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1.
Int J Obes (Lond) ; 48(3): 315-323, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38151611

RESUMEN

BACKGROUND: Obesity is a chronic disease associated with adverse outcomes and its prevalence is increasing, which makes it a concern. One of the obesity treatment options is bariatric surgery, which effectively reduces calorie absorption and total body mass, but its effects on physical activity (PA) levels need to be clarified, considering the protective effect of the PA against cardiovascular disease, independently of the weight loss alone. OBJECTIVES: To carry out a systematic review and meta-analysis of observational studies that evaluated PA in pre- and post-bariatric surgery periods through objective evaluation. METHODS: A systematic search was carried out following the PRISMA criteria of studies with adult individuals who underwent bariatric surgery and were objectively evaluated for PA pre- and post-surgery. Studies with interventions were excluded. RESULTS: A total of 419 records were found, and after excluding duplicates and applying the eligibility criteria, 10 studies remained. This meta-analysis found a significant increase in the steps by day (MD = 1340; 95% CI = 933.90; 1745.35, p < 0.001) and the light physical activity level (MD = 16.8 min/day; 95% CI = 2.60; 30.98, p = 0.02), but not in moderate to vigorous physical activity (MD = 0.24; 95% CI = -0.08; 1.57, p = 0.92). CONCLUSIONS: Patients undergoing bariatric surgery increased their steps by day and light physical activity but did not increase moderate to vigorous physical activity.


Asunto(s)
Cirugía Bariátrica , Ejercicio Físico , Humanos , Cirugía Bariátrica/estadística & datos numéricos , Cirugía Bariátrica/métodos , Ejercicio Físico/fisiología , Obesidad/cirugía , Pérdida de Peso/fisiología , Obesidad Mórbida/cirugía
2.
Faraday Discuss ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291342

RESUMEN

We determine the complete atomic-level structure of the amorphous form of the drug atuliflapon, a 5-lipooxygenase activating protein (FLAP) inhibitor, via chemical-shift-driven NMR crystallography. The ensemble of preferred structures allows us to identify a number of specific conformations and interactions that stabilize the amorphous structure. These include preferred hydrogen-bonding motifs with water and with other drug molecules, as well as conformations of the cyclohexane and pyrazole rings that stabilize structure by indirectly allowing for optimization of hydrogen bonding.

3.
Vet Pathol ; 61(4): 582-589, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38146917

RESUMEN

Although tick infestation is a significant health problem in livestock, there are limited studies on the dermatopathological aspects of natural tick infestation in cattle. This study aimed to describe the gross and histologic aspects of cutaneous lesions caused by tick infestation in cattle. Thirteen cases were selected based on necropsy data from a 10-year retrospective study. Predispositions were observed in beef cattle (P = .049) and the Angus breed (P = .012), and lesions occurred mainly in the fall (P = .007). Gross lesions included hypotrichosis (13/13; 100%), scales (12/13; 92%), alopecia (11/13; 85%), ulcers (7/13; 54%), crusts (7/13; 54%), and erosions (2/13; 15%). These gross lesions were mainly located in the thorax (12/13; 92%), head (11/13; 85%), abdomen (10/13; 77%), neck (9/13; 69%), limbs (9/13; 69%), and perineum (9/13; 69%). Histologically, all cases had ticks adhered to the epidermis with erosions (13/13; 100%), ulcers (11/13; 85%), orthokeratotic hyperkeratosis (13/13; 100%), irregular acanthosis (13/13; 100%), intraepidermal pustules (13/13; 100%), crusts (10/13; 77%), and ballooning degeneration (4/13; 31%). In the dermis, just below the tick insertion site, there was coagulation necrosis, fibrin deposition, and inflammatory infiltrate composed of mixed cells (neutrophils, lymphocytes, plasma cells, macrophages, and few eosinophils) (9/13; 69%), neutrophils (3/13; 23%), or eosinophils (1/13; 8%). This study reinforces the different patterns of cutaneous lesions caused by tick infestation in cattle, which should be considered as a potential cause of dermatitis in this species.


Asunto(s)
Enfermedades de los Bovinos , Infestaciones por Garrapatas , Animales , Bovinos , Enfermedades de los Bovinos/patología , Enfermedades de los Bovinos/parasitología , Infestaciones por Garrapatas/veterinaria , Infestaciones por Garrapatas/patología , Infestaciones por Garrapatas/parasitología , Estudios Retrospectivos , Femenino , Masculino , Piel/patología , Piel/parasitología , Garrapatas , Enfermedades de la Piel/veterinaria , Enfermedades de la Piel/patología , Enfermedades de la Piel/parasitología
4.
J Immunol ; 206(10): 2441-2452, 2021 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-33941658

RESUMEN

Intestinal barrier is essential for dietary products and microbiota compartmentalization and therefore gut homeostasis. When this barrier is broken, cecal content overflows into the peritoneal cavity, leading to local and systemic robust inflammatory response, characterizing peritonitis and sepsis. It has been shown that IL-1ß contributes with inflammatory storm during peritonitis and sepsis and its inhibition has beneficial effects to the host. Therefore, we investigated the mechanisms underlying IL-1ß secretion using a widely adopted murine model of experimental peritonitis. The combined injection of sterile cecal content (SCC) and the gut commensal bacteria Bacteroides fragilis leads to IL-1ß-dependent peritonitis, which was mitigated in mice deficient in NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome components. Typically acting as a damage signal, SCC, but not B. fragilis, activates canonical pathway of NLRP3 promoting IL-1ß secretion in vitro and in vivo. Strikingly, absence of fiber in the SCC drastically reduces IL-1ß production, whereas high-fiber SCC conversely increases this response in an NLRP3-dependent manner. In addition, NLRP3 was also required for IL-1ß production induced by purified dietary fiber in primed macrophages. Extending to the in vivo context, IL-1ß-dependent peritonitis was worsened in mice injected with B. fragilis and high-fiber SCC, whereas zero-fiber SCC ameliorates the pathology. Corroborating with the proinflammatory role of dietary fiber, IL-1R-deficient mice were protected from peritonitis induced by B. fragilis and particulate bran. Overall, our study highlights a function, previously unknown, for dietary fibers in fueling peritonitis through NLRP3 activation and IL-1ß secretion outside the gut.


Asunto(s)
Infecciones por Bacteroides/inmunología , Bacteroides fragilis/inmunología , Fibras de la Dieta/efectos adversos , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/deficiencia , Peritonitis/inmunología , Animales , Infecciones por Bacteroides/microbiología , Dieta , Fibras de la Dieta/administración & dosificación , Modelos Animales de Enfermedad , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Peritonitis/microbiología , Receptores de Interleucina-1/deficiencia , Receptores de Interleucina-1/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología
5.
Vet Pathol ; 60(1): 8-20, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36112908

RESUMEN

Feline pulmonary carcinoma (FPC) is an uncommon neoplasm with unique morphological features. We describe the gross, histological, metastatic, and immunohistochemical aspects of FPC, based on postmortem examinations from an 11-year retrospective study. Thirty-nine cases were selected. Predispositions were observed in senior (P < .001) and Persian (P = .039) cats. There were three gross patterns of the pulmonary tumors: (a) a large nodule and additional smaller nodules, (b) a solitary nodule, and (c) small, multifocal to coalescent nodules. Extrapulmonary metastases were present in 22/39 cases (56.4%), mainly in the regional lymph nodes (17/39, 43.5%), skeletal muscles (9/39, 23%), kidneys (6/39, 15.3%), and parietal pleura (4/39, 10.2%). The primary tumor size was correlated with the occurrence of extrapulmonary metastases (P = .002). Histologically, the tumors were classified as papillary adenocarcinoma (19/39, 48.7%), adenosquamous carcinoma (ADS) (8/39, 20.5%), acinar adenocarcinoma (6/39, 15.3%), solid adenocarcinoma (3/39, 7.6%), lepidic adenocarcinoma (2/39, 5.1%), and micropapillary adenocarcinoma (1/39, 2.5%). By immunohistochemistry, 39/39 cases (100%) were positive for pancytokeratin, 34/39 (87.1%) for thyroid transcription factor-1, and 8/39 (20.5%) for vimentin. Immunoreactivity for p40 was detected in the squamous component of all ADSs (8/8, 100%) and occasionally in the glandular component of adenocarcinomas (10/31, 32.2%). Napsin A expression was absent in all feline tissue tested. The results indicate that a modified and simplified histological classification based on current human and domestic animal systems is appropriate for cats. Additionally, this study highlights the utility of p40 as an immunohistochemical marker for the diagnosis of FPC with squamous differentiation.


Asunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma , Carcinoma de Células Escamosas , Enfermedades de los Gatos , Neoplasias Pulmonares , Gatos , Animales , Humanos , Estudios Retrospectivos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/veterinaria , Adenocarcinoma del Pulmón/veterinaria , Adenocarcinoma/patología , Adenocarcinoma/veterinaria , Carcinoma de Células Escamosas/veterinaria , Biomarcadores de Tumor/metabolismo
6.
Lett Appl Microbiol ; 76(12)2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-37968138

RESUMEN

Streptococcus didelphis was once reported as related to severe infections in opossums. Thus, we present the first comprehensive whole-genome characterization of clinical S. didelphis strains isolated from white-eared opossums (Didelphis albiventris). Long-read whole-genome sequencing was performed using the MinION platform, which allowed the prediction of several genomic features. We observed that S. didelphis genomes harbor a cluster for streptolysin biosynthesis and a conserved genomic island with genes involved in transcriptional regulation (arlR) and transmembrane transport (bcrA). Antimicrobial resistance genes for several drug classes were found, including beta-lactam, which is the main antimicrobial class used in Streptococcus spp. infections; however, no phenotypical resistance was observed. In addition, we predicted the presence of 33 virulence factors in the analyzed genomes. High phylogenetic similarity was observed between clinical and reference strains, yet no clonality was suggested. We also proposed dnaN, gki, pros, and xpt as housekeeping candidates to be used in S. didelphis sequence typing. This is the first whole-genome characterization of S. didelphis, whose data provide important insights into its pathogenicity.


Asunto(s)
Antiinfecciosos , Didelphis , Infecciones Estreptocócicas , Animales , Filogenia , Streptococcus/genética , Infecciones Estreptocócicas/veterinaria , Brasil
7.
J Stroke Cerebrovasc Dis ; 32(1): 106864, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36434859

RESUMEN

BACKGROUND: Although sleep apnea and peripheral artery disease are prognostic factors for stroke, their added benefit in the acute stage to further prognosticate strokes has not been evaluated. OBJECTIVES: We tested the accuracy in the acute stroke stage of a novel score called the Non-Invasive Prognostic Stroke Scale (NIPSS). PATIENTS AND METHODS: Prospective cohort with imaging-confirmed ischemic stroke. Clinical data, sleep apnea risk score (STOPBANG) and blood pressure measures were collected at baseline. Primary outcome was the 90-day modified Rankin Scale (mRS), with poor outcome defined as mRS 3-6. Area under the ROC curve (AUC) was calculated for NIPSS and compared to six other stroke prognostic scores in our cohort: SPAN-100 index, S-SMART, SOAR, ASTRAL, THRIVE, and Dutch Stroke scores. RESULTS: We enrolled 386 participants. After 90 days, there were 56% with poor outcome, more frequently older, female predominant and with higher admission National Institute of Health Stroke Scale (NIHSS). Four variables remained significantly associated with primary endpoint in the multivariable model: age (OR 1.87), NIHSS (OR 7.08), STOPBANG category (OR 1.61), and ankle-braquial index (OR 2.11). NIPSS AUC was 0.86 (0.82-0.89); 0.83 (0.79-0.87) with bootstrapping. When compared to the other scores, NIPSS, ASTRAL, S-SMART and DUTCH scores had good abilities in predicting poor outcome, with AUC of 0.86, 0.86, 0.83 and 0.82, respectively. THRIVE, SOAR and SPAN-100 scores were fairly predictive. DISCUSSION AND CONCLUSIONS: Non-invasive and easily acquired emergency room data can predict clinical outcome after stroke. NIPSS performed equal to or better than other prognostic stroke scales.


Asunto(s)
Isquemia Encefálica , Enfermedad Arterial Periférica , Síndromes de la Apnea del Sueño , Accidente Cerebrovascular , Humanos , Femenino , Pronóstico , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Estudios Prospectivos , Triaje , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Enfermedad Arterial Periférica/diagnóstico , Resultado del Tratamiento
8.
Chimia (Aarau) ; 77(4): 212-216, 2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38047798

RESUMEN

Magic angle spinning (MAS) in 1H NMR has allowed progress from featureless spectra in static samples to linewidths of a few hundreds of Hertz for powdered solids at the fastest spinning rates available today (100-150 kHz). While this is a remarkable improvement, this level of resolution is still limiting to the widespread use of 1H NMR for complex systems. This review will discuss two recent alternative strategies that have significantly improved 1H resolution, when combined with fast MAS. The first is based on anti-z-COSY, a 2D experiment originally used for J decoupling in liquids, which removes residual broadening due to splittings caused by imperfect coherent averaging of MAS. The second strategy is to obtain pure isotropic proton (PIP) spectra in solids, by parametrically mapping any residual broadening due to imperfect averaging into a second dimension of a multidimensional correlation spectrum.

9.
Angew Chem Int Ed Engl ; 62(8): e202216607, 2023 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-36562545

RESUMEN

The resolution of proton solid-state NMR spectra is usually limited by broadening arising from dipolar interactions between spins. Magic-angle spinning alleviates this broadening by inducing coherent averaging. However, even the highest spinning rates experimentally accessible today are not able to completely remove dipolar interactions. Here, we introduce a deep learning approach to determine pure isotropic proton spectra from a two-dimensional set of magic-angle spinning spectra acquired at different spinning rates. Applying the model to 8 organic solids yields high-resolution 1 H solid-state NMR spectra with isotropic linewidths in the 50-400 Hz range.

10.
Angew Chem Int Ed Engl ; 62(21): e202301963, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-36929691

RESUMEN

One key bottleneck of solid-state NMR spectroscopy is that 1 H NMR spectra of organic solids are often very broad due to the presence of a strong network of dipolar couplings. We have recently suggested a new approach to tackle this problem. More specifically, we parametrically mapped errors leading to residual dipolar broadening into a second dimension and removed them in a correlation experiment. In this way pure isotropic proton (PIP) spectra were obtained that contain only isotropic shifts and provide the highest 1 H NMR resolution available today in rigid solids. Here, using a deep-learning method, we extend the PIP approach to a second dimension, and for samples of L-tyrosine hydrochloride and ampicillin we obtain high resolution 1 H-1 H double-quantum/single-quantum dipolar correlation and spin-diffusion spectra with significantly higher resolution than the corresponding spectra at 100 kHz MAS, allowing the identification of previously overlapped isotropic correlation peaks.

11.
Anaerobe ; 78: 102668, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36368601

RESUMEN

OBJECTIVES: Bacteroides fragilis is an anaerobic bacterium that is commonly found in the human gut microbiota and an opportunistic pathogen in extra-intestinal infections. B. fragilis displays a robust response to oxidative stress which allows for survival in oxygenated tissues such as the peritoneal cavity and lead to the formation of abscesses. In this study, we investigated the synergy of the oxidative stress response regulators OxyR and BmoR in the ability of B. fragilis to resist oxidative damage and to survive in extra-intestinal infection. METHODS: A ΔbmoR ΔoxyR double mutant B. fragilis strain was constructed, and its oxidative stress response was compared to parental and single mutant strains in phenotypical assays and gene expression analysis. The pathogenic potential in an in vivo mouse model of abscess formation was also evaluated. RESULTS: Expression analysis showed a coordinated control of thioredoxin C (trxC) gene expression by BmoR and OxyR during oxygen exposure, with upregulation of trxC in the bmoR mutant strain (4.9-fold increase), downregulation in the oxyR mutant (2.5-fold decrease), and an intermediate level of deregulation (2-fold increase) in the double mutant strain compared to the parent strain. Expression analysis during oxidative stress conditions also showed that BmoR is a major repressor of the CoA-disulfide reductase gene (upregulated 47-fold in the bmoR mutant) while OxyR plays a minor repression role in this gene (upregulated 2.5-fold in the oxyR mutant). Exposure to atmospheric oxygen for up to 72 h revealed that the deletion of bmoR alone had no significant effect in in vitro survival phenotype assays, though it partially abolishes the OxyR sensitivity phenotype in the bmoR/oxyR double mutant strain compared to oxyR mutant. In vivo assays showed that bmoR and oxyR mutants were significantly impaired in the formation and development of abscesses compared to the parent strain in an experimental intra-abdominal infection mouse model. CONCLUSION: Although the full extent of genes whose expression are modulated by BmoR and OxyR is yet to be defined, we present evidence that these regulators have overlapping functions in B. fragilis response to oxidative stress and ability to form abscess in extra-intestinal tissues.


Asunto(s)
Bacteroides fragilis , Infecciones Intraabdominales , Ratones , Humanos , Animales , Regulón , Absceso , Composición de Base , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Filogenia , ARN Ribosómico 16S/metabolismo , Análisis de Secuencia de ADN , Estrés Oxidativo/genética , Oxígeno/metabolismo , Regulación Bacteriana de la Expresión Génica
12.
Int J Mol Sci ; 23(16)2022 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-36012447

RESUMEN

Several species of Tityus (Scorpiones, Buthidae) present multi-chromosomal meiotic associations and failures in the synaptic process, originated from reciprocal translocations. Holocentric chromosomes and achiasmatic meiosis in males are present in all members of this genus. In the present study, we investigated synapse dynamics, transcriptional silencing by γH2AX, and meiotic microtubule association in bivalents and a quadrivalent of the scorpion Tityus maranhensis. Additionally, we performed RT-PCR to verify the expression of mismatch repair enzymes involved in crossing-over formation in Tityus silvestris gonads. The quadrivalent association in T. maranhensis showed delay in the synaptic process and long asynaptic regions during pachytene. In this species, γH2AX was recorded only at the chromosome ends during early stages of prophase I; in metaphase I, bivalents and quadrivalents of T. maranhensis exhibited binding to microtubules along their entire length, while in metaphase II/anaphase II transition, spindle fibers interacted only with telomeric regions. Regarding T. silvestris, genes involved in the recombination process were transcribed in ovaries, testes and embryos, without significant difference between these tissues. The expression of these genes during T. silvestris achiasmatic meiosis is discussed in the present study. The absence of meiotic inactivation by γH2AX and holo/telokinetic behavior of the chromosomes are important factors for the maintenance of the quadrivalent in T. maranhensis and the normal continuation of the meiotic cycle in this species.


Asunto(s)
Cromosomas , Escorpiones , Animales , Cromosomas/genética , Masculino , Meiosis/genética , Metafase , Recombinación Genética , Escorpiones/genética , Telómero
13.
Trop Anim Health Prod ; 54(5): 293, 2022 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-36097231

RESUMEN

Porcine circovirus type 3 (PCV3) has been widely detected worldwide in healthy and sick pigs. Recently its association with clinical disease and reproductive failure has been proven through the detection of intralesional viral mRNA in affected pigs. This study aims to describe the occurrence of PCV3-associated reproductive failure (abortions) in sow herds in southern Brazil. Eleven fetuses from five different litters from two herds were analyzed. These herds reported an increase in the rate of late-gestation abortions, stillbirths, and the percentage of mummified piglets. At gross examination, six of the fetuses had large caudally rotated ears and one fetus was mummified. Microscopically, multisystemic vasculitis, lymphocytic interstitial pneumonia, myocarditis, and encephalitis were observed. These six fetuses with gross and histological lesions were positive in qPCR analysis for PCV3, and PCV3 transcription was shown through in situ hybridization (ISH-RNA) within the histologic lesions. Samples from all 11 fetuses tested negative in PCR exam for Porcine Circovirus type 1 and 2, Porcine Reproductive and Respiratory Syndrome, Porcine Parvovirus, and Atypical Porcine Pestivirus. Furthermore, based on the ORF2 analysis, the PCV3a clade was identified. This is the first report of PCV3a-associated reproductive failure in pig herds in South America.


Asunto(s)
Infecciones por Circoviridae , Circovirus , Enfermedades de los Porcinos , Animales , Brasil/epidemiología , Infecciones por Circoviridae/veterinaria , Femenino , Embarazo , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Porcinos , Enfermedades de los Porcinos/epidemiología
14.
J Am Chem Soc ; 143(26): 9834-9841, 2021 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-34170672

RESUMEN

Resolution in proton solid state magic angle sample spinning (MAS) NMR is limited by the intrinsically imperfect nature of coherent averaging induced by either MAS or multiple pulse sequence methods. Here, we suggest that instead of optimizing and perfecting a coherent averaging scheme, we could approach the problem by parametrically mapping the error terms due to imperfect averaging in a k-space representation, in such a way that they can be removed in a multidimensional correlation leaving only the desired pure isotropic signal. We illustrate the approach here by determining pure isotropic 1H spectra from a series of MAS spectra acquired at different spinning rates. For six different organic solids, the approach is shown to produce pure isotropic 1H spectra that are significantly narrower than the MAS spectrum acquired at the fastest possible rate, with linewidths down to as little as 48 Hz. On average, we observe a 7-fold increase in resolution, and up to a factor of 20, as compared with spectra acquired at 100 kHz MAS. The approach is directly applicable to a range of solids, and we anticipate that the same underlying principle for removing errors introduced here can be applied to other problems in NMR spectroscopy.

15.
J Chem Inf Model ; 61(1): 67-75, 2021 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-33350814

RESUMEN

In this study, machine learning algorithms were investigated for the classification of organic molecules with one carbon chiral center according to the sign of optical rotation. Diverse heterogeneous data sets comprising up to 13,080 compounds and their corresponding optical rotation were retrieved from Reaxys and processed independently for three solvents: dichloromethane, chloroform, and methanol. The molecular structures were represented by chiral descriptors based on the physicochemical and topological properties of ligands attached to the chiral center. The sign of optical rotation was predicted by random forests (RF) and artificial neural networks for independent test sets with an accuracy of up to 75% for dichloromethane, 82% for chloroform, and 82% for methanol. RF probabilities and the availability of structures in the training set with the same spheres of atom types around the chiral center defined applicability domains in which the accuracy is higher.


Asunto(s)
Aprendizaje Automático , Redes Neurales de la Computación , Algoritmos , Estructura Molecular , Rotación Óptica , Estereoisomerismo
16.
J Chem Phys ; 155(8): 084201, 2021 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-34470347

RESUMEN

The homonuclear dipolar coupling is the internal spin interaction that contributes the most to the line shapes in magic-angle-spinning (MAS) 1H NMR spectra of solids, and linewidths typically extend over several hundred Hertz, limiting the 1H resolution. Understanding and reducing this contribution could provide rich structural information for organic solids. Here, we use average Hamiltonian theory to study two- and three-spin systems in the fast MAS regime. Specifically, we develop analytical expressions to third order in the case of two and three inequivalent spins (I = ½). The results show that the full third-order expression of the Hamiltonian, without secular approximations or truncation to second order, is the description that agrees the best, by far, with full numerical calculations. We determine the effect on the NMR spectrum of the different Hamiltonian terms, which are shown to produce both residual shifts and splittings in the three-spin systems. Both the shifts and splittings have a fairly complex dependence on the spinning rate with the eigenstates having a polynomial ωr dependence. The effect on powder line shapes is also shown, and we find that the anisotropic residual shift does not have zero average so that the powder line shape is broadened and shifted from the isotropic position. This suggests that in 1H MAS spectra, even at the fastest MAS rates attainable today, the positions observed are not exactly the isotropic shifts.

17.
Pharmacol Res ; 161: 105198, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32942016

RESUMEN

Methylglyoxal was shown to impair adipose tissue capillarization and insulin sensitivity in obese models. We hypothesized that glyoxalase-1 (GLO-1) activity could be diminished in the adipose tissue of type 2 diabetic obese patients. Moreover, we assessed whether such activity could be increased by GLP-1-based therapies in order to improve adipose tissue capillarization and insulin sensitivity. GLO-1 activity was assessed in visceral adipose tissue of a cohort of obese patients. The role of GLP-1 in modulating GLO-1 was assessed in type 2 diabetic GK rats submitted to sleeve gastrectomy or Liraglutide treatment, in the adipose tissue angiogenesis assay and in the HUVEC cell line. Glyoxalase-1 activity was decreased in visceral adipose tissue of pre-diabetic and diabetic obese patients, together with other markers of adipose tissue dysfunction and correlated with increased HbA1c levels. Decreased adipose tissue GLO-1 levels in GK rats were increased by sleeve gastrectomy and Liraglutide, being associated with overexpression of angiogenic and vasoactive factors, as well as insulin receptor phosphorylation (Tyr1161). Moreover, GLP-1 increased adipose tissue capillarization and HUVEC proliferation in a glyoxalase-dependent manner. Lower adipose tissue GLO-1 activity was observed in dysmetabolic patients, being a target for GLP-1 in improving adipose tissue capillarization and insulin sensitivity.


Asunto(s)
Tejido Adiposo/irrigación sanguínea , Capilares/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/farmacología , Incretinas/farmacología , Resistencia a la Insulina , Lactoilglutatión Liasa/metabolismo , Liraglutida/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Adulto , Anciano , Animales , Capilares/enzimología , Capilares/fisiopatología , Células Cultivadas , Diabetes Mellitus Tipo 2/enzimología , Diabetes Mellitus Tipo 2/fisiopatología , Modelos Animales de Enfermedad , Femenino , Gastrectomía , Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/enzimología , Humanos , Masculino , Persona de Mediana Edad , Obesidad/enzimología , Obesidad/fisiopatología , Obesidad/cirugía , Ratas Wistar , Transducción de Señal
18.
BMC Oral Health ; 20(1): 329, 2020 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-33213442

RESUMEN

BACKGROUND: Peri-implantitis is a biological complication that affects soft and hard tissues around dental implants. Implantoplasty (IP) polishes the exposed implant surface, to decontaminate it and make it less prone to bacterial colonization. This study investigates whether a higher clinical crown-to-implant-ratio (CIR) reduces implant fracture resistance and whether implants are more fracture-prone after IP in the presence of 50% of bone loss. METHODS: Forty-eight narrow platform (3.5 mm) 15 mm long titanium dental implants with a rough surface and hexagonal external connection were placed in standardized bone-like resin casts leaving 7.5 mm exposed. Half were selected for IP. The IP and control groups were each divided into 3 subgroups with different clinical CIRs (2:1, 2.5:1 and 3:1). The implant wall width measurements were calculated using the software ImageJ v.1.51 through the analysis of plain x-ray examination of all the samples using standardized mounts. A fracture test was performed and scanning electron microscopy was used to evaluate maximum compression force (Fmax) and implant fractures. RESULTS: IP significantly reduced the implant wall width (P < 0.001) in all reference points of each subgroup. Fmax was significantly higher in the 2:1 subgroup (control = 1276.16 N ± 169.75; IP = 1211.70 N ± 281.64) compared with the 2.5:1 (control = 815.22 N ± 185.58, P < 0.001; IP = 621.68 N ± 186.28, P < 0.001) and the 3:1 subgroup (control = 606.55 N ± 111.48, P < 0.001; IP = 465.95 N ± 68.57, P < 0.001). Only the 2.5:1 subgroup showed a significant reduction (P = 0.037) of the Fmax between the controls and the IP implants. Most fractures were located in the platform area. Only 5 implants with IP of the 2:1 CIR subgroup had a different fracture location (4 fractures in the implant body and 1 in the prosthetic screw). CONCLUSIONS: IP significantly reduces the fracture resistance of implants with a 2.5:1 CIR. The results also suggest that the CIR seems to be a more relevant variable when considering the resistance to fracture of implants, since significant reductions were observed when unfavorable CIR subgroups (2.5:1 and 3:1 CIR) were compared with the 2:1 CIR samples.


Asunto(s)
Pérdida de Hueso Alveolar , Implantes Dentales , Periimplantitis , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/etiología , Coronas , Implantes Dentales/efectos adversos , Diseño de Prótesis Dental , Humanos , Periimplantitis/etiología , Titanio
19.
Angew Chem Int Ed Engl ; 59(15): 6235-6238, 2020 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-31967378

RESUMEN

The typical linewidths of 1 H NMR spectra of powdered organic solids at 111 kHz magic-angle spinning (MAS) are of the order of a few hundred Hz. While this is remarkable in comparison to the tens of kHz observed in spectra of static samples, it is still the key limit to the use of 1 H in solid-state NMR, especially for complex systems. Here, we demonstrate a novel strategy to further improve the spectral resolution. We show that the anti-z-COSY experiment can be used to reduce the residual line broadening of 1 H NMR spectra of powdered organic solids. Results obtained with the anti-z-COSY sequence at 100 kHz MAS on thymol, ß-AspAla, and strychnine show an improvement in resolution of up to a factor of two compared to conventional spectra acquired at the same spinning rate.

20.
Epilepsia ; 60(8): 1661-1669, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31273778

RESUMEN

OBJECTIVE: To determine the diagnostic yield of a commercial epilepsy gene panel in adults with chronic epilepsy and accompanying intellectual disability, given that genetic evaluation is often overlooked in this group of patients. METHODS: This is a cross-sectional study analyzing the results of epilepsy gene panels including up to 185 genes in adult epilepsy patients with intellectual disability, according to Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Patients with acquired structural brain abnormalities or known chromosomal abnormalities were excluded. RESULTS: From approximately 600 patients seen from January 2017 to June 2018 at a single academic epilepsy center, 64 probands and two affected relatives (32 males, mean age = 31 years ± 10) were selected and clinically tested. Fourteen probands (14/64 = 22%; four males, mean age = 32 years ± 10) were found to have pathogenic or likely pathogenic variants in the following genes: SCN1A, GABRB3, UBE3A, KANSL1, SLC2A1, KCNQ2, SLC6A1, HNRNPU, STX1B, SCN2A, PURA, and CHD2. Six variants arose de novo, and the inheritance was not determined in eight. Nine probands (64%) had severe or profound intellectual disability, and five (35%) had autistic features. Eight patients (57%) had a diagnostic change from presumptive clinical diagnosis prior to genetic testing. SIGNIFICANCE: We were able to demonstrate that a commercial epilepsy gene panel can be an important resource in clinical practice, identifying the etiology in 22% of adults with epilepsy and intellectual disability. The diagnostic yield is similar to previously reported pediatric cohorts. Larger samples would be required to evaluate the more prevalent genotypes among adult epilepsy patients.


Asunto(s)
Epilepsia/complicaciones , Pruebas Genéticas/métodos , Discapacidad Intelectual/complicaciones , Adulto , Estudios Transversales , Epilepsia/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Discapacidad Intelectual/genética , Masculino
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