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2.
Sci Total Environ ; 867: 161287, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36587666

RESUMO

Many countries have made pledges to reduce CO2 emissions over the upcoming decades to meet the Paris Agreement targets of limiting warming to no >1.5 °C, aiming for net zero by mid-century. To achieve national reduction targets, there is a further need for CO2 removal (CDR) approaches on a scale of millions of tonnes, necessitating a better understanding of feasible methods. One approach that is gaining attention is geochemical CDR, encompassing (1) in-situ injection of CO2-rich gases into Ca and Mg-rich rocks for geological storage by mineral carbonation, (2) ex-situ ocean alkalinity enhancement, enhanced weathering and mineral carbonation of alkaline-rich materials, and (3) electrochemical separation processes. In this context, Spain may host a notionally high geochemical CDR capacity thanks to its varied geological setting, including extensive mafic-ultramafic and carbonate rocks. However, pilot schemes and large-scale strategies for CDR implementation are presently absent in-country, partly due to gaps in current knowledge and lack of attention paid by regulatory bodies. Here, we identify possible materials, localities and avenues for future geochemical CDR research and implementation strategies within Spain. This study highlights the kilotonne to million tonne scale CDR options for Spain over the rest of the century, with attention paid to chemically and mineralogically appropriate materials, suitable implementation sites and potential strategies that could be followed. Mafic, ultramafic and carbonate rocks, mine tailings, fly ashes, slag by-products, desalination brines and ceramic wastes hosted and produced in Spain are of key interest, with industrial, agricultural and coastal areas providing opportunities to launch pilot schemes. Though there are obstacles to reaching the maximum CDR potential, this study helps to identify focused targets that will facilitate overcoming such barriers. The CDR potential of Spain warrants dedicated investigations to achieve the highest possible CDR to make valuable contributions to national reduction targets.

3.
Life (Basel) ; 12(11)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36362892

RESUMO

Patients with obstructive sleep apnea (OSA) that do not tolerate/accept continuous positive airway pressure (CPAP) are candidates for surgical alternatives. Hypoglossal nerve stimulation (HNS) through the implantation of the Inspire® device constitutes a minimally invasive operative option. The main objective of this study is to estimate, under real-world clinical practice conditions, the 3-month impact on the quality of life (IQoL) of the HNS in patients with moderate/severe OSA who do not tolerate or accept CPAP, compared to patients who did not receive HNS. As a baseline, the unadjusted EuroQol utility index was 0.764 (SD:0.190) in the intervention group (IGr) and 0.733 (SD:0.205) in the control group (CGr); three months later, the indexes were 0.935 (SD: 0.101) and 0.727 (SD:0.200), respectively. The positive impact on quality of life was estimated to be +0.177 (95% CI: 0.044−0.310; p = 0.010). All dimensions in the IGr improved compared to CGr, especially for usual activities (p < 0.001) and anxiety/depression (p > 0.001). At the end of the follow-up, there was no significant difference in the quality of life between the general Spanish population and the IGr (difference: 0.012; CI95%: −0.03 to −0.057; p = 0.0578) for the same age range; however, there was a difference concerning the CGr (difference: −0.196; CI95%: −0.257 to −0.135; p < 0.001). In conclusion, patients with moderate/severe OSA implanted with the Inspire® device showed a positive IQoL.

5.
Eur Arch Otorhinolaryngol ; 279(11): 5347-5353, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35771281

RESUMO

PURPOSE: To describe the anatomic relationship of the lingual nerve with the lateral oropharyngeal structures. METHODS: An anatomic dissection of the lateral oropharyngeal wall was conducted in eight sides from four fresh-frozen cadaveric heads. Small titanium clips were placed along the lingual nerve and the most anterior and medial border of the medial pterygoid muscle. Radiological reconstructions were employed for optimal visualization; the coronal view was preferred to resemble the surgical position. The distance between the lingual nerve and the medial pterygoid muscle at its upper and lower portion was measured radiologically. The trajectory angle of the lingual nerve with respect to the pterygomandibular raphe was obtained from the intersection between the vector generated between the clips connecting the upper and lower portion of the medial pterygoid muscle with the vector generated from the lingual nerve clips. RESULTS: The mean distance from the upper portion of the medial pterygoid muscle and superior lingual nerve clips was 10.16 ± 2.18 mm (mean ± standard deviation), and the lower area of the medial pterygoid muscle to the lingual nerve was separated 5.05 ± 1.49 mm. The trajectory angle of the lingual nerve concerning to the vector that describes the upper portion of the most anterior and medial border of the medial pterygoid muscle with its lower part was 43.73º ± 11.29. CONCLUSIONS: The lingual nerve runs lateral to the lateral oropharyngeal wall, from superiorly-inferiorly and laterally-medially, and it is closer to it at its lower third.


Assuntos
Nervo Lingual , Procedimentos Cirúrgicos Bucais , Cadáver , Humanos , Nervo Lingual/anatomia & histologia , Nervo Lingual/cirurgia , Palato , Músculos Pterigoides/diagnóstico por imagem , Músculos Pterigoides/cirurgia , Titânio
6.
Ann Vasc Surg ; 78: 378.e1-378.e8, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34455052

RESUMO

INTRODUCTION: Brachial artery aneurysms constitute 0.5% of peripheral aneurysms. These can be true or secondary to trauma or arteriovenous fistulas. These present as an asymptomatic pulsatile mass or may cause symptoms due to compression of adjacent neurological structures. CASE REPORT: We present a review of the literature on clinical, histological, and therapeutic characteristics of true brachial aneurysms, motivated by the case of a 67-year-old woman with an asymptomatic pulsatile mass dependent on the brachial artery of the left arm who underwent open surgical correction with resection of the aneurysmal sac and interposition of great saphenous vein graft with adequate postoperative results.


Assuntos
Aneurisma/cirurgia , Artéria Braquial/cirurgia , Veia Safena/transplante , Idoso , Aneurisma/diagnóstico por imagem , Artéria Braquial/diagnóstico por imagem , Feminino , Humanos , Resultado do Tratamento
7.
Molecules ; 26(24)2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34946726

RESUMO

Cannabinoids act as pleiotropic compounds exerting, among others, a broad-spectrum of neuroprotective effects. These effects have been investigated in the last years in different preclinical models of neurodegeneration, with the cannabinoid type-1 (CB1) and type-2 (CB2) receptors concentrating an important part of this research. However, the issue has also been extended to additional targets that are also active for cannabinoids, such as the orphan G-protein receptor 55 (GPR55). In the present study, we investigated the neuroprotective potential of VCE-006.1, a chromenopyrazole derivative with biased orthosteric and positive allosteric modulator activity at GPR55, in murine models of two neurodegenerative diseases. First, we proved that VCE-006.1 alone could induce ERK1/2 activation and calcium mobilization, as well as increase cAMP response but only in the presence of lysophosphatidyl inositol. Next, we investigated this compound administered chronically in two neurotoxin-based models of Parkinson's disease (PD), as well as in some cell-based models. VCE-006.1 was active in reversing the motor defects caused by 6-hydroxydopamine (6-OHDA) in the pole and the cylinder rearing tests, as well as the losses in tyrosine hydroxylase-containing neurons and the elevated glial reactivity detected in the substantia nigra. Similar cytoprotective effects were found in vitro in SH-SY5Y cells exposed to 6-OHDA. We also investigated VCE-006.1 in LPS-lesioned mice with similar beneficial effects, except against glial reactivity and associated inflammatory events, which remained unaltered, a fact confirmed in BV2 cells treated with LPS and VCE-006.1. We also analyzed GPR55 in these in vivo models with no changes in its gene expression, although GPR55 was down-regulated in BV2 cells treated with LPS, which may explain the lack of efficacy of VCE-006.1 in such an assay. Furthermore, we investigated VCE-006.1 in two genetic models of amyotrophic lateral sclerosis (ALS), mutant SOD1, or TDP-43 transgenic mice. Neither the neurological decline nor the deteriorated rotarod performance were prevented with this compound, and the same happened with the elevated microglial and astroglial reactivities, albeit modest spinal motor neuron preservation was achieved in both models. We also analyzed GPR55 in these in vivo models and found no changes in both TDP-43 transgenic and mSOD1 mice. Therefore, our findings support the view that targeting the GPR55 may afford neuroprotection in experimental PD, but not in ALS, thus stressing the specificities for the development of cannabinoid-based therapies in the different neurodegenerative disorders.


Assuntos
Esclerose Lateral Amiotrófica , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson , Receptores de Canabinoides/metabolismo , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Animais , Modelos Animais de Doenças , Humanos , Ligantes , Masculino , Camundongos , Camundongos Transgênicos , Neuroglia/metabolismo , Fármacos Neuroprotetores/química , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Substância Negra/metabolismo , Células U937
8.
Ann Vasc Surg ; 72: 196-204, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33388408

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection can cause alterations in the coagulation mechanism conditioning thrombotic phenomena such as acute limb ischemia (ALI) as the only manifestation of the infection. The aim of the study was to describe clinical and surgical characteristics of a group of patients infected with severe acute respiratory syndrome coronavirus 2 who presented ALI in the context of the COVID-19 pandemic at Lima, Peru. METHODS: A multicenter, observational, and retrospective study was performed in six general hospitals, from March to July 2020. The variables considered were the pathological history and associated habits, laboratory tests, the severity of COVID-19 infection and ALI, the anatomic location of the lesion, treatment, evolution, and discharge conditions. RESULTS: Thirty patients with ALI infected with COVID-19 were evaluated. Their mean age was 60 ± 15 years, the condition being more frequent in men (76.6%). The main comorbidities were arterial hypertension (33.3%), obesity (33.3%), and diabetes mellitus 2 (26.6%). There were 23.3% asymptomatic patients, and their only manifestation was ALI. Rutherford IIA and IIB stage included 93.2% of patients. The most frequent location of the thrombosis was the lower limbs (73.3% vs. 26.6%). Thrombectomy was performed in 76.6% of the patients, and amputation (primary and secondary) was performed in 30% of the patients. The mortality rate was 23.3%, all of it because of acute respiratory distress syndrome. CONCLUSIONS: ALI is a vascular pathology associated with embolic and thrombotic processes. COVID-19 infection can cause severe alterations in coagulation mechanisms, leading some patients to present severe acute arterial complications such as thrombosis, as the only associated manifestation. We report a younger cohort than those described in other studies and with a high frequency of amputations despite adequate surgical treatment.


Assuntos
COVID-19/complicações , Isquemia/etiologia , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Doença Aguda , Amputação Cirúrgica , COVID-19/epidemiologia , COVID-19/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Peru/epidemiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Estudos Retrospectivos , SARS-CoV-2 , Trombectomia
9.
Arch Biochem Biophys ; 697: 108680, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33220265

RESUMO

The study of calmodulin (CaM) functions in living cells has been tackled up to date using cell-permeant CaM inhibitors or interference-RNA methods. CaM inhibitors may lack specificity and the siRNA interference approach is challenging, as all three CaM genes expressing an identical protein in mammals have to be blocked. Therefore, we recently introduced a novel genetic system using CRISPR/Cas9-mediated gene deletion and conditional CaM expression to study the function of CaM in HeLa cells. Here, we describe the effect of CaM downregulation on the basal and epidermal growth factor (EGF)-dependent 2D- and 3D-migration in HeLa cells. CaM downregulation inhibited cell migration on a 2D-surface in the absence but not in the presence of EGF. In contrast, CaM downregulation led to inhibition of 3D-migration across a porous membrane both in the absence and presence of EGF. CaM downregulation decreased the expression of Rac1, Cdc42 and RhoA, all known to play crucial roles in cell migration. These results show that EGF-dependent 2D- and 3D-migration utilize distinct CaM-regulated systems and identify several essential migratory proteins directly or indirectly regulated by CaM.


Assuntos
Calmodulina/deficiência , Calmodulina/genética , Movimento Celular/genética , Regulação para Baixo , Técnicas de Inativação de Genes , Fator de Crescimento Epidérmico/metabolismo , Células HeLa , Humanos , Proteína cdc42 de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
10.
Radiother Oncol ; 154: 128-134, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32941955

RESUMO

BACKGROUND: The Head and Neck and Skin (HNS) Working group of the GEC-ESTRO acknowledges the lack of widely accepted Dose Volume Histogram (DVH) constraints in adjuvant head and neck brachytherapy and issues recommendations to minimize mandibular Osteoradionecrosis (ORN) and Soft Tissue Necrosis (STN). METHODS: A total of 227 patients with the diagnosis of head and neck cancer treated with surgery and adjuvant HDR brachytherapy alone or combined with other treatment modalities during the period 2000-2018 were analyzed. RESULTS: STN was observed in 28 out of 227 cases (12.3%) with an average time to appearance of 4.0 months. In previously unirradiated cases, there was a positive correlation between CTV size and STN (p = 0.017) and a trend towards significance between Total EQD2-DVH TV100 dose and STN (p = 0.06). The risk of STN in the absence of both factors (i.e, CTV < 15 cm3 and Total EQD2-DVH TV100 dose < 87 Gy) was 2%, with one factor present 15.7% and with both factors 66.7% (p = 0.001). ORN was observed in 13 out of 227 cases (5.7%) with an average time to appearance of 26.2 months. In unirradiated cases, ORN correlated with Total Physical Dose to Mandible2cm3 (p = 0.027). Patients receiving Total Physical Doses greater than 61 Gy had a 20-fold increased risk of ORN. CONCLUSIONS: In Unirradiated patients the panel recommends to avoid implantation of postoperative CTVs exceeding 15 cm3 at Total EQD2-DVH TV100 doses in excess of 87 Gy as well as to limit the irradiation of the Mandible2cm3 to 61 Gy. In previously irradiated patients the panel cannot make a recommendation based on the available results.


Assuntos
Braquiterapia , Neoplasias de Cabeça e Pescoço , Osteorradionecrose , Braquiterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Mandíbula , Osteorradionecrose/etiologia , Dosagem Radioterapêutica
12.
J Cell Physiol ; 236(7): 4997-5011, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33305427

RESUMO

The epidermal growth factor receptor (EGFR) harbors a calmodulin (CaM)-binding domain (CaM-BD) and a CaM-like domain (CaM-LD) upstream and downstream, respectively, of the tyrosine kinase (TK) domain. We demonstrate in this paper that deletion of the positively charged CaM-BD (EGFR/CaM-BD∆) inactivated the TK activity of the receptor. Moreover, deletion of the negatively charged CaM-LD (EGFR/CaM-LD∆), leaving a single negative residue (glutamate), reduced the activity of the receptor. In contrast, substituting the CaM-LD with a histidine/valine-rich peptide (EGFR/InvCaM-LD) caused full inactivation. We also demonstrated using confocal microscopy and flow cytometry that the chimera EGFR-green fluorescent protein (GFP)/CaM-BD∆, the EGFR/CaM-LD∆, and EGFR/InvCaM-LD mutants all bind tetramethylrhodamine-labelled EGF. These EGFR mutants were localized at the plasma membrane as the wild-type receptor does. However, only the EGFR/CaM-LD∆ and EGFR/InvCaM-LD mutants appear to undergo ligand-dependent internalization, while the EGFR-GFP/CaM-BD∆ mutant seems to be deficient in this regard. The obtained results and in silico modelling studies of the asymmetric structure of the EGFR kinase dimer support a role of a CaM-BD/CaM-LD electrostatic interaction in the allosteric activation of the EGFR TK.


Assuntos
Calmodulina/metabolismo , Membrana Celular/metabolismo , Animais , Células CHO , Sinalização do Cálcio/fisiologia , Linhagem Celular , Cricetulus , Ativação Enzimática/fisiologia , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Ligação Proteica/fisiologia , Domínios Proteicos/fisiologia , Proteínas Tirosina Quinases/metabolismo
13.
Fetal Diagn Ther ; 47(12): 873-881, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32937625

RESUMO

OBJECTIVE: To report the experience with prenatal repair of open spina bifida (OSB) from 2 centers in Chile. METHODS: Women with a second-trimester fetus with OSB were offered intrauterine neurosurgical repair following the protocol from the Management of Myelomeningocele Study (MOMS) trial. Pediatric follow-up with infants reaching 12 and 30 months of life was also reviewed. RESULTS: Fifty-eight fetuses with OSB underwent intrauterine repair at an average (±SD) gestational age of 24.8 ± 0.9 weeks. There were 3 (5.1%) intrauterine deaths. The average gestational age at delivery of the remaining 55 cases was 33.3 ± 3.6 weeks, and the average birth weight was 2,172 ± 751 g. Delivery before 30 weeks occurred in 11 cases (20.0%). Two (3.6%) neonatal deaths (<28 days) occurred. At 12 months, a ventriculoperitoneal shunt or an endoscopic third ventriculostomy was required in 25% of the cases. At 30 months, 72.4% of the infants were able to walk. DISCUSSION: Prenatal neurosurgical repair of OSB is a complex and challenging intervention. Major complications include perinatal death and severe prematurity. No major maternal complications occurred in our series. A reduction in the need for cerebrospinal fluid diversion and an improved ability to walk seem to be the greatest long-term advantages of this procedure.


Assuntos
Meningomielocele , Neurocirurgia , Espinha Bífida Cística , Disrafismo Espinal , Criança , Chile/epidemiologia , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Meningomielocele/cirurgia , Gravidez , Espinha Bífida Cística/diagnóstico por imagem , Espinha Bífida Cística/cirurgia , Disrafismo Espinal/cirurgia
14.
J Speech Lang Hear Res ; 63(7): 2177-2184, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32615843

RESUMO

Objective The aims of this study were to test the hypothesis that greater supraglottic compression (anteroposterior or lateral) correlates with higher subglottic pressure (SGP) and to develop a classification of muscle tension dysphonia (MTD), based on the degree of supraglottic compression during speech. Method A prospective, cross-sectional study was conducted in a series of 37 consecutive patients diagnosed with MTD with an altered aerodynamic profile characterized by high SGP (more than 90 mmH2O). Supraglottic anteroposterior and lateral compression were categorized in three grades and assessed during the laryngoscopic examination. All patients completed the Spanish Voice Handicap Index (VHI) questionnaire and completed an acoustic and aerodynamic voice assessment. The relationship between compression grade and VHI with SGP was analyzed. Results More than 90% of patients demonstrated some degree of anteroposterior compression, and 67% had some degree of lateral compression. The mean (SD) SGP was 111.03 (16.7) mmH2O, and the mean VHI was 27.86 (12.5). The degree of SGP was statistically different in the different grades of anteroposterior compression, and also anteroposterior compression correlated with an SGP (p < .05). The degree of lateral compression was not correlated with SGP. Neither the degree of anteroposterior or lateral compression nor the value of SGP was found to correlate with VHI. Conclusions Because grade of anteroposterior compression correlates with SGP, these grades can be used for diagnosis and follow-up of MTD patients. To this end and on this basis, we propose a new classification for MTD. Unlike the established classification, our proposed one makes it possible to combine different laryngoscopic features, improving the description of the larynx during phonation.


Assuntos
Disfonia , Estudos Transversais , Humanos , Tono Muscular , Fonação , Estudos Prospectivos , Qualidade da Voz
15.
Endocrine ; 70(3): 538-543, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32507966

RESUMO

PURPOSE: The adequate extent of surgery for 1-4 cm low-risk papillary thyroid carcinoma (PTC) is unclear. Our objective was to analyze the applicability of the 2015 ATA Guidelines recommendation 35B (R35) for the management low-risk PTC. METHODS: This multicentre study included patients with low-risk PTC who had undergone total thyroidectomy (TT). Retrospectively we selected those who met the R35 criteria for the performance of a thyroid lobectomy (TL). The aim was to identify the proportion of low-risk PTC patients treated using TT who would have required reintervention had they had a TL in accordance with R35. RESULTS: We identified 497 patients (400 female; 80.5%). Median tumor size (mm): 21.2 (11-40). A tumor size ≥2 cm was found in 252 (50.7%). Most of them, 320 (64.4%), were in Stage I (AJCC 7th Edition). Following R35, 286 (57.5%) would have needed TT. Thus, they would have required a second surgery had they undergone TL. The indications for reintervention would have included lymph node involvement (35%), extrathyroidal extension (22.9%), aggressive subtype (8%), or vascular invasion (22.5%). No presurgical clinical data predict TT. CONCLUSIONS: The appropriate management of low-risk PTC is unclear. Adherence to ATA R35 could lead to a huge increase in reinterventions when a TL is performed, though the need for them would be questionable. In our sample, more than half of patients (57.5%) who may undergo a TL for a seemingly low-risk PTC would have required a second operation to satisfy international guidelines, until better preoperative diagnostic tools become available.


Assuntos
Craniossinostoses , Neoplasias da Glândula Tireoide , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
16.
Heliyon ; 6(5): e03922, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32420488

RESUMO

The growth factor receptor bound protein 7 (Grb7) is a Ca2+-dependent calmodulin (CaM)-binding adaptor protein implicated, among other functions, in cell proliferation, migration and tumor-associated angiogenesis. The goal of this study was to determine whether a peptide based on the CaM binding site of Grb7 disrupts cellular processes, relevant for the malignancy of tumor cells, in which this adaptor protein is implicated. We designed synthetic myristoylated and non-myristoylated peptides corresponding to the CaM-binding domain of human Grb7 with the sequence 243RKLWKRFFCFLRRS256 and a variant peptide with the mutated sequence RKLERFFCFLRRE (W246E-ΔK247-S256E). The two non-myristoylated peptides bind dansyl-CaM with higher efficiency in the presence than in the absence of Ca2+ and they enter into the cell, as tested with 5(6)-carboxytetramethylrhodamine (TAMRA)-labeled peptides. The myristoylated and non-myristoylated peptides inhibit the proliferation, migration and invasiveness of A431 tumor cells while they enhance their adhesion to the substrate. The myristoylated peptides have stronger inhibitory effect than the non-myristoylated counterparts, in agreement with their expected higher cell-permeant capacity. The myristoylated and non-myristoylated W246E-ΔK247-S256E mutant peptide has a lesser inhibitory effect on cell proliferation as compared to the wild-type peptide. We also demonstrated that the myristoylated peptides were more efficient than the CaM antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) inhibiting cell migration and equally efficient inhibiting cell proliferation.

17.
Cell Calcium ; 88: 102207, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32408024

RESUMO

Calmodulin (CaM) is the principle mediator of the Ca2+ signal in all eukaryotic cells. A huge variety of basic cellular processes including cell cycle control, proliferation, secretion and motility, among many others are governed by CaM, which regulates activities of myriads of target proteins. Mammalian CaM is encoded by three genes localized on different chromosomes all producing an identical protein. In this study, we have generated HeLa human cancer cells conditionally expressing CaM in a genetic background with all three genes inactivated by CRISPR/Cas9. We demonstrate that downregulation of ectopically expressed CaM is achieved after 120 h, when cells are arrested in the M phase of the cell cycle. We show for the first time that CaM downregulation in human cancer cells is followed by a multinucleated senescent state as indicated by expression of ß-galactosidase as well as cell morphology typical for senescent cells. Our newly generated genetic system may be useful for the analysis of other CaM regulated processes in eukaryotic cells in the absence of endogenous CaM genes.


Assuntos
Calmodulina/metabolismo , Ciclo Celular/genética , Células/metabolismo , Calmodulina/deficiência , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Doxiciclina/farmacologia , Células HeLa , Humanos , Mitose/efeitos dos fármacos , Fosforilação/efeitos dos fármacos
18.
Int. arch. otorhinolaryngol. (Impr.) ; 23(4): 422-426, Out.-Dez. 2019. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1024327

RESUMO

Introduction: Chronic rhinosinusitis (CRS) is a highly prevalent pathology in our society. Due to the prevalence of this condition and to the persisting symptoms despite an appropriate medical treatment, surgical techniques are often required. Lately, minimal invasive techniques have been described, such as lacrimal diversion devices (LDDs). This technique offers a fast and convenient choice for delivery of sinus irrigation and topical medication. Objective: We aimed to describe our experience with LDDs and evaluate the safety and effectiveness of the procedure in patients with moderate to severe CRS without nasal polyposis (CRSsNP) and persistent symptomatology despite medical therapy. Methods: A total of 7 patients underwent bilateral lacrimal stents placement in the operating room. A retrospective observational study was conducted. The Sino-Nasal Outcome Test-20 (SNOT-20) survey was performed and the score obtained was compared before and 1 month after the procedure. Results: The LDDs were used for an average of 80 days. During the follow-up, only three patients had a mild complication with the device (granuloma in the punctum, obstruction, and early extrusion). The mean baseline SNOT-20 score dropped significantly ( p = 0.015) from 25.85 to 11.57 (mean: - 14.29) 1 month after the procedure. Conclusion: According to our experience and results, the use of LDD is a novel, feasible, and less invasive technique to treat refractory CRS. It reduces the risk of mucosal stripping, provides short-term outcomes, and the surgical procedure does not require advanced training in endoscopic sinus surgery. Moreover, it can be performed in-office under local anesthesia or sedation (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Sinusite/cirurgia , Stents , Rinite/cirurgia , Procedimentos Cirúrgicos Nasais/métodos , Estudos Retrospectivos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Aparelho Lacrimal/cirurgia
19.
Int Arch Otorhinolaryngol ; 23(4): e422-e426, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31649762

RESUMO

Introduction Chronic rhinosinusitis (CRS) is a highly prevalent pathology in our society. Due to the prevalence of this condition and to the persisting symptoms despite an appropriate medical treatment, surgical techniques are often required. Lately, minimal invasive techniques have been described, such as lacrimal diversion devices (LDDs). This technique offers a fast and convenient choice for delivery of sinus irrigation and topical medication. Objective We aimed to describe our experience with LDDs and evaluate the safety and effectiveness of the procedure in patients with moderate to severe CRS without nasal polyposis (CRSsNP) and persistent symptomatology despite medical therapy. Methods A total of 7 patients underwent bilateral lacrimal stents placement in the operating room. A retrospective observational study was conducted. The Sino-Nasal Outcome Test-20 (SNOT-20) survey was performed and the score obtained was compared before and 1 month after the procedure. Results The LDDs were used for an average of 80 days. During the follow-up, only three patients had a mild complication with the device (granuloma in the punctum, obstruction, and early extrusion). The mean baseline SNOT-20 score dropped significantly ( p = 0.015) from 25.85 to 11.57 (mean: - 14.29) 1 month after the procedure. Conclusion According to our experience and results, the use of LDD is a novel, feasible, and less invasive technique to treat refractory CRS. It reduces the risk of mucosal stripping, provides short-term outcomes, and the surgical procedure does not require advanced training in endoscopic sinus surgery. Moreover, it can be performed in-office under local anesthesia or sedation.

20.
Nat Commun ; 9(1): 2201, 2018 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-29895846

RESUMO

Carbon capture and storage (CCS) can help nations meet their Paris CO2 reduction commitments cost-effectively. However, lack of confidence in geologic CO2 storage security remains a barrier to CCS implementation. Here we present a numerical program that calculates CO2 storage security and leakage to the atmosphere over 10,000 years. This combines quantitative estimates of geological subsurface CO2 retention, and of surface CO2 leakage. We calculate that realistically well-regulated storage in regions with moderate well densities has a 50% probability that leakage remains below 0.0008% per year, with over 98% of the injected CO2 retained in the subsurface over 10,000 years. An unrealistic scenario, where CO2 storage is inadequately regulated, estimates that more than 78% will be retained over 10,000 years. Our modelling results suggest that geological storage of CO2 can be a secure climate change mitigation option, but we note that long-term behaviour of CO2 in the subsurface remains a key uncertainty.

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