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1.
Acta Biomater ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39245308

RESUMO

Cell therapy is a promising strategy for treating neurological pathologies but requires invasive methods to bypass the blood-brain barrier restrictions. The nose-to-brain route has been presented as a direct and less invasive alternative to access the brain. The primary limitations of this route are low retention in the olfactory epithelium and poor cell survival in the harsh conditions of the nasal cavity. Thus, using chitosan-based hydrogel as a vehicle is proposed in this work to overcome the limitations of nose-to-brain cell administration. The hydrogel's design was driven to achieve gelification in response to body temperature and a mucosa-interacting chemical structure biocompatible with cells. The hydrogel showed a <30 min gelation time at 37°C and >95% biocompatibility with 2D and 3D cultures of mesenchymal stromal cells. Additionally, the viability, stability, and migration capacity of oligodendrocyte precursor cells (OPCs) within the hydrogel were maintained in vitro for up to 72 hours. After the intranasal administration of the OPCs-containing hydrogel, histological analysis showed the presence of viable cells in the nasal cavity for up to 72 hours post-administration in healthy athymic mice. These results demonstrate the hydrogel's capacity to increase the residence time in the nasal cavity while providing the cells with a favorable environment for their viability. This study presents for the first time the use of thermosensitive hydrogels in nose-to-brain cell therapy, opening the possibility of increasing the delivery efficiency in future approaches in translational medicine. STATEMENT OF SIGNIFICANCE: : This work highlights the potential of biomaterials, specifically hydrogels, in improving the effectiveness of cell therapy administered through the nose. The nose-to-brain route has been suggested as a non-invasive way to directly access the brain. However, delivering stem cells through this route poses a challenge since their viability must be preserved and cells can be swept away by nasal mucus. Earlier attempts at intranasal cell therapy have shown low efficiency, but still hold promise to the future. The hydrogels designed for this study can provide stem cells with a biocompatible environment and adhesion to the nasal atrium, easing the successful migration of viable cells to the brain.

2.
J Clin Med ; 13(15)2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39124745

RESUMO

Background: Colorectal cancer is a leading cause of morbidity and mortality worldwide, with chemotherapy being a crucial treatment despite its significant side effects, such as chemotherapy-induced peripheral neuropathy (CIPN). Physical exercise has shown potential benefits in mitigating these side effects and improving patients' overall well-being. Objective: This study aims to evaluate the efficacy of a strength exercise program in reducing CIPN in patients with colorectal cancer undergoing chemotherapy, along with secondary objectives including impacts on quality of life, body mass index, oxygen consumption, anxiety and depression, fatigue, sleep quality, and various analytical parameters. Methods: A double-blind randomized controlled trial was conducted with 44 participants, divided into an intervention group (supervised resistance training twice a week and home exercises) and a control group (home exercises only). The primary outcome measure was CIPN, assessed using the EORTC QLQ-CIPN20 questionnaire. Secondary outcomes included assessments using the EORTC QLQ-C30, the 6-minute walk test, HADS, FACT-F, and MISS, along with various blood parameters. Results and Conclusions: The study will provide insights into the effectiveness of physical exercise in managing CIPN and improving various health parameters in colorectal cancer patients. By developing tailored exercise protocols, this research aims to enhance patient quality of life, optimize treatment outcomes, and reduce the incidence of debilitating side effects, thereby supporting the integration of physical exercise into standard oncological care.

3.
Cureus ; 16(7): e63552, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39087168

RESUMO

Background Cardiovascular disease is a leading cause of premature career termination in commercial airline pilots (APs). In this cross-sectional study, we sought to investigate the relationship between intima-media thickness (IMT), a marker of subclinical atherosclerosis, and cardiovascular risk factors in APs, focusing on overweight status and sleep quality. Methods A total of 140 male APs were categorized into four groups based on body mass index (BMI) and Pittsburgh Sleep Quality Index (PSQI) score: overweight poor sleepers (OW-PS), overweight good sleepers (OW-GS), normal weight poor sleepers (NW-PS), and normal weight good sleepers (NW-GS). IMT was quantified in the common carotid artery (CCA) and carotid bulb using ultrasound, yielding a composite IMT (IMTcom) measure. Common cardiovascular risk factors were assessed in all participants. Results The prevalence of overweight and poor sleep quality was 43.6% and 32.9%, respectively. The OW-PS group had significantly higher age, heart rate, total cholesterol, and low-density lipoprotein (LDL) cholesterol compared to other groups (p<0.05). Overweight pilots, regardless of sleep quality, had increased IMTcom compared to normal-weight pilots (p<0.001). Age and LDL cholesterol were independent predictors of IMTcom in the OW-PS and OW-GS groups (p<0.05). Conclusions Overweight status, irrespective of sleep quality, is associated with increased IMT in APs, suggesting a higher burden of subclinical atherosclerosis. Interventions focused on reducing LDL cholesterol levels and managing age-related cardiovascular risk factors could be advantageous in mitigating the risk of atherosclerotic vascular disease in overweight pilots.

4.
Nanomaterials (Basel) ; 14(15)2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39120381

RESUMO

Non-conventional resonances, both acoustic and photonic, are found in metallic particles with a toroidal nanopropeller geometry, which is generated by sweeping a three-lobed 2D shape along a spiral with twisting angle α. For both optical and acoustic cases, the spectral location of resonances experiences a red-shift as a function of α. We demonstrate that the optical case can be understood as a natural evolution of resonances as the spiral length of the toroidal nanopropeller increases with α, implying a huge helicity-dependent absorption cross-section. In the case of acoustic response, two red-shifting breathing modes are identified. Additionally, even a small α allows the appearance of new low-frequency resonances, whose spectral dispersion depends on a competition between the length of the generative spiral and the pitch of the toroidal nanopropeller.

5.
Phys Rev Lett ; 133(4): 046901, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39121417

RESUMO

In contrast with the typical electric currents accelerated under the influence of a Coulombic force, there are only a few condensed matter examples of particles experiencing a force proportional to a constant, external magnetic field. In this Letter, we present a new alternative, based on an isotropic radiation spinning field and the magneto-optical effect, in which a particle is propelled by a magnetic field just like a magnetic monopole will do. This is a purely nonreciprocal effect as the reciprocal equivalent (a chiral dipole), despite presenting a dichroic response, does not experience any force when illuminated by the spinning field. The "magnetic charge" induced by impinging radiation on the magneto-optical dipole is found to depend linearly on the helicity of the field. In addition, this artificial monopole experiences a dichroic permanent optical torque and does not interact with an external electric field.

6.
Environ Res ; 262(Pt 1): 119802, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39147188

RESUMO

Forest disturbance regimes across biomes are being altered by interactive effects of global change. Establishing baselines for assessing change requires detailed quantitative data on past disturbance events, but such data are scarce and difficult to obtain over large spatial and temporal scales. The integration of remote sensing with dense time series analysis and cloud computing platforms is enhancing the ability to monitor historical disturbances, and especially non-stand replacing events along climatic gradients. Since the integration of such tools is still scarce in Mediterranean regions, here, we combine dense Landsat time series and the Continuous Change Detection and Classification - Spectral Mixture Analysis (CCDC-SMA) method to monitor forest disturbance in continental Spain from 1985 to 2023. We adapted the CCDC-SMA method for improved disturbance detection creating new spectral libraries representative of the study region, and quantified the year, month, severity, return interval, and type of disturbance (stand replacing, non-stand replacing) at a 30 m resolution. In addition, we characterised forest disturbance regimes and trends (patch size and severity, and frequency of events) of events larger than 0.5 ha at the national scale by biome (Mediterranean and temperate) and forest type (broadleaf, needleleaf and mixed). We quantified more than 2.9 million patches of disturbed forest, covering 4.6 Mha over the region and period studied. Forest disturbances were on average larger but less severe in the Mediterranean than in the temperate biome, and significantly larger and more severe in needleleaf than in mixed and broadleaf forests. Since the late 1980s, forest disturbances have decreased in size and severity while increasing in frequency across all biomes and forest types. These results have important implications as they confirm that disturbance regimes in continental Spain are changing and should therefore be considered in forest strategic planning for policy development and implementation.

7.
RNA Biol ; 21(1): 23-34, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39194147

RESUMO

GEMIN5 is a multifunctional protein involved in various aspects of RNA biology, including biogenesis of snRNPs and translation control. Reduced levels of GEMIN5 confer a differential translation to selective groups of mRNAs, and biallelic variants reducing protein stability or inducing structural conformational changes are associated with neurological disorders. Here, we show that upregulation of GEMIN5 can be detrimental as it modifies the steady state of mRNAs and enhances alternative splicing (AS) events of genes involved in a broad range of cellular processes. RNA-Seq identification of the mRNAs associated with polysomes in cells with high levels of GEMIN5 revealed that a significant fraction of the differential AS events undergo translation. The association of mRNAs with polysomes was dependent on the type of AS event, being more frequent in the case of exon skipping. However, there were no major differences in the percentage of genes showing open-reading frame disruption. Importantly, differential AS events in mRNAs engaged in polysomes, eventually rendering non-functional proteins, encode factors controlling cell growth. The broad range of mRNAs comprising AS events engaged in polysomes upon GEMIN5 upregulation supports the notion that this multifunctional protein has evolved as a gene expression balancer, consistent with its dual role as a member of the SMN complex and as a modulator of protein synthesis, ultimately impinging on cell homoeostasis.


Assuntos
Processamento Alternativo , Polirribossomos , Biossíntese de Proteínas , RNA Mensageiro , Proteínas do Complexo SMN , Humanos , Proteínas do Complexo SMN/metabolismo , Proteínas do Complexo SMN/genética , Polirribossomos/metabolismo , Polirribossomos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Éxons , Células HeLa , Regulação da Expressão Gênica
8.
Healthcare (Basel) ; 12(16)2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39201232

RESUMO

BACKGROUND: Cancer is a leading cause of morbidity and mortality globally. Dyspnea, affecting up to 60% of cancer patients, exacerbates physical and psychological distress, reducing quality of life. This study aims to explore the relationship between dyspnea and factors such as age, sex, clinical diagnosis, and treatment lines in cancer patients, with the goal of improving understanding and management of this debilitating symptom to enhance patient care and quality of life. METHODS: This study employed an observational, cross-sectional, and descriptive approach to investigate patients with oncological disease at the University Hospital of Salamanca between March 2021 and April 2024. A convenience sample was selected, including patients over 18 years old with a pathological diagnosis of cancer, experiencing any degree of dyspnea, and who consented to participate by signing the informed consent. Exclusion criteria included lack of consent and clinical conditions that prevented an interview. The studied variables encompass sociodemographic (age, gender, diagnosis, tumor stage, number of treatment lines) and clinical aspects (daily activities, degree of dyspnea, functional capacity, physical performance), evaluated using the Barthel Index, the mMRC Dyspnea Scale, the ECOG Scale, and the Short Physical Performance Battery (SPPB). Data were collected through semistructured interviews and medical records, and analyzed using specialized software. This research has ethical approval CEiM Code 2023 12 1472, Reference 2024/01. RESULTS: The mean age was 66.82 years. Lung cancer was predominant (60.2%), with most patients in stage 3 (65.7%) and receiving three treatment lines (68.7%). Higher age, advanced disease stage, and more treatment lines correlated with lower Barthel and SPPB scores, and higher ECOG and mMRC scores, indicating worse functionality, physical performance, and greater dyspnea. No significant correlations were found between gender or pathological diagnosis and the studied variables. CONCLUSIONS: Advanced age, higher disease stage, and more treatment lines are associated with decreased functionality, poorer physical performance, and increased dyspnea in cancer patients. Gender and specific cancer diagnosis do not significantly affect these relationships. Addressing dyspnea is crucial to improving the quality of life and physical performance in this population. Future studies should explore additional factors like treatment types and nutritional status.

9.
Am J Trop Med Hyg ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39191240

RESUMO

The objective of this study was to evaluate the knowledge level and perception of dengue fever management among Peruvian physicians and to determine the factors associated with higher knowledge. We conducted an analytical cross-sectional study based on an online survey. To evaluate the factors associated with a high level of knowledge (≥70% of correct answers), we used crude (cPR) and adjusted (aPR) prevalence ratios by the Poisson regression model. Of 359 respondents (median age: 33 years; male: 56.5%), 78.8% achieved a high level of knowledge. Multivariable analysis showed an independent association with having read the Peruvian clinical practice guidelines for dengue management (aPR: 1.29; 95% CI: 1.12-1.49), having experience in treating patients (aPR: 1.32; 95% CI: 1.03-1.68), and having treated cases frequently (aPR: 1.22; 95% CI: 1.02-1.46). Residing in the eastern macroregion (aPR: 0.83; 95% CI: 0.71-0.97) was associated with a low level of knowledge. In conclusion, Peruvian physicians had a high level of knowledge about dengue fever. This was associated with having clinical experience in dengue management. However, given the low level of knowledge in the eastern macroregion, educational campaigns are necessary in this area.

10.
Nat Commun ; 15(1): 7483, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39209825

RESUMO

Enhancing thermogenic brown adipose tissue (BAT) function is a promising therapeutic strategy for metabolic disease. However, predominantly thermoneutral modern human living conditions deactivate BAT. We demonstrate that selective adipocyte deficiency of the oxygen-sensor HIF-prolyl hydroxylase (PHD2) gene overcomes BAT dormancy at thermoneutrality. Adipocyte-PHD2-deficient mice maintain higher energy expenditure having greater BAT thermogenic capacity. In human and murine adipocytes, a PHD inhibitor increases Ucp1 levels. In murine brown adipocytes, antagonising the major PHD2 target, hypoxia-inducible factor-(HIF)-2a abolishes Ucp1 that cannot be rescued by PHD inhibition. Mechanistically, PHD2 deficiency leads to HIF2 stabilisation and binding of HIF2 to the Ucp1 promoter, thus enhancing its expression in brown adipocytes. Serum proteomics analysis of 5457 participants in the deeply phenotyped Age, Gene and Environment Study reveal that serum PHD2 associates with increased risk of metabolic disease. Here we show that adipose-PHD2-inhibition is a therapeutic strategy for metabolic disease and identify serum PHD2 as a disease biomarker.


Assuntos
Tecido Adiposo Marrom , Metabolismo Energético , Prolina Dioxigenases do Fator Induzível por Hipóxia , Termogênese , Proteína Desacopladora 1 , Animais , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Humanos , Camundongos , Tecido Adiposo Marrom/metabolismo , Termogênese/genética , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genética , Masculino , Camundongos Knockout , Feminino , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Adipócitos/metabolismo , Oxigênio/metabolismo , Camundongos Endogâmicos C57BL , Adipócitos Marrons/metabolismo , Adulto , Regiões Promotoras Genéticas , Pessoa de Meia-Idade
11.
Microb Cell Fact ; 23(1): 234, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39182107

RESUMO

BACKGROUND: Several two-component systems of Streptomyces coelicolor, a model organism used for studying antibiotic production in Streptomyces, affect the expression of the bfr (SCO2113) gene that encodes a bacterioferritin, a protein involved in iron storage. In this work, we have studied the effect of the deletion mutant ∆bfr in S. coelicolor. RESULTS: The ∆bfr mutant exhibits a delay in morphological differentiation and produces a lesser amount of the two pigmented antibiotics (actinorhodin and undecylprodigiosin) compared to the wild type on complex media. The effect of iron in minimal medium was tested in the wild type and ∆bfr mutant. Consequently, we also observed different levels of production of the two pigmented antibiotics between the two strains, depending on the iron concentration and the medium (solid or liquid) used. Contrary to expectations, no differences in intracellular iron concentration were detected between the wild type and ∆bfr mutant. However, a higher level of reactive oxygen species in the ∆bfr mutant and a higher tolerance to oxidative stress were observed. Proteomic analysis showed no variation in iron response proteins, but there was a lower abundance of proteins related to actinorhodin and ribosomal proteins, as well as others related to secondary metabolite production and differentiation. Additionally, a higher abundance of proteins related to various types of stress, such as respiration and hypoxia among others, was also revealed. Data are available via ProteomeXchange with identifier PXD050869. CONCLUSION: This bacterioferritin in S. coelicolor (Bfr) is a new element in the complex regulation of secondary metabolism in S. coelicolor and, additionally, iron acts as a signal to modulate the biosynthesis of active molecules. Our model proposes an interaction between Bfr and iron-containing regulatory proteins. Thus, identifying these interactions would provide new information for improving antibiotic production in Streptomyces.


Assuntos
Antraquinonas , Antibacterianos , Proteínas de Bactérias , Ferritinas , Ferro , Streptomyces coelicolor , Streptomyces coelicolor/metabolismo , Streptomyces coelicolor/genética , Streptomyces coelicolor/crescimento & desenvolvimento , Antibacterianos/biossíntese , Antibacterianos/metabolismo , Ferritinas/metabolismo , Ferritinas/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Ferro/metabolismo , Antraquinonas/metabolismo , Grupo dos Citocromos b/metabolismo , Grupo dos Citocromos b/genética , Regulação Bacteriana da Expressão Gênica , Prodigiosina/metabolismo , Prodigiosina/análogos & derivados , Prodigiosina/biossíntese , Espécies Reativas de Oxigênio/metabolismo , Proteômica , Benzoisocromanequinonas
12.
Insects ; 15(8)2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39194776

RESUMO

Tick-borne rickettsioses (TBRs) are distributed worldwide and are recognized as important emerging vector-borne zoonotic diseases in Europe. The aim of this study was to identify tick-associated Rickettsia among ticks removed from humans, and to track how tick populations and their associated pathogens have changed over the years. For this purpose, we conducted a tick surveillance study in northwestern Spain between 2018 and 2022. Ticks were morphologically identified and analyzed for the presence of rickettsial pathogens through the amplification of the citrate synthase (gltA) and the outer membrane protein A (ompA) genes. PCR products were sequenced and subjected to phylogenetic analyses. We collected 7397 ticks, with Ixodes ricinus being the species most frequently isolated. Based on the PCR results, Rickettsia DNA was detected in 1177 (15.91%) ticks, and 10 members of Rickettsia were identified: R. aeschlimannii, R. conorii subsp. conorii, R. conorii subsp. raoultii, R. massiliae, R. monacensis, R. sibirica subsp. mongolitimonae, R. slovaca, R. helvetica, Candidatus R. barbariae, and Candidatus R. rioja. Some of these Rickettsia have gone previously undetected in the study region. There is clear geographic and seasonal expansion not only of tick populations, but also of the associated Rickettsia. The comparison of our data with those obtained years ago provides a clear idea of how the spatiotemporal distributions of ticks and their associated Rickettsiae have changed over the years.

13.
Cardiovasc Diabetol ; 23(1): 311, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39182106

RESUMO

BACKGROUND: Typical bone proteins, such as sclerostin and periostin, have been associated with cardiovascular disease (CVD). Simultaneously, several risk scores have been developed to predict CVD in the general population. Therefore, we aimed to evaluate the association of these bone proteins related to CVD, with the main vascular risk scales: Framingham Risk Score (FRS), REGICOR and SCORE2-Diabetes, in patients with type 2 diabetes. We focus in particular on the SCORE2-Diabetes algorithm, which predicts 10-year CVD risk and is specific to the study population. METHODS: This was a cross-sectional study including 104 patients with type 2 diabetes (62 ± 6 years, 60% males). Clinical data, biochemical measurements, and serum bioactive sclerostin and periostin levels were collected, and different risk scales were calculated. The association between bioactive sclerostin or periostin with the risk scales was analyzed. RESULTS: A positive correlation was observed between circulating levels of bioactive sclerostin (p < 0.001) and periostin (p < 0.001) with SCORE2-Diabetes values. However, no correlation was found with FRS or REGICOR scales. Both serum bioactive sclerostin and periostin levels were significantly elevated in patients at high-very high risk of CVD (score ≥ 10%) than in the low-moderate risk group (score < 10%) (p < 0.001 for both). Moreover, analyzing these proteins to identify patients with type 2 diabetes at high-very high vascular risk using ROC curves, we observed significant AUC values for bioactive sclerostin (AUC = 0.696; p = 0.001), periostin (AUC = 0.749; p < 0.001), and the model combining both (AUC = 0.795; p < 0.001). For diagnosing high-very high vascular risk, serum bioactive sclerostin levels > 131 pmol/L showed 51.6% sensitivity and 78.6% specificity. Similarly, serum periostin levels > 1144 pmol/L had 64.5% sensitivity and 76.2% specificity. CONCLUSIONS: Sclerostin and periostin are associated with vascular risk in the SCORE2-Diabetes algorithm, opening a new line of investigation to identify novel biomarkers of cardiovascular risk in the type 2 diabetes population.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Algoritmos , Biomarcadores , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Fatores de Risco de Doenças Cardíacas , Valor Preditivo dos Testes , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Medição de Risco , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Idoso , Biomarcadores/sangue , Proteínas Adaptadoras de Transdução de Sinal/sangue , Prognóstico , Marcadores Genéticos , Moléculas de Adesão Celular/sangue , Técnicas de Apoio para a Decisão
14.
Chem Mater ; 36(12): 6017-6026, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38947979

RESUMO

Li6PS5Cl has attracted significant attention due to its high Li-ion conductivity and processability, facilitating large-scale solid-state battery applications. However, when paired with high-voltage cathodes, it experiences adverse side reactions. Li3InCl6 (LIC), known for its higher stability at high voltages and moderate Li-ion conductivity, is considered a catholyte to address the limitations of Li6PS5Cl. To extend the stability of Li6PS5Cl toward LiNi0.8Co0.15Al0.05O2 (NCA), we applied nanocrystalline LIC as a 180 nm-thick protective coating in a core-shell-like fashion (LIC@NCA) via mechanofusion. Solid-state batteries with LIC@NCA allow an initial discharge specific capacity of 148 mA h/g at 0.1C and 80% capacity retention for 200 cycles at 0.2C with a cutoff voltage of 4.2 V (vs Li/Li+), while cells without LIC coating suffers from low initial discharge capacity and poor retention. Using a wide spectrum of advanced characterization techniques, such as operando XRD, XPS, FIB-SEM, and TOF-SIMS, we reveal that the superior performance of solid-state batteries employing LIC@NCA is related to the suppression of detrimental interfacial reactions of NCA with Li6PS5Cl, delamination, and particle cracking compared to uncoated NCA.

15.
Phys Rev Lett ; 132(26): 268401, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38996302

RESUMO

Common models of circadian rhythms are typically constructed as compartmental reactions of well-mixed biochemicals, incorporating a negative-feedback loop consisting of several intermediate reaction steps essentially required to produce oscillations. Spatial transport of each reactant is often represented as an extra compartmental reaction step. Contrary to this traditional understanding, in this Letter we demonstrate that a single activation-repression biochemical reaction pair is sufficient to generate sustained oscillations if the sites of both reactions are spatially separated and molecular transport is mediated by diffusion. Our proposed scenario represents the simplest configuration in terms of the participating chemical reactions and offers a conceptual basis for understanding biological oscillations and inspiring in vitro assays aimed at constructing minimal clocks.


Assuntos
Ritmo Circadiano , Modelos Biológicos , Difusão , Ritmo Circadiano/fisiologia , Retroalimentação Fisiológica
16.
Spine Deform ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026125

RESUMO

Scheuermann´s kyphosis (SK) is the most common cause of painful and progressive structural hyperkyphosis in adolescents. Surgical treatment should be considered in cases of refractory pain or progressive deformities. We present the clinical and radiological results obtained using a bipolar, hybrid posterior instrumentation tecnique. We analysed 12 males and 6 females, with mean age of 15.8 years. Minimum follow-up was 2 years. We used transverse process hooks at the cranial level and polyaxial screws for the remaining levels. We did not instrument the periapical segment. We used the sagittal stable vertebra (SSV) as the lower instrumented vertebra (LIV) in most cases, the "barely touched SSV" if the above disc space is lordotic. The mean preoperative kyphosis was 73.6º, mean postoperative kyphosis 44.7º, and mean correction of 28.9º (p = 0.0002). The mean reduction in lumbar lordosis (LL) was 8.9º (p = 0.0018). There were no significant differences in the spinopelvic parameters or sagittal balance. The mean number of instrumented levels was 8.9. Type II osteotomies were necessary in only three patients. Three patients had a cranial sagittal angle greater than 10°, all of them asymptomatic. Postoperatively, all patients had VAS scores less than 2 and SRS-22 scores greater than 4. Hybrid bipolar posterior instrumentation offers adequate curve correction, less operative time, implant density, bleeding, material protrusion and risk of spinal cord injury, leaving a large periapical bed for graft supply. We propose to measure the flexibility of the curve in MRI. In flexible curves (those that correct at least 20% in the supine decubitus position), wide facetectomies offer adequate correction of the deformity.

17.
Vet Res Commun ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954258

RESUMO

A 4-month-old female Shar-pei dog was admitted with apathy, anorexia, and vomiting. The patient had an appropriate vaccination protocol, with the last vaccine administered 2.5 weeks prior to the onset of clinical signs. Physical examination revealed tachycardia, fever and swelling of the tibiotarsal joints. Several diagnostic tests including complete blood cell count, biochemistry profile, urinalysis, thoracic radiographs, hind limbs radiographs, abdominal ultrasound, and infectious diseases tests, were conducted to determine the underlying cause. Shar-Pei Auto-inflammatory Disease (SPAID) was diagnosed. Additionally, the patient developed skin necrosis in the inner aspect of the tibiotarsal joints as a complication. A skin biopsy revealed cutaneous vasculopathy causing degeneration, abrupt ulceration, and ischemic necrosis with intense neutrophilic inflammation of the dermis and subcutis. Moreover, a hospital-acquired infection was identified by skin culture. Debridement of the necrotic skin was performed, and due to its' severity and extent, the wound was closed by secondary intention. A diagnostic protocol and the therapeutic dose of acetylsalicylic acid, which led to clinical improvement, are recommended here. The patient has continued to present episodic manifestations of SPAID mainly fever and swelling of the tibiotarsal joints, but there has been no recurrence of necrosis or other cutaneous lesion in the last two years.

18.
J Spine Surg ; 10(2): 224-231, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38974489

RESUMO

Background: "Convex Pedicle Screw Technique" reduces the theoretical risk of neurovascular injury. Our aim is to evaluate the efficacy of this technique in patients with neuromuscular scoliosis (NMS). Methods: Retrospective study of 12 patients who underwent a Convex Pedicle Screw Technique and were diagnosed with NMS. Patients who had undergone previous spinal surgery were excluded. The minimum follow-up required was 24 months. Demographic data, intraoperative data, neurovascular complications and neurophysiological events requiring implant repositioning, as well as pre- and postoperative radiological variables were collected. Results: Twelve patients diagnosed with NMS underwent surgery. The median operative time was 217 minutes. Mean blood loss was 3.8±1.1 g/dL hemoglobin (Hb). The median postoperative stay was 8.8±4 days. A reduction of the Cobb angle in primary curve of 49.1% (from 52.8°±18° to 26.5°±12.6°; P<0.001) and in secondary curve of 25.2% (from 27.8°±18.9° to 18.3°±13.3°; P=0.10) was achieved. Coronal balance improved by 69.4% (7.5±46.2 vs. 2.3±20.9 mm; P=0.72) and sagittal balance by 75% (from -14.1±71.8 vs. -3.5±48.6 mm; P=0.50). There were no neurovascular complications. There were no intraoperative neurophysiological events requiring implant repositioning, nor during reduction maneuvers. No infections were reported. Conclusions: The correction of the deformity from convexity in NMS achieves similar results to other techniques, and a very low complication rate.

19.
Microb Ecol ; 87(1): 93, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008123

RESUMO

Huanglongbing, also known as citrus greening, is currently the most devastating citrus disease with limited success in prevention and mitigation. A promising strategy for Huanglongbing control is the use of antimicrobials fused to a carrier protein (phloem protein of 16 kDa or PP16) that targets vascular tissues. This study investigated the effects of genetically modified citrus trees expressing Citrus sinensis PP16 (CsPP16) fused to human lysozyme and ß-defensin-2 on the soil microbiome diversity using 16S amplicon analysis. The results indicated that there were no significant alterations in alpha diversity, beta diversity, phylogenetic diversity, differential abundance, or functional prediction between the antimicrobial phloem-overexpressing plants and the control group, suggesting minimal impact on microbial community structure. However, microbiota diversity analysis revealed distinct bacterial assemblages between the rhizosphere soil and root environments. This study helps to understand the ecological implications of crops expressing phloem-targeted antimicrobials for vascular disease management, with minimal impact on soil microbiota.


Assuntos
Bactérias , Citrus , Microbiota , Floema , Doenças das Plantas , Rizosfera , Microbiologia do Solo , Floema/microbiologia , Floema/metabolismo , Bactérias/genética , Bactérias/classificação , Bactérias/metabolismo , Bactérias/isolamento & purificação , Doenças das Plantas/microbiologia , Citrus/microbiologia , Plantas Geneticamente Modificadas/microbiologia , Plantas Geneticamente Modificadas/genética , Filogenia , Metagenômica , Muramidase/metabolismo , Muramidase/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , beta-Defensinas/genética , RNA Ribossômico 16S/genética , Anti-Infecciosos/farmacologia , Anti-Infecciosos/metabolismo , Citrus sinensis/microbiologia , Raízes de Plantas/microbiologia
20.
J Clin Med ; 13(13)2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38999433

RESUMO

Hepatitis C virus still represents a major cause of morbidity and mortality worldwide. In Peru, two national practice guidelines for the management of this infection were published more than 5 years ago; however, the latest breakthroughs in the treatment make it necessary to update these guidelines. We reviewed the most recent recommendations of the international guidelines and compared them with the current Peruvian guidelines. We found major differences, such as the use of Glecaprevir/Pibrentasvir as a first-line therapy, which is contemplated in the World Health Organization guideline, and recommended by American and European guidelines, but is not considered in the Peruvian guidelines. Another crucial difference lies in the management of patients with chronic kidney disease, who are treated nowadays with a variety of direct-acting antivirals, with no restrictions on the use of Sofosbuvir-based regimens in first-world countries, an approach that has not been adopted in Peru. We believe that standardization of the recommendations of the Peruvian guidelines is imperative, including the new therapeutic strategies that have emerged in recent years. We also suggest conducting a cost effectiveness analysis in the Peruvian context to allow for the implementation of new antivirals, and to achieve a better control of hepatitis C in the country.

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