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1.
Rev Sci Instrum ; 95(10)2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39360876

RESUMO

Measurement of proton spectra is an important diagnostic for a variety of high energy density physics experiments. Current diagnostics are either not designed to capture the spectrum of low-energy protons or are unsuitable for high debris experiments. To bridge the gap, a new CR-39 based compact magnetic spectrometer (MagSpec) has been developed to measure proton spectra in the 1-20 MeV energy range, with a particular focus on the low-energy (1-6 MeV) spectrum, for use in experiments at the OMEGA Laser Facility and the National Ignition Facility (NIF). In the MagSpec diagnostic, protons of different energies are dispersed as they pass through a magnetic field before impinging on a differentially filtered CR-39 surface, resulting in a spatial distribution of CR-39 tracks that corresponds to the energy spectrum. In this paper, we discuss details of the design and implementation of MagSpec on the NIF and OMEGA.

2.
Cureus ; 16(8): e67355, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39310615

RESUMO

Introduction  As a medical condition, obesity is a global public health concern that still has no satisfactory solution. Endoscopic sleeve gastroplasty (ESG) and intragastric balloon (IGB) are proven to be safe and efficient in producing weight loss. Endoscopic sleeve gastroplasty has achieved significant success; therefore, it is timely to compare it to intragastric balloon therapy. Methods  We retrospectively reviewed prospectively collected data for patients undergoing ESG or IGB. Weight was recorded at one week, one month, and three months post-procedure, and the percentage of total body weight loss (%TBWL) was calculated. Severe adverse events requiring hospital admission/procedure reversal were also recorded. We aim to see if one procedure is more efficient in providing weight loss in a short-term period.  Results A total of 20 patients underwent ESG and 31 patients underwent IGB insertion. ESG patients showed a superior mean %TBWL at one-week post-procedure (%TBWL±SD = 4.87±1.88 vs 3.76±1.95). IGB patients showed a higher mean of %TBWL at one-month post-procedure (%TBWL±SD = 8.00±3.60 vs 7.25±3.29). Both procedures show similar %TBWL at three months post-procedure (%TBWL±SD ESG = 10.857±3.83 vs %TBWL ± SD IGB = 10.852±5.78). Conclusions  We found that both the IGB insertion and ESG procedures result in clinically significant weight loss. However, the short-term weight loss between these two procedures is similar. Although similar, the number of adverse events in the IGB group is significantly higher than in the ESG group.

3.
Soft Matter ; 20(37): 7535-7545, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39279506

RESUMO

We utilize the results of surface-enhanced Raman spectroscopy (SERS)-based interdiffusion experiments on meso-structured substrates to independently validate direct observations of plasmonic enhancements on these elements. The plasmonic enhancement function (PEF) is crucial for accurately determining interdiffusion coefficients using this newly proposed SERS-based methodology. The substrates feature a microscale inverted pyramid geometry, coated with nanoscale sputtered gold. Interdiffusion experiments involve the sequential deposition of polymer bilayers, with deuterated polystyrene (dPS) at the bottom and polystyrene (PS) on top, followed by annealing while periodically acquiring Raman spectra. The temporal evolution of the PS Raman signal reflects not only the interdiffusion process but also plasmonic effects, as the Raman scattering primarily arises from the substrate's plasmonic hotspots. High-resolution finite element (FE) diffusion simulations, combined with experimental SERS data, are used to infer the PEF of the substrate. The derived PEF is consistent with two hotspots located at the apex and vertices of the pyramidal cavity, extending along the edges and spreading into the molecular layer in direct contact with the substrate. This finding is tested against experiments conducted at various diffusion rates, showing excellent agreement. It corroborates recent observations by Steuwe et al. regarding the localization of hotspots on this specific substrate but contradicts other studies that attribute hotspots solely to the micron-scale geometry. This analysis establishes a solid foundation for reliably determining diffusion coefficients using this SERS-based methodology.

4.
Psychol Med ; : 1-14, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39324387

RESUMO

This study aimed to review and synthesize the need estimates for psychiatric beds, explore how they changed over time and compare them against the prevalence of actually existing beds. We searched PubMed, Embase classic and Embase, PsycINFO and PsycIndex, Open Grey, Google Scholar, Global Health EBSCO and Proquest Dissertations, from inception to September 13, 2022. Publications providing estimates for the required number of psychiatric inpatient beds were included. Need estimates, length of stay, and year of the estimate were extracted. Need estimates were synthesized using medians and interquartile ranges (IQRs). We also computed prevalence ratios of the need estimates and the existing bed capacities at the same time and place. Sixty-five publications with 98 estimates were identified. Estimates for bed needs were trending lower until 2000, after which they stabilized. The twenty-six most recent estimates after 2000 were submitted to data synthesis (n = 15 for beds with unspecified length of stay, n = 7 for short-stay, and n = 4 for long-stay beds). Median estimates per 100 000 population were 47 (IQR: 39 to 50) beds with unspecified length of stay, 28 (IQR: 23 to 31) beds for short-stay, and 10 (IQR: 8 to 11) for long-stay beds. The median prevalence ratio of need estimates and the actual bed prevalence was 1.8 (IQR: 1.3 to 2.3) from 2000 onwards. Historically, the need estimates for psychiatric beds have decreased until about 2000. In the past two decades, they were stable over time and consistently higher than the actual bed numbers provided.

5.
Nat Commun ; 15(1): 7843, 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39245687

RESUMO

Pompe disease (PD) is a rare autosomal recessive glycogen storage disorder that causes proximal muscle weakness and loss of respiratory function. While enzyme replacement therapy (ERT) is the only effective treatment, biomarkers for disease monitoring are scarce. Following ex vivo biomarker validation in phantom studies, we apply multispectral optoacoustic tomography (MSOT), a laser- and ultrasound-based non-invasive imaging approach, in a clinical trial (NCT05083806) to image the biceps muscles of 10 late-onset PD (LOPD) patients and 10 matched healthy controls. MSOT is compared with muscle magnetic resonance imaging (MRI), ultrasound, spirometry, muscle testing and quality of life scores. Next, results are validated in an independent LOPD patient cohort from a second clinical site. Our study demonstrates that MSOT enables imaging of subcellular disease pathology with increases in glycogen/water, collagen and lipid signals, providing higher sensitivity in detecting muscle degeneration than current methods. This translational approach suggests implementation in the complex care of these rare disease patients.


Assuntos
Doença de Depósito de Glicogênio Tipo II , Glicogênio , Imageamento por Ressonância Magnética , Técnicas Fotoacústicas , Humanos , Doença de Depósito de Glicogênio Tipo II/diagnóstico por imagem , Doença de Depósito de Glicogênio Tipo II/metabolismo , Doença de Depósito de Glicogênio Tipo II/patologia , Glicogênio/metabolismo , Técnicas Fotoacústicas/métodos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Estudos de Casos e Controles , Ultrassonografia/métodos , Imagens de Fantasmas
6.
Front Mol Neurosci ; 17: 1411384, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39228795

RESUMO

Retinoic acid receptor ß2 (RARß2) is an emerging therapeutic target for spinal cord injuries (SCIs) with a unique multimodal regenerative effect. We have developed a first-in-class RARß agonist drug, C286, that modulates neuron-glial pathways to induce functional recovery in a rodent model of sensory root avulsion. Here, using genome-wide and pathway enrichment analysis of avulsed rats' spinal cords, we show that C286 also influences the extracellular milieu (ECM). Protein expression studies showed that C286 upregulates tenascin-C, integrin-α9, and osteopontin in the injured cord. Similarly, C286 remodulates these ECM molecules, hampers inflammation and prevents tissue loss in a rodent model of spinal cord contusion C286. We further demonstrate C286's efficacy in human iPSC-derived neurons, with treatment resulting in a significant increase in neurite outgrowth. Additionally, we identify a putative efficacy biomarker, S100B, which plasma levels correlated with axonal regeneration in nerve-injured rats. We also found that other clinically available retinoids, that are not RARß specific agonists, did not lead to functional recovery in avulsed rats, demonstrating the requirement for RARß specific pathways in regeneration. In a Phase 1 trial, the single ascending dose (SAD) cohorts showed increases in expression of RARß2 in white blood cells correlative to increased doses and at the highest dose administered, the pharmacokinetics were similar to the rat proof of concept (POC) studies. Collectively, our data suggests that C286 signalling in neurite/axonal outgrowth is conserved between species and across nerve injuries. This warrants further clinical testing of C286 to ascertain POC in a broad spectrum of neurodegenerative conditions.

7.
PLoS One ; 19(8): e0307137, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39146345

RESUMO

BACKGROUND: University students typically face acute financial pressure, which can adversely impact mental health, wellbeing, and academic outcomes. This scoping review of qualitative and quantitative studies aimed to identify distinct money-management behaviours, and psychological determinants, to inform future interventions. METHODS: Two electronic databases were searched for observational studies focusing on money-management behaviours and their correlates (in quantitative studies) or reflections on experiences of such behaviours (qualitative studies). Of 789 unique papers identified, 12 papers, reporting 10 distinct studies (six quantitative, two qualitative, two mixed-methods), were entered into review. We inductively categorised all behaviours and psychological correlates, and narratively synthesised findings. RESULTS: We documented 15 distinct money-management behaviours, which fitted five higher-order categories: budgeting, saving (i.e., building funds), spending, borrowing, and settling debts. Twenty-two distinct potential correlates were observed, which fitted six categories: personality characteristics, financial beliefs and knowledge, attitudes, affective responses, self-efficacy and control, and social influences. Financial beliefs and knowledge, attitudes, self-efficacy and control, and social support from parents and peers were generally associated with 'better' money management practices. CONCLUSION: Heterogeneity in behaviours and correlates studied precluded definitive conclusions. Future studies should more comprehensively adopt theories and concepts from behavioural science, to distinguish between different money-management behaviours, identify which behaviours have most impact on students, and establish which specific determinants are most related to which money-management behaviours.


Assuntos
Estudantes , Humanos , Estudantes/psicologia , Universidades , Autoeficácia , Administração Financeira
8.
Artigo em Inglês | MEDLINE | ID: mdl-39091119

RESUMO

BACKGROUND: Fractional flow reserve (FFR) represents the gold standard in guiding the decision to proceed or not with coronary revascularization of angiographically intermediate coronary lesion (AICL). Optical coherence tomography (OCT) allows to carefully characterize coronary plaque morphology and lumen dimensions. OBJECTIVES: We sought to develop machine learning (ML) models based on clinical, angiographic and OCT variables for predicting FFR. METHODS: Data from a multicenter, international, pooled analysis of individual patient's level data from published studies assessing FFR and OCT on the same target AICL were collected through a dedicated database to train (n = 351) and validate (n = 151) six two-class supervised ML models employing 25 clinical, angiographic and OCT variables. RESULTS: A total of 502 coronary lesions in 489 patients were included. The AUC of the six ML models ranged from 0.71 to 0.78, whereas the measured F1 score was from 0.70 to 0.75. The ML algorithms showed moderate sensitivity (range: 0.68-0.77) and specificity (range: 0.59-0.69) in detecting patients with a positive or negative FFR. In the sensitivity analysis, using 0.75 as FFR cut-off, we found a higher AUC (0.78-0.86) and a similar F1 score (range: 0.63-0.76). Specifically, the six ML models showed a higher specificity (0.71-0.84), with a similar sensitivity (0.58-0.80) with respect to 0.80 cut-off. CONCLUSIONS: ML algorithms derived from clinical, angiographic, and OCT parameters can identify patients with a positive or negative FFR.

9.
J Soc Cardiovasc Angiogr Interv ; 3(4): 101288, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-39130179

RESUMO

Background: Optical coherence tomography (OCT) allows to carefully characterize coronary plaque morphology and lumen dimensions. We sought to evaluate the value of OCT in predicting fractional flow reserve (FFR). Methods: We performed a multicenter, international, pooled analysis of individual patient-level data from published studies assessing FFR and OCT on the same vessel. Data from stable or unstable patients who underwent both FFR and OCT of the same coronary artery were collected through a dedicated database. Predefined OCT parameters were minimum lumen area (MLA), percentage area stenosis (%AS), and presence of thrombus or plaque rupture. Primary end point was FFR ≤0.80. Secondary outcome was the incidence of major adverse cardiac events in patients not undergoing revascularization based on negative FFR (>0.80). Results: A total of 502 coronary lesions in 489 patients were included. A significant correlation was observed between OCT-MLA and FFR values (R = 0.525; P < .001), and between OCT-%AS and FFR values (R = -0.482; P < .001). In Receiver operating characteristic analysis, MLA <2.0 mm2 showed a good discriminative power to predict an FFR ≤0.80 (AUC, 0.80), whereas %AS >73% showed a moderate discriminative power (AUC, 0.73). When considering proximal coronary segments, the best OCT cutoff values predicting an FFR ≤0.80 were MLA <3.1 mm2 (AUC, 0.82), and %AS >61% (AUC, 0.84). In patients with a negative FFR not revascularized, the combination of lower MLA and higher %AS had a trend toward worse outcome (which was statistically significant in the analysis restricted to proximal vessels). Conclusions: OCT lumen measures (MLA, %AS) may predict FFR, and different cutoffs are needed for proximal vessels.

10.
Mol Cell Biochem ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39167271

RESUMO

Cardiovascular diseases represent the major cause of morbidity mainly due to chronic heart failure. Epicardial (EAT) and perivascular adipose tissues (PVAT) are considered major contributors to the pathogenesis of cardiometabolic pathologies. Monoamine oxidases (MAOs) are mitochondrial enzymes recognized as sources of reactive oxygen species (ROS) in cardiometabolic pathologies. Methylene blue (MB) is one of the oldest protective agents, yet no data are available about its effects on adipose tissue. The present pilot study was aimed at assessing the effects of MB: (i) on MAO expression and (ii) oxidative stress in EAT and PVAT harvested from patients with heart failure subjected to cardiac surgery (n = 25). Adipose tissue samples were incubated with MB (0.1 µM/24 h) and used for the assessment of MAO gene and protein expression (qPCS and immune fluorescence) and ROS production (confocal microscopy and spectrophotometry). The human cardiovascular adipose tissues contain both MAO isoforms, predominantly MAO-A. Incubation with MB reduced MAOs expression and oxidative stress; co-incubation with serotonin, the MAO-A substrate, further augmented ROS generation, an effect partially reversed by MB. In conclusion, MAO-A is the major isoform expressed in EAT and PVAT and contribute to local oxidative stress; both effects can be mitigated by methylene blue.

11.
Artigo em Inglês | MEDLINE | ID: mdl-39172316

RESUMO

Intracoronary continuous thermodilution has been recently proposed as an invasive method to quantify absolute coronary flow (Qabs) and resistance (Rabs) in vivo. The aim of the present study is to develop and validate of a novel pressure-wire- and microcatheter-free surrogate of coronary flow and resistance derived from a standard coronary angiogram. Angiography derived coronary flow (Qangio) and resistance (Rangio) was prospectively validated in a two-center cohort of patients from Oxford Heart Centre and the Essex Cardiothoracic Centre. Qabs and Rabs were measured during resting and hyperemic conditions with continuous thermodilution using the Rayflow microcatheter. Qangio and Rangio were computed from the diagnostic coronary angiogram in a blinded fashion in resting and hyperemic conditions. A total of 62 patients and 115 vessels were included in the present analysis. The median Qabs at rest was 75 ml/min (53-95) and 151 ml/min (105-203) during hyperemia; Qangio at rest was 84 ml/min (66-108) and 154 ml/min (115-195) during hyperemia. There was a strong correlation between Qabs and Qangio (R = 0,72; p < 0.001, R = 0,86; p < 0.001 respectively) with satisfactory interclass correlation (0.841, 95% CI 0.509-0.957; p = 0.0003). The median Rabs was 1111 mmHg/(L/min) (830-1581.4) at rest and 454 mmHg/(L/min) (348-610) during hyperemia; angiographic resistance (Rangio) was 937.4 mmHg/(L/min) (695.4-1261.9) at rest and 492.4 mmHg/(L/min) (406-697) during hyperemia. There was a strong correlation between Rabs and Rangio in both conditions (R = 0,81; p < 0.001 and R = 0,78; p < 0.001 respectively). The was a good correlation between absolute coronary flow reserve (CFR) and angiography-derived CFR (R = 0,61; p < 0.001) and between absolute microvascular resistance reserve (MRR) and angiography-derived MRR (R = 0,49; p < 0.001).

13.
Phys Rev E ; 109(6-2): 065201, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39020911

RESUMO

Shock-driven implosions with 100% deuterium (D_{2}) gas fill compared to implosions with 50:50 nitrogen-deuterium (N_{2}D_{2}) gas fill have been performed at the OMEGA laser facility to test the impact of the added mid-Z fill gas on implosion performance. Ion temperature (T_{ion}) as inferred from the width of measured DD-neutron spectra is seen to be 34%±6% higher for the N_{2}D_{2} implosions than for the D_{2}-only case, while the DD-neutron yield from the D_{2}-only implosion is 7.2±0.5 times higher than from the N_{2}D_{2} gas fill. The T_{ion} enhancement for N_{2}D_{2} is observed in spite of the higher Z, which might be expected to lead to higher radiative loss, and higher shock strength for the D_{2}-only versus N_{2}D_{2} implosions due to lower mass, and is understood in terms of increased shock heating of N compared to D, heat transfer from N to D prior to burn, and limited amount of ion-electron-equilibration-mediated additional radiative loss due to the added higher-Z material. This picture is supported by interspecies equilibration timescales for these implosions, constrained by experimental observables. The one-dimensional (1D) kinetic Vlasov-Fokker-Planck code ifp and the radiation hydrodynamic simulation codes hyades (1D) and xrage [1D, two-dimensional (2D)] are brought to bear to understand the observed yield ratio. Comparing measurements and simulations, the yield loss in the N_{2}D_{2} implosions relative to the pure D_{2}-fill implosion is determined to result from the reduced amount of D_{2} in the fill (fourfold effect on yield) combined with a lower fraction of the D_{2} fuel being hot enough to burn in the N_{2}D_{2} case. The experimental yield and T_{ion} ratio observations are relatively well matched by the kinetic simulations, which suggest interspecies diffusion is responsible for the lower fraction of hot D_{2} in the N_{2}D_{2} relative to the D_{2}-only case. The simulated absolute yields are higher than measured; a comparison of 1D versus 2D xrage simulations suggest that this can be explained by dimensional effects. The hydrodynamic simulations suggest that radiative losses primarily impact the implosion edges, with ion-electron equilibration times being too long in the implosion cores. The observations of increased T_{ion} and limited additional yield loss (on top of the fourfold expected from the difference in D content) for the N_{2}D_{2} versus D_{2}-only fill suggest it is feasible to develop the platform for studying CNO-cycle-relevant nuclear reactions in a plasma environment.

14.
Plants (Basel) ; 13(13)2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38999714

RESUMO

Plants reprogramme their proteome to alter cellular metabolism for effective stress adaptation. Intracellular proteomic responses have been extensively studied, and the extracellular matrix stands as a key hub where peptide signals are generated/processed to trigger critical adaptive signal transduction cascades inaugurated at the cell surface. Therefore, it is important to study the plant extracellular proteome to understand its role in plant development and stress response. This study examined changes in the soluble extracellular sub-proteome of sorghum cell cultures exposed to a combination of sorbitol-induced osmotic stress and heat at 40 °C. The combined stress significantly reduced metabolic activity and altered protein secretion. While cells treated with osmotic stress alone had elevated proline content, the osmoprotectant in the combined treatment remained unchanged, confirming that sorghum cells exposed to combined stress utilise adaptive processes distinct from those invoked by the single stresses applied separately. Reactive oxygen species (ROS)-metabolising proteins and proteases dominated differentially expressed proteins identified in cells subjected to combined stress. ROS-generating peroxidases were suppressed, while ROS-degrading proteins were upregulated for protection from oxidative damage. Overall, our study provides protein candidates that could be used to develop crops better suited for an increasingly hot and dry climate.

15.
Pharm Stat ; 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39073285

RESUMO

Correctly characterising the dose-response relationship and taking the correct dose forward for further study is a critical part of the drug development process. We use optimal design theory to compare different designs and show that using longitudinal data from all available timepoints in a continuous-time dose-response model can substantially increase the efficiency of estimation of the dose-response compared to a single timepoint model. We give theoretical results to calculate the efficiency gains for a large class of these models. For example, a linearly growing Emax dose-response in a population with a between/within-patient variance ratio ranging from 0.1 to 1 measured at six visits can be estimated with between 1.43 and 2.22 times relative efficiency gain, or equivalently, with 30% to a 55% reduced sample size, compared to a single model of the final timepoint. Fractional polynomials are a flexible way to incorporate data from repeated measurements, increasing precision without imposing strong constraints. Longitudinal dose-response models using two fractional polynomial terms are robust to mis-specification of the true longitudinal process while maintaining, often large, efficiency gains. These models have applications for characterising the dose-response at interim or final analyses.

16.
ACS Appl Mater Interfaces ; 16(29): 37545-37554, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38985802

RESUMO

Successful therapeutic delivery of siRNA with polymeric nanoparticles seems to be a promising but not vastly understood and complicated goal to achieve. Despite years of research, no polymer-based delivery system has been approved for clinical use. Polymers, as a delivery system, exhibit considerable complexity and variability, making their consistent production a challenging endeavor. However, a better understanding of the polymerization process of polymer excipients may improve the reproducibility and material quality for more efficient use in drug products. Here, we present a combination of Design of Experiment and Python-scripted data science to establish a prediction model, from which important parameters can be extracted that influence the synthesis results of polybeta-amino esters (PBAEs), a common type of polymer used preclinically for nucleic acid delivery. We synthesized a library of 27 polymers, each one at different temperatures with different reaction times and educt ratios using an orthogonal central composite (CCO-) design. This design allowed a detailed characterization of factor importance and interactions using a very limited number of experiments. We characterized the polymers by analyzing the resulting composition by 1H-NMR and the size distribution by GPC measurements. To further understand the complex mechanism of block polymerization in a one-pot synthesis, we developed a Python script that helps us to understand possible step-growth steps. We successfully developed and validated a predictive response surface and gathered a deeper understanding of the synthesis of polyspermine-based amphiphilic PBAEs.


Assuntos
Polímeros , Espermina , Polímeros/química , Polímeros/síntese química , Espermina/química , Nanopartículas/química , Polimerização
18.
ACS Phys Chem Au ; 4(4): 385-392, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39069981

RESUMO

Water and ice are routinely studied with X-rays to reveal their diverse structures and anomalous properties. We employ a hybrid collisional-radiative/molecular-dynamics method to explore how femtosecond X-ray pulses interact with hexagonal ice. We find that ice makes a phase transition into a crystalline plasma where its initial structure is maintained up to tens of femtoseconds. The ultrafast melting process occurs anisotropically, where different geometric configurations of the structure melt on different time scales. The transient state and anisotropic melting of crystals can be captured by X-ray diffraction, which impacts any study of crystalline structures probed by femtosecond X-ray lasers.

19.
Clin Exp Immunol ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39044534

RESUMO

T cells are one of the main drivers of inflammatory bowel diseases (IBD). Infliximab (IFX) is used in the treatment of IBD as an anti-inflammatory drug to induce remission by neutralizing TNFα. We determined the individual chemokine/homing receptor and cytokine profile in pediatric IBD patients before and during IFX therapy to identify predictive biomarkers for therapy success. Peripheral blood CD4+ cells from pediatric patients with IBD were immunomagnetically isolated and either directly analyzed by FACS for cell distribution and chemokine/homing receptor expression or evaluated for cytokine production after in-vitro-stimulation. 21 responders (RS) and 21 non-responders (NRS) were recruited. Before IFX therapy, flow cytometry revealed decreased percentages of naïve conventional T cells in pediatric IBD patients. The proportions of CD62-L+ T cells were decreased in both CD and UC therapy responders. The cytokine profile of T cells was highly altered in IBD patients compared to healthy controls (HC). During IFX therapy, the frequencies of conventional memory and regulatory memory T cells expanded in both cohorts. IFX response was marked by a decrease of α4ß7+ and IFNγ+ memory T cells in both CD and UC. In contrast, frequencies of Lag-3+ T cells proved to be significantly increased in NRS. These observations were irrespective of the underlying disease. T cells of pediatric IBD patients display an activated and rather Th1/Th17 shifted phenotype The increased expression of the checkpoint molecule Lag-3 on T cells of NRS resembles a more exhausted phenotype than in RS and HC which appeared to be a relevant predictive marker for therapy failure.

20.
Lancet Psychiatry ; 11(7): 536-544, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38823401

RESUMO

BACKGROUND: Suicide is a leading cause of death during imprisonment. This systematic review aimed to synthesise available evidence of prison suicide incidence worldwide. METHODS: We systematically searched the scientific literature, data repositories, and prison system reports, supplemented by correspondence with prison administrations. We included reports on people living in prison but excluded studies in preselected groups (by age or offence type). Absolute numbers and incidence rates of suicide mortality per 100 000 person-years by sex and country were extracted from 2000 to 2021. IQRs were used to describe the suicide incidence in different world regions. Incidence rate ratios comparing suicides of people living in prison with age-standardised general populations were calculated. We conducted meta-regression analyses on national-level and prison-level factors to examine heterogeneity. The study protocol was pre-registered with PROSPERO, CRD42021296819. FINDINGS: We included three scientific studies, 124 official reports, and 11 datasets from email correspondence. Between 2000 and 2021, there were 29 711 reported suicides during 91·2 million person-years of imprisonment in 82 jurisdictions worldwide (sex-specific data available for 13 289 individuals: 12 544 [94·4%] male and 745 [5·6%] female individuals). There were large variations between countries, with most studies reporting suicide rates in the range of 24-89 per 100 000 person-years in both sexes (22-86 in male individuals and 25-107 in female individuals). In meta-regression analyses, Europe (vs other regions), high-income countries (vs low-income and middle-income countries), and countries with lower incarceration rates (vs those with higher incarceration rates) had higher suicide rates. Incidence rate ratios between people who are incarcerated and age-standardised general populations in the same jurisdictions were typically in the range of 1·9-6·0 in male and 10·4-32·4 in female individuals. INTERPRETATION: Prison services worldwide, and particularly in Europe, should prioritise suicide prevention. Assessment and management of suicide risk in female individuals living in prison need particular attention due to excess mortality relative to community-based populations. Interpretation of synthesised data needs to be done with caution due to high heterogeneity between jurisdictions. FUNDING: Agencia Nacional de Investigación y Desarrollo, Economic and Social Research Council, and Wellcome Trust.


Assuntos
Prisioneiros , Suicídio , Humanos , Incidência , Suicídio/estatística & dados numéricos , Prisioneiros/estatística & dados numéricos , Prisioneiros/psicologia , Masculino , Feminino , Prisões/estatística & dados numéricos , Saúde Global/estatística & dados numéricos , Análise de Regressão
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