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1.
Artigo em Inglês | MEDLINE | ID: mdl-38738586

RESUMO

Chronic pruritus (CP) is frequent in general medicine and the most common complaint in general dermatology. The prevalence of CP is expected to rise in the future due to the ageing population. The clinical presentation, underlying aetiology and treatment strategy of CP are heterogeneous. Also, individual treatment aims and physical, psychic and economic burdens of patients might vary. Chronic prurigo (CPG) is the most severe disease in the chronic pruritus spectrum, being associated with long-standing scratch-induced skin lesions and a therapy refractory itch-scratch-cycle. It is thus important to raise disease awareness for CP and CPG in the general public and among decision-makers in the health system. Further, there is a need to support a rational clinical framework to optimize both diagnostics and therapeutics. Currently, there is still a shortcoming regarding approved therapies and understanding CP/CPG as severe medical conditions. Therefore, the EADV Task Force Pruritus decided to publish this white paper based on several consensus meetings. The group consented on the following goals: (a) ensure that CP is recognized as a serious condition, (b) increase public awareness and understanding of CP and CPG as chronic and burdensome diseases that can greatly affect a person's quality of life, (c) clarify that in most cases CP and CPG are non-communicable and not caused by a psychiatric disease, (d) improve the support and treatment given to patients with CP to help them manage their disease and (e) publicize existing therapies including current guidelines. We aim to point to necessary improvements in access and quality of care directed to decision-makers in health policy, among payers and administrations as well as in practical care.

2.
Br J Haematol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747092

RESUMO

Idecabtagene vicleucel (ide-cel), a chimeric antigen receptor T-cell therapy targeting B-cell maturation antigen (BCMA), received early access program (EAP) authorization in France in April 2021 for relapsed/refractory multiple myeloma (RRMM). We conducted a real-world registry-based multicentre observational study in 11 French hospitals to evaluate ide-cel outcomes. Data from 176 RRMM patients who underwent apheresis between June 2021 and November 2022 were collected from the French national DESCAR-T registry. Of these, 159 patients (90%) received ide-cel. Cytokine release syndrome occurred in 90% with 2% grade ≥3, and neurotoxicity occurred in 12% with 3% grade ≥3. Over the first 6 months, the best overall response and ≥complete response rates were 88% and 47% respectively. The median progression-free survival (PFS) from the ide-cel infusion was 12.5 months, the median overall survival (OS) was 20.8 months and the estimated OS rate at 12 months was 73.3%. Patients with extra-medullary disease (EMD) had impaired PFS (6.2 months vs. 14.8 months). On multivariable analysis, EMD and previous exposure to BCMA-targeted immunoconjugate or T-cell-redirecting GPRC5D bispecific antibody were associated with inferior PFS. Our study supports ide-cel's feasibility, safety and efficacy in real-life settings, emphasizing the importance of screening for EMD and considering prior treatments to optimize patient selection.

3.
J Eur Acad Dermatol Venereol ; 38(8): 1555-1565, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38717285

RESUMO

BACKGROUND: Response to biologics in psoriasis varies in real-world settings. Serum biomarkers could aid biologic selection and dose modifications to improve patient outcomes while encouraging cost-effective care. OBJECTIVES: To explore the exposure-response relationship for guselkumab (GUS), to define a GUS concentration target for optimal response and to evaluate the potential of serum protein levels as predictive biomarker candidates. METHODS: This is a prospective, multicentric, cohort study in psoriasis patients treated with GUS. Serum GUS trough concentrations (TCs) collected at multiple timepoints were measured using an in-house immunoassay. Next, proximity extension assay technology (Target 96 Inflammation Panel Olink®) was used to measure serum protein levels in a subcohort including 38 GUS patients (week 0 and week 4), six psoriasis patients naive for systemic treatment and four healthy controls. RESULTS: Seventy-five patients participated and 400 samples were collected. Guselkumab TCs and clinical response were correlated at week 4, week 12 and in steady-state (≥20 weeks). Optimal responders (Psoriasis Area and Severity Index [PASI] ≤ 2) had significantly higher TCs than suboptimal responders from week 4 onwards in treatment. An optimal steady-state TC of 1.6 µg/mL was defined. Although TC and absolute PASI were lower and worse, respectively, in patients weighing ≥90 kg, clinical outcomes referred to desirable to excellent PASI ranges. Therefore, we do not recommend systematically higher GUS doses in obese patients. We could not reveal early differentially expressed proteins to distinguish future optimal from suboptimal responders. CONCLUSIONS: We demonstrated an exposure-response relationship for GUS and an optimal steady-state TC of 1.6 µg/mL in real-world psoriasis patients. Hereby, we deliver more evidence that therapeutic drug monitoring poses a promising strategy in optimizing GUS treatment. No biomarker candidates were identified through serum proteomics. We propose protein screening should be repeated in larger cohorts to continue the quest for predictive biomarkers.


Assuntos
Anticorpos Monoclonais Humanizados , Biomarcadores , Proteômica , Psoríase , Humanos , Psoríase/tratamento farmacológico , Psoríase/sangue , Feminino , Masculino , Proteômica/métodos , Pessoa de Meia-Idade , Biomarcadores/sangue , Estudos Prospectivos , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Idoso , Índice de Gravidade de Doença , Relação Dose-Resposta a Droga
4.
Int J Oral Maxillofac Implants ; 0(0): 1-14, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38607358

RESUMO

A technique for virtually planning single implant by combining an intraoral digital scan, an opensource computer-aided design software program, bone sounding, and 2-dimensional radiographic imaging is described. The surgical implant guide is fabricated by using additive manufacturing technologies. Furthermore, the surgical implant guide positioned in the patient's mouth is used to radiographically verify the estimated mesio-distal implant angulation before proceeding with the surgical intervention and modified, if necessary. When a cone bean computed tomography scan is not available, this technique eases implant planning procedures and minimize possible surgical complications.

5.
Spectrochim Acta A Mol Biomol Spectrosc ; 314: 124177, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38554690

RESUMO

The SERS response of adenine is one of the most studied, due to its outstanding exaltation. However, the spectra obtained strongly differ according to the experimental conditions and still remain not well understood. To be able to search for the presence of this molecule in complex environments, it is essential to better understand the SERS response of adenine alone. After a brief presentation of the literature on the subject, we present results suggesting that the experimental spectra would result from the overlap of different spectroscopic signatures, that may probably be due to different non-covalent interactions or different electromagnetic fields experienced by adenine molecules. An independent component analysis is reported. Our results underline the difficulty to precisely analyze the experimental data, the need to continue this research and to constitute data banks that would allow comparing the spectra obtained in different laboratories according to the experimental conditions.

6.
J Infect Dis ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38214571

RESUMO

Despite inflammation being implicated in cardiovascular disease (CVD) in people with HIV (PWH), considerable heterogeneity within populations of PWH exists. Stratifying CVD risk based on inflammatory phenotype could play an important role. Using principal component analyses and unsupervised hierarchical clustering, we examined 38 biomarkers to identify inflammatory phenotypes in two independent cohorts of PWH. We identified three distinct inflammatory clusters present in both cohorts that associated with altered risk of both subclinical CVD (cohort 1) and prevalent clinical CVD (cohort 2) after adjusting for CVD risk factors. These data support precision medicine approaches to enhance CVD risk assessment in PWH.

7.
Compend Contin Educ Dent ; 45(1): 30-38, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38289633

RESUMO

A strong body of scientific evidence indicates that a four dental implant-supported prosthesis is well suited for a full-arch rehabilitation. Yet, countless edentulous patients who could benefit from this established concept are left untreated because of high costs. This article describes a novel workflow that enables the fabrication of a metal-resin fixed hybrid prosthesis supported on four implants, with a variable cost for parts and material of around $400 and a (laboratory) production time of approximately 4 hours. This approach allows for the possibility of delivering a final or long-term provisional restoration on the day of implant placement. Because of the relatively low cost and the feasibility of in-house production, this workflow can potentially allow more patients to access high-quality full-arch implant care.


Assuntos
Implantes Dentários , Boca Edêntula , Humanos , Fluxo de Trabalho , Custos e Análise de Custo
8.
Int J Implant Dent ; 9(1): 28, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37698775

RESUMO

OBJECTIVES: The aim of the ITI Consensus Workshop on zygomatic implants was to provide Consensus Statements and Clinical Recommendations for the use of zygomatic implants. MATERIALS AND METHODS: Three systematic reviews and one narrative review were written to address focused questions on (1) the indications for the use of zygomatic implants; (2) the survival rates and complications associated with surgery in zygomatic implant placement; (3) long-term survival rates of zygomatic implants and (4) the biomechanical principles involved when zygoma implants are placed under functional loads. Based on the reviews, three working groups then developed Consensus Statements and Clinical Recommendations. These were discussed in a plenary and finalized in Delphi rounds. RESULTS: A total of 21 Consensus Statements were developed from the systematic reviews. Additionally, the group developed 17 Clinical Recommendations based on the Consensus Statements and the combined expertise of the participants. CONCLUSIONS: Zygomatic implants are mainly indicated in cases with maxillary bone atrophy or deficiency. Long-term mean zygomatic implant survival was 96.2% [95% CI 93.8; 97.7] over a mean follow-up of 75.4 months (6.3 years) with a follow-up range of 36-141.6 months (3-11.8 years). Immediate loading showed a statistically significant increase in survival over delayed loading. Sinusitis presented with a total prevalence of 14.2% [95% CI 8.8; 22.0] over a mean 65.4 months follow-up, representing the most common complication which may lead to zygomatic implant loss. The international experts suggested clinical recommendations regarding planning, surgery, restoration, outcomes, and the patient's perspective.


Assuntos
Implantes Dentários , Humanos , Implantes Dentários/efeitos adversos , Redação , Atrofia , Consenso , Resultado do Tratamento
9.
Mar Pollut Bull ; 194(Pt B): 115365, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37579595

RESUMO

Increasing levels of Artificial Light At Night (ALAN) alter the natural diel cycles of organisms at global scale. ALAN constitutes a potential threat to the light-dependent functioning of symbiotic scleractinian corals, the habit-founders of warm, shallow water reefs. Here, we show that ALAN disrupts the natural diel tentacle expansion and contraction behaviour, a key mechanism for prey capture and nutrient acquisition in corals. We exposed four symbiotic scleractinian coral species to different ALAN treatments (0.4-2.5 µmol quanta m-2 s-1). Exposure to ALAN levels of 1.2 µmol quanta m-2 s-1 and above altered the normal tentacle expansion response in diurnal species (Stylophora pistillata and Duncanopsammia axifuga). The tentacle expansion pattern of nocturnal species (Montastraea cavernosa and Lobophyllia hemprichii) was less affected, which may indicate a greater capacity to tolerate ALAN exposure. The results of this work suggest that ALAN has the potential to affect nutrient acquisition mechanisms of symbiotic corals which may in turn result in changes in the coral community structure in shallow water reefs in ALAN-exposed areas.


Assuntos
Antozoários , Animais , Antozoários/fisiologia , Poluição Luminosa , Hábitos , Simbiose , Luz , Recifes de Corais
10.
Exp Dermatol ; 32(10): 1815-1822, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37564000

RESUMO

BACKGROUND: Healthcare professionals (HCPs) should strive to create the maximum value for their patients in which value is defined as the patient-relevant health outcomes achieved per costs made. However, currently it remains difficult to determine which outcomes matter to an individual psoriasis patient. OBJECTIVE: To define outcome profiles, or so called 'patient value profiles', within a cohort of psoriasis patients that can be translated to daily practice to increase value for the individual patient. METHODS: Hierarchical clustering on principal components (HCPC) was used to identify groups of patients sharing the same profile within an outcome ranking exercise. Once the clusters were defined, their characterization was provided based on a V-test. In a final step, a multi-class decision tree (MDT) based on relevant socio-demographic and clinical variables was built to allocate patients to a cluster. RESULTS: In the ranking exercise 120 patients participated. The median age was 50.0 (IQR 25.0) years and 36.7% were female. Median PASI score was 2.4 (IQR 5.2) and median duration of psoriasis was 17.0 (IQR 20.0) years. Primary treatment varied from topicals to biologicals. We found three distinct patient value profiles in this cohort (QoL, cost and treatment). A MDT was built which had an accuracy of 64%. CONCLUSION: We found three distinct patient value profiles in a cohort of psoriasis patients and patients can be easily assigned to one of these profiles based on a MDT. HCPs can use these profiles to steer psoriasis management accordingly allowing for a more goal-orientated approach.


Assuntos
Psoríase , Qualidade de Vida , Humanos , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Psoríase/psicologia , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto , Idoso , Masculino , Feminino , Valor da Vida
11.
Clin Neurophysiol ; 153: 102-110, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37473484

RESUMO

OBJECTIVE: This study aimed to investigate scalp gamma-band oscillations (GBOs) induced by mechanical stimuli activating skin nociceptors before and after the induction of mechanical hypersensitivity using high-frequency electrical stimulation (HFS) of the skin. METHODS: In twenty healthy volunteers, we recorded the electroencephalogram during robot-controlled mechanical pinprick stimulation (512 mN) applied at the right ventral forearm before and after HFS. RESULTS: HFS induced a significant increase in mechanical pinprick sensitivity, but this increased pinprick sensitivity was, at the group level, not accompanied by a significant increase in GBOs. Visual inspection of the individual data revealed that possible GBOs were present in eight out of twenty participants (40%) and the frequency of these GBOs varied substantially across participants. CONCLUSIONS: Based on the low number of participants showing GBOs we question the (clinical) utility of mechanically-induced GBOs as an electrophysiological marker of pinprick hypersensitivity in humans. SIGNIFICANCE: Mechanical pinprick-induced scalp GBOs are not useful for evaluating mechanical pinprick hypersensitivity in humans.


Assuntos
Hiperalgesia , Pele , Humanos , Estimulação Elétrica , Nociceptores/fisiologia , Antebraço
12.
AJNR Am J Neuroradiol ; 44(8): 894-900, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37500286

RESUMO

BACKGROUND AND PURPOSE: ASPECTS quantifies early ischemic changes in anterior circulation stroke on NCCT but has interrater variability. We examined the agreement of conventional and automated ASPECTS and studied the value of computer-aided detection. MATERIALS AND METHODS: We retrospectively collected imaging data from consecutive patients with acute ischemic stroke with large-vessel occlusion undergoing thrombectomy. Five raters scored conventional ASPECTS on baseline NCCTs, which were also processed by RAPID software. Conventional and automated ASPECTS were compared with a consensus criterion standard. We determined the agreement over the full ASPECTS range as well as dichotomized, reflecting thrombectomy eligibility according to the guidelines (ASPECTS 0-5 versus 6-10). Raters subsequently scored ASPECTS on the same NCCTs with assistance of the automated ASPECTS outputs, and agreement was obtained. RESULTS: For the total of 175 cases, agreement among raters individually and the criterion standard varied from fair to good (weighted κ = between 0.38 and 0.76) and was moderate (weighted κ = 0.59) for the automated ASPECTS. The agreement of all raters individually versus the criterion standard improved with software assistance, as did the interrater agreement (overall Fleiss κ = 0.15-0.23; P < .001 and .39 to .55; P = .01 for the dichotomized ASPECTS). CONCLUSIONS: Automated ASPECTS had agreement with the criterion standard similar to that of conventional ASPECTS. However, including automated ASPECTS during the evaluation of NCCT in acute stroke improved the agreement with the criterion standard and improved interrater agreement, which could, therefore, result in more uniform scoring in clinical practice.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Software , Computadores
13.
Phys Med Biol ; 68(17)2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37414003

RESUMO

Objective. To report the use of a portable primary standard level graphite calorimeter for direct dose determination in clinical pencil beam scanning proton beams, which forms part of the recommendations of the proposed Institute of Physics and Engineering in Medicine (IPEM) Code of Practice (CoP) for proton therapy dosimetry.Approach. The primary standard proton calorimeter (PSPC) was developed at the National Physical Laboratory (NPL) and measurements were performed at four clinical proton therapy facilities that use pencil beam scanning for beam delivery. Correction factors for the presence of impurities and vacuum gaps were calculated and applied, as well as dose conversion factors to obtain dose to water. Measurements were performed in the middle of 10 × 10 × 10 cm3homogeneous dose volumes, centred at 10.0, 15.0 and 25.0 g·cm-2depth in water. The absorbed dose to water determined with the calorimeter was compared to the dose obtained using PTW Roos-type ionisation chambers calibrated in terms of absorbed dose to water in60Co applying the recommendations in the IAEA TRS-398 CoP.Main results.The relative dose difference between the two protocols varied between 0.4% and 2.1% depending on the facility. The reported overall uncertainty in the determination of absorbed dose to water using the calorimeter is 0.9% (k= 1), which corresponds to a significant reduction of uncertainty in comparison with the TRS-398 CoP (currently with an uncertainty equal or larger than 2.0% (k= 1) for proton beams).Significance. The establishment of a purpose-built primary standard and associated CoP will considerably reduce the uncertainty of the absorbed dose to water determination and ensure improved accuracy and consistency in the dose delivered to patients treated with proton therapy and bring proton reference dosimetry uncertainty in line with megavoltage photon radiotherapy.


Assuntos
Grafite , Terapia com Prótons , Humanos , Prótons , Radiometria/métodos , Água , Calibragem
14.
J Eur Acad Dermatol Venereol ; 37(9): 1697-1705, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37259959

RESUMO

BACKGROUND: Psoriasis is associated with an increased mortality risk, with cardiovascular disease being the leading excess cause (in a dose-response manner with psoriasis severity). Statins have demonstrated a reduction in all-cause mortality with no excess of adverse events among the general population. The underuse of interventions in cardiovascular prevention, such as statins, for patients with psoriasis may be the result of an insufficient evaluation. OBJECTIVES: To provide the dermatologist with a tool for systematizing the treatment of dyslipidemia in psoriasis, which generally escapes the scope of dermatological practice, and to facilitate decision-making about the referral and treatment of patients. METHODS: The Psoriasis Task Force of the European Academy of Dermatology and Venereology performed this two-phase study to achieve a consensus and create recommendations on the use of statin therapy in patients with psoriasis. The first phase included a systematic review to identify a list of outline concepts and recommendations according to guidelines. The second phase consisted in a two-round Delphi study to evaluate those recommendations not literally taken from guidelines. RESULTS: A list of 47 concepts and recommendations to be followed by dermatologists involved in the treatment of patients with moderate-severe psoriasis was created. It included six main concepts about cardiovascular risk and psoriasis, six items related with the role of low-density lipoprotein cholesterol (LDL-c) and the benefits of statin treatment in psoriasis patients, eight recommendations about how cardiovascular risk should be assessed, three on the role of non-invasive cardiovascular imaging, three on LDL-c thresholds, eight key points related to statin prescription, 10 on statin treatment follow-up and three on patient referral to another specialist. CONCLUSIONS: The application of this position statement (close final list of concepts and recommendations) will help dermatologists to manage dyslipidemia and help psoriasis patients to reduce their cardiovascular risk.


Assuntos
Doenças Cardiovasculares , Dermatologia , Dislipidemias , Inibidores de Hidroximetilglutaril-CoA Redutases , Psoríase , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , LDL-Colesterol , Psoríase/tratamento farmacológico , Psoríase/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico
15.
Anaesth Crit Care Pain Med ; 42(4): 101223, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37030393

RESUMO

BACKGROUND: The adductor canal block provides pain relief on the anterior aspect of the knee after arthroplasty. Pain on the posterior aspect may be treated either by partial local infiltration analgesia of the posterior capsule or by a tibial nerve block. This randomized, controlled, triple-blinded trial tests the hypothesis that a tibial nerve block would provide superior analgesia compared to posterior capsule infiltration in patients scheduled for total knee arthroplasty under spinal anesthesia with an adductor canal block. METHODS: Sixty patients were randomized to receive either infiltration of the posterior capsule by the surgeon with ropivacaine 0.2%, 25 mL, or a tibial nerve block with 10 mL of ropivacaine 0.5%. Sham injections were performed to guarantee proper blinding. The primary outcome was intravenous morphine consumption at 24 h. Secondary outcomes included intravenous morphine consumption, pain scores at rest and on movement, and different functional outcomes, measured at up to 48 h. When necessary, longitudinal analyses were performed with a mixed-effects linear model. RESULTS: The median (interquartile range) of cumulative intravenous morphine consumption at 24 h was 12 mg (4-16) and 8 mg (2-14) in patients having the infiltration or the tibial nerve block respectively (p = 0.20). Our longitudinal model showed a significant interaction between group and time in favor of the tibial nerve block (p = 0.015). No significant differences were present between groups in the other above-mentioned secondary outcomes. CONCLUSION: A tibial nerve block does not provide superior analgesia when compared to infiltration. However, a tibial nerve block might be associated with a slower increase in morphine consumption over time.


Assuntos
Analgesia , Artroplastia do Joelho , Bloqueio Nervoso , Humanos , Ropivacaina , Artroplastia do Joelho/métodos , Anestésicos Locais , Dor Pós-Operatória/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Bloqueio Nervoso/métodos , Resultado do Tratamento , Analgésicos , Analgesia/métodos , Morfina/uso terapêutico
16.
Dig Liver Dis ; 55(9): 1280-1287, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36872200

RESUMO

BACKGROUND: Little is known about the prognosis of colorectal cancer associated with inflammatory bowel disease (CRC-IBD) in a real-world cohort in France. METHODS: We conducted a retrospective observational study including all patients presenting CRC-IBD in a French tertiary center. RESULTS: Among 6510 patients, the rate of CRC was 0.8% with a median delay of 19.5 years after IBD diagnosis (median age 46 years, ulcerative colitis 59%, initially localized tumor 69%). There was a previous exposure to immunosuppressants (IS) in 57% and anti-TNF in 29% of the cases. A RAS mutation was observed in only 13% of metastatic patients. OS of the whole cohort was 45 months. OS and PFS of synchronous metastatic patients was 20.4 months and 8.5 months respectively. Among the patients with localized tumor those previously exposed to IS had a better PFS (39 months vs 23 months; p = 0.05) and OS (74 vs 44 months; p = 0.03). The IBD relapse rate was 4%. No unexpected chemotherapy side-effect was observed CONCLUSIONS: OS of CRC-IBD is poor in metastatic patients although IBD is not associated with under-exposure or increased toxicity to chemotherapy. Previous IS exposure may be associated with a better prognosis.


Assuntos
Neoplasias Colorretais , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Pessoa de Meia-Idade , Doença de Crohn/complicações , Inibidores do Fator de Necrose Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/complicações , Fatores de Risco , Recidiva Local de Neoplasia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Prognóstico , Imunossupressores
18.
Aquat Toxicol ; 258: 106474, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36893699

RESUMO

Methylmercury (MeHg) is a ubiquitous bioaccumulative neurotoxicant present in aquatic ecosystems. It is known to alter behaviors, sensory functions and learning abilities in fish and other vertebrates. Developmental and early-life stages exposure to MeHg can lead to brain damage with immediate consequences on larvae behavior, but may also induce long term effects in adults after a detoxification period. However, very little is known about developmental origin of behavioral impairment in adults due to early exposure to MeHg. The aim of this study is to assess whether early-life MeHg exposure induces immediate and/or delayed effects on behaviors, related genes expression and DNA methylation (one of epigenetic mechanisms). To reach this goal, newly hatched larvae of mangrove rivulus fish, Kryptolebias marmoratus, were exposed to two sub-lethal concentrations of MeHg (90 µg/L and 135 µg/L) for 7 days, and immediate and delayed effects were assessed respectively in 7 dph (days post-hatching) and 90 dph fish. This species naturally produces isogenic lineages due to its self-fertilizing reproduction system, which is unique among vertebrates. It allows to study how environment stressors can influence organism's phenotype while minimizing genetic variability. As results, both MeHg exposures are associated with a decreased foraging efficiency and thigmotaxis, and a dose-dependent reduction in larvae locomotor activity. Regarding molecular analysis in larvae whole bodies, both MeHg exposures induced significant decreased expression of DNMT3a, MAOA, MeCP2 and NIPBL, and significant increase of GSS, but none of those genes underwent methylation changes in targeted CpGs. None of significant behavioral and molecular impairments observed in 7-dph larvae were found in 90-dph adults, which highlight a distinction between immediate and delayed effects of developmental MeHg exposure. Our results suggest implications of aminergic system and its neurotransmitters, redox/methylation trade-off and possibly other epigenetic mechanisms in MeHg neurotoxicity underlying behavioral alterations in rivulus.


Assuntos
Ciprinodontiformes , Peixes Listrados , Compostos de Metilmercúrio , Poluentes Químicos da Água , Animais , Compostos de Metilmercúrio/toxicidade , Ecossistema , Poluentes Químicos da Água/toxicidade , Peixes Listrados/genética , Ciprinodontiformes/genética , Larva , Expressão Gênica
19.
Semin Cell Dev Biol ; 145: 52-59, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-35659164

RESUMO

Clade-specific (a.k.a. lineage-specific) genes are very common and found at all taxonomic levels and in all clades examined. They can arise by duplication of previously existing genes, which can involve partial truncations or combinations with other protein domains or regulatory sequences. They can also evolve de novo from non-coding sequences, leading to potentially truly novel protein domains. Finally, since clade-specific genes are generally defined by lack of sequence homology with other proteins, they can also arise by sequence evolution that is rapid enough that previous sequence homology can no longer be detected. In such cases, where the rapid evolution is followed by constraint, we consider them to be ontologically non-novel but likely novel at a functional level. In general, clade-specific genes have received less attention from biologists but there are increasing numbers of fascinating examples of their roles in important traits. Here we review some selected recent examples, and argue that attention to clade-specific genes is an important corrective to the focus on the conserved developmental regulatory toolkit that has been the habit of evo-devo as a field. Finally, we discuss questions that arise about the evolution of clade-specific genes, and how these might be addressed by future studies. We highlight the hypothesis that clade-specific genes are more likely to be involved in synapomorphies that arose in the stem group where they appeared, compared to other genes.

20.
J Rehabil Med ; 55: jrm00299, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36017667

RESUMO

OBJECTIVES: Physiotherapy leads to improvements in critically ill patients who receive mechanical ventilation. However, cancer patients have not been included in previous studies on this subject. This study explored the feasibility and safety of physiotherapy in the intensive care unit for patients with malignancy. DESIGN: Observational prospective single-centre study, comparing cancer and control patients. PATIENTS: All consecutive patients admitted to the intensive care unit who needed invasive mechanical ventilation for more than 2 days with no contraindication to physiotherapy were included in the study. METHODS: The main outcome was the proportion of physiotherapy sessions at the prescribed level in each group. RESULTS: A total of 60 patients were included within 1 year. A total of 576 days were screened for physiotherapy sessions and 367 physiotherapy-days were analysed (137 days for control patients and 230 days for cancer patients). The ratio of physiotherapy sessions performed/prescribed did not differ between groups: 0.78 (0.47-1) in the control group vs 0.69 (0.6-1) in the cancer group (odds ratio 1.18 (IC95% 0.74-1.89); p = 0.23). A sensitivity analysis including patient effect as random variable confirmed those results (odds ratio 1.16 (0.56-2.38), p = 0.69). Adverse events occurred with the same frequency in cancer patients and non-cancer patients. CONCLUSION: Physiotherapy in cancer patients who require intubation is feasible and safe. However, only two-thirds of prescribed physiotherapy sessions were performed. Studies are warranted to explore the barriers to physiotherapy in the intensive care unit setting.


Assuntos
Unidades de Terapia Intensiva , Neoplasias , Humanos , Estudos Prospectivos , Estudos de Viabilidade , Modalidades de Fisioterapia , Estado Terminal , Neoplasias/terapia
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