Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 1.353
Filter
1.
Ultrasound Med Biol ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38729810

ABSTRACT

OBJECTIVE: The purpose of this study was to quantify the accuracy of partial volume-corrected three-dimensional volume flow (3DVF) measurements as a function of spatial sampling beam density using carefully-designed parametric analyses in order to inform the target applications of 3DVF. METHODS: Experimental investigations employed a mechanically-swept curvilinear ultrasound array to acquire 3D color flow (6.3 MHz) images in flow phantoms consisting of four lumen diameters (6.35, 4.88, 3.18 and 1.65 mm) with volume flow rates of 440, 260, 110 and 30 mL/min, respectively. Partial volume-corrected three-dimensional volume flow (3DVF) measurements, based on the Gaussian surface integration principle, were computed at five regions of interest positioned between depths of 2 and 6 cm in 1 cm increments. At each depth, the color flow beam point spread function (PSF) was also determined, using in-phase/quadrature data, such that 3DVF bias could then be related to spatial sampling beam density. Corresponding simulations were performed for a laminar parabolic flow profile that was sampled using the experimentally-measured PSFs. Volume flow was computed for all combinations of lumen diameters and the PSFs at each depth. RESULTS: Accurate 3DVF measurements, i.e., bias less than ±20%, were achieved for spatial sampling beam densities where at least 6 elevational color flow beams could be positioned across the lumen. In these cases, greater than 8 lateral color flow beams were present. PSF measurements showed an average lateral-to-elevational beam width asymmetry of 1:2. Volume flow measurement bias increased as the color flow beam spatial sampling density within the lumen decreased. CONCLUSION: Applications of 3DVF, particularly those in the clinical domain, should focus on areas where a spatial sampling density of 6 × 6 (lateral x elevational) beams can be realized in order to minimize measurement bias. Matrix-based ultrasound arrays that possess symmetric PSFs may be advantageous to achieve adequate beam densities in smaller vessels.

2.
ArXiv ; 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38699163

ABSTRACT

Periodontal diseases affect 45.9\% of adults aged 30 or older in the United States. Current diagnostic methods for clinical assessment of these diseases are visual examination and bleeding on probing that are subjective, qualitative, and/or invasive. Thus, there is a critical need for research on noninvasive modalities for periodontal tissue characterization. Quantitative Ultrasound (QUS) has shown promising results in noninvasive characterization of various soft tissues; however, it has not been used in periodontics. This study is among initial investigations into the application of QUS for periodontal tissue characterization in the literature. Here, QUS analysis of oral soft tissues (alveolar mucosa and gingiva) is performed in an in vivo animal study including 10 swine. US scanning was performed at the first molar of all four oral quadrants, resulting in a total of 40 scans. We investigated first order speckle statistics of oral tissues by using the two-parameter Burr (power-law b and scale factor l) and Nakagami models (shape factor m and scale factor $\alpha$). Parametric imaging of these parameters was created using a sliding kernel method sweeping regions of interest with a kernel size of 10 wavelengths from a phantom study. Results showed that the difference between gingiva and alveolar mucosa were statistically significant using Burr and Nakagami parameters ($p-value<0.0001$). The Burr b and Nakagami m were higher in gingiva while the Burr l and Nakagami {$\alpha$} were higher in alveolar mucosa. Findings from QUS analyses agreed with observation from histology that showed denser stains for gingiva. Linear classifications of these tissues using 2D parameter spaces of the Burr and Nakagami models resulted in a segmentation accuracy of 93.51\% and 90.91\%, respectively. We propose that QUS holds promising potentials as an augmented tool for disease diagnosis in periodontology.

3.
Forensic Sci Int ; 360: 112062, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38781837

ABSTRACT

The use of controlled precursors for reaction optimisation is not always practical. One approach to limiting the use of controlled substances is to instead use 'model compounds'. Herein, two model compounds resembling norephedrine and ephedrine were selected based on their (i) structural similarity (i.e., presence of key functional groups) and (ii) availability from multiple suppliers without restriction. Model compounds 2-amino-1-phenylethanol and 2-(methylamino)-1-phenylethanol (halostachine), were compared to norephedrine and pseudoephedrine by firstly subjecting them to transformations known in the synthesis of amphetamines, and secondly, comparing the compounds using colourimetric spot tests, FTIR and NMR.

4.
J Periodontol ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38742564

ABSTRACT

BACKGROUND: Bone readiness for implant placement is typically evaluated by bone quality/density on 2-dimensional radiographs and cone beam computed tomography at an arbitrary time between 3 and 6 months after tooth extraction and alveolar ridge preservation (ARP). The aim of this study is to investigate if high-frequency ultrasound (US) can classify bone readiness in humans, using micro-CT as a reference standard to obtain bone mineral density (BMD) and bone volume fraction (BVTV) of healed sockets receiving ARP in humans. METHODS: A total of 27 bone cores were harvested during the implant surgery from 24 patients who received prior extraction with ARP. US images were taken immediately before the implant surgery at a site co-registered with the tissue biopsy collection location, made possible with a specially designed guide, and then classified into 3 tiers using B-mode image criteria (1) favorable, (2) questionable, and (3) unfavorable. Bone mineral density (hydroxyapatite) and BVTV were obtained from micro-CT as the gold standard. RESULTS: Hydroxyapatite and BVTV were evaluated within the projected US slice plane and thresholded to favorable (>2200 mg/cm3; >0.45 mm3/mm3), questionable (1500-2200 mg/cm3; 0.4-0.45 mm3/mm3), and unfavorable (<1500 mg/cm3; <0.4 mm3/mm3). The present US B-mode classification inversely scales with BMD. Regression analysis showed a significant relation between US classification and BMD as well as BVTV. T-test analysis demonstrated a significant correlation between US reader scores and the gold standard. When comparing Tier 1 with the combination of Tier 2 and 3, US achieved a significant group differentiation relative to mean BMD (p = 0.004, true positive 66.7%, false positive 0%, true negative 100%, false negative 33.3%, specificity 100%, sensitivity 66.7%, receiver operating characteristics area under the curve 0.86). Similar results were found between US-derived tiers and BVTV. CONCLUSION: Preliminary data suggest US could classify jawbone surface quality that correlates with BMD/BVTV and serve as the basis for future development of US-based socket healing evaluation after ARP.

6.
EJNMMI Res ; 14(1): 41, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38632153

ABSTRACT

BACKGROUND: Mitochondrial function plays a key role in regulating neurotransmission and may contribute to general intelligence. Mitochondrial complex I (MC-I) is the largest enzyme of the respiratory chain. Recently, it has become possible to measure MC-I distribution in vivo, using a novel positron emission tomography tracer [18F]BCPP-EF, thus, we set out to investigate the association between MC-I distribution and measures of cognitive function in the living healthy brain. RESULTS: Analyses were performed in a voxel-wise manner and identified significant associations between [18F]BCPP-EF DVRCS-1 in the precentral gyrus and parietal lobes and WAIS-IV predicted IQ, WAIS-IV arithmetic and WAIS-IV symbol-digit substitution scores (voxel-wise Pearson's correlation coefficients transformed to Z-scores, thresholded at Z = 2.3 family-wise cluster correction at p < 0.05, n = 16). Arithmetic scores were associated with middle frontal and post-central gyri tracer uptake, symbol-digit substitution scores were associated with precentral gyrus tracer uptake. RAVLT recognition scores were associated with [18F]BCPP-EF DVRCS-1 in the middle frontal gyrus, post-central gyrus, occipital and parietal regions (n = 20). CONCLUSIONS: Taken together, our findings support the theory that mitochondrial function may contribute to general intelligence and indicate that interindividual differences in MC-I should be a key consideration for research into mitochondrial dysfunction in conditions with cognitive impairment.

7.
Eur Neuropsychopharmacol ; 84: 35-47, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38657339

ABSTRACT

Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia (TRS). Although a large body of evidence supports its efficacy and favorable risk-benefit ratio in individuals who have failed two or more antipsychotics, clozapine remains underused. However, variations in clozapine utilization across geographic and clinical settings suggest that it could be possible to improve its use. In this narrative review and expert opinion, we summarized information available in the literature on the mechanisms of action, effectiveness, and potential adverse events of clozapine. We identified barriers leading to discouragement in clozapine prescription internationally, and we proposed practical solutions to overcome each barrier. One of the main obstacles identified to the use of clozapine is the lack of appropriate training for physicians: we highlighted the need to develop specific professional programs to train clinicians, both practicing and in residency, on the relevance and efficacy of clozapine in TRS treatment, initiation, maintenance, and management of potential adverse events. This approach would facilitate physicians to identify eligible patients and offer clozapine as a treatment option in the early stage of the disease. We also noted that increasing awareness of the benefits of clozapine among healthcare professionals, people with TRS, and their caregivers can help promote the use of clozapine. Educational material, such as leaflets or videos, could be developed and distributed to achieve this goal. The information provided in this article may be useful to improve disease burden and support healthcare professionals, patients, and caregivers navigating the complex pathways to TRS management.

8.
J Clin Med ; 13(8)2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38673627

ABSTRACT

We would like to comment on the systemic review article published in the Journal of Clinical Medicine by Barbieri et al [...].

9.
Nat Commun ; 15(1): 3342, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38688917

ABSTRACT

The polygenic architecture of schizophrenia implicates several molecular pathways involved in synaptic function. However, it is unclear how polygenic risk funnels through these pathways to translate into syndromic illness. Using tensor decomposition, we analyze gene co-expression in the caudate nucleus, hippocampus, and dorsolateral prefrontal cortex of post-mortem brain samples from 358 individuals. We identify a set of genes predominantly expressed in the caudate nucleus and associated with both clinical state and genetic risk for schizophrenia that shows dopaminergic selectivity. A higher polygenic risk score for schizophrenia parsed by this set of genes predicts greater dopamine synthesis in the striatum and greater striatal activation during reward anticipation. These results translate dopamine-linked genetic risk variation into in vivo neurochemical and hemodynamic phenotypes in the striatum that have long been implicated in the pathophysiology of schizophrenia.


Subject(s)
Corpus Striatum , Dopamine , Schizophrenia , Humans , Dopamine/metabolism , Dopamine/biosynthesis , Schizophrenia/genetics , Schizophrenia/metabolism , Male , Female , Corpus Striatum/metabolism , Adult , Caudate Nucleus/metabolism , Signal Transduction , Middle Aged , Hippocampus/metabolism , Multifactorial Inheritance , Genetic Predisposition to Disease , Dorsolateral Prefrontal Cortex/metabolism , Reward
11.
Lancet Gastroenterol Hepatol ; 9(6): 577-582, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38428439

ABSTRACT

The American, European, and Latin American liver societies have proposed a change in the nomenclature we use to describe alcohol-related liver disease and non-alcoholic fatty liver disease. Additionally, a term encompassing both is now advocated: steatotic liver disease, which includes metabolic dysfunction associated steatotic liver disease (MASLD) and MASLD with greater alcohol consumption (MetALD). These classifications offer increased relevance for clinicians, researchers, and patients alike. In this Viewpoint, we discuss the basis for this nomenclature shift and how it was developed. We also explore the challenges that will be faced in the adoption of such change. The proposed change seeks to banish stigma associated with phrasing such as alcoholic and fatty. However stigma, particularly related to the term fatty, is culturally nuanced, and reflects different entities depending on location. If such a change is internationally accepted, there will be wide-reaching effects on practitioners in primary care and metabolic medicine, and on patients. We discuss those effects and the opportunities the nomenclature change could offer, particularly for patients with alcohol and metabolic risk factors who represent a group previously ignored by clinical trials.


Subject(s)
Terminology as Topic , Humans , Fatty Liver/classification , Non-alcoholic Fatty Liver Disease/classification , Gastroenterology , Fatty Liver, Alcoholic/classification , Risk Factors , Social Stigma
12.
Ultrasound Med Biol ; 50(6): 817-824, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38429202

ABSTRACT

BACKGROUND: Blood flow to the brain is a critical physiological function and is useful to monitor in critical care settings. Despite that, a surrogate is most likely measured instead of actual blood flow. Such surrogates include velocity measurements in the carotid artery and systemic blood pressure, even though true blood flow can actually be obtained using MRI and other modalities. Ultrasound is regularly used to measure blood flow and is, under certain conditions, able to provide quantitative volumetric blood flow in milliliters per minute. Unfortunately, most times the resulting flow data is not valid due to unmet assumptions (such as flow profile and angle correction). Color flow, acquired in three dimensions, has been shown to yield quantitative blood flow without any assumptions (3DVF). METHODS: Here we are testing whether color flow can perform during physiological conditions common to severe injury. Specifically, we are simulating severe traumatic brain injury (epidural hematoma) as well as hemorrhagic shock with 50% blood loss. Blood flow was measured in the carotid artery of a cohort of 7 Yorkshire mix pigs (40-60 kg) using 3DVF (4D16L, LOGIQ 9, GE HealthCare, Milwaukee, WI, USA) and compared to an invasive flow meter (TS420, Transonic Systems Inc., Ithaca, NY, USA). RESULTS: Six distinct physiological conditions were achieved: baseline, hematoma, baseline 2, hemorrhagic shock, hemorrhagic shock plus hematoma, and post-hemorrhage resuscitation. Mean cerebral oxygen extraction ratio varied from 40.6% ± 13.0% of baseline to a peak of 68.4% ± 15.6% during hemorrhagic shock. On average 3DVF estimated blood flow with a bias of -9.6% (-14.3% root mean squared error) relative to the invasive flow meter. No significant flow estimation error was detected during phases of flow reversal, that was seen in the carotid artery during traumatic conditions. The invasive flow meter showed a median error of -11.5% to 39.7%. CONCLUSIONS: Results suggest that absolute volumetric carotid blood flow to the brain can be obtained and potentially become a more specific biomarker related to cerebral hemodynamics than current surrogate markers.


Subject(s)
Brain , Cerebrovascular Circulation , Hemodynamics , Cerebrovascular Circulation/physiology , Animals , Swine , Hemodynamics/physiology , Brain/diagnostic imaging , Brain/blood supply , Brain/metabolism , Blood Flow Velocity/physiology , Brain Injuries, Traumatic/diagnostic imaging , Brain Injuries, Traumatic/physiopathology , Brain Injuries, Traumatic/metabolism
13.
Clin Res Cardiol ; 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38466346

ABSTRACT

BACKGROUND: Previous reports suggest septal hypertrophy with an interventricular septum depth (IVSD) ≥ 14 mm may adversely affect outcomes after transcatheter aortic valve implantation (TAVI) due to suboptimal valve placement, valve migration, or residual increased LVOT pressure gradients. AIMS: This analysis investigates the impact of interventricular septal hypertrophy on acute outcomes after TAVI. METHODS: Between 2009 and 2021, 1033 consecutive patients (55.8% male, 80.5 ± 6.7 years, EuroSCORE II 6.3 ± 6.5%) with documented IVSD underwent TAVI at our center and were included for analysis. Baseline, periprocedural, and 30-day outcome parameters of patients with normal IVSD (< 14 mm; group 1) and increased IVSD (≥ 14 mm; group 2) were compared. Data were retrospectively analyzed according to updated Valve Academic Research Consortium-3 (VARC-3) definitions. Comparison of outcome parameters was adjusted for baseline differences between groups using logistic and linear regression analyses. RESULTS: Of 1033 patients, 585 and 448 patients were allocated to groups 1 and 2, respectively. There was no significant difference between groups regarding transfemoral access rate (82.6% (n = 478) vs. 86.0% (n = 381), p = 0.157). Postprocedural mean transvalvular pressure gradient was significantly increased in group 2 (group 1, 7.8 ± 4.1 mmHg, vs. group 2, 8.9 ± 4.9 mmHg, p = 0.046). Despite this finding, there was no significant difference between groups regarding the rates of VARC-3 adjudicated composite endpoint device success (90.0% (n = 522) vs. 87.6% (n = 388), p = 0.538) or technical success (92.6% (n = 542) vs. 92.6% (n = 415), p = 0.639). Moreover, the groups showed no significant differences regarding the rates of paravalvular leakage ≥ moderate (3.1% (n = 14) vs. 2.6% (n = 9), p = 0.993), postprocedural permanent pacemaker implantation (13.4% (n = 77) vs. 13.8% (n = 61), p = 0.778), or 30-day mortality (5.1% (n = 30) vs. 4.5% (n = 20), p = 0.758). CONCLUSION: Although transvalvular mean pressure gradients were significantly higher in patients with increased IVSD after TAVI, acute outcomes were comparable between groups suggesting no early impact of adverse hemodynamics due to elevated IVSD. However, how these differences in hemodynamic findings may affect mid- and long-term outcomes, especially in terms of valve durability, needs to be evaluated in further investigations.

14.
Expert Opin Ther Targets ; 28(3): 179-191, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38487923

ABSTRACT

INTRODUCTION: Morbidity and mortality from liver disease continues to rise worldwide. There are currently limited curative treatments for patients with liver failure syndromes, encompassing acute liver failure and decompensated cirrhosis states, outside of transplantation. Whilst there have been improvements in therapeutic options for patients with hepatocellular carcinoma (HCC), there remain challenges necessitating novel therapeutic agents. microRNA have long been seen as potential therapeutic targets but there has been limited clinical translation. AREAS COVERED: We will discuss the limitations of conventional non-transplant management of patients with liver failure syndromes and HCC. We will provide an overview of microRNA and the challenges in developing and delivering microRNA-based therapeutic agents. We will finally provide an overview of microRNA-based therapeutic agents which have progressed to clinical trials. EXPERT OPINION: microRNA have great potential to be developed into therapeutic agents due to their association with critical biological processes which govern health and disease. Utilizing microRNA sponges to target multiple microRNA associated with specific biological processes may improve their therapeutic efficacy. However, there needs to be significant improvements in delivery systems to ensure the safe delivery of microRNA to target sites and minimize systemic distribution. This currently significantly impacts the clinical translation of microRNA-based therapeutic agents.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Humans , MicroRNAs/genetics , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/therapy , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Animals , Liver Failure/therapy , Liver Failure/physiopathology , Liver Failure, Acute/therapy , Liver Failure, Acute/physiopathology , Liver Cirrhosis/therapy , Drug Delivery Systems , Molecular Targeted Therapy
15.
BJPsych Open ; 10(2): e49, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38362901

ABSTRACT

This prospective study examines the immune response to SARS-CoV-2 vaccination in patients with psychotic disorders compared with healthy volunteers. Participants were recruited naturalistically as part of the UK's COVID-19 vaccination programme. Prior to receiving their first COVID-19 vaccine, blood samples were provided by participants to examine anti-SARS-CoV-2 immunoglobulins (IgG) at baseline, followed by a repeat assay 1 month after receiving their first vaccine to assess vaccine response. The increase of IgG levels from baseline to 1 month post-vaccination was significantly lower in patients compared with controls, supporting evidence of impaired vaccine response in people with psychotic disorders. When excluding patients treated with clozapine from the analysis, this difference was no longer significant, suggesting that effects may be particularly marked in people taking clozapine.

16.
Open Biol ; 14(2): 230414, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38320620

ABSTRACT

In this work, we have developed an expansion microscopy (ExM) protocol that combines ExM with photoactivated localization microscopy (ExPALM) for yeast cell imaging, and report a robust protocol for single-molecule and expansion microscopy of fission yeast, abbreviated as SExY. Our optimized SExY protocol retains about 50% of the fluorescent protein signal, doubling the amount obtained compared to the original protein retention ExM (proExM) protocol. It allows for a fivefold, highly isotropic expansion of fission yeast cells, which we carefully controlled while optimizing protein yield. We demonstrate the SExY method on several exemplary molecular targets and explicitly introduce low-abundant protein targets (e.g. nuclear proteins such as cbp1 and mis16, and the centromere-specific histone protein cnp1). The SExY protocol optimizations increasing protein yield could be beneficial for many studies, when targeting low abundance proteins, or for studies that rely on genetic labelling for various reasons (e.g. for proteins that cannot be easily targeted by extrinsic staining or in case artefacts introduced by unspecific staining interfere with data quality).


Subject(s)
Schizosaccharomyces pombe Proteins , Schizosaccharomyces , Schizosaccharomyces/genetics , Schizosaccharomyces pombe Proteins/genetics , Microscopy , Carrier Proteins/metabolism , Centromere/metabolism , Chromosomal Proteins, Non-Histone/genetics
17.
Cureus ; 16(1): e51892, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38333474

ABSTRACT

Hay-holes are a design feature in many traditionally built barns that serve as a portal through which stored hay is passed to the lower level where animals are fed. Unfortunately, children sometimes fall through the hay-hole to the concrete or packed earth below. Available data on the frequency and types of hay-hole injuries is limited. The purpose of this study was to better characterize the resultant injuries and identify prognostic factors that predict outcomes from them. We performed a retrospective review of 53 children admitted to the Penn State Hershey Children's Hospital at the Penn State Hershey Medical Center with injuries due to a fall through a hay-hole over 15 years. Compared to urban trauma, hay-hole falls more frequently involve younger children and craniofacial injuries. Although they may result in significant injuries, they are rarely fatal. Greater fall height is associated with longer length of stay (LOS) but not with a greater frequency of intubation, intracranial hemorrhage, or skull fracture. A re-examination of barn design may help to reduce the frequency of this injury type.

18.
Front Neurol ; 15: 1301003, 2024.
Article in English | MEDLINE | ID: mdl-38375465

ABSTRACT

Introduction: Degenerative cervical myelopathy (DCM) is a form of chronic spinal cord injury, with a natural history of potential for progression over time. Whilst driven by mechanical stress on the spinal cord from degenerative and congenital pathology, the neurological phenotype of DCM is likely to be modified by multiple systemic factors. The role of metabolic factors is therefore of interest, particularly given that ischaemia is considered a key pathological mechanism of spinal cord injury. The objective was therefore to synthesise current evidence on the effect of metabolism on DCM susceptibility, severity, and surgical outcomes. Methods: A systematic review in MEDLINE and Embase was conducted following PRISMA guidelines. Full-text papers in English, with a focus on DCM and metabolism, including diabetes, cardiovascular disease, anaemia, and lipid profile, were eligible for inclusion. Risk of methodological bias was assessed using the Joanna Briggs Institute (JBI) critical assessment tools. Quality assessments were performed using the GRADE assessment tool. Patient demographics, metabolic factors and the relationships between metabolism and spinal cord disease, spinal column disease and post-operative outcomes were assessed. Results: In total, 8,523 papers were identified, of which 57 met criteria for inclusion in the final analysis. A total of 91% (52/57) of included papers assessed the effects of diabetes in relation to DCM, of which 85% (44/52) reported an association with poor surgical outcomes; 42% of papers (24/57) discussed the association between cardiovascular health and DCM, of which 88% (21/24) reported a significant association. Overall, DCM patients with diabetes or cardiovascular disease experienced greater perioperative morbidity and poorer neurological recovery. They were also more likely to have comorbidities such as obesity and hyperlipidaemia. Conclusion: Metabolic factors appear to be associated with surgical outcomes in DCM. However, evidence for a more specific role in DCM susceptibility and severity is uncertain. The pathophysiology and natural history of DCM are critical research priorities; the role of metabolism is therefore a key area for future research focus. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021268814.

19.
Int J Neuropsychopharmacol ; 27(3)2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38373256

ABSTRACT

BACKGROUND: The histamine-3 receptor (H3R) may have a role in cognitive processes through its action as a presynaptic heteroreceptor inhibiting the release of glutamate in the brain. To explore this, we examined anterior cingulate cortex (ACC) and striatum H3R availability in patients with schizophrenia and characterized their relationships with glutamate levels in corresponding brain regions. METHODS: We employed a cross-sectional study, recruiting 12 patients with schizophrenia and 12 healthy volunteers. Participants underwent positron emission tomography using the H3R-specific radio ligand [11C]MK-8278, followed by proton magnetic resonance spectroscopy to measure glutamate levels, recorded as Glu and Glx. Based on existing literature, the ACC and striatum were selected as regions of interest. RESULTS: We found significant inverse relationships between tracer uptake and Glu (r = -0.66, P = .02) and Glx (r = -0.62, P = .04) levels in the ACC of patients, which were absent in healthy volunteers (Glu: r = -0.19, P = .56, Glx: r = 0.10, P = .75). We also found a significant difference in striatal (F1,20 = 6.00, P = .02) and ACC (F1,19 = 4.75, P = .04) Glx levels between groups. CONCLUSIONS: These results provide evidence of a regionally specific relationship between H3Rs and glutamate levels, which builds on existing preclinical literature. Our findings add to a growing literature indicating H3Rs may be a promising treatment target in schizophrenia, particularly for cognitive impairment, which has been associated with altered glutamate signaling.


Subject(s)
Glutamic Acid , Schizophrenia , Humans , Histamine , Proton Magnetic Resonance Spectroscopy/methods , Schizophrenia/diagnostic imaging , Schizophrenia/drug therapy , Cross-Sectional Studies , Brain/diagnostic imaging , Positron-Emission Tomography , Gyrus Cinguli , Glutamine
20.
Cornea ; 43(4): 531-533, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38166178

ABSTRACT

PURPOSE: The aim of this study was to present the surgical management of a patient with ocular copper deposition associated with monoclonal gammopathy of undetermined significance (MGUS). METHODS: This is a case report of a 44-year-old man with MGUS who presented to us with bilateral diffuse deposition of copper in the cornea and lens. RESULTS: Despite initiating systemic therapy for MGUS, no corneal clearing was observed. A decision was made to proceed with cataract extraction in the left eye given worsening vision. Despite trypan blue staining and a central descemetorhexis, visualization remained too poor to complete phacoemulsification. Pars plana lensectomy and vitrectomy to remove the residual lens material and placement of a posterior chamber intraocular lens in the sulcus with endoillumination was subsequently performed. As vision in the left eye steadily improved postoperatively, cataract surgery was then performed in the right eye. With use of trypan blue, creation of a 6-mm central descemetorhexis, and a retinal light pipe for endoillumination anteriorly to augment visualization, capsulorhexis, phacoemulsification, and insertion of intraocular lens in the bag were completed without difficulty. The patient's vision improved at subsequent follow-ups, reaching a final best-corrected visual acuity of 20/20-1 in the right eye and 20/25-1 in the left eye. CONCLUSIONS: Ocular copper deposition is a rare manifestation of MGUS. Cataract extraction is challenging, often requiring advanced techniques. Endoillumination is useful to improve visualization through the dense corneal copper deposition.


Subject(s)
Cataract , Monoclonal Gammopathy of Undetermined Significance , Phacoemulsification , Male , Humans , Adult , Copper , Cataract/complications , Monoclonal Gammopathy of Undetermined Significance/complications , Trypan Blue , Visual Acuity , Phacoemulsification/methods , Vitrectomy/methods
SELECTION OF CITATIONS
SEARCH DETAIL
...