Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 598
Filter
1.
Mar Pollut Bull ; 206: 116721, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39024911

ABSTRACT

This study aimed at identifying the importance of the thermal framework preceding Posidonia oceanica flowering induction (autumn before the flowering year) and anthesis (summer of the flowering year). In 53 locations of Sardinia (Italy), 35 vertical shoots were collected in 2001, 2020 and 2023 and analyzed through lepidochronology, detecting past flowering events from 1991 to 2022. Flowering probability was positively correlated with autumn SST range and MHWs, stressing the importance of the temperature in the year preceding the flowering. Summer SST mean and Marine Cold Spell duration (the latter emerged as a novel outcome) also positively influenced flowering. A negative association was highlighted with the summer SST range. As the occurrence of MHWs will increase, and the SST range will also increase in the autumn and decrease in the summer, P. oceanica might benefit through a higher flowering frequency, leading to a greater resilience to disturbances due to higher genetic variation.

2.
Article in English | MEDLINE | ID: mdl-38995611

ABSTRACT

Coronary artery disease (CAD), acute coronary syndrome (ACS), and heart failure (HF) are major global health issues with high morbidity and mortality rates. Biomarkers like cardiac troponins (cTn) and natriuretic peptides (NPs) are crucial tools in cardiology, but numerous new biomarkers have emerged, proving increasingly valuable in CAD/ACS. These biomarkers are classified based on their mechanisms, such as fibrosis, metabolism, inflammation, and congestion. The integration of established and emerging biomarkers into clinical practice is an ongoing process, and recognizing their strengths and limitations is crucial for their accurate interpretation, incorporation into clinical settings, and improved management of CVD patients. We explored established biomarkers like cTn, NPs, and CRP, alongside newer biomarkers such as Apo-A1, IL-17E, IgA, Gal-3, sST2, GDF-15, MPO, H-FABP, Lp-PLA2, and ncRNAs; provided evidence of their utility in CAD/ACS diagnosis and prognosis; and empowered clinicians to confidently integrate these biomarkers into clinical practice based on solid evidence.

3.
CNS Neurosci Ther ; 30(7): e14863, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39036868

ABSTRACT

OBJECTIVE: Childhood sensory abnormalities experience has a crucial influence on the structure and function of the adult brain. The underlying mechanism of neurological function induced by childhood sensory abnormalities experience is still unclear. Our study was to investigate whether the GABAergic neurons in the anterior cingulate cortex (ACC) regulate social disorders caused by childhood sensory abnormalities experience. METHODS: We used two mouse models, complete Freund's adjuvant (CFA) injection mice and bilateral whisker trimming (BWT) mice in childhood. We applied immunofluorescence, chemogenetic and optogenetic to study the mechanism of parvalbumin (PV) neurons and somatostatin (SST) neurons in ACC in regulating social disorders induced by sensory abnormalities in childhood. RESULTS: Inflammatory pain in childhood leads to social preference disorders, while BWT in childhood leads to social novelty disorders in adult mice. Inflammatory pain and BWT in childhood caused an increase in the number of PV and SST neurons, respectively, in adult mice ACC. Inhibiting PV neurons in ACC improved social preference disorders in adult mice that experienced inflammatory pain during childhood. Inhibiting SST neurons in ACC improved social novelty disorders in adult mice that experienced BWT in childhood. CONCLUSIONS: Our study reveals that PV and SST neurons of the ACC may play a critical role in regulating social disorders induced by sensory abnormalities in childhood.


Subject(s)
Gyrus Cinguli , Mice, Inbred C57BL , Parvalbumins , Somatostatin , Animals , Mice , Somatostatin/metabolism , Male , Parvalbumins/metabolism , GABAergic Neurons/physiology , Freund's Adjuvant/toxicity , Vibrissae/physiology , Vibrissae/innervation , Neurons , Social Behavior Disorders/etiology , Mice, Transgenic
4.
Heliyon ; 10(11): e31859, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38841499

ABSTRACT

Wind is an emerging renewable energy resource, but more useful in cold regions. With the increasing threat of climate change and global warming, the unpredictability of wind energy patterns has been affected. With continual threats from extremes and uncertainties, icing on wind turbines has been noted to grow affecting aerodynamic performance. The effect of turbulence intensity at its impact on aerodynamic performance was numerically done using ANSYS Fluent and FENSAP ICE software. Conditions considered for the study included turbulence intensities, median volume diameter (MVD), liquid water content (LWC), angle of attack, and ambient temperature for 180 min. The study's conditions aimed at providing a wide range of effects covering the in-cloud icing and freezing drizzle. The mass of ice increased with an increase in LWC when it increased from 0.05 g/m3 to 0.3 g/m3, and MVD with 1000 µm compared to 40 µm, but when temperature decreased led to an increase from -1 °C to -15 °C. Increasing the angle of attack led to reduced aerodynamic performance with stall angle occurring at α = 0-18°. An increase in the turbulence intensity from 0.01 % to 50 % resulted in decreased CL/CD.

5.
Med Mycol J ; 65(2): 29-32, 2024.
Article in English | MEDLINE | ID: mdl-38825527

ABSTRACT

Mucormycosis is a fungal infectious disease caused by Rhizopus oryzae and other members of the order Mucorales, and it is known as one of the most lethal fungal infections. Early diagnosis of mucormycosis improves prognosis because of limited effective treatments and the rapid progression of the disease. On the other hand, the lack of characteristic clinical findings in mucormycosis and the challenge of early definitive diagnosis make early treatment difficult. Our goal was to establish a serodiagnostic method to detect Rhizopus specific antigen (RSA), and we have developed a diagnostic kit by Enzyme-linked immuno-sorbent assay (ELISA) using a monoclonal antibody against this antigen. RSA increased over time in the serum and alveolar lavage fluid of R. oryzae-infected mice. RSA was also detected in serum and alveolar fluid, even at an early stage (Day 1), when the tissue invasion of R. oryzae mycelium was not histopathologically detectable in the lungs of R. oryzae-infected mice. Further evaluation is needed to determine the feasibility of using this assay in clinical practice.


Subject(s)
Antigens, Fungal , Biomarkers , Enzyme-Linked Immunosorbent Assay , Mucormycosis , Rhizopus oryzae , Mucormycosis/diagnosis , Animals , Mice , Antigens, Fungal/immunology , Antigens, Fungal/blood , Biomarkers/blood , Bronchoalveolar Lavage Fluid/microbiology , Disease Models, Animal , Antibodies, Monoclonal , Rhizopus/isolation & purification , Lung/microbiology , Lung/pathology , Humans , Serologic Tests/methods
6.
Sci Rep ; 14(1): 14206, 2024 06 20.
Article in English | MEDLINE | ID: mdl-38902310

ABSTRACT

Record mean sea surface temperatures (SST) during the past decades and marine heatwaves have been identified as responsible for severe impacts on marine ecosystems, but the role of changes in the patterns of temporal variability under global warming has been much less studied. We compare descriptors of two time series of SST, encompassing extirpations (i.e. local extinctions) of six cold-temperate macroalgae species at their trailing range edge. We decompose the effects of gradual warming, extreme events and intrinsic variability (e.g. seasonality). We also relate the main factors determining macroalgae range shifts with their life cycles characteristics and thermal tolerance. We found extirpations of macroalgae were related to stretches of coast where autumn SST underwent warming, increased temperature seasonality, and decreased skewness over time. Regardless of the species, the persisting populations shared a common environmental domain, which was clearly differentiated from those experiencing local extinction. However, macroalgae species responded to temperature components in different ways, showing dissimilar resilience. Consideration of multiple thermal manifestations of climate change is needed to better understand local extinctions of habitat-forming species. Our study provides a framework for the incorporation of unused measures of environmental variability while analyzing the distributions of coastal species.


Subject(s)
Ecosystem , Global Warming , Seaweed , Temperature , Seaweed/physiology , Climate Change , Seasons , Oceans and Seas , Aquatic Organisms/physiology
7.
Front Psychiatry ; 15: 1377177, 2024.
Article in English | MEDLINE | ID: mdl-38863611

ABSTRACT

Introduction: With the introduction of the new psychiatric diagnostic manuals, personality functioning has gained new prominence. Several studies have reported consistent findings that individual showing high levels of antisocial features are associated with alterations in interpersonal functioning domains such as empathy and mentalisation. The focus of the current study (N = 198) is to examine antisocial cognitions, as measured by the Scrambled Sentences Task (SST), and to what extent this approach can help to better understand the relationship between antisocial traits and personality functioning/empathy. Method: We implemented a hypothesis-driven approach using logistic regression and a data-driven approach using machine learning to examine distinct but related measures of personality functioning as predictors of antisocial cognitions. Results: Antisocial cognitions were associated with low interpersonal functioning as expected, but only when not adjusting for antisocial traits, which accounted for almost all the association. The data-driven analysis revealed that individual items assessing empathic concern in personality functioning scales (as opposed to the whole scores) explained low antisocial cognitions even when adjusting for antisocial traits. Discussion: Antisocial cognitions appear to be associated to two distinct traits, the antisocial and a specific type of personality functioning. This finding is discussed in terms of the possible distinction between two motivational forces: to harm others/prioritize one's advantage, and to help suffering others.

8.
Mar Environ Res ; 199: 106578, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38838431

ABSTRACT

Oceanic dissolved oxygen (DO) is crucial for oceanic material cycles and marine biological activities. However, obtaining subsurface DO values directly from satellite observations is limited due to the restricted observed depth. Therefore, it is essential to develop a connection between surface oceanic parameters and subsurface DO values. Machine learning (ML) methods can effectively grasp the complex relationship between input attributes and target variables, making them a valuable approach for estimating subsurface DO values based on surface oceanic parameters. In this study, the potential of ML methods for subsurface DO retrieval is analyzed. Among the selected ML methods, namely support vector regression (SVR), random forest (RF) regression, and extreme gradient boosting (XGBoosting) regression, the RF method generally demonstrates superior performance. As the depth increases, the accuracy of DO estimates tends to initially decrease, then gradually improve, with the poorest performance occurring at the depth of 600 dbar. The range of determination coefficients (R2) and root mean square error (RMSE) values based on the test dataset at different depths lies between 0.53 and 47.59 µmol/kg to 0.99 and 4.01 µmol/kg. In addition, compared to sea surface salinity (SSS) and sea surface chlorophyll-a (SCHL), sea surface temperature (SST) plays a more significant role in DO retrieval. Finally, compared to the pelagic interactions scheme for carbon and ecosystem studies (PISCES) model, the RF method achieves higher retrieval accuracies at depths above 700 dbar. In the deep ocean, the primary differences in DO values obtained from the RF method and the PISCES model-based method are noticeable in the vicinity of the equatorial region.


Subject(s)
Environmental Monitoring , Machine Learning , Oceans and Seas , Oxygen , Seawater , Oxygen/analysis , Environmental Monitoring/methods , Seawater/chemistry , Salinity , Chlorophyll A/analysis
9.
Environ Geochem Health ; 46(7): 254, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38884664

ABSTRACT

Submarine Groundwater Discharge (SGD) and Seawater Intrusion (SWI) are two contrary hydrological processes that occur across the land-sea continuum and understanding their nature is essential for management and development of coastal groundwater resource. Present study has attempted to demarcate probable zones of SGD and SWI along highly populated Odisha coastal plains which is water stressed due to indiscriminate-exploitation of groundwater leading to salinization and fresh groundwater loss from the alluvial aquifers. A multi-proxy investigation approach including decadal groundwater level dynamics, LANDSAT derived sea surface temperature (SST) anomalies and in-situ physicochemical analysis (pH, EC, TDS, salinity and temperature) of porewater, groundwater and seawater were used to locate the SGD and SWI sites. A total of 340 samples for four seasons (85 samples i.e., 30 porewater, 30 seawater and 25 groundwater in each season) were collected and their in-situ parameters were measured at every 1-2 km gap along ~ 145 km coastline of central Odisha (excluding the estuarine region). Considering high groundwater EC values (> 3000 µS/cm), three probable SWI and low porewater salinities (< 32 ppt in pre- and < 25 ppt in post-monsoons), four probable SGD zones were identified. The identified zones were validated with observed high positive hydraulic gradient (> 10 m) at SGD and negative hydraulic gradient (< 0 m) at SWI sites along with anomalous SST (colder in pre- and warmer in post-monsoon) near probable SGD locations. This study is first of its kind along the Odisha coast and may act as initial basis for subsequent investigations on fresh-saline interaction along the coastal plains where environmental integrity supports the livelihood of coastal communities and the ecosystem.


Subject(s)
Environmental Monitoring , Groundwater , Salinity , Seawater , Groundwater/chemistry , Seawater/chemistry , India , Environmental Monitoring/methods , Water Movements , Temperature , Seasons
10.
Int Ophthalmol ; 44(1): 293, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38940962

ABSTRACT

BACKGROUND: This prospective clinical study evaluates the effect of a silicone stent tube (SST) on the success rate of endonasal-endoscopic dacryocystorhinostomy (EN-DCR) to treat primary acquired nasolacrimal duct obstruction. METHODS: Patients were randomly assigned to receive EN-DCR with or without SST intubation over a period of 3 months. The surgery was performed using standardized techniques. Patients were assessed at three different timepoints: one day, 12 weeks and 24 weeks after the surgery. The results were compared in order to evaluate statistical differences. Surgical success was determined by means of positive irrigation procedures, as well as by the improvement of symptoms and a high level of patient satisfaction. RESULTS: A total of 56 randomized cases completed 24 weeks of follow up. 1 Patient dropped out due to malignant genesis of the nasolacrimal duct obstruction. After 24 weeks of follow up no statistically significant differences in levels of epiphora (p > .10) or patency (p > .16) were revealed. Comparisons regarding changes in time did not show levels of significance (p > .28). CONCLUSIONS: This study could not confirm a statistically significant benefit or disadvantage for SST Insertion in EN-DCR.


Subject(s)
Dacryocystorhinostomy , Intubation , Lacrimal Duct Obstruction , Nasolacrimal Duct , Stents , Humans , Dacryocystorhinostomy/methods , Lacrimal Duct Obstruction/diagnosis , Lacrimal Duct Obstruction/therapy , Prospective Studies , Female , Male , Middle Aged , Intubation/methods , Intubation/instrumentation , Nasolacrimal Duct/surgery , Aged , Adult , Silicones , Endoscopy/methods , Follow-Up Studies , Treatment Outcome , Aged, 80 and over
11.
Dig Dis Sci ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38940973

ABSTRACT

OBJECTIVES: Necroptosis, a programmed inflammatory cell death, is involved in the pathogenesis of acute pancreatitis (AP). We compared levels of interleukin (IL)-33 (released upon necroptosis), sST2 (soluble IL-33 receptor), MLKL, RIPK1 and RIPK3 (necroptosis executioner proteins), and proinflammatory cytokines IL-6, TNF and IL-1ß at various severity categories and stages of AP. METHODS: Plasma from 20 patients with early mild AP (MAP) (symptom onset < 72 h), 7 with severe AP (SAP) without and 4 with persistent organ failure (OF) at sampling, 8 patients with late SAP and 20 healthy controls (HC) were studied by ELISAs. RESULTS: Early sST2 and IL-6 levels predicted the development of SAP and were higher in both MAP and early and late SAP than in HC. RIPK3 levels were higher than in HC in the patients who had or would later have SAP. MLKL levels were associated with the presence of OFs, particularly in the late phase, but were also higher in MAP than in HC. CONCLUSIONS: sST2, RIPK3 and IL-6 levels may have prognostic value in AP. Elevated MLKL levels are associated with OF in AP. Better understanding of necroptosis in AP pathophysiology is needed to evaluate whether inhibiting and targeting necroptosis is a potential therapeutic option in AP.

12.
J Pers Med ; 14(6)2024 May 25.
Article in English | MEDLINE | ID: mdl-38929785

ABSTRACT

BACKGROUND: Chest pain is a prevalent reason for emergency room referrals and presents diagnostic challenges. The physician must carefully differentiate between cardiac and noncardiac causes, including various vascular and extracardiovascular conditions. However, it is crucial not to overlook serious conditions such as acute coronary syndrome (ACS). Diagnosis of acute myocardial infarction (AMI) and early discharge management become difficult when traditional clinical criteria, ECG, and troponin values are insufficient. Recently, the focus has shifted to a "multi-marker" approach to improve diagnostic accuracy and prognosis in patients with chest pain. METHODS: This observational, prospective, single-center study involved, with informed consent, 360 patients presenting to the emergency department with typical chest pain and included a control group of 120 healthy subjects. In addition to routine examinations, including tests for hsTnI (Siemens TNIH kit), according to the 0-1 h algorithm, biochemical markers sST2 (tumorigenicity suppression-2) and suPAR (soluble urokinase plasminogen activator receptor) were also evaluated for each patient. A 12-month follow-up was conducted to monitor outcomes and adverse events. RESULTS: We identified two groups of patients: a positive one (112 patients) with high levels of hsTnI, sST2 > 24.19 ng/mL, and suPAR > 2.9 ng/mL, diagnosed with ACS; and a negative one (136 patients) with low levels of hsTnI, suPAR < 2.9 ng/mL, and sST2 < 24.19 ng/mL. During the 12-month follow-up, no adverse events were observed in the negative group. In the intermediate group, patients with hsTnI between 6 ng/L and the ischemic limit, sST2 > 29.1 ng/mL and suPAR > 2.9 ng/mL, showed the highest probability of adverse events during follow-up, while those with sST2 < 24.19 ng/mL and suPAR < 2.9 ng/mL had a better outcome with no adverse events at 12 months. CONCLUSION: Our data suggest that sST2 and suPAR, together with hsTnI, may be useful in the prognosis of cardiovascular patients with ACS, providing additional information on endothelial damage. These biomarkers could guide the clinical decision on further diagnostic investigations. In addition, suPAR and sST2 emerge as promising for event prediction in patients with chest pain. Their integration into the standard approach in PS could facilitate more efficient patient management, allowing safe release or timely admission based on individual risk.

13.
EJNMMI Rep ; 8(1): 18, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38910232

ABSTRACT

INTRODUCTION: A physiological increase in the uptake of [68Ga]Ga-labeled somatostatin analogues ([68Ga]Ga-SST) PET tracers has been reported in the uncinate pancreatic process (UP) and might be even higher in latest generation of PET/CT scanners and might be falsely interpreted as NET. We aimed to investigate the uptake of UP in a large population of NET patients who underwent [68Ga]Ga-SST PET/CT with digital SiPM detectors. We also explored potential associations between UP uptake and various clinical, imaging, and pathological factors routinely assessed in NET patients. METHODS: We analyzed all consecutive NET patients from July 2018 to June 2022 in this retrospective, single-center study. All patients underwent a [68Ga]Ga-SST PET/CT scan on a digital SiPM PET/CT scanner. On visual analysis, we distinguished between normal linear and homogenous UP uptake or abnormal if otherwise. We compared SUVmax/mean in patients with normal UP uptake to those with abnormal UP uptake with suspicious NET lesions on contrast-enhanced CT (ce-CT) and according to the site of the primary NET (pancreatic NET vs. other), patient gender (female vs. male) and tumor grade (grade 1-2 vs. 3) using a Mann-Whitney test. We also assessed the correlation between SUVmax/mean values in UP with patients' age, primary NET Ki-67 counting, and its SUVmax/mean, TLA and MTV values. RESULTS: We included 131 NET patients with a total of 34 [68Ga]Ga-DOTATATE PET/CT and 113 [68Ga]Ga-DOTATOC PET/CT scans. An abnormal UP uptake was seen in 32 patients with 65.7% of suspicious NET lesion or extrinsic compression on morphological imaging. Normal UP uptake SUVmax/mean were measured in 115 [68Ga]Ga-SST scans (78.2%) with normal UP uptake and without suspicious lesion on morphological imaging. We found an average SUVmax of 12.3 ± 4.1 for [68Ga]Ga-DOTATATE and 19.8 ± 9.8 g/ml for [68Ga]Ga-DOTATOC, hence higher than those reported in the literature [SUVmax 5 ± 1.6 to 12.6 ± 2.2 g/ml] with significant difference with abnormal UP uptake and between both PET tracers (both p < 0.01). Significant results were a higher UP uptake on [68Ga]Ga-DOTATOC in male patients (p = 0.02) and significant associations between UP uptake on [68Ga]Ga-DOTATOC and SUVmax/mean of the primary tumor (ρ [0.337-0.363]; p [0.01-0.02]). CONCLUSION: We confirmed a higher and very frequent UP uptake in latest SiPM-detector [68Ga]Ga-SST PET/CT with an even higher uptake in patients that had [68Ga]Ga-DOTATOC PET/CT. SUVmean/max were significantly higher in abnormal UP uptake but there were overlaps with UP SUV values for both [68Ga]Ga-SST and a correlation to morphological imaging is crucial. Besides, significant associations between UP uptake and SUVmean/max of the primary NET as well as patients' gender were seen in the larger cohort of [68Ga]Ga-DOTATOC patients suggesting that both physiological and pathological parameters could affect UP uptake.

14.
Front Immunol ; 15: 1369202, 2024.
Article in English | MEDLINE | ID: mdl-38774876

ABSTRACT

Atherosclerosis poses a significant threat to human health, impacting overall well-being and imposing substantial financial burdens. Current treatment strategies mainly focus on managing low-density lipids (LDL) and optimizing liver functions. However, it's crucial to recognize that Atherosclerosis involves more than just lipid accumulation; it entails a complex interplay of immune responses. Research highlights the pivotal role of lipid-laden macrophages in the formation of atherosclerotic plaques. These macrophages attract lymphocytes like CD4 and CD8 to the inflamed site, potentially intensifying the inflammatory response. γδ T lymphocytes, with their diverse functions in innate and adaptive immune responses, pathogen defense, antigen presentation, and inflammation regulation, have been implicated in the early stages of Atherosclerosis. However, our understanding of the roles of γδ T cells in Atherosclerosis remains limited. This mini-review aims to shed light on the characteristics and functions of γδ T cells in Atherosclerosis. By gaining insights into the roles of γδ T cells, we may uncover a promising strategy to mitigate plaque buildup and dampen the inflammatory response, thereby opening new avenues for effectively managing this condition.


Subject(s)
Atherosclerosis , Receptors, Antigen, T-Cell, gamma-delta , Humans , Atherosclerosis/immunology , Atherosclerosis/metabolism , Animals , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Receptors, Antigen, T-Cell, gamma-delta/immunology , Macrophages/immunology , Macrophages/metabolism , Plaque, Atherosclerotic/immunology , Intraepithelial Lymphocytes/immunology , Intraepithelial Lymphocytes/metabolism , Immunity, Innate , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Inflammation/immunology , Adaptive Immunity
15.
Environ Sci Pollut Res Int ; 31(23): 34271-34281, 2024 May.
Article in English | MEDLINE | ID: mdl-38702483

ABSTRACT

The southwest coast of India experiences frequent Indian oil sardine (IOS) nearshore aggregation events, especially in the coastal waters off Kerala. These ephemeral dense IOS aggregation events are known as "Sardine Run". To investigate the reason and provide a scientific basis for these sporadic events, satellite/model-derived physical, meteorological, and biological parameters were analysed. Sea Surface Temperature during a majority of events was in the range of 26-29 °C, agreeing with the reported temperature conditions for IOS in the Arabian Sea. Additionally, a marginal lowering of SST as an effect of precipitation before most of the events might have attracted IOS towards the near-coastal waters in addition to the phytoplankton diet availability, resulting in the aggregation event. However, different scenarios also depicted coastal warming and probable hypoxic conditions in degrading IOS habitat and resulting in beach aggregation events. During most of the IOS aggregation events, the wind and surface current direction was alongshore/coastward, which complemented the propagation of live IOS shoals towards the beach.


Subject(s)
Environmental Monitoring , India , Animals , Phytoplankton , Seawater/chemistry , Ecosystem
16.
Cell Rep ; 43(5): 114212, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38743567

ABSTRACT

Diverse types of inhibitory interneurons (INs) impart computational power and flexibility to neocortical circuits. Whereas markers for different IN types in cortical layers 2-6 (L2-L6) have been instrumental for generating a wealth of functional insights, only the recent identification of a selective marker (neuron-derived neurotrophic factor [NDNF]) has opened comparable opportunities for INs in L1 (L1INs). However, at present we know very little about the connectivity of NDNF L1INs with other IN types, their input-output conversion, and the existence of potential NDNF L1IN subtypes. Here, we report pervasive inhibition of L2/3 INs (including parvalbumin INs and vasoactive intestinal peptide INs) by NDNF L1INs. Intersectional genetics revealed similar physiology and connectivity in the NDNF L1IN subpopulation co-expressing neuropeptide Y. Finally, NDNF L1INs prominently and selectively engage in persistent firing, a physiological hallmark disconnecting their output from the current input. Collectively, our work therefore identifies NDNF L1INs as specialized master regulators of superficial neocortex according to their pervasive top-down afferents.


Subject(s)
Interneurons , Interneurons/metabolism , Animals , Mice , Neuropeptide Y/metabolism , Neocortex/metabolism , Neocortex/cytology , Neocortex/physiology , Vasoactive Intestinal Peptide/metabolism , Male , Parvalbumins/metabolism
17.
Heliyon ; 10(9): e29804, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38698979

ABSTRACT

Background: This study aimed to investigate the relationship between baseline soluble suppression of tumorigenesis-2 (sST2) concentration and the outcomes of heart failure (HF), atrial fibrillation (AF) or death in patients with coronary heart disease (CHD) with or without renal insufficiency (RI). Methods: Between March 2011 and December 2015, 3454 patients with CHD from the Chinese PLA General Hospital were enrolled in this cohort study. The patients were followed up until October 2021. AF, HF, and death events were recorded. Associations between baseline sST2 concentrations and clinical outcomes were assessed using Kaplan-Meier (K-M) curves, and Cox regression and generalised additive models. Subgroup analysis were carried out between RI and non-RI groups. Results: Among the patients with CHD (61.5 ± 11.8 years; 78.6 % men), 415 (12.02 %) had RI. During a median follow-up of 8.37 years, HF and AF were reported in 216 (6.25 %) and 174 (5.04 %) patients, respectively, and 297 (8.60 %) died. The K-M curves indicated that patients in the higher quartiles of sST2 concentrations were correlated with a poor survival rate of HF, AF, or death (all Ps < 0.001). Generalised additive model (GAM) demonstrated a nonlinear positive association between sST2 concentration and the risk of HF, AF, and death in CHD patients. The cut-off value of sST2 for predicting HF, AF and death were 32.1, 25.4 and 28.6 ng/mL, respectively. CHD patients with sST2 higher than the cut-off value had higher risks of HF (HR: 3.02, 95%CI: 2.24-4.05), AF (HR: 2.86; 95%CI: 2.10-3.90), and death (HR:2.11, 95%CI: 1.67-2.67). Furthermore, in patients with RI (12.02 %, n = 415), the prognostic value of sST2 over the cut-off value for HF and death remained unchanged (HR: 3.21 and 2.35; P < 0.05). In patients with CHD with or without RI, sST2 improved the area under the curve (AUC) of traditional risk models for predicting clinical endpoint events. Conclusions: The biomarker sST2 may be useful for predicting HF, AF, and death in patients with CHD. The predicted value was not affected by renal function.

18.
ESC Heart Fail ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773746

ABSTRACT

AIMS: This study aimed to investigate the association of soluble suppression of tumorigenicity-2 (sST2) measured by point-of-care testing assay with clinical outcomes in patients hospitalized with heart failure after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). METHODS: A total of 1726 consecutive patients hospitalized with heart failure from July 2015 to December 2021 were enrolled. Baseline serum sST2 concentrations were measured by immunofluorescence assay. Primary endpoint event was the composite of all-cause death, heart transplantation, or left ventricular assist device. RESULTS: During the median follow-up duration of 682 days, 434 patients (25.1%) suffered from primary endpoint events. Baseline sST2 remained an independent predictor of the primary endpoint event in patients hospitalized with heart failure after adjusting for other predictors including NT-proBNP and hs-cTnT [per log (unit) increase, adjusted hazard ratio (HR) (95% confidence interval) (CI): 1.20 (1.09, 1.32), P < 0.001]. And baseline sST2 had a better prognostic value for patients with chronic decompensated heart failure [per log (unit) increase, adjusted HR (95% CI): 1.19 (1.07, 1.31)] than for those with acute new onset heart failure [per log (unit) increase, adjusted HR (95% CI): 1.28 (0.94, 1.75), P value for interaction <0.001], as well as a better prognostic value for patients with New York Heart Association (NYHA) functional class I-II [per log (unit) increase, adjusted HR (95% CI): 1.67 (1.11, 2.52)] than for those with NYHA functional class III-IV [per log (unit) increase, adjusted HR (95% CI): 1.18 (1.07, 1.31), P value for interaction <0.001]. Baseline sST2 was also a good predictor of the primary endpoint event in patients hospitalized with heart failure at 1 month, 3 months, 1 year and 2 years (area under the curve: 0.789, 0.775, 0.736 and 0.733, respectively), and the best cut-off values were 27.2 ng/ml, 27.1 ng/ml, 27.1 ng/ml and 25.1 ng/ml, respectively. Furthermore, baseline sST2 could provide additional prognostic value when added to baseline NT-proBNP and hs-cTnT (all P values <0.05). According to the category of elevated biomarkers (including NT-proBNP, hs-cTnT, and sST2), patients with three elevated biomarkers had a higher risk of the primary endpoint event compared with those with one or two elevated biomarkers (all P values <0.05). CONCLUSIONS: Baseline sST2 remained an independent predictor of adverse events after adjusting for other predictors including NT-proBNP and hs-cTnT, particularly in patients with chronic decompensated heart failure and NYHA functional class I-II. And in the basis of baseline NT-proBNP and hs-cTnT, adding baseline sST2 could provide additional prognostic value for patients hospitalized with heart failure.

19.
Drug Test Anal ; 2024 May 24.
Article in English | MEDLINE | ID: mdl-38794805

ABSTRACT

The monitoring of endogenous steroids in urine has been an important component of the Athlete Biological Passport (ABP) for the last decade. Recently, the quantitation of endogenous steroids in blood has been incorporated into the ABP to increase sensitivity in circumstances where the excretion of urinary ABP biomarkers is low. Current ABP guidelines mandate the use of venous blood draws for blood steroid sample collections, however, recent efforts have focused on investigating the use of less invasive sample collection methods, such as capillary blood collected from the upper arm. The focus of this study was to compare the analytical results of venous and capillary blood collected weekly from 20 individuals, 10 males and 10 females, over six weeks. The two primary biomarkers of the blood steroid ABP module, testosterone (T) and the testosterone/androstenedione (T/A4) ratio, were compared, as well as luteinizing hormone (LH) and the T/LH ratio in male participants, two biomarkers known to be responsive to T use. All biomarkers showed excellent agreement between venous and capillary blood. Longitudinal stability between sample types within individuals was also comparable for all biomarkers. Finally, storage of simultaneously collected capillary samples at room temperature and frozen conditions was compared with evaluate the potential impact of non-cold chain shipping conditions. Most biomarkers showed excellent agreement between frozen and room temperature storage conditions. These results indicate capillary blood collections represent a promising alternative to venous blood collections for the blood steroid module of the ABP.

20.
iRadiology ; 2(2): 128-155, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38708130

ABSTRACT

Optimal therapeutic and diagnostic efficacy is essential for healthcare's global mission of advancing oncologic drug development. Accurate diagnosis and detection are crucial prerequisites for effective risk stratification and personalized patient care in clinical oncology. A paradigm shift is emerging with the promise of multi-receptor-targeting compounds. While existing detection and staging methods have demonstrated some success, the traditional approach of monotherapy is being reevaluated to enhance therapeutic effectiveness. Heterodimeric site-specific agents are a versatile solution by targeting two distinct biomarkers with a single theranostic agent. This review describes the innovation of dual-targeting compounds, examining their design strategies, therapeutic implications, and the promising path they present for addressing complex diseases.

SELECTION OF CITATIONS
SEARCH DETAIL