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Communications Biology Jun 2024The locus coeruleus (LC), our main source of norepinephrine (NE) in the brain, declines with age and is a potential epicentre of protein pathologies in neurodegenerative...
The locus coeruleus (LC), our main source of norepinephrine (NE) in the brain, declines with age and is a potential epicentre of protein pathologies in neurodegenerative diseases (ND). In vivo measurements of LC integrity and function are potentially important biomarkers for healthy ageing and early ND onset. In the present study, high-resolution functional MRI (fMRI), a reversal reinforcement learning task, and dedicated post-processing approaches were used to visualise age differences in LC function (N = 50). Increased LC responses were observed during emotionally and task-related salient events, with subsequent accelerations and decelerations in reaction times, respectively, indicating context-specific adaptive engagement of the LC. Moreover, older adults exhibited increased LC activation compared to younger adults, indicating possible compensatory overactivation of a structurally declining LC in ageing. Our study shows that assessment of LC function is a promising biomarker of cognitive aging.
Topics: Locus Coeruleus; Humans; Male; Aging; Magnetic Resonance Imaging; Aged; Female; Adult; Norepinephrine; Middle Aged; Young Adult
PubMed: 38937535
DOI: 10.1038/s42003-024-06446-5 -
Neuro-ophthalmology (Aeolus Press) 2024Millard-Gubler syndrome is a pontine syndrome caused by a lesion in the lower pons region. It is characterised by ipsilateral facial paralysis and VI paresis and...
Millard-Gubler syndrome is a pontine syndrome caused by a lesion in the lower pons region. It is characterised by ipsilateral facial paralysis and VI paresis and contralateral brachiocrural palsy. We present the case of a female patient, G4P2A1, at 21 weeks of gestation, with preeclampsia, complaints of blurred vision, diplopia, and right hemiparesis, in whom a clinical diagnosis of Millard-Gubler syndrome was made. Neuroimaging showed an intraparenchymal haemorrhage towards the central portion of the bulbopontine junction. An extensive aetiological study was carried out to determine the cause of the hypertensive disorder syndrome during pregnancy. The patient improved satisfactorily from the neurological deficit after delivery of an early stillbirth.
PubMed: 38933747
DOI: 10.1080/01658107.2024.2303708 -
Molecules (Basel, Switzerland) Jun 2024This work proposes the development of new vesicular systems based on anesthetic compounds (lidocaine (LID) and capsaicin (CA)) and antimicrobial agents (amino acid-based...
BACKGROUND
This work proposes the development of new vesicular systems based on anesthetic compounds (lidocaine (LID) and capsaicin (CA)) and antimicrobial agents (amino acid-based surfactants from phenylalanine), with a focus on physicochemical characterization and the evaluation of antimicrobial and cytotoxic properties.
METHOD
Phenylalanine surfactants were characterized via high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). Different niosomal systems based on capsaicin, lidocaine, cationic phenylalanine surfactants, and dipalmitoyl phosphatidylcholine (DPPC) were characterized in terms of size, polydispersion index (PI), zeta potential, and encapsulation efficiency using dynamic light scattering (DLS), transmitted light microscopy (TEM), and small-angle X-ray scattering (SAXS). Furthermore, the interaction of the pure compounds used to prepare the niosomal formulations with DPPC monolayers was determined using a Langmuir balance. The antibacterial activity of the vesicular systems and their biocompatibility were evaluated, and molecular docking studies were carried out to obtain information about the mechanism by which these compounds interact with bacteria.
RESULTS
The stability and reduced size of the analyzed niosomal formulations demonstrate their potential in pharmaceutical applications. The nanosystems exhibit promising antimicrobial activity, marking a significant advancement in pharmaceutical delivery systems with dual therapeutic properties. The biocompatibility of some formulations underscores their viability.
CONCLUSIONS
The proposed niosomal formulations could constitute an important advance in the pharmaceutical field, offering delivery systems for combined therapies thanks to the pharmacological properties of the individual components.
Topics: Liposomes; Surface-Active Agents; Amino Acids; Anti-Infective Agents; Molecular Docking Simulation; Anesthetics; Drug Compounding; Microbial Sensitivity Tests
PubMed: 38930908
DOI: 10.3390/molecules29122843 -
Materials (Basel, Switzerland) Jun 2024Implantoplasty is a technique increasingly used to remove the biofilm that causes peri-implantitis on dental implants. This technique of mechanization of the titanium...
Implantoplasty is a technique increasingly used to remove the biofilm that causes peri-implantitis on dental implants. This technique of mechanization of the titanium surface makes it possible to eliminate bacterial colonies, but it can generate variations in the properties of the implant. These variations, especially those in fatigue resistance and electrochemical corrosion behavior, have not been studied much. In this work, fatigue tests were performed on 60 dental implants without implantoplasty, namely 30 in air and 30 in Hank's solution at 37 °C, and 60 with implatoplasty, namely 30 in air and 30 in Hank's solution at 37 °C, using triaxial tension-compression and torsion stresses simulating human chewing. Mechanical tests were performed with a Bionix servo-hydraulic testing machine and fracture surfaces were studied by scanning electron microcopyElectrochemical corrosion tests were performed on 20 dental implants to determine the corrosion potentials and corrosion intensity for control implants and implantoplasty implants. Studies of titanium ion release to the physiological medium were carried out for each type of dental implants by Inductively Coupled-Plasma Mass Spectrometry at different immersion times at 37 °C. The results show a loss of fatigue caused by the implantoplasty of 30%, observing that the nucleation points of the cracks are in the areas of high deformation in the areas of the implant neck where the mechanization produced in the treatment of the implantoplasty causes an exaltation of fatigue cracks. It has been observed that tests performed in Hank's solution reduce the fatigue life due to the incorporation of hydrogen in the titanium causing the formation of hydrides that embrittle the dental implant. Likewise, the implantoplasty causes a reduction of the corrosion resistance with some pitting on the machined surface. Ion release analyses are slightly higher in the implantoplasted samples but do not show statistically significant differences. It has been observed that the physiological environment reduces the fatigue life of the implants due to the penetration of hydrogen into the titanium forming titanium hydrides which embrittle the implant. These results should be taken into account by clinicians to determine the convenience of performing a treatment such as implantoplasty that reduces the mechanical behavior and increases the chemical degradation of the titanium dental implant.
PubMed: 38930312
DOI: 10.3390/ma17122944 -
Scientific Reports Jun 2024Based on the auditory periphery and the small head size, Etruscan shrews (Suncus etruscus) approximate ancestral mammalian conditions. The auditory brainstem in this...
Based on the auditory periphery and the small head size, Etruscan shrews (Suncus etruscus) approximate ancestral mammalian conditions. The auditory brainstem in this insectivore has not been investigated. Using labelling techniques, we assessed the structures of their superior olivary complex (SOC) and the nuclei of the lateral lemniscus (NLL). There, we identified the position of the major nuclei, their input pattern, transmitter content, expression of calcium binding proteins (CaBPs) and two voltage-gated ion channels. The most prominent SOC structures were the medial nucleus of the trapezoid body (MNTB), the lateral nucleus of the trapezoid body (LNTB), the lateral superior olive (LSO) and the superior paraolivary nucleus (SPN). In the NLL, the ventral (VNLL), a specific ventrolateral VNLL (VNLLvl) cell population, the intermediate (INLL) and dorsal (DNLL) nucleus, as well as the inferior colliculus's central aspect were discerned. INLL and VNLL were clearly separated by the differential distribution of various marker proteins. Most labelled proteins showed expression patterns comparable to rodents. However, SPN neurons were glycinergic and not GABAergic and the overall CaBPs expression was low. Next to the characterisation of the Etruscan shrew's auditory brainstem, our work identifies conserved nuclei and indicates variable structures in a species that approximates ancestral conditions.
Topics: Animals; Shrews; Superior Olivary Complex; Auditory Pathways; Neurons; Inferior Colliculi; Calcium-Binding Proteins; Brain Stem; Male; Olivary Nucleus
PubMed: 38926520
DOI: 10.1038/s41598-024-65451-0 -
Revue Des Maladies Respiratoires Jun 2024Up to 30% patients newly diagnosed with advanced non-small cell lung cancer (NSCLC) present with brain metastases. In the absence of oncogenic addiction, first-line... (Review)
Review
INTRODUCTION
Up to 30% patients newly diagnosed with advanced non-small cell lung cancer (NSCLC) present with brain metastases. In the absence of oncogenic addiction, first-line immunotherapy, alone or in combination with chemotherapy, is the current standard of care. This review aims to synthesize the available data regarding the efficacy of immunotherapy in these patients, and to discuss the possibility of its being coordinated with local treatments such as radiotherapy.
STATE OF THE ART
NSCLC patients with brain metastases appear to have survival benefits with immunotherapy similar to those of NSCLC patients without brain metastases. However, this finding is based on mainly prospective studies having included highly selected patients with pre-treated and stable brain metastases. Several retrospective studies and two prospective single-arm studies have confirmed the intracranial efficacy of immunotherapy, either alone or in combination with chemotherapy.
PERSPECTIVES
The indications and optimal timing for cerebral radiotherapy remain subjects of debate. To date, there exists no randomized study assessing the addition of brain radiotherapy to first-line immunotherapy. That said, a recent meta-analysis showed increased intracerebral response when radiotherapy complemented immunotherapy.
CONCLUSIONS
For NSCLC patients with brain metastases, the available data suggest a clear benefit of first-line immunotherapy, whether alone or combined with chemotherapy. However, most of these data are drawn from retrospective, non-randomized studies with small sample sizes.
PubMed: 38926022
DOI: 10.1016/j.rmr.2024.05.004 -
Pediatric Neurology Jun 2024Pontocerebellar hypoplasia type 10 (PCH10) due to CLP1 gene mutations is characterized by structural brain anomalies, progressive microcephaly, severe intellectual and...
BACKGROUND
Pontocerebellar hypoplasia type 10 (PCH10) due to CLP1 gene mutations is characterized by structural brain anomalies, progressive microcephaly, severe intellectual and physical disabilities, and spasticity. In this follow-up study, evolution of phenotypic and neurological characteristics of patients with PCH10 is discussed.
METHODS
Phenotype, growth parameters, motor functions, developmental tests, spasticity assessments, functional independence assessments, electroencephalography (EEG), and brain magnetic resonance imaging (MRI) of 10 patients with PCH10 were monitored on separate examinations. Alterations were recorded.
RESULTS
Patients were followed-up for an average of 2.83 years. The tone of the upper extremities was significantly higher than that of the lower extremities, according to Modified Ashworth Scale (MAS) values. Sixty percent of patients could sit unsupported; 20% achieved supported sitting initially but lost the ability during follow-up. Absence of grabbing or sitting was observed in 20% of patients. During follow-up, one person achieved supported sitting and one person achieved head holding. Only one patient was able to speak a few words. Cerebellar atrophy (two of 10), pons hypoplasia (four of 10), cortical atrophy (seven of 10), enlarged ventricles (10 of 10), thinning of the corpus callosum (10 of 10), hypomyelination (six of 10), and increased white matter signal intensity (six of 10) were the observed MRI findings.
CONCLUSIONS
Progressive cerebral and cerebellar atrophy was demonstrated radiologically for the first time in a PCH10 cohort. It is of crucial importance to identify these patients promptly with the help of dysmorphic findings and spasticity being pronounced in the upper extremities. Furthermore, we note that phenotypic and neurological examination findings tend to change slightly over time.
PubMed: 38925092
DOI: 10.1016/j.pediatrneurol.2024.05.017 -
Cells Jun 2024Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies...
BACKGROUND
Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies between individuals and over the course of the disease. Recognising the clinicopathological features that most strongly associate with disease outcomes will inform future efforts at patient phenotyping.
AIMS
We used a digital pathology workflow, involving high-resolution image acquisition of immunostained slides and opensource software for quantification, to investigate the relationship between clinical and neuropathological features in an autopsy cohort of progressive MS.
METHODS
Sequential sections of frontal, cingulate and occipital cortex, thalamus, brain stem (pons) and cerebellum including dentate nucleus (n = 35 progressive MS, females = 28, males = 7; age died = 53.5 years; range 38-98 years) were immunostained for myelin (anti-MOG), neurons (anti-HuC/D) and microglia/macrophages (anti-HLA). The extent of demyelination, neurodegeneration, the presence of active and/or chronic active lesions and quantification of brain and leptomeningeal inflammation was captured by digital pathology.
RESULTS
Digital analysis of tissue sections revealed the variable extent of pathology that characterises progressive MS. Microglia/macrophage activation, if found at a higher level in a single block, was typically elevated across all sampled blocks. Compartmentalised (perivascular/leptomeningeal) inflammation was associated with age-related measures of disease severity and an earlier death.
CONCLUSION
Digital pathology identified prognostically important clinicopathological correlations in MS. This methodology can be used to prioritise the principal pathological processes that need to be captured by future MS biomarkers.
Topics: Humans; Middle Aged; Female; Male; Multiple Sclerosis; Aged; Adult; Biomarkers; Aged, 80 and over; Inflammation; Brain; Microglia; Macrophages
PubMed: 38920650
DOI: 10.3390/cells13121020 -
Journal of Neuroendovascular Therapy 2024To report the rare case of a patient with a perianeurysmal cyst following stent-assisted coil embolization of an unruptured vertebral artery aneurysm.
OBJECTIVE
To report the rare case of a patient with a perianeurysmal cyst following stent-assisted coil embolization of an unruptured vertebral artery aneurysm.
CASE PRESENTATION
A 63-year-old woman underwent stent-assisted coil embolization for an unruptured vertebral artery aneurysm embedded in the brainstem (pons). Complete occlusion of the aneurysm was successfully achieved. However, subsequent magnetic resonance imaging (MRI) conducted 8 months after the procedure showed perilesional edematous changes surrounding the aneurysm, and at 20 months, cyst formation was observed in the vicinity of the aneurysm. Progressive enlargement of the cyst eventually led to the development of paralysis and dysphagia, necessitating cyst fenestration surgery. Although postoperative reduction in the cyst size was achieved, the patient experienced complications in the form of aspiration pneumonia and bacterial meningitis, which resulted in a life-threatening condition.
CONCLUSION
Aneurysms embedded in the brain parenchyma should be carefully followed up, recognizing the risk of perianeurysmal cyst formation after coil embolization.
PubMed: 38911484
DOI: 10.5797/jnet.cr.2023-0088 -
Radiologia 2024The 2021 World Health Organization classification of CNS tumours was greeted with enthusiasm as well as an initial potential overwhelm. However, with time and...
The 2021 World Health Organization classification of CNS tumours was greeted with enthusiasm as well as an initial potential overwhelm. However, with time and experience, our understanding of its key aspects has notably improved. Using our collective expertise gained in neuro-oncology units in hospitals in different countries, we have compiled a practical guide for radiologists that clarifies the classification criteria for diffuse gliomas in adults. Its format is clear and concise to facilitate its incorporation into everyday clinical practice. The document includes a historical overview of the classifications and highlights the most important recent additions. It describes the main types in detail with an emphasis on their appearance on imaging. The authors also address the most debated issues in recent years. It will better prepare radiologists to conduct accurate presurgical diagnoses and collaborate effectively in clinical decision making, thus impacting decisions on treatment, prognosis, and overall patient care.
Topics: Humans; Glioma; Brain Neoplasms; Adult; World Health Organization; Preoperative Care
PubMed: 38908887
DOI: 10.1016/j.rxeng.2024.03.002