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1.
BMC Geriatr ; 24(1): 638, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39085777

ABSTRACT

BACKGROUND: The ageing process is characterized by a change of body composition with an increase of fat mass and a reduction of muscle mass. Above a certain threshold these alterations configure a condition named sarcopenic obesity (SO). SO is associated with physical frailty in Asian and Brazilian populations. SO impacts on physical frailty in other ethnic groups but its influence on general frailty which is multidimensional and includes cognitive, social and physical factors, remain insufficiently explored in the Italian population. METHODS: Frailty was measured in community dwelling Italian older adults enrolled in the FRASNET study with the frailty index (FI). The FI quantifies frailty as the ratio of the number of present health deficits to the total number of health deficits considered. Regression analyses were performed to assess the association between body composition categories and frailty. Classification and regression tree models were run to evaluate the frailty predictors. RESULTS: One Thousand One Hundred Fourteen participants of the FRASNET study were included in the present analysis. The sample was composed for the 60.5% by females and its median age was 72 years. The median FI score was 0.11 (IQR 0.07-0.20); 234 individuals (21%) were frail (FI ≥ 0.25). SO (B 0.074, 95% C.I. 0.05-0.1, p < 0.001) and pre-sarcopenia (without obesity B 0.03, 95% C.I, 0.007-0.044, p < 0.001, with obesity B 0.11, 95% C.I. 0.05-0.16, p < 0.001) were associated with frailty. Fat mass percentage predicted frailty in people aged 65-70 years whereas, muscle strength predicted general frailty in people aged 70-81 years. CONCLUSION: Pre-sarcopenia and SO represent potentially treatable predictors of frailty.


Subject(s)
Frail Elderly , Frailty , Independent Living , Obesity , Sarcopenia , Humans , Female , Male , Aged , Sarcopenia/epidemiology , Sarcopenia/diagnosis , Sarcopenia/physiopathology , Frailty/epidemiology , Frailty/diagnosis , Italy/epidemiology , Obesity/epidemiology , Independent Living/trends , Aged, 80 and over , Geriatric Assessment/methods , Body Composition/physiology
2.
Nat Commun ; 15(1): 6270, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39054318

ABSTRACT

The prefusion conformation of human metapneumovirus fusion protein (hMPV Pre-F) is critical for eliciting the most potent neutralizing antibodies and is the preferred immunogen for an efficacious vaccine against hMPV respiratory infections. Here we show that an additional cleavage event in the F protein allows closure and correct folding of the trimer. We therefore engineered the F protein to undergo double cleavage, which enabled screening for Pre-F stabilizing substitutions at the natively folded protomer interfaces. To identify these substitutions, we developed an AI convolutional classifier that successfully predicts complex polar interactions often overlooked by physics-based methods and visual inspection. The combination of additional processing, stabilization of interface regions and stabilization of the membrane-proximal stem, resulted in a Pre-F protein vaccine candidate without the need for a heterologous trimerization domain that exhibited high expression yields and thermostability. Cryo-EM analysis shows the complete ectodomain structure, including the stem, and a specific interaction of the newly identified cleaved C-terminus with the adjacent protomer. Importantly, the protein induces high and cross-neutralizing antibody responses resulting in near complete protection against hMPV challenge in cotton rats, making the highly stable, double-cleaved hMPV Pre-F trimer an attractive vaccine candidate.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Metapneumovirus , Viral Fusion Proteins , Viral Vaccines , Metapneumovirus/immunology , Metapneumovirus/genetics , Animals , Antibodies, Neutralizing/immunology , Humans , Antibodies, Viral/immunology , Viral Fusion Proteins/immunology , Viral Fusion Proteins/chemistry , Viral Fusion Proteins/genetics , Viral Vaccines/immunology , Paramyxoviridae Infections/prevention & control , Paramyxoviridae Infections/immunology , Cryoelectron Microscopy , Protein Engineering/methods , Sigmodontinae , Female , Protein Multimerization , Models, Molecular
3.
Sci Rep ; 14(1): 16119, 2024 07 12.
Article in English | MEDLINE | ID: mdl-38997256

ABSTRACT

Pre-existing mental disorders are considered a risk factor for severe COVID-19 outcomes, possibly because of higher vascular burden. Moreover, an unconventional platelet activation characterizes COVID-19 and contributes to inflammatory and thrombotic manifestations. In the light of the inflammation theory of mental disorders, we hypothesized that patients with mental disorders could be sensitive to the SARS-CoV-2 elicited platelet activation. We investigated platelet activation in 141 COVID-19 survivors at one month after clearance of the virus, comparing subjects with or without an established pre-existing diagnosis of mental disorder according to the DSM-5. We found that platelets from patients with a positive history of psychiatric disorder underwent unconventional activation more frequently than conventional activation or no activation at all. Such preferential activation was not detected when platelets from patients without a previous psychiatric diagnosis were studied. When testing the effects of age, sex, and psychiatric history on the platelet activation, GLZM multivariate analysis confirmed the significant effect of diagnosis only. These findings suggest a preferential platelet activation during acute COVID-19 in patients with a pre-existing psychiatric disorder, mediated by mechanisms associated with thromboinflammation. This event could have contributed to the higher risk of severe outcome in the psychiatric population.


Subject(s)
COVID-19 , Mental Disorders , Platelet Activation , SARS-CoV-2 , Survivors , Humans , COVID-19/blood , COVID-19/complications , COVID-19/psychology , Male , Female , Middle Aged , Adult , SARS-CoV-2/isolation & purification , Aged , Blood Platelets , Risk Factors
5.
Chest ; 165(5): e137-e142, 2024 May.
Article in English | MEDLINE | ID: mdl-38724152

ABSTRACT

CASE PRESENTATION: A newborn girl presented to the hospital on the first day of life because of respiratory failure. She was born at home at 37 weeks' gestation with minimal prenatal care and was found to be small for gestational age. The patient was found to have partial sternal agenesis and sternal cleft, cutis aplasia, left facial hemangioma, micrognathia, wide-spaced nipples, and low-set ears. The mother's and baby's urine toxicology screening were positive for amphetamines. Chest radiographs on admission showed bilateral hazy opacities. CT scan of the chest showed an absent sternum with midline chest wall concavity. The patient was monitored preoperatively in the cardiac ICU for risks of arrythmia, respiratory failure, altered cardiac output, and acute cardiopulmonary decompensation.


Subject(s)
Sternum , Humans , Female , Sternum/abnormalities , Sternum/diagnostic imaging , Infant, Newborn , Abnormalities, Multiple/diagnosis , Tomography, X-Ray Computed , Hemangioma/diagnosis , Hemangioma/complications , Hemangioma/diagnostic imaging , Musculoskeletal Abnormalities/diagnostic imaging , Musculoskeletal Abnormalities/diagnosis
6.
CNS Drugs ; 38(6): 459-472, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38658499

ABSTRACT

BACKGROUND AND OBJECTIVES: Clinical manifestations of coronavirus disease 2019 (COVID-19) often persist after acute disease resolution. Underlying molecular mechanisms are unclear. The objective of this original article was to longitudinally measure plasma levels of markers of the innate immune response to investigate whether they associate with and predict post-COVID symptomatology. METHODS: Adult patients with previous severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the first pandemic wave who underwent the 6-month multidisciplinary follow-up were included. Plasma levels of pentraxin 3 (PTX3), the complement components C3a and C5a, and chitinase-3 like-protein-1 (CHI3L1) were measured at hospital admission during acute disease (baseline) and at 1 and 6 months after hospital discharge. Associations with post-COVID-19 sequelae at 6 months were investigated using descriptive statistic and multiple regression models. RESULTS: Ninety-four COVID-19 patients were included. Baseline PTX3, C5a, C3a, and CHI3L1 did not predict post-COVID-19 sequelae. The extent of the reduction of PTX3 over time (delta PTX3) was associated with lower depressive and anxiety symptoms at 6 months (both p < 0.05). When entering sex, age, need for intensive care unit or non-invasive ventilation during hospital stay, psychiatric history, and baseline PTX3 as nuisance covariates into a generalized linear model (GLM), the difference between baseline and 6-month PTX3 levels (delta PTX3) significantly predicted depression (χ2 = 4.66, p = 0.031) and anxiety (χ2 = 4.68, p = 0.031) at 6 months. No differences in PTX3 levels or PTX3 delta were found in patients with or without persistent or new-onset other COVID-19 symptoms or signs at 6 months. Plasma levels of C3a, C5a, and CHI3L1 did not correlate with PTX3 levels at either time point and failed to associate with residual or de novo respiratory or systemic clinical manifestations of the disease at 6 months. CONCLUSIONS: A lower reduction of plasma PTX3 after acute COVID-19 associates with the presence of depression and anxiety, suggesting an involvement of inflammation in post-COVID-19 psychopathology and a potential role of PTX3 as a biomarker.


Subject(s)
Anxiety , Biomarkers , C-Reactive Protein , COVID-19 , Post-Acute COVID-19 Syndrome , Serum Amyloid P-Component , Humans , C-Reactive Protein/metabolism , C-Reactive Protein/analysis , Serum Amyloid P-Component/metabolism , COVID-19/blood , COVID-19/complications , Male , Female , Middle Aged , Anxiety/blood , Anxiety/epidemiology , Aged , Biomarkers/blood , Depression/blood , Adult , Longitudinal Studies , Follow-Up Studies
7.
Article in English | MEDLINE | ID: mdl-38546963

ABSTRACT

Pentraxin 3 (PTX3) is an acute phase protein produced in various tissues in response to microbial and sterile stimuli, which regulates the inflammation outcomes. PTX3 has not been investigated in myocarditis. Our aim was to assess circulating and cardiac tissue expression of PTX3 in 55 patients with myocarditis proven by magnetic resonance and/or endomyocardial biopsy. A major proportion of patients with myocarditis displayed significantly increased plasma PTX3 levels as compared with controls (26/30 vs. 0/10), with higher diagnostic yield than conventional biomarkers in the study group. Cardiac tissue analysis revealed PTX3 expression in all patients (40/40), with viral myocarditis exhibiting higher signal intensity than autoimmune myocarditis, and with a predominant localization in cardiomyocytes. Abnormal plasma PTX3 was associated with systolic dysfunction and heart failure at presentation. Interestingly, patients who recovered by 12 months had higher baseline PTX3 levels. Our preliminary data support the potential use of PTX3 as a biomarker in myocarditis.

8.
Plast Reconstr Surg Glob Open ; 12(3): e5652, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38463702

ABSTRACT

Background: The objective of this meta-analysis was to examine the effectiveness of keloid intralesional excision (KILE) in preventing recurrence. Treatment of keloids using surgical excision alone leads to high rates of recurrence. To date, there are no widely accepted guidelines for keloid treatment, and a multitude of adjunctive therapies are used to reduce recurrence. Despite these efforts, recurrence remains high. In this study, we conducted a meta-analysis of the existing literature on KILE to determine its role in recurrence reduction. Methods: A literature review using PubMed, Scopus, and Web of Science databases was performed. Two authors independently evaluated studies for eligibility. Incidence of keloid recurrence was recorded, and a comprehensive meta-analysis was performed to assess the pooled keloid recurrence rate, as well as the effect of additional therapies. Results: Twenty-two studies evaluating intralesional excision of 608 keloids were included in the study. Average time to follow-up was 19.2 months (range 6-35 months). A meta-analysis of proportions was conducted, demonstrating a pooled recurrence rate of 13% (95% confidence interval, 9%-16%). There was no evidence that using therapies in addition to KILE had a significant effect on the overall pooled recurrence rate. Conclusions: A meta-analysis of 608 keloids shows that KILE is an effective technique in preventing keloid recurrence, with a pooled recurrence rate of 13% compared with previously reported rates of 45%-100% after complete excision. Although there are no standard guidelines for keloid treatment, our meta-analysis shows that KILE is promising in recurrence reduction.

9.
Environ Manage ; 73(5): 913-919, 2024 May.
Article in English | MEDLINE | ID: mdl-38424176

ABSTRACT

Brazil is among the main contributors to global biodiversity, which, in turn, provides extensive ecosystem services. Agriculture is an activity that benefits greatly from these ecosystem services, but at the same time is degrading aquatic and terrestrial ecosystems and eroding Brazilian biodiversity. This conflict is growing, as emerging unsustainable legislative proposals that will benefit the agricultural sector are likely to accelerate the decline of biodiversity. One such initiative (Bill 1282/2019) would change Brazil's "Forest Code" (Law 12,651/2012) to facilitate construction of irrigation dams in Permanent Preservation Areas, a category that includes strips (with or without vegetation) along the edges of watercourses. Two other similar bills are advancing through committees in the Chamber of Deputies. Here we provide details of these three bills and discuss their consequences for Brazil's biodiversity if they are approved. Expected negative impacts with changes in the legislation include: increased deforestation; siltation; habitat fragmentation; introduction of non-native species; reduction in the availability of aquatic habitats; and changes in biogeochemical process. These proposals jeopardize biodiversity and may compromise the negotiations for an agreement between Mercosur and the European Union.


Subject(s)
Conservation of Natural Resources , Ecosystem , Brazil , Biodiversity , Forests , Agriculture
10.
Cureus ; 16(1): e52391, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38361711

ABSTRACT

Primary spontaneous pneumothorax occurs in patients without apparent clinical lung disease, with a higher incidence in tall, thin males between the ages of 10 and 30. Tension pneumothorax is a life-threatening condition that can develop within minutes due to progressive air accumulation in the pleural space; mechanical pressure can lead to significant cardiorespiratory compromise. Tobacco association with a higher incidence of spontaneous pneumothorax has been well documented, but marijuana and spontaneous pneumothorax connection has not been well studied. However, it has been observed that patients who use marijuana and tobacco simultaneously have a higher incidence of spontaneous tension and larger pneumothoraces, as well as longer postoperative stay and higher recurrence than cigarette-only users. We present a case of a 26-year-old young male with a history only significant for excessive tobacco and marijuana smoking who developed multiple recurrent spontaneous pneumothorax and had to undergo right-sided video-assisted thoracoscopic surgery (VATS) with minimally invasive thoracotomy and had a prolonged hospital stay. With our case report, we hope to add to the evidence the effects of combined marijuana and tobacco smoking on bullous lung disease and pneumothorax while emphasizing the importance of conducting a detailed substance use history in patients with spontaneous pneumothorax.

11.
Clin Ter ; 175(1): 47-56, 2024.
Article in English | MEDLINE | ID: mdl-38358477

ABSTRACT

Abstract: Oxygen is essential for human life. However, it could cause damaging effects on biological systems causing oxidative stress. Oxidative stress defined as "an alteration in the pro-oxidant-antioxidant balance in favor of the former that leads to potential damage" is characterized by the release of Reactive Oxygen Species (ROS). Oxidative stress is now recognized to play a central role in the pathophysiology of many different disorders, including complications of pregnancy such as placental pathology, PreEclampsia (PE), Intrauterine Growth Restriction (IUGR), gestational diabetes, and miscarriage. This narrative review aims to summarize pieces of evidence about the role of oxidative stress in the pathophysiology of the main obstetric complications with par-ticular interest in the neglected role of alcohol abuse.


Subject(s)
Alcoholism , Pregnancy , Female , Humans , Alcoholism/complications , Placenta , Ethanol , Oxidative Stress , Reactive Oxygen Species
12.
Nanomaterials (Basel) ; 14(4)2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38392705

ABSTRACT

Hybrid perovskites, materials composed of metals and organic substances in their structure, have emerged as potential materials for the new generation of photovoltaic cells due to a unique combination of optical, excitonic and electrical properties. Inspired by sensitization techniques on TiO2 substrates (DSSC), CH3NH3PbBr3 and CH3NH3PbI3 perovskites were studied as a light-absorbing layer as well as an electron-hole pair generator. Photovoltaic cells based on per-ovskites have electron and hole transport layers (ETL and HTL, respectively), separated by an ac-tive layer composed of perovskite itself. Major advances subsequently came in the preparation methods of these devices and the development of different architectures, which resulted in an efficiency exceeding 23% in less than 10 years. Problems with stability are the main barrier to the large-scale production of hybrid perovskites. Partially or fully inorganic perovskites appear promising to circumvent the instability problem, among which the black perovskite phase CsPbI3 (α-CsPbI3) can be highlighted. In more advanced studies, a partial or total substitution of Pb by Ge, Sn, Sb, Bi, Cu or Ti is proposed to mitigate potential toxicity problems and maintain device efficiency.

13.
Cureus ; 16(1): e52805, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38389617

ABSTRACT

A parachute mitral valve (PMV) is a congenital mitral valve anomaly diagnosed in infancy, and it can also be discovered in adults during echocardiography. Surgical management is common in infants to prevent complications from left-heart obstructions. In adults, PMV may be found independently or with other cardiac defects. Prophylactic antibiotics are recommended for certain congenital heart anomalies before dental procedures. A study suggests reconsidering guidelines to include anomalies like bicuspid aortic valve and MVP for antibiotic prophylaxis. PMV, with transvalvular blood flow turbulence, may increase the risk of infective endocarditis, as seen in a reported case with a parachute-like mitral valve. Here, we present the case of a 62-year-old female incidentally found to have a PMV during an echocardiogram.

15.
Hum Reprod ; 39(1): 139-146, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-37968233

ABSTRACT

STUDY QUESTION: What do fertility staff and patients think is bad news in fertility care? SUMMARY ANSWER: Staff and patients agree bad news is any news that makes patients less likely to achieve parenthood spontaneously or access and do successful treatment, but their appraisals of how bad the news is are differently influenced by specific news features and the context of its delivery. WHAT IS KNOWN ALREADY: Bad news is common in fertility care, but staff feel unprepared to share it and four in 10 patients react to it with unanticipated emotional or physical reactions. Research has paid much attention to how bad news should be shared, but considerably less to what news is perceived as bad, despite the fact this may dictate elements of its delivery. STUDY DESIGN, SIZE, DURATION: Two cross-sectional, online, mixed-method surveys (active 7 January-16 July 2022) were distributed to fertility staff and patients across the UK and Europe. PARTICIPANTS/MATERIALS, SETTING, METHODS: Staff inclusion criteria were being a healthcare professional working in fertility care and having experience of sharing bad news at least once a month. Patients' inclusion criteria were being adults and having had a conversation in which staff shared or explained bad news concerning their fertility care within the last 2 months. Surveys were created in English using Qualtrics, reviewed by patients and healthcare professionals, and distributed via social media, Prolific, fertility organizations, and scientific societies. Patients were asked, regarding the last time bad news were shared with them, 'What was the bad news?' and 'What other news would you consider bad news in fertility care?'. Staff were asked to 'List the three most challenging topics of bad news you share with your patients'. Staff and patient data were separately thematically analysed to produce basic codes, organized into sub-themes and themes. Themes emerging from patients' and staff data were compared and synthesized into meta themes. MAIN RESULTS AND THE ROLE OF CHANCE: Three hundred thirty-four staff accessed the survey, 286 consented, and 217 completed (65% completion rate). Three hundred forty-four patients accessed the survey, 304 consented, and 222 completed (64% completion rate). Eighty-five percent of participants were women, 62% resided in Europe, and 59% were in private care. Average staff age was 45.2 (SD = 12.0), 44% were embryologists or lab technicians, 40% were clinicians (doctors, consultants, or physicians), and 8% nurses or midwifes. Average patient age was 32.2 (SD = 6.4) and 54% had children. Staff answers originated 100 codes, 19 sub-themes and six themes. Patients' answers produced 196 codes, 34 sub-themes, and 7 themes. Staff and patient themes were integrated into three meta-themes reflecting main topics of bad news. These were Diagnosis and negative treatment events and outcomes, Inability to do (more) treatment, and Care and patient factors disrupting communication. Staff and patients agreed that some news features (uncertain, disruptive, definitive) made news more challenging but disagreed in relation to other features (e.g. unexpected/expected). Patient factors made bad news more challenging to staff (e.g. difficult emotions) and care factors made bad news more challenging to patients (e.g. disorganized care). LIMITATIONS, REASONS FOR CAUTION: Participants were self-selected, and most were women from private European clinics. Questions differed for staff and patients, focused on subjective perceptions of news, and did not measure news impact. WIDER IMPLICATIONS OF THE FINDINGS: The badness of fertility news is not only a product of the extent to which the news compromises parenthood goals but also of its features (timing, nature, number) and the context in which the news is delivered. Guidance on sharing bad news in fertility care needs to go beyond easing the process for patients to also consider staff experiences. Guidance may need to be tailored to news features and context. STUDY FUNDING/COMPETING INTEREST(S): Cardiff University funded the research. S.G., J.B., O'.H., and A.D. report funding from the Higher Education Funding Council for Wales and the European Society for Human Reproduction and Embryology (ESHRE) to develop fertiShare: a sharing bad news eLearning course for fertility care. fertiShare will be distributed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Licence (CC BY-NC-SA 4.0). No other conflicts are reported in relation to this work. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
Fertility Preservation , Physicians , Adult , Child , Humans , Female , Male , Cross-Sectional Studies , Fertility , Health Personnel
16.
Arthritis Rheumatol ; 76(5): 739-750, 2024 May.
Article in English | MEDLINE | ID: mdl-38111123

ABSTRACT

OBJECTIVE: The aim of this study was to assess whether circulating histone-specific T cells represent tools for precision medicine in systemic lupus erythematosus (SLE). METHODS: Seroprevalence of autoantibodies and HLA-DR beta (DRB) 1 profile were assessed among 185 patients with SLE and combined with bioinformatics and literature evidence to identify HLA-peptide autoepitope couples for ex vivo detection of antigen-specific T cells through flow cytometry. T cell differentiation and polarization was investigated in patients with SLE, patients with Takayasu arteritis, and healthy controls carrying HLA-DRB1*03:01 and/or HLA-DRB1*11:01. SLE Disease Activity Index 2000 and Lupus Low Disease Activity State were used to estimate disease activity and remission. RESULTS: Histone-specific CD4+ T cells were selectively detected in patients with SLE. Among patients with a history of anti-DNA antibodies, 77% had detectable histone-specific T cells, whereas 50% had lymphocytes releasing cytokines or upregulating activation markers after in vitro challenge with histone peptide antigens. Histone-specific regulatory and effector T helper (Th) 1-, Th2-, and atypical Th1/Th17 (Th1*)-polarized cells were significantly more abundant in patients with SLE with quiescent disease. In contrast, total Th1-, Th2-, and Th1*-polarized and regulatory T cells were similarly represented between patients and controls or patients with SLE with active versus quiescent disease. Histone-specific effector memory T cells accumulated in the blood of patients with quiescent SLE, whereas total effector memory T cell counts did not change. Immunosuppressants were associated with expanded CD4+ histone-specific naive T (TN) and terminally differentiated T cells. CONCLUSION: Histone-specific T cells are selectively detected in patients with SLE, and their concentration in the blood varies with disease activity, suggesting that they represent innovative tools for patient stratification and therapy.


Subject(s)
CD4-Positive T-Lymphocytes , Histones , Lupus Erythematosus, Systemic , Humans , Lupus Erythematosus, Systemic/immunology , Histones/immunology , Histones/metabolism , CD4-Positive T-Lymphocytes/immunology , Adult , Male , Female , Middle Aged , HLA-DRB1 Chains/genetics , HLA-DRB1 Chains/immunology , Autoantibodies/immunology , Antibodies, Antinuclear/immunology , Case-Control Studies , Th1 Cells/immunology
17.
Br J Pharmacol ; 180 Suppl 2: S289-S373, 2023 10.
Article in English | MEDLINE | ID: mdl-38123154

ABSTRACT

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16176. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.


Subject(s)
Databases, Pharmaceutical , Ion Channels , Humans , Ligands , Receptors, Cytoplasmic and Nuclear , Receptors, G-Protein-Coupled
18.
World J Oncol ; 14(6): 570-574, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38022410

ABSTRACT

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is an extremely rare and aggressive subtype of diffuse large B-cell lymphoma (DLBCL) that typically presents in middle-aged patients and carries a poor prognosis. Hypercalcemia presenting as the initial manifestation of the disease is rare, with only one other case reported in the literature. We report a case of a 90-year-old male who presented with progressive lethargy and unintentional weight loss. Initial workup showed elevated serum calcium of 14.6 mg/dL, corrected for albumin, and creatinine of 1.51 mg/dL. He had a suppressed iPTH of 6.3 pg/mL and normal PTHrP (13 pg/mL). Computed tomography (CT) scan of the abdomen and pelvis was performed to rule out underlying malignancy, which showed splenomegaly and enlarged retrocrural and porta hepatis lymph nodes. Bone marrow biopsy was performed to evaluate for hematological malignancy, which revealed findings diagnostic of THRLBCL. While rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the mainstay therapies for DLBCL and has been shown to have comparable outcomes in THRLBCL, there are documented concerns with its toxicity profile limiting the ability of older patients (60 years and older) to complete therapy. Our patient was treated with R-mini-CHOP, which is much better tolerated in this patient demographic. R-mini-CHOP features decreased doses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with the conventional dose of rituximab. This case discusses a rare subtype of non-Hodgkin lymphoma presenting with a unique manifestation of hypercalcemia. We highlight the importance of thorough investigation for causes of hypercalcemia as well as the efficacy and tolerability of R-mini-CHOP in this elderly patient demographic.

19.
Mol Psychiatry ; 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38036603

ABSTRACT

Choroid plexus (CP) enlargement is proposed as a marker of neuroinflammation in immune-mediated conditions. CP involvement has also been hypothesized in the immunopathology of systemic lupus erythematosus (SLE). We investigated whether CP enlargement occurs in SLE patients and its association with neuropsychiatric involvement. Additionally, we explored abnormalities along the glymphatic system in SLE patients through enlarged perivascular space (PVS) quantification. Clinical assessment and 3 Tesla brain dual-echo and T1-weighted MRI scans were obtained from 32 SLE patients and 32 sex and age-matched healthy controls (HC). CPs were manually segmented on 3D T1-weighted sequence and enlarged PVS (ePVS) were assessed through Potter's score. Compared to HC, SLE patients showed higher normalized CP volume (nCPV) (p = 0.023), with higher CP enlargement in neuropsychiatric SLE (NPSLE) (n = 12) vs. non-NPSLE (p = 0.027) patients. SLE patients with antiphospholipid antibodies (APA) positivity (n = 18) had higher nCPV compared to HC (p = 0.012), while APA negative ones did not. SLE patients also had higher Potter's score than HC (p < 0.001), with a tendency towards a higher number of basal ganglia ePVS in NPSLE vs. non-NPSLE patients. Using a random forest analysis, nCPV emerged as a significant predictor of NPSLE, together with T2-hyperintense white matter (WM) lesion volume (LV) and APA positivity (out-of-bag AUC 0.81). Our findings support the hypothesis of a role exerted by the CP in SLE physiopathology, especially in patients with neuropsychiatric involvement. The higher prevalence of ePVS in SLE patients, compared to HC, suggests the presence of glymphatic system impairment in this population.

20.
Cureus ; 15(9): e45868, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37885493

ABSTRACT

Spontaneous coronary artery dissection is a medical condition characterized by the rupture of the coronary artery wall, occurring without any external trauma. This ailment has been linked to various inflammatory, rheumatologic, and connective tissue disorders, as well as pregnancy-related changes. Despite being a less familiar cause of acute coronary syndrome, it has a considerable mortality rate, with incidence rates reaching up to 4%. This review will discuss the occurrence, pathophysiology, categorization, risk factors, diagnostic techniques, and treatment approaches related to spontaneous coronary artery dissection.

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