pathogenesis. NLRP3 inflammasome activation in microglia, the primary immune effector cells of the brain, results in caspase-1 activation and secretion of IL-1ß and IL-18. Recent studies have demonstrated a dramatic interplay between the metabolic state and effector functions of immune cells. Microglial metabolism in AD is of particular interest, as ketone bodies (acetone, acetoacetate (AcAc), and ß-hydroxybutyrate (BHB)) serve as an alternative energy source when glucose utilization is compromised in the brain of patients with AD. Furthermore, reduced cerebral glucose metabolism concomitant with increased BHB levels has been demonstrated to inhibit NLRP3 inflammasome activation. Here, we review the role of the NLRP3 inflammasome and microglial ketone body metabolism in AD pathogenesis. We also highlight NLRP3 inflammasome inhibition by several ketone body therapies as a promising new treatment strategy for AD.

3.
J Alzheimers Dis ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38968048

RESUMO

This manuscript reviews the significant skin manifestations of Lewy body disease, including Parkinson's disease and dementia with Lewy bodies, and the diagnostic utility of skin biopsy. Besides classic motor and cognitive symptoms, non-motor manifestations, particularly dermatologic disorders, can play a crucial role in disease presentation and diagnosis. This review explores the intricate relationship between the skin and Lewy body disease. Seborrheic dermatitis, autoimmune blistering diseases (bullous pemphigoid and pemphigus), rosacea, and melanoma are scrutinized for their unique associations with Parkinson's disease, revealing potential links through shared pathophysiological mechanisms. Advances in diagnostic techniques allow the identification of promising biomarkers such as α-synuclein in samples obtained by skin punch biopsy. Understanding the dermatologic aspects of Lewy body disease not only contributes to its holistic characterization but also holds implications for innovative diagnostic approaches.

4.
Contemp Nurse ; : 1-11, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968437

RESUMO

Background: Many of the overseas qualified nurses educated work as health care assistants and support workers for a decreased wage without scope for professional advancement. There is an imperative to ease their entry to the nursing register.Aim: To gather and provide evidence to the regulatory bodies regarding the demographics of this cohort of nurses and the challenges they face in attempting to register as a nurse.Design: This study used a mixed-method explanatory sequential design. The survey was completed by 857 unregistered nurses followed by five in-depth interviews. Results from both phases were triangulated.Results: The results signpost to the characteristics and challenges of these nurses working as unqualified grades of staff for a decreased wage without scope for professional advance.Discussion and conclusion: The downward occupational spiral of internationally educated nurses underscores the paradoxical nature of the pedagogical application of transition theory, as these nurses are compelled to revert to a novice status.

5.
Alzheimers Res Ther ; 16(1): 146, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961441

RESUMO

BACKGROUND: Increasing evidence supports the use of plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation for diagnosis of dementia. However, their performance for positive and differential diagnosis of dementia with Lewy bodies (DLB) in clinical settings is still uncertain. METHODS: We conducted a retrospective biomarker study in two tertiary memory centers, Paris Lariboisière and CM2RR Strasbourg, France, enrolling patients with DLB (n = 104), Alzheimer's disease (AD, n = 76), and neurological controls (NC, n = 27). Measured biomarkers included plasma Aß40/Aß42 ratio, p-tau181, NfL, and GFAP using SIMOA and plasma YKL-40 and sTREM2 using ELISA. DLB patients with available CSF analysis (n = 90) were stratified according to their CSF Aß profile. RESULTS: DLB patients displayed modified plasma Aß ratio, p-tau181, and GFAP levels compared with NC and modified plasma Aß ratio, p-tau181, GFAP, NfL, and sTREM2 levels compared with AD patients. Plasma p-tau181 best differentiated DLB from AD patients (ROC analysis, area under the curve [AUC] = 0.80) and NC (AUC = 0.78), and combining biomarkers did not improve diagnosis performance. Plasma p-tau181 was the best standalone biomarker to differentiate amyloid-positive from amyloid-negative DLB cases (AUC = 0.75) and was associated with cognitive status in the DLB group. Combining plasma Aß ratio, p-tau181 and NfL increased performance to identify amyloid copathology (AUC = 0.79). Principal component analysis identified different segregation patterns of biomarkers in the DLB and AD groups. CONCLUSIONS: Amyloid, tau, neurodegeneration and neuroinflammation plasma biomarkers are modified in DLB, albeit with moderate diagnosis performance. Plasma p-tau181 can contribute to identify Aß copathology in DLB.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Doença por Corpos de Lewy , Proteínas tau , Humanos , Doença por Corpos de Lewy/sangue , Doença por Corpos de Lewy/líquido cefalorraquidiano , Doença por Corpos de Lewy/diagnóstico , Proteínas tau/sangue , Proteínas tau/líquido cefalorraquidiano , Feminino , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Masculino , Idoso , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Estudos Retrospectivos , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Axônios/patologia , Doenças Neuroinflamatórias/sangue , Doenças Neuroinflamatórias/diagnóstico , Doenças Neuroinflamatórias/líquido cefalorraquidiano , Proteína 1 Semelhante à Quitinase-3/sangue , Proteína 1 Semelhante à Quitinase-3/líquido cefalorraquidiano , Proteína Glial Fibrilar Ácida/sangue , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Proteínas de Neurofilamentos/sangue , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/líquido cefalorraquidiano , Receptores Imunológicos/sangue , Diagnóstico Diferencial , Glicoproteínas de Membrana
6.
Arch Acad Emerg Med ; 12(1): e45, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962371

RESUMO

Carotid complications resulting from extra-luminal migration of ingested foreign bodies (FB) are rare but potentially life-threatening. Previous data on the topic predominantly comprises isolated case reports, leaving a gap in comprehensive evidence necessary to guide clinical decision-making. In this article, we offer a narrative review alongside a novel case report, aimed at providing a broad, evidence-based perspective on the topic to guide clinical practice. The search strategy employed keywords related to carotid artery complications from ingested FB across the following electronic databases: PubMed, Scopus, Google Scholar, and Cochrane Central. Screening involved standardized data extraction by two independent reviewers, with a focus on abstracts meeting inclusion criteria and excluding non-English literature and non-relevant studies from further analysis. Moreover, we present a novel case report on the topic that was successfully managed using a unique surgical approach. Overall, a total of sixteen case reports were finally included, data on clinical presentations, diagnostic strategies and findings, surgical management and outcome were extracted, tabulated, and discussed. In carotid complications from extra-luminal migration of ingested FB, high clinical suspicion is crucial due to potentially mild symptoms and negative first-level examinations. Computed tomography (CT) scan plays a pivotal role for accurate diagnosis and surgical planning, along with neck ultrasound to detect complications. Tailored surgical strategies based on the severity of carotid involvement, including venous patch grafts in severe vessels involvement, are crucial for optimal patient outcomes. As a novelty, in our case report, carotid shunt was successfully employed instead of prolonged carotid clamping to reduce the risk of associated neurological sequelae. It could be concluded that, diagnosis and managing carotid complications from extra-luminal migration of ingested FB remains challenging and a multidisciplinary approach is warranted.

7.
J Contam Hydrol ; 265: 104388, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38964149

RESUMO

The understanding of spatio-temporal variation in land use and land cover (LULC) patterns is crucial for managing catchment land use planning, as it directly influences of tropical reservoir water quality and the subsequent Nutrient Contamination (NC) of unmonitored water bodies. The current research attempts to accurately measure the influence of LULC and its associated determinants on the quantities of NC loads by using Chl-a as a proxy, within tropical reservoirs, i.e. Bhadra and Tungabhadra, located in same river catchment. This Chl-a spread calculated by the Maximum Chlorophyll Index (MCI) derived from Sentinel 2 satellite data products covering the period from July 2016 to June 2021 were done using Google Earth Engine (GEE) platform. The validation analysis confirms the robustness of the methodology with a strong correlation between MCI-calculated values and EOMAP (Earth Observation and Environmental Services Mapping) Chl-a (µg/L) data points for both reservoirs, Bhadra (R2 = 0.64) and Tungabhadra (R2 = 0.68). The findings reveal that, Tungabhadra reservoir consistently exhibits an excessive spatial distribution of Chl-a spread area (17 km2 to 335 km2), reflecting nutrient-rich water inflows, particularly evident during the post-monsoon period. This notable rise could be linked to harvesting the Kharif crop, resulting in elevated nutrient concentrations. In contrast Bhadra reservoir, dominated by forested areas, maintains relatively lower Chl-a spread areas (<20 km2), highlighting its pivotal role in maintaining water cleanliness and serves as a riparian boundary. In addition, the changes in LULC classes show a strong relationship with variation in Chl-a during the studied period, for the Bhadra Reservoir R2 = 0.51 (F- statistics = 3.983, p = 0.021), and the Tungabhadra Reservoir R2 = 0.802 (F- statistics = 7.489, p = 0.0143). This highlights how changes in land use significantly shape contamination dynamics, deepening our understanding of nutrient inputs and contamination drivers in tropical reservoirs.

8.
Cureus ; 16(6): e61703, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38975380

RESUMO

Heart rate variability (HRV) correlates well with a person's overall physiological function. Clinically, HRV is successfully used in acute care to identify impending infections, but little is known about its potential in the management of chronic diseases like cognitive decline/dementia. The aim of this study was to identify the best available knowledge about HRV in cognitively impaired populations that might be applied to improve clinical practice in community settings. We conducted a systematic literature search in PubMed, Embase, and Cochrane databases published from January 2009 to August 2022. Eligible studies were selected using Covidence and each study underwent qualitative assessment using the Mixed Method Appraisal Tool. At each stage of selection, each study was reviewed independently by two members of the team, and any disputes were discussed along the way. The literature identified that the brain regions controlling HRV are also those affected by dementias of Alzheimer's type (AD) and Lewy body types (DLB). HRV was impaired in both types, with DLB showing greater impairment in all HRV parameters compared to AD. No studies explored the temporal changes of HRV or its use in the clinical management of people with cognitive impairment (CI). The current lack of standardization of HRV recording and analysis limits its use in clinical practice. HRV may emerge as a potentially useful tool to identify people with early/preclinical memory impairment and help to differentiate AD from DLB. Longitudinal HRV measurement is emerging as a useful way to monitor disease progression and treatment response, and continuous HRV measurement may prove useful in the early identification of sepsis and its complications in patients no longer able to communicate their illness experiences.

9.
Adv Biol (Weinh) ; : e2400081, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977421

RESUMO

Embryoid bodies (EB) are sensitive to changes in the culture conditions. Recent studies show that the addition of PEG 300 to culture medium affects cell growth and differentiation; however, its effect on the embryoid body is unclear. This study aims to understand the role of PEG 300 in the process of EB formation and germ layer differentiation. EBs formed more efficiently and differentiated toward the mesoderm when cultured in a medium supplemented with appropriate concentrations of PEG 300. The expression of T/Bry, a marker of mesodermal differentiation, increases in EBs in the PEG group, and the expression of TUBB3 generally decreases, showing a quantitative relationship with PEG. Furthermore, further differentiation of PEG-pretreated EB into vascular smooth muscle cells (VSMCs) by directional induction shows that PEG 300-pretreated induced VSMCs have higher expression of phenotypic markers and greater secretory and contractile functions. This study highlights the role of PEG 300 in the culture medium during EB differentiation, which can significantly enhance mesodermal gene expression and the efficiency of subsequent differentiation into smooth muscle cells and other target cells.

10.
BMC Pulm Med ; 24(1): 313, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961422

RESUMO

BACKGROUND: Primary pulmonary myxoid sarcoma (PPMS) is a rare, low-grade malignant tumor, constituting approximately 0.2% of all lung tumors. Despite its rarity, PPMS possesses distinctive histological features and molecular alterations, notably the presence of EWSR1-CREB1 gene fusion. However, its precise tissue origin remains elusive, posing challenges in clinical diagnosis. CASE DEMONSTRATION: A 20-year-old male patient underwent a routine physical examination 6 months prior, revealing a pulmonary mass. Following surgical excision, microscopic evaluation unveiled predominantly short spindle-shaped tumor cells organized in a fascicular, beam-like, or reticular pattern. The stromal matrix exhibited abundant mucin, accompanied by lymphocytic and plasma cell infiltration, with Russell bodies evident in focal areas. Immunophenotypic profiling revealed positive expression of vimentin and epithelial membrane antigen in tumor cells, whereas smooth muscle actin and S-100, among others, were negative. Ki-67 proliferation index was approximately 5%. Subsequent second-generation sequencing identified the characteristic EWSR1-CREB1 gene fusion. The definitive pathological diagnosis established PPMS. The patient underwent no adjuvant chemotherapy or radiotherapy and remained recurrence-free during a 30-month follow-up period. CONCLUSIONS: We report a rare case of PPMS located within the left lung lobe interlobar fissure, featuring Russell body formation within the tumor stroma, a novel finding in PPMS. Furthermore, the histomorphological characteristics of this case highlight the diagnostic challenge it poses, as it may mimic inflammatory myofibroblastic tumor, extraskeletal myxoid chondrosarcoma, or hemangiopericytoma-like fibrous histiocytoma. Therefore, accurate diagnosis necessitates an integrated approach involving morphological, immunohistochemical, and molecular analyses.


Assuntos
Neoplasias Pulmonares , Humanos , Masculino , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Adulto Jovem , Proteínas de Fusão Oncogênica/genética , Tomografia Computadorizada por Raios X , Mixossarcoma/patologia , Mixossarcoma/genética , Mixossarcoma/cirurgia , Mixossarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patologia , Sarcoma/diagnóstico , Sarcoma/cirurgia , Pulmão/patologia , Pulmão/diagnóstico por imagem
11.
Surg Neurol Int ; 15: 219, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974532

RESUMO

Background: Intraorbital wooden foreign bodies (IOWFBs) constitute a relatively rare ocular trauma. Clinically, it can be difficult to diagnose them due to their wide variety of clinical manifestations. In addition, radiologic diagnosis of IOWFBs is always uncertain and challenging since their low density and low intensity on initial images are identical to air and fat. Therefore, IOWFBs are commonly missed and may not be confirmed for days or months after the initial injury. This article endeavors to contribute to the existing literature on IOWFBs by adding a case of an unusual occurrence of retained wood penetrating the inferior orbital fissure (IOF). To date, there have been no documented instances of a similar occurrence in this particular anatomical location. Case Description: A 58-year-old female with a history of trauma sustained by a slipping accident 10 months before her referral to our hospital. She underwent multiple surgeries and was referred to us due to persistent right eye pain, periorbital swelling, recurrent eye discharge, and inferior orbital paresthesia. The imaging revealed a retained foreign body located in the right orbital floor inferior to the inferior rectus muscle extending to the sub-temporal fossa through the IOF. The residue was successfully removed without complications. Conclusion: A history of trauma followed by persistent symptoms should raise the suspicion of a retained foreign body, regardless of the severity of trauma or the time between trauma and clinical presentation. Appropriate and timely imaging, followed by surgical removal, remains the cornerstone of treatment with a favorable prognosis.

12.
Int Arch Otorhinolaryngol ; 28(3): e468-e472, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38974621

RESUMO

Introduction The presence of foreign bodies in the airways remain a diagnostic challenge to healthcare professionals. They can become life threatening emergencies that require immediate intervention or go unnoticed for weeks and even months. Prevention is best but early recognition remains a critical factor in treatment of foreign body inhalation in children. Objective To study the diagnostic advantages of virtual over rigid bronchoscopy in the evaluation of children with suspected foreign body in the tracheobronchial tree and plan for early management. Methods A crossectional study conducted at a tertiary care hospital & medical college in India. A total 24 patients (0-12-years-old) who presented with complaints of sudden onset of coughing, choking, and breathing difficulty were included during the 2-year duration, from January 2018 to December 2019. All patients underwent virtual and rigid bronchoscopy. Results In 8 patients, foreign bodies detected by virtual bronchoscopy were confirmed by rigid bronchoscopy. There was one case in which virtual bronchoscopy showed no foreign body, but rigid bronchoscopy detected it. In 15 cases virtual and rigid bronchoscopy did not show foreign bodies. The sensitivity, specificity, positive and negative predictive value of virtual bronchoscopy were 88.88, 100, 100, and 93.75%, respectively. Conclusions Virtual bronchoscopy is less invasive and does not require general anesthesia but cost and availability are limitations. It can be used as method of investigation in children with suspected foreign body aspiration.

13.
Neurobiol Dis ; 199: 106595, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38972360

RESUMO

Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are characterized by neuronal α-synuclein (α-syn) inclusions termed Lewy Pathology, which are abundant in the amygdala. The basolateral amygdala (BLA), in particular, receives projections from the thalamus and cortex. These projections play a role in cognition and emotional processing, behaviors which are impaired in α-synucleinopathies. To understand if and how pathologic α-syn impacts the BLA requires animal models of α-syn aggregation. Injection of α-syn pre-formed fibrils (PFFs) into the striatum induces robust α-syn aggregation in excitatory neurons in the BLA that corresponds with reduced contextual fear conditioning. At early time points after aggregate formation, cortico-amygdala excitatory transmission is abolished. The goal of this project was to determine if α-syn inclusions in the BLA induce synaptic degeneration and/or morphological changes. In this study, we used C57BL/6 J mice injected bilaterally with PFFs in the dorsal striatum to induce α-syn aggregate formation in the BLA. A method was developed using immunofluorescence and three-dimensional reconstruction to analyze excitatory cortico-amygdala and thalamo-amygdala presynaptic terminals closely juxtaposed to postsynaptic densities. The abundance and morphology of synapses were analyzed at 6- or 12-weeks post-injection of PFFs. α-Syn aggregate formation in the BLA did not cause a significant loss of synapses, but cortico-amygdala and thalamo-amygdala presynaptic terminals and postsynaptic densities with aggregates of α-syn show increased volumes, similar to previous findings in human DLB cortex, and in non-human primate models of PD. Transmission electron microscopy showed that asymmetric synapses in mice with PFF-induced α-syn aggregates have reduced synaptic vesicle intervesicular distances, similar to a recent study showing phospho-serine-129 α-syn increases synaptic vesicle clustering. Thus, pathologic α-syn causes major alterations to synaptic architecture in the BLA, potentially contributing to behavioral impairment and amygdala dysfunction observed in synucleinopathies.

14.
Neuropathology ; 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38972833

RESUMO

The first postmortem neuropathological findings of a hemiparkinsonism and hemiatrophy (HPHA) patient are presented. A 50-year-old man developed resting tremors affecting the right hand and leg, followed by mild clumsiness of the right hand. On examination, he exhibited muscle atrophy of the right leg extremity, accompanied by right-sided parkinsonism. Brain magnetic resonance imaging was normal. Based on the clinical and radiological findings, HPHA syndrome was diagnosed, showing a good response to L-DOPA. He gradually developed muscular atrophy of the right distal upper extremity. Thirteen years after the onset of the disease, left-sided parkinsonism appeared. The patient died of Trousseau's syndrome associated with a rapidly emerging pancreatic tumor. The total duration of the disease was 14 years. Neuropathologically, the substantia nigra showed markedly left-predominant neuronal loss, along with almost symmetrical Lewy body (LB) pathology. These findings indicated that the patient originally had fewer neurons in the left substantia nigra than in the right, probably caused by congenital or childhood cerebral injury, followed by the development of unilateral parkinsonism due to the progression of LB pathology. Despite our extensive neuropathological analysis, we could not specify the etiology or anatomical substrate responsible for the development of right upper and lower extremity atrophy. Further clinicopathological studies are needed to elucidate the pathoanatomical areas causing hemiparkinsonism and hemiatrophy.

15.
Heliyon ; 10(11): e32243, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38947477

RESUMO

The Wnt signaling pathway is one of the most ancient and pivotal signaling cascades, governing diverse processes in development and cancer regulation. Within the realm of cancer treatment, genistein emerges as a promising candidate due to its multifaceted modulation of various signaling pathways, including the Wnt pathway. Despite promising preclinical studies, the precise mechanisms underlying genistein's therapeutic effects via Wnt modulation remain elusive. In this study, we unveil novel insights into the therapeutic mechanisms of genistein by elucidating its inhibitory effects on Wnt signaling through macropinocytosis. Additionally, we demonstrate its capability to curtail cell growth, proliferation, and lysosomal activity in the SW480 colon adenocarcinoma cell model. Furthermore, our investigation extends to the embryonic context, where genistein influences gene regulatory networks governed by endogenous Wnt pathways. Our findings shed light on the intricate interplay between genistein, Wnt signaling, membrane trafficking, and gene regulation, paving the way for further exploration of genistein's therapeutic potential in cancer treatment strategies.

17.
Front Neurosci ; 18: 1412356, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988772

RESUMO

Background: Dementia with Lewy bodies (DLB) can be difficult to distinguish from Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) at different stages of its progression due to some overlaps in the clinical and neuropathological presentation of these conditions compared with DLB. Metallomic changes have already been observed in the AD and PDD brain-including widespread decreases in Cu levels and more localised alterations in Na, K, Mn, Fe, Zn, and Se. This study aimed to determine whether these metallomic changes appear in the DLB brain, and how the metallomic profile of the DLB brain appears in comparison to the AD and PDD brain. Methods: Brain tissues from ten regions of 20 DLB cases and 19 controls were obtained. The concentrations of Na, Mg, K, Ca, Zn, Fe, Mn, Cu, and Se were determined using inductively coupled plasma-mass spectrometry (ICP-MS). Case-control differences were evaluated using Mann-Whitney U tests. Results were compared with those previously obtained from AD and PDD brain tissue, and principal component analysis (PCA) plots were created to determine whether cerebral metallomic profiles could distinguish DLB from AD or PDD metallomic profiles. Results: Na was increased and Cu decreased in four and five DLB brain regions, respectively. More localised alterations in Mn, Ca, Fe, and Se were also identified. Despite similarities in Cu changes between all three diseases, PCA plots showed that DLB cases could be readily distinguished from AD cases using data from the middle temporal gyrus, primary visual cortex, and cingulate gyrus, whereas DLB and PDD cases could be clearly separated using data from the primary visual cortex alone. Conclusion: Despite shared alterations in Cu levels, the post-mortem DLB brain shows very few other similarities with the metallomic profile of the AD or PDD brain. These findings suggest that while Cu deficiencies appear common to all three conditions, metal alterations otherwise differ between DLB and PDD/AD. These findings can contribute to our understanding of the underlying pathogenesis of these three diseases; if these changes can be observed in the living human brain, they may also contribute to the differential diagnosis of DLB from AD and/or PDD.

18.
Acta Neuropathol ; 148(1): 3, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980423

RESUMO

This study investigates various pathological tau isoforms in the retina of individuals with early and advanced Alzheimer's disease (AD), exploring their connection with disease status. Retinal cross-sections from predefined superior-temporal and inferior-temporal subregions and corresponding brains from neuropathologically confirmed AD patients with a clinical diagnosis of either mild cognitive impairment (MCI) or dementia (n = 45) were compared with retinas from age- and sex-matched individuals with normal cognition (n = 30) and non-AD dementia (n = 4). Retinal tau isoforms, including tau tangles, paired helical filament of tau (PHF-tau), oligomeric-tau (Oligo-tau), hyperphosphorylated-tau (p-tau), and citrullinated-tau (Cit-tau), were stereologically analyzed by immunohistochemistry and Nanostring GeoMx digital spatial profiling, and correlated with clinical and neuropathological outcomes. Our data indicated significant increases in various AD-related pretangle tau isoforms, especially p-tau (AT8, 2.9-fold, pS396-tau, 2.6-fold), Cit-tau at arginine residue 209 (CitR209-tau; 4.1-fold), and Oligo-tau (T22+, 9.2-fold), as well as pretangle and mature tau tangle forms like MC-1-positive (1.8-fold) and PHF-tau (2.3-fold), in AD compared to control retinas. MCI retinas also exhibited substantial increases in Oligo-tau (5.2-fold), CitR209-tau (3.5-fold), and pS396-tau (2.2-fold). Nanostring GeoMx analysis confirmed elevated retinal p-tau at epitopes: Ser214 (2.3-fold), Ser396 (2.6-fold), Ser404 (2.4-fold), and Thr231 (1.8-fold), particularly in MCI patients. Strong associations were found between retinal tau isoforms versus brain pathology and cognitive status: a) retinal Oligo-tau vs. Braak stage, neurofibrillary tangles (NFTs), and CDR cognitive scores (ρ = 0.63-0.71), b) retinal PHF-tau vs. neuropil threads (NTs) and ABC scores (ρ = 0.69-0.71), and c) retinal pS396-tau vs. NTs, NFTs, and ABC scores (ρ = 0.67-0.74). Notably, retinal Oligo-tau strongly correlated with retinal Aß42 and arterial Aß40 forms (r = 0.76-0.86). Overall, this study identifies and quantifies diverse retinal tau isoforms in MCI and AD patients, underscoring their link to brain pathology and cognition. These findings advocate for further exploration of retinal tauopathy biomarkers to facilitate AD detection and monitoring via noninvasive retinal imaging.


Assuntos
Doença de Alzheimer , Isoformas de Proteínas , Retina , Proteínas tau , Humanos , Proteínas tau/metabolismo , Masculino , Feminino , Idoso , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Retina/patologia , Retina/metabolismo , Idoso de 80 Anos ou mais , Disfunção Cognitiva/patologia , Disfunção Cognitiva/metabolismo , Pessoa de Meia-Idade , Emaranhados Neurofibrilares/patologia , Emaranhados Neurofibrilares/metabolismo , Encéfalo/patologia , Encéfalo/metabolismo
19.
Mol Genet Metab Rep ; 40: 101104, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38983107

RESUMO

Several disorders of energy metabolism have been treated with exogenous ketone bodies. The benefit of this treatment is best documented in multiple acyl-CoA dehydrogenase deficiency (MADD) (MIM#231680). One might also expect ketone bodies to help in other disorders with impaired ketogenesis or in conditions that profit from a ketogenic diet. Here, we report the use of a novel preparation of dextro-ß-hydroxybutyrate (D-ßHB) salts in two cases of MADD and one case of pyruvate dehydrogenase (PDH) deficiency (MIM#312170). The two patients with MADD had previously been on a racemic mixture of D- and L­sodium hydroxybutyrate. Patient #1 found D-ßHB more palatable, and the change in formulation corrected hypernatraemia in patient #2. The patient with PDH deficiency was on a ketogenic diet but had not previously been given hydroxybutyrate. In this case, the addition of D-ßHB improved ketosis. We conclude that NHS101 is a good candidate for further clinical studies in this group of diseases of inborn errors of metabolism.

20.
World J Clin Cases ; 12(18): 3548-3554, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38983406

RESUMO

BACKGROUND: Colorectal foreign bodies are commonly encountered during surgery. They are frequently observed in men 20 to 90 years of age and have bimodal age distribution. Surgical management is necessary for cases of rectal perforation. However, surgical site infections are the most common complications after colorectal surgery. CASE SUMMARY: We discuss a case of rectal perforation in a patient who presented to our hospital 2 d after its occurrence. The perforation occurred as a result of the patient inserting a sex toy in his rectum. Severe peritonitis was attributable to delayed presentation. CONCLUSION: Vacuum-assisted closure was performed to treat the wound, which healed well after therapy. No complications were noted.

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