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1.
Doc Ophthalmol ; 145(2): 163-174, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35947237

RESUMEN

PURPOSE: The purpose of this paper is to present a case study illustrating the importance of electrophysiological investigation in the diagnosis and serial monitoring of isolated congenital nystagmus. RESULTS: Serial electophysiological monitoring was undertaken in the male proband over a 9-year period commencing with initial assessment at 12 weeks of age: Skin electroretinograms (sERGs) were initially absent but subsequently revealed low-amplitude responses, electronegative morphologies and notched flicker responses suggestive of incomplete congenital stationary night blindness (CSNB2), but with an absent dark-adapted rod-specific response, while flash visual evoked potentials (fVEPs) demonstrated persistent crossed asymmetry, typical of albinoid misrouting of the optic nerves. Molecular investigation confirmed a novel hemizygous frame shift mutation in the CACNA1F gene, considered to be pathogenic and causative of X-linked CSNB2; additionally, a novel heterozygous missense variation in one copy of the RIMS1 gene was identified, pathogenic mutations of which underpin late-onset autosomal dominant cone-rod dystrophy (type 7). Segregation studies confirmed maternal inheritance of both mutations in the clinically asymptomatic mother in whom depressed rod-specific responses were confirmed on sERG. The child's visual acuity has remained stable as have the sERGs which have been verified by recordings using scleral electrodes. CONCLUSIONS: The importance of recording ERGs as part of evaluating infants who present with nystagmus, even with a normal fundus appearance, is supported. Further, sERGs were able to distinguish an apparent variant of CSNB2 and could give consistent results over many years. FVEP results add to the evidence that albinoid misrouting of the optic nerves may occur in cases of CSNB2. ERGs and fVEPs can provide valuable information in discriminating the relative diagnostic importance of multiple genetic abnormalities.


Asunto(s)
Enfermedades Genéticas Ligadas al Cromosoma X , Ceguera Nocturna , Canales de Calcio Tipo L/genética , Niño , Electrorretinografía , Potenciales Evocados Visuales , Enfermedades Hereditarias del Ojo , Mutación del Sistema de Lectura , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Humanos , Lactante , Masculino , Mutación , Miopía , Ceguera Nocturna/diagnóstico , Ceguera Nocturna/genética
3.
Plant Biol (Stuttg) ; 24(5): 766-779, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35398958

RESUMEN

Low-temperature thermal acclimation may require adjustments to N and water use to sustain photosynthesis because of slow enzyme functioning and high water viscosity. However, understanding of photosynthetic acclimation to temperatures below 11 °C is limited. We acclimated Populus balsamifera to 6 °C and 10 °C (6A and 10A, respectively) and provided the trees with either high or low N fertilizer. We measured net CO2 assimilation (Anet ), stomatal conductance (gs ), maximum rates of Rubisco carboxylation (Vcmax ), electron transport (Jmax ) and dark respiration (Rd ) at leaf temperatures of 2, 6, 10, 14 and 18 °C, along with leaf N concentrations. The 10A trees had higher Anet than the 6A trees at warmer leaf temperatures, which was correlated with higher gs in the 10A trees. The instantaneous temperature responses of Vcmax , Jmax and Rd were similar for trees from both acclimation temperatures. While soil N availability increased leaf N concentrations, this had no effect on acclimation of photosynthesis or respiration. Our results indicate that acclimation below 11 °C occurred primarily through changes in stomatal conductance, not photosynthetic biochemistry, and was unaffected by short-term N supply. Thermal acclimation of stomatal conductance should therefore be a priority for future carbon cycle model development.


Asunto(s)
Populus , Aclimatación/fisiología , Dióxido de Carbono , Nitrógeno , Fotosíntesis/fisiología , Hojas de la Planta/fisiología , Populus/fisiología , Temperatura , Árboles/fisiología , Agua
4.
J Small Anim Pract ; 63(8): 597-602, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35316860

RESUMEN

OBJECTIVES: To determine the prevalence of iatrogenic heart murmurs in a population of apparently healthy cats and to investigate factors that may predispose cats to iatrogenic murmurs. MATERIALS AND METHODS: Apparently healthy cats presenting for routine examinations were prospectively enrolled. Following a physical examination to confirm there were no abnormalities, a cardiac examination was performed before and during a provocative manoeuvre performed independently by two clinicians. The provocative manoeuvre was performed on the right side of the chest wall by applying gentle pressure with a stethoscope to ascertain whether a murmur became audible, graded using a modified descriptive scale (soft/moderate). The cat's heart rate before and during the provocative manoeuvre and their age, sex, body condition score and bodyweight were recorded. RESULTS: One hundred and six cats were prospectively enrolled. The average prevalence of iatrogenic murmurs was 28.2% with good interobserver agreement recorded on both the presence (kappa 0.67 and 0.62) and grade of the murmur (kappa 0.6 and 0.53). A significant association was noted between age and body condition score, with iatrogenic murmurs more likely in cats with increasing age and decreasing body condition score. There was no association between heart rate and the presence of an iatrogenic murmur. CLINICAL SIGNIFICANCE: Iatrogenic murmurs are a common finding in cats with increasing prevalence noted in older and lean cats. Iatrogenic murmurs should therefore be considered as a differential diagnosis in a cat when an audible soft systolic right-sided murmur occurs with gentle pressure application to the chest wall during auscultation.


Asunto(s)
Enfermedades de los Gatos , Ecocardiografía , Animales , Enfermedades de los Gatos/epidemiología , Enfermedades de los Gatos/etiología , Gatos , Ecocardiografía/veterinaria , Soplos Cardíacos/epidemiología , Soplos Cardíacos/etiología , Soplos Cardíacos/veterinaria , Enfermedad Iatrogénica/epidemiología , Enfermedad Iatrogénica/veterinaria , Prevalencia
5.
Anat Rec (Hoboken) ; 305(7): 1563-1591, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34813153

RESUMEN

Of the more than 6,000 members of the most speciose avian clade, Passeriformes (perching birds), only the five species of dippers (Cinclidae, Cinclus) use their wings to swim underwater. Among nonpasserine wing-propelled divers (alcids, diving petrels, penguins, and plotopterids), convergent evolution of morphological characteristics related to this highly derived method of locomotion have been well-documented, suggesting that the demands of this behavior exert strong selective pressure. However, despite their unique anatomical attributes, dippers have been the focus of comparatively few studies and potential convergence between dippers and nonpasseriform wing-propelled divers has not been previously examined. In this study, a suite of characteristics that are shared among many wing-propelled diving birds were identified and the distribution of those characteristics across representatives of all clades of extant and extinct wing-propelled divers were evaluated to assess convergence. Putatively convergent characteristics were drawn from a relatively wide range of sources including osteology, myology, endocranial anatomy, integument, and ethology. Comparisons reveal that whereas nonpasseriform wing-propelled divers do in fact share some anatomical characteristics putatively associated with the biomechanics of underwater "flight", dippers have evolved this highly derived method of locomotion without converging on the majority of concomitant changes observed in other taxa. Changes in the flight musculature and feathers, reduction of the keratin bounded external nares and an increase in subcutaneous fat are shared with other wing-propelled diving birds, but endocranial anatomy shows no significant shifts and osteological modifications are limited. Muscular and integumentary novelties may precede skeletal and neuroendocranial morphology in the acquisition of this novel locomotory mode, with implications for understanding potential biases in the fossil record of other such transitions. Thus, dippers represent an example of a highly derived and complex behavioral convergence that is not fully associated with the anatomical changes observed in other wing-propelled divers, perhaps owing to the relative recency of their divergence from nondiving passeriforms.


Asunto(s)
Pájaros Cantores , Animales , Evolución Biológica , Vuelo Animal , Fósiles , Osteología , Natación , Alas de Animales/anatomía & histología
6.
Sci Rep ; 11(1): 23626, 2021 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-34880294

RESUMEN

We show a method to control magnetic interfacial effects in multilayers with Dzyaloshinskii-Moriya interaction (DMI) using helium (He[Formula: see text]) ion irradiation. We report results from SQUID magnetometry, ferromagnetic resonance as well as Brillouin light scattering results on multilayers with DMI as a function of irradiation fluence to study the effect of irradiation on the magnetic properties of the multilayers. Our results show clear evidence of the He[Formula: see text] irradiation effects on the magnetic properties which is consistent with interface modification due to the effects of the He[Formula: see text] irradiation. This external degree of freedom offers promising perspectives to further improve the control of magnetic skyrmions in multilayers, that could push them towards integration in future technologies.

7.
Nature ; 600(7888): 253-258, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34880429

RESUMEN

The global terrestrial carbon sink is increasing1-3, offsetting roughly a third of anthropogenic CO2 released into the atmosphere each decade1, and thus serving to slow4 the growth of atmospheric CO2. It has been suggested that a CO2-induced long-term increase in global photosynthesis, a process known as CO2 fertilization, is responsible for a large proportion of the current terrestrial carbon sink4-7. The estimated magnitude of the historic increase in photosynthesis as result of increasing atmospheric CO2 concentrations, however, differs by an order of magnitude between long-term proxies and terrestrial biosphere models7-13. Here we quantify the historic effect of CO2 on global photosynthesis by identifying an emergent constraint14-16 that combines terrestrial biosphere models with global carbon budget estimates. Our analysis suggests that CO2 fertilization increased global annual photosynthesis by 11.85 ± 1.4%, or 13.98 ± 1.63 petagrams carbon (mean ± 95% confidence interval) between 1981 and 2020. Our results help resolve conflicting estimates of the historic sensitivity of global photosynthesis to CO2, and highlight the large impact anthropogenic emissions have had on ecosystems worldwide.


Asunto(s)
Atmósfera/química , Dióxido de Carbono/metabolismo , Mapeo Geográfico , Internacionalidad , Fotosíntesis , Secuestro de Carbono , Respiración de la Célula , Ecosistema , Actividades Humanas , Aprendizaje Automático , Plantas/metabolismo , Tecnología de Sensores Remotos , Imágenes Satelitales , Análisis Espacio-Temporal
8.
J Postgrad Med ; 2021 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-34708699

RESUMEN

Unilateral acquired diaphragmatic paresis is a known complication of thoracic surgeries. Direct mechanical injury to the phrenic nerve during surgery results in this complication. However its occurrence post-percutaneous nephrolithotomy (PCNL) has not been described. We report a 43-year-old man who underwent prone PCNL for endourological management of left complete staghorn calculus. Access via the 10th left intercostal space, under fluoroscopy, was carried out to remove the calculus. Post-operative, the routine chest radiograph revealed left hemidiaphragmatic blunting. Computerized tomography of the chest confirmed left hemidiaphragmatic elevation, suggesting unilateral diaphragmatic paresis. He did not have any respiratory symptoms, was managed conservatively with chest physiotherapy and incentive spirometry and responded extremely well. The absence of reported cases of diaphragmatic paresis post PCNL lends to a dearth in knowledge regarding recognition and management. This case report aims to acquaint urologists with this rare complication associated with supracostal PCNL and provide a rational management plan.

9.
Philos Trans A Math Phys Eng Sci ; 379(2212): 20200262, 2021 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-34689617

RESUMEN

The electrocardiogram (ECG) is a widespread diagnostic tool in healthcare and supports the diagnosis of cardiovascular disorders. Deep learning methods are a successful and popular technique to detect indications of disorders from an ECG signal. However, there are open questions around the robustness of these methods to various factors, including physiological ECG noise. In this study, we generate clean and noisy versions of an ECG dataset before applying symmetric projection attractor reconstruction (SPAR) and scalogram image transformations. A convolutional neural network is used to classify these image transforms. For the clean ECG dataset, F1 scores for SPAR attractor and scalogram transforms were 0.70 and 0.79, respectively. Scores decreased by less than 0.05 for the noisy ECG datasets. Notably, when the network trained on clean data was used to classify the noisy datasets, performance decreases of up to 0.18 in F1 scores were seen. However, when the network trained on the noisy data was used to classify the clean dataset, the decrease was less than 0.05. We conclude that physiological ECG noise impacts classification using deep learning methods and careful consideration should be given to the inclusion of noisy ECG signals in the training data when developing supervised networks for ECG classification. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.


Asunto(s)
Electrocardiografía , Redes Neurales de la Computación
10.
Br J Dermatol ; 185(6): 1176-1185, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34611893

RESUMEN

BACKGROUND: The outbreak of chilblain-like lesions (CLL) during the COVID-19 pandemic has been reported extensively, potentially related to SARS-CoV-2 infection, yet its underlying pathophysiology is unclear. OBJECTIVES: To study skin and blood endothelial and immune system activation in CLL in comparison with healthy controls and seasonal chilblains (SC), defined as cold-induced sporadic chilblains occurring during 2015 and 2019 with exclusion of chilblain lupus. METHODS: This observational study was conducted during 9-16 April 2020 at Saint-Louis Hospital, Paris, France. All patients referred with CLL seen during this period of the COVID-19 pandemic were included in this study. We excluded patients with a history of chilblains or chilblain lupus. Fifty patients were included. RESULTS: Histological patterns were similar and transcriptomic signatures overlapped in both the CLL and SC groups, with type I interferon polarization and a cytotoxic-natural killer gene signature. CLL were characterized by higher IgA tissue deposition and more significant transcriptomic activation of complement and angiogenesis factors compared with SC. We observed in CLL a systemic immune response associated with IgA antineutrophil cytoplasmic antibodies in 73% of patients, and elevated type I interferon blood signature in comparison with healthy controls. Finally, using blood biomarkers related to endothelial dysfunction and activation, and to angiogenesis or endothelial progenitor cell mobilization, we confirmed endothelial dysfunction in CLL. CONCLUSIONS: Our findings support an activation loop in the skin in CLL associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestations.


Asunto(s)
COVID-19 , Eritema Pernio , Interferón Tipo I , COVID-19/inmunología , Eritema Pernio/virología , Francia , Humanos , Interferón Tipo I/inmunología , Pandemias
11.
Int J Pediatr Otorhinolaryngol ; 150: 110874, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34392101

RESUMEN

INTRODUCTION: The best strategy to manage an interarytenoid defect [Type 1 laryngeal cleft (LC-1) or deep interarytenoid groove (DIG)] in pediatric aerodigestive patients with dysphagia remains uncertain. This study compared benefit of interarytenoid augmentation (IAA) to suture repair or clinical observation alone in pediatric patients. METHODS: A 3-year retrospective, single-center analysis of children with dysphagia undergoing endoscopic airway evaluation was performed. Physician preference guided treatment plan: suture repair with CO2 laser, IAA (carboxy methylcellulose or calcium hydroxyapatite), or observation. Primary outcome was improved post-operative diet. Significance was assumed at p < 0.05. RESULTS: 449 patients underwent diagnostic endoscopy. Mean age (±SD) at procedure was 21 ± 13 months, with nearly one fourth (28 %) of children ≤ 12 months. Eighty (18 %) had either an LC-1 (n = 55) or DIG (n = 25). Of these, 35 (42 %) underwent suture repair, 22 (28 %) IAA, and 23 (30 %) observation only. Aspiration improved overall in the interventional groups compared to observational controls (58 % vs. 9 %, p < 0.05), with no change in benefit observed by age of intervention. IAA was as effective as suture repair (59 % vs 55 %, p = 0.46). In patients with only a DIG, IAA intervention alone significantly improved swallow function (66.6 % vs. 0 %, p < 0.05). CONCLUSION: In pediatric aerodigestive patients with dysphagia, 18 % of children have an addressable lesion. IAA or suture repair similarly improves dietary advancement. IAA improves swallow function in patients with DIG. These findings support a novel protocol to intervene in dysphagia patients with LC-1 or DIG via IAA at the initial operative evaluation.


Asunto(s)
Trastornos de Deglución , Laringe , Preescolar , Trastornos de Deglución/etiología , Trastornos de Deglución/cirugía , Durapatita , Endoscopía , Humanos , Lactante , Laringe/cirugía , Estudios Retrospectivos
12.
Ann R Coll Surg Engl ; 103(6): 415-419, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34058122

RESUMEN

INTRODUCTION: During the first wave of the COVID-19 pandemic, University Hospitals Birmingham NHS Foundation trust was able to recommence elective orthopaedic surgery using private hospitals procured by the NHS as COVID-19 free 'green' sites. We report on the safety of elective orthopaedic surgery with high rates of community transmission. METHODS: We conducted an observational cohort study on consecutive NHS patients attending three private hospitals between 4 May 2020 and 16 June 2020. Patients attended preoperative assessment, including coronavirus disease (COVID-19) symptom screening, were instructed to self-isolate for 14 days and had a negative COVID-19 swab within 72 hours of surgery. Patient age, American Society of Anesthesiologists (ASA) grade, body mass index, surgery performed, type of anaesthetic and length of stay were collected. Our primary outcome was a positive COVID-19 swab, secondary outcomes were COVID-19 symptoms, readmission, surgical complications and mortality. RESULTS: Between 4 May 2020 and 16 June 2020, 191 patients were admitted to three private hospitals for elective surgery; 121 (67%) patients underwent general or regional anaesthetic, 179 patients were ASA grades 1 or 2 (94%) and 12 (6%) were ASA 3. In total, 187 (98%) patients were successfully contacted at 30 days postoperative and no COVID-19 symptoms, positive COVID-19 swabs or mortality or were recorded. One patient was readmitted following a pulmonary embolism and two patients were treated as outpatients for a deep vein thrombosis and a superficial infection. CONCLUSION: With 'green pathways' elective orthopaedic surgery can safely be performed while rates of COVID-19 in the community are high.


Asunto(s)
COVID-19/epidemiología , Procedimientos Quirúrgicos Electivos , Procedimientos Ortopédicos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/prevención & control , Control de Enfermedades Transmisibles/métodos , Infección Hospitalaria/prevención & control , Procedimientos Quirúrgicos Electivos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Ortopédicos/efectos adversos , Adulto Joven
13.
Sci Adv ; 7(18)2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33910907

RESUMEN

Relative brain size has long been considered a reflection of cognitive capacities and has played a fundamental role in developing core theories in the life sciences. Yet, the notion that relative brain size validly represents selection on brain size relies on the untested assumptions that brain-body allometry is restrained to a stable scaling relationship across species and that any deviation from this slope is due to selection on brain size. Using the largest fossil and extant dataset yet assembled, we find that shifts in allometric slope underpin major transitions in mammalian evolution and are often primarily characterized by marked changes in body size. Our results reveal that the largest-brained mammals achieved large relative brain sizes by highly divergent paths. These findings prompt a reevaluation of the traditional paradigm of relative brain size and open new opportunities to improve our understanding of the genetic and developmental mechanisms that influence brain size.

14.
Sci Rep ; 11(1): 442, 2021 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-33432078

RESUMEN

We describe experiments and simulations to investigate the dynamics of a ball bouncing on a rough vibrating surface. Directly measuring the impulse due to each bounce we find that the frictional interaction with the surface is strongly enhanced near to the side wall. The enhanced dissipation arises as a consequence of the coupling between the collision, rotation and surface friction. This dissipation, which for our experimental conditions was estimated to be up to three times larger than the more obvious inelastic collision, can result in an enhanced probability density near boundaries and particle-particle spatial correlations. Our findings imply that the effective particle collision properties cannot be considered independently of the surface's frictional properties.

16.
Phys Rev Lett ; 127(26): 268002, 2021 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-35029468

RESUMEN

We experimentally investigate the nature of 2D phase transitions in a quasi-2D granular fluid. Using a surface decorated with periodically spaced dimples we observe interfacial tension between coexisting granular liquid and crystal phases. Measurements of the orientational and translational order parameters and associated susceptibilities indicate that the surface topography alters the order of the phase transition from a two-step continuous one to a first-order liquid-solid one. The interplay of boundary inelasticity and geometry, either order promoting or inhibiting, controls whether it is the granular crystal or the granular fluid which makes contact with the edge. This order induced wetting has important consequences, determining how coexisting phases separate spatially.

17.
Colorectal Dis ; 22(11): 1614-1625, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32663900

RESUMEN

AIM: The decision to perform an abdominoperineal excision (APR) rather than restorative bowel resection relies on a number of clinical factors. There remains great variability in APR rates internationally. The aim of this study was to demonstrate trends of APR surgery in low rectal cancer (< 6 cm from the anal verge) in Australasia and identify predictors of nonrestoration. METHOD: This study reviewed a prospectively maintained colorectal registry - the Binational Colorectal Cancer Audit (BCCA) - from general/colorectal surgical units across Australia and New Zealand. Data were analysed to determine factors predictive of nonrestorative resection. Patients were analysed based on the presence (control) or absence (comparison) of a primary anastomosis. RESULTS: Of 3628 patients with rectal cancer, 2096 were diagnosed with low rectal cancer between 2007 and 2017. The incidence of APR remained constant over the study period, with 58% of all resections of low rectal cancer being APR. The majority of resections were performed by consultants in urban hospitals (86% vs 14%). Tumours ≤ 3 cm from the anal verge, T4, M1 disease and neoadjuvant therapy were the greatest predictors of APR (P < 0.001). A significantly increased rate of restorative surgery was observed in public hospital settings (59% vs 41%, P < 0.05). The rate of positive circumferential resection margin (CRM) was 7.95%, with significantly increased rates in patients undergoing APR (12.2% vs 6.2%, P < 0.001). CRM positivity was increased in open approaches, T4, N2 and M1 staged disease and in an emergency/urgent setting (P < 0.001 and P < 0.045, respectively). Significantly increased wound and pulmonary complications were observed in the APR cohort (P < 0.01). CONCLUSION: The rates of APR in Australia and New Zealand remain high but are comparable to international figures, with one-third of rectal cancers being treated by APR. The main determinants of APR are tumour height, T stage and neoadjuvant therapy requirement. CRM positivity was higher in APR patients.


Asunto(s)
Proctectomía , Neoplasias del Recto , Humanos , Recurrencia Local de Neoplasia , Perineo/cirugía , Proctectomía/efectos adversos , Neoplasias del Recto/epidemiología , Neoplasias del Recto/cirugía , Recto/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
18.
Tech Coloproctol ; 24(11): 1145-1153, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32662050

RESUMEN

BACKGROUND: Pelvic exenteration remains a viable and effective treatment option for the management of locally advanced or recurrent pelvic malignancy. The aim of this study was to present an early experience of robotic multivisceral resection of pelvic malignancy, and to compare this experience with similar series through a systematic review of the literature. METHODS: A retrospective study was performed on patients who had robotic-assisted multi-visceral resection for pelvic malignancy at a single Colorectal Surgical unit based between two tertiary academic hospitals. Primary outcomes observed included operation type, operation time, perioperative complications, and hospital length of stay. Secondary outcomes included R0 resection status, lymph node harvest, and rate of recurrence at clinical follow-up. RESULTS: Eight cases of robotic multivisceral resection were performed for primary locally advanced pelvic malignancy involving a rectal resection as part of their operative management. The median age of patients undergoing resection was 56 years (range 29-83 years). The male:female ratio was 6:2. The mean total operating time was 8.3 h (range 6-10 h). Perioperative blood transfusion requirements were minimal. Mean hospital length of stay was 15 days (range 7-26 days). No patients experienced any serious postoperative morbidity or mortality. All patients had clear margins on histological assessment and no patients have recurrence at 12-month follow-up. CONCLUSIONS: Robotic multivisceral resection for malignant disease of the pelvis is a safe and feasible minimally invasive approach in highly selected cases.


Asunto(s)
Exenteración Pélvica , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Robótica , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
19.
Clin Microbiol Infect ; 26(9): 1256.e1-1256.e8, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32387437

RESUMEN

OBJECTIVES: Optimal combination therapy for Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) is unknown. The present study sought to characterize the pharmacodynamics (PD) of polymyxin B (PMB), meropenem (MEM) and rifampin (RIF) alone and in combination using a hollow fibre infection model (HFIM) coupled with mechanism-based modelling (MBM). METHODS: A 10-day HFIM was utilized to simulate human pharmacokinetics (PK) of various PMB, MEM and RIF dosing regimens against a clinical KPC-Kp isolate, with total and resistant subpopulations quantified to capture PD response. A MBM was developed to characterize bacterial subpopulations and synergy between agents. Simulations using the MBM and published population PK models were employed to forecast the bacterial time course and the extent of its variability in infected patients for three-drug regimens. RESULTS: In the HFIM, a PMB single-dose ('burst') regimen of 5.53 mg/kg combined with MEM 8 g using a 3-hr prolonged infusion every 8 hr and RIF 600 mg every 24 hr resulted in bacterial counts below the quantitative limit within 24 hr and remained undetectable throughout the 10-day experiment. The final MBM consisted of two bacterial subpopulations of differing PMB and MEM joint susceptibility and the ability to form a non-replicating, tolerant subpopulation. Synergistic interactions between PMB, MEM and RIF were well quantified, with the MBM providing adequate capture of the observed data. DISCUSSION: An in vitro-in silico approach answers questions related to PD optimization as well as overall feasibility of combination therapy against KPC-Kp, offering crucial insights in the absence of clinical trials.


Asunto(s)
Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Klebsiella pneumoniae/enzimología , beta-Lactamasas/metabolismo , Técnicas Bacteriológicas , Quimioterapia Combinada , Meropenem/administración & dosificación , Meropenem/farmacología , Polimixina B/administración & dosificación , Polimixina B/farmacología , Rifampin/administración & dosificación , Rifampin/farmacología
20.
Curr Biol ; 30(11): 2026-2036.e3, 2020 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-32330422

RESUMEN

Relative brain sizes in birds can rival those of primates, but large-scale patterns and drivers of avian brain evolution remain elusive. Here, we explore the evolution of the fundamental brain-body scaling relationship across the origin and evolution of birds. Using a comprehensive dataset sampling> 2,000 modern birds, fossil birds, and theropod dinosaurs, we infer patterns of brain-body co-variation in deep time. Our study confirms that no significant increase in relative brain size accompanied the trend toward miniaturization or evolution of flight during the theropod-bird transition. Critically, however, theropods and basal birds show weaker integration between brain size and body size, allowing for rapid changes in the brain-body relationship that set the stage for dramatic shifts in early crown birds. We infer that major shifts occurred rapidly in the aftermath of the Cretaceous-Paleogene mass extinction within Neoaves, in which multiple clades achieved higher relative brain sizes because of a reduction in body size. Parrots and corvids achieved the largest brains observed in birds via markedly different patterns. Parrots primarily reduced their body size, whereas corvids increased body and brain size simultaneously (with rates of brain size evolution outpacing rates of body size evolution). Collectively, these patterns suggest that an early adaptive radiation in brain size laid the foundation for subsequent selection and stabilization.


Asunto(s)
Evolución Biológica , Aves/anatomía & histología , Aves/genética , Encéfalo/anatomía & histología , Animales , Tamaño de los Órganos
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