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Immunity & Ageing : I & A Jun 2024Alzheimer's disease (AD) is a serious brain disorder characterized by the presence of beta-amyloid plaques, tau pathology, inflammation, neurodegeneration, and... (Review)
Review
Alzheimer's disease (AD) is a serious brain disorder characterized by the presence of beta-amyloid plaques, tau pathology, inflammation, neurodegeneration, and cerebrovascular dysfunction. The presence of chronic neuroinflammation, breaches in the blood-brain barrier (BBB), and increased levels of inflammatory mediators are central to the pathogenesis of AD. These factors promote the penetration of immune cells into the brain, potentially exacerbating clinical symptoms and neuronal death in AD patients. While microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in AD, recent evidence suggests the infiltration of cerebral vessels and parenchyma by peripheral immune cells, including neutrophils, T lymphocytes, B lymphocytes, NK cells, and monocytes in AD. These cells participate in the regulation of immunity and inflammation, which is expected to play a huge role in future immunotherapy. Given the crucial role of peripheral immune cells in AD, this article seeks to offer a comprehensive overview of their contributions to neuroinflammation in the disease. Understanding the role of these cells in the neuroinflammatory response is vital for developing new diagnostic markers and therapeutic targets to enhance the diagnosis and treatment of AD patients.
PubMed: 38877498
DOI: 10.1186/s12979-024-00445-0 -
Microbiology Spectrum Jun 2024The human polyomavirus, JCPyV, establishes a lifelong persistent infection in the peripheral organs of a majority of the human population worldwide. Patients who are...
JCPyV infection of primary choroid plexus epithelial cells reduces expression of critical junctional proteins and increases expression of barrier disrupting inflammatory cytokines.
UNLABELLED
The human polyomavirus, JCPyV, establishes a lifelong persistent infection in the peripheral organs of a majority of the human population worldwide. Patients who are immunocompromised due to underlying infections, cancer, or to immunomodulatory treatments for autoimmune disease are at risk for developing progressive multifocal leukoencephalopathy (PML) when the virus invades the CNS and infects macroglial cells in the brain parenchyma. It is not yet known how the virus enters the CNS to cause disease. The blood-choroid plexus barrier is a potential site of virus invasion as the cells that make up this barrier are known to be infected with virus both and . To understand the effects of virus infection on these cells we challenged primary human choroid plexus epithelial cells with JCPyV and profiled changes in host gene expression. We found that viral infection induced the expression of proinflammatory chemokines and downregulated junctional proteins essential for maintaining blood-CSF and blood-brain barrier function. These data contribute to our understanding of how JCPyV infection of the choroid plexus can modulate the host cell response to neuroinvasive pathogens.
IMPORTANCE
The human polyomavirus, JCPyV, causes a rapidly progressing demyelinating disease in the CNS of patients whose immune systems are compromised. JCPyV infection has been demonstrated in the choroid plexus both and and this highly vascularized organ may be important in viral invasion of brain parenchyma. Our data show that infection of primary choroid plexus epithelial cells results in increased expression of pro-inflammatory chemokines and downregulation of critical junctional proteins that maintain the blood-CSF barrier. These data have direct implications for mechanisms used by JCPyV to invade the CNS and cause neurological disease.
PubMed: 38874395
DOI: 10.1128/spectrum.00628-24 -
ESC Heart Failure Jun 2024Cognitive impairment (CI) is a common, yet frequently unrecognized co-morbidity in chronic heart failure (HF). We quantified trajectories of cognitive performance, brain...
AIMS
Cognitive impairment (CI) is a common, yet frequently unrecognized co-morbidity in chronic heart failure (HF). We quantified trajectories of cognitive performance, brain volume, and related clinical outcome over a time course of 6 years.
METHODS AND RESULTS
The Cognition.Matters-HF cohort study recruited patients with stable HF of any aetiology and severity. Beyond cardiological assessment, the workup included cognitive testing and brain magnetic resonance imaging (MRI). Of 148 recruited patients, 70% exhibited CI at baseline. During the median follow-up time of 69 months (quartiles: 68, 70), indicators of HF severity remained essentially unaltered. CI was also stable, with the exception of intensity of attention, where age-adjusted t-scores decreased from 42 (38, 46) to 38 (34, 44; P < 0.001). Complete sets of four serial brain MRI scans were available in 47 patients (32% of total sample). Total brain volume shrank by 0.4% per year, from 1103 (1060, 1143) cm to 1078 (1027, 1117) cm, which was within limits observed in non-diseased ageing individuals. During follow-up, 29 study participants (20%) died, and 26 (18%) were at least once hospitalized due to worsening HF. The presence of CI was not associated with overall (P = 0.290) or hospitalization-free (P = 0.450) survival.
CONCLUSIONS
In patients with stable HF patients receiving guideline-directed pharmacologic treatment and regular medical care, the presence of CI did not affect overall and hospitalization-free 6-year survival. The loss of brain parenchyma observed in patients with stable HF did not exceed that of normal ageing.
PubMed: 38873878
DOI: 10.1002/ehf2.14909 -
Respiratory Medicine Case Reports 2024Metastatic pulmonary calcification (MPC) is a metabolic disorder characterized by an ectopic deposition of calcium in the lung parenchyma, prevalent in patients with...
Metastatic pulmonary calcification (MPC) is a metabolic disorder characterized by an ectopic deposition of calcium in the lung parenchyma, prevalent in patients with chronic kidney disease. A combination of parenchymal lung abnormalities on high resolution chest computed tomography (CT) and pulmonary radiotracer uptake in Tc-methyl diphosphate (MDP) bone scintigraphy can establish diagnosis of MPC. We herein present a case of MPC with documented stability of chest CT abnormalities after renal transplant. We also describe novel findings of diffuse pulmonary uptake of F-sodium fluoride, a calcium-avid radiotracer, in positron emission tomography (PET)/CT performed in the same patient.
PubMed: 38872935
DOI: 10.1016/j.rmcr.2024.102043 -
Cureus May 2024Emphysematous pyelonephritis (EPN) represents a severe and acute infection localized in the renal parenchyma and surrounding perirenal area, typically observed in...
Emphysematous pyelonephritis (EPN) represents a severe and acute infection localized in the renal parenchyma and surrounding perirenal area, typically observed in individuals with predisposing factors such as urinary tract obstruction, diabetes mellitus, or compromised immune function. Here, we present a unique case involving a 23-year-old female patient presenting to the emergency department with complaints of discomfort localized to the right side of her abdomen. Despite the absence of diabetes mellitus, the patient was diagnosed with EPN based on clinical presentation and imaging findings. Prompt and effective management was initiated under the care of the urology department, highlighting the importance of early recognition and intervention in mitigating the potential complications associated with this severe infectious process.
PubMed: 38872701
DOI: 10.7759/cureus.60291 -
Plastic and Reconstructive Surgery.... Jun 2024Patients with previous breast augmentation may need implant removal for mechanical complications or other causes. After prosthesis removal, the residual parenchyma can...
BACKGROUND
Patients with previous breast augmentation may need implant removal for mechanical complications or other causes. After prosthesis removal, the residual parenchyma can be reshaped through a mastopexy with rearrangement of breast tissue. Several techniques have been described in the literature, but none of them can be considered the gold standard. In this study, we present our preliminary experience in breast tissue rearranging after implant removal through a novel technique: the "octopus head" dermoglandular flap.
METHODS
From January 2019 to October 2022, nine patients (18 breasts) underwent implant removal and simultaneous breast remodeling with the tissue obtained from the dermoglandular excess of the breast and shaped like an octopus head. Patient's demographic and clinical characteristics, postoperative complications, and patient-reported satisfaction were recorded.
RESULTS
Mean age was 46.7 years. Body mass index ranged between 22.5 and 27.6 kg per m. The majority of patients had moderate ptosis (67%). Breast implants were removed due to bilateral capsular contracture (n = 3), unilateral implant rupture with contralateral capsular contracture (n = 2), bilateral implant rupture (n = 3), and unilateral periprosthetic seroma (n = 1). We observed two minor complications: one postoperative hemorrhage with subsequent hematoma that was managed conservatively, and one nipple-areola complex malposition that underwent revision surgery. All patients were satisfied with the aesthetic and functional result.
CONCLUSIONS
The octopus head dermoglandular flap has proved to be a safe and reliable option for breast tissue rearranging after implant removal, providing a good and stable cosmetic result, a low complication rate, and high patient-reported satisfaction.
PubMed: 38868620
DOI: 10.1097/GOX.0000000000005882 -
IScience Jun 2024Astrocyte endfeet enwrap brain vasculature, forming a boundary for perivascular glymphatic flow of fluid and solutes along and across the astrocyte endfeet into the...
Astrocyte endfeet enwrap brain vasculature, forming a boundary for perivascular glymphatic flow of fluid and solutes along and across the astrocyte endfeet into the brain parenchyma. We evaluated astrocyte sensitivity to shear stress generated by such flow, finding a set point for downstream calcium signaling that is below about 0.1 dyn/cm. This set point is modulated by albumin levels encountered in cerebrospinal fluid (CSF) under normal conditions and following a blood-brain barrier breach or immune response. The astrocyte mechanosome responsible for the detection of shear stress includes sphingosine-1-phosphate (S1P)-mediated sensitization of the mechanosensor Piezo1. Fluid flow through perivascular channels delimited by vessel wall and astrocyte endfeet thus generates sufficient shear stress to activate astrocytes, thereby potentially controlling vasomotion and parenchymal perfusion. Moreover, S1P receptor signaling establishes a set point for Piezo1 activation that is finely tuned to coincide with CSF albumin levels and to the low shear forces resulting from glymphatic flow.
PubMed: 38868201
DOI: 10.1016/j.isci.2024.110069 -
Porcine Health Management Jun 2024Immediately after birth, newborn piglets fight to establish a teat order. During this process, lesions appear on the piglets' faces and on the sows' teats, which is why...
BACKGROUND
Immediately after birth, newborn piglets fight to establish a teat order. During this process, lesions appear on the piglets' faces and on the sows' teats, which is why tooth resection is carried out on many farms in Germany even though it is known that this procedure is frequently resulting in pulp openings. The opening of a pulp cave is suspected to cause painful tooth alterations and may be an entrance for infectious agents. The purpose of this study was to analyse the effect of tooth resection on skin lesions, development of bodyweight and behaviour in suckling piglets. Four days prepartum, 110 sows in farrow-to-finish production were assigned to one of three treatments. Litters had their teeth left intact (control group, CG), ground with a tea-cup roller head (Tea-cup head grinder group, TCG, Wilofa Diamant, D-56,133 Fachbach, Germany) or ground with a diamond rolling head (rolling head grinder group, RG, IBS/E Company Proxxon GmbH, 54,343 Föhren, Germany). The number of pulp openings in the RG and TCG was examined using a random sample. Piglet body weight and skin lesion scores were recorded within the first 24 h after birth and during each week of the suckling period. Each sow's udder was examined before farrowing, in the second week of lactation and at weaning. The behaviour of the litters from nine sows was video-recorded throughout the suckling period. The aim of this study was to investigate the effects of tooth grinding by a tea-cup head (compared to grinding by a diamond roller head and no grinding [control group]) on the behaviour and average daily gain of piglets as well as on skin lesions on sow udder.
RESULTS
The number of dental injuries was significantly greater in the RG than in the TCG (p < 0.01). Head lesions on piglets were significantly more common in the CG than in the RG (p = 0. 02). Compared to CG piglets, TCG piglets had a significantly greater weight at the end of the suckling period (p = 0.02). No significant difference between treatments was found in the sows' udder (parenchyma, skin, or teat) or in the behaviour of the litters.
CONCLUSION
As tooth grinding is frequently inducing pulp openings, the necessity of the procedure should be carefully and critically scrutinised. In case tooth resection seems inevitable until the underlying management problems have been solved, the Tea-cup grinding head should be used due to significantly fewer pulp openings.
PubMed: 38867344
DOI: 10.1186/s40813-024-00373-x -
Nature Communications Jun 2024Multiple sclerosis (MS) is characterized by heterogeneity in disease course and prediction of long-term outcome remains a major challenge. Here, we investigate five...
Multiple sclerosis (MS) is characterized by heterogeneity in disease course and prediction of long-term outcome remains a major challenge. Here, we investigate five myeloid markers - CHIT1, CHI3L1, sTREM2, GPNMB and CCL18 - in the cerebrospinal fluid (CSF) at diagnostic lumbar puncture in a longitudinal cohort of 192 MS patients. Through mixed-effects and machine learning models, we show that CHIT1 is a robust predictor for faster disability progression. Integrative analysis of 11 CSF and 26 central nervous system (CNS) parenchyma single-cell/nucleus RNA sequencing samples reveals CHIT1 to be predominantly expressed by microglia located in active MS lesions and enriched for lipid metabolism pathways. Furthermore, we find CHIT1 expression to accompany the transition from a homeostatic towards a more activated, MS-associated cell state in microglia. Neuropathological evaluation in post-mortem tissue from 12 MS patients confirms CHIT1 production by lipid-laden phagocytes in actively demyelinating lesions, already in early disease stages. Altogether, we provide a rationale for CHIT1 as an early biomarker for faster disability progression in MS.
Topics: Humans; Microglia; Disease Progression; Multiple Sclerosis; Biomarkers; Female; Male; Adult; Middle Aged; Hexosaminidases; Longitudinal Studies; Chitinase-3-Like Protein 1
PubMed: 38866782
DOI: 10.1038/s41467-024-49312-y -
Frontiers in Immunology 2024Historically, the central nervous system (CNS) was regarded as 'immune-privileged', possessing its own distinct immune cell population. This immune privilege was thought... (Review)
Review
Historically, the central nervous system (CNS) was regarded as 'immune-privileged', possessing its own distinct immune cell population. This immune privilege was thought to be established by a tight blood-brain barrier (BBB) and blood-cerebrospinal-fluid barrier (BCSFB), which prevented the crossing of peripheral immune cells and their secreted factors into the CNS parenchyma. However, recent studies have revealed the presence of peripheral immune cells in proximity to various brain-border niches such as the choroid plexus, cranial bone marrow (CBM), meninges, and perivascular spaces. Furthermore, emerging evidence suggests that peripheral immune cells may be able to infiltrate the brain through these sites and play significant roles in driving neuronal cell death and pathology progression in neurodegenerative disease. Thus, in this review, we explore how the brain-border immune niches may contribute to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). We then discuss several emerging options for harnessing the neuroimmune potential of these niches to improve the prognosis and treatment of these debilitative disorders using novel insights from recent studies.
Topics: Humans; Neurodegenerative Diseases; Animals; Blood-Brain Barrier; Brain; Immune Privilege
PubMed: 38863704
DOI: 10.3389/fimmu.2024.1380063