With the proliferation of different fixation screws, there is an increasing trend to recommend early internal fixation of the broken scaphoid even if the fracture is not displaced. The benefits and ...risks of early fixation of scaphoid fractures have not been established. These were investigated in eighty-eight patients who were of working age with clearly defined minimally displaced or undisplaced bicortical fractures of the waist of the scaphoid.
Patients who provided informed consent were randomized to treatment with early internal fixation with use of a Herbert screw without a cast (forty-four patients) or to nonoperative treatment for eight weeks with immobilization in a below-the-elbow plaster cast with the thumb left free (forty-four patients). The patients were evaluated at two, eight, twelve, twenty-six, and fifty-two weeks with respect to the severity of pain; tenderness; swelling; wrist movement; grip strength; and symptoms and disability, which were assessed with the Patient Evaluation Measure. In addition, radiographs were made and assessed at each visit.
No difference was detected between the groups with respect to age, sex, hand dominance, side of injury, mechanism of injury, or the occupation of the patients. The range of motion, score on the Patient Evaluation Measure, and grip strength were significantly better in the group managed operatively than in the group managed nonoperatively at the eight-week follow-up evaluation, which corresponded with the visit when the cast was removed in that group. Patients returned to work at five to six weeks after the injury in both groups. At twelve weeks, grip strength was better in patients who had had surgery. No significant difference was detected between the two groups with respect to any other outcome measure at any other time. Ten of the forty-four fractures treated nonoperatively had not healed radiographically at twelve weeks, and, as a consequence, the treatment was altered. Complications occurred in thirteen patients who had been managed operatively. All complications were minor, and ten were related to the scar.
This study did not demonstrate a clear overall benefit of early fixation of acute scaphoid fractures beyond the decrease in the rate of a change in treatment because of a delayed union at twelve weeks. Early internal fixation of minimally displaced or nondisplaced fractures of the scaphoid waist, which would heal in a cast, could lead to overtreatment of a large proportion of such fractures, exposing such patients to avoidable surgical risk. Thus, we have adopted a program of so-called aggressive conservative treatment, whereby we carefully assess fracture-healing with plain radiographs, and computed tomography scans if necessary, after six to eight weeks of cast immobilization and recommend surgical fixation with or without bone-grafting at that time if a gap is identified at the fracture site. Such an approach should result in fracture union in over 95% of such patients.
Therapeutic Level I.
The consumption of psychoactive substances is considered a growing problem in many communities. Moreover, new psychoactive substances (NPS) designed as (legal) substitutes to traditional illicit ...drugs are relatively easily available to the public through e-commerce and retail shops, but there is little knowledge regarding the extent and actual use of these substances. This study aims to gain new and complementary information on NPS and traditional illicit drug use at six music festivals across Europe by investigating wastewater and pooled urine. Samples were collected, between 2015 and 2018, at six music festivals across Europe with approximately 465.000 attendees. Wastewater samples were also collected during a period not coinciding with festivals. A wide-scope screening for 197 NPS, six illicit drugs and known metabolites was applied using different chromatography-mass spectrometric strategies. Several illicit drugs and in total 21 different NPS, mainly synthetic cathinones, phenethylamines and tryptamines, were identified in the samples. Ketamine and the traditional illicit drugs, such as amphetamine-type stimulants, cannabis and cocaine were most abundant and/or frequently detected in the samples collected, suggesting a higher use compared to NPS.
The analyses of urine and wastewater is quick and a high number of attendees may be monitored anonymously by analysing only a few samples which allows identifying the local profiles of use of different drugs within a wide panel of psychoactive substances. This approach contributes to the development of an efficient surveillance system which can provide timely insight in the trends of NPS and illicit drugs use.
Display omitted
•Substance use was assessed at music festivals across six European countries.•Urine and wastewater analyses can provide timely complementary information.•Wastewater-based epidemiology provides information on the pattern of drug use at festivals.•Specific local patterns of substance use were identified.•NPS were identified but cocaine, MDMA, cannabis and ketamine were most frequently detected.
Internal waves (IWs) in the ocean span across a wide range of time and spatial scales and are now acknowledged as important sources of turbulence and mixing, with the largest observations having ...200 m in amplitude and vertical velocities close to 0.5 m s
. Their origin is mostly tidal, but an increasing number of non-tidal generation mechanisms have also been observed. For instance, river plumes provide horizontally propagating density fronts, which were observed to generate IWs when transitioning from supercritical to subcritical flow. In this study, satellite imagery and autonomous underwater measurements are combined with numerical modeling to investigate IW generation from an initial subcritical density front originating at the Douro River plume (western Iberian coast). These unprecedented results may have important implications in near-shore dynamics since that suggest that rivers of moderate flow may play an important role in IW generation between fresh riverine and coastal waters.
Aims/hypothesis
A high-fat dietary intake induces obesity and subclinical inflammation, which play important roles in insulin resistance. Recent studies have suggested that increased concentrations ...of circulating lipopolysaccharide (LPS), promoted by changes in intestinal permeability, may have a pivotal role in insulin resistance. Thus, we investigated the effect of gut microbiota modulation on insulin resistance and macrophage infiltration.
Methods
Swiss mice were submitted to a high-fat diet with antibiotics or pair-feeding for 8 weeks. Metagenome analyses were performed on DNA samples from mouse faeces. Blood was collected to determine levels of glucose, insulin, LPS, cytokines and acetate. Liver, muscle and adipose tissue proteins were analysed by western blotting. In addition, liver and adipose tissue were analysed, blinded, using histology and immunohistochemistry.
Results
Antibiotic treatment greatly modified the gut microbiota, reducing levels of Bacteroidetes and Firmicutes, overall bacterial count and circulating LPS levels. This modulation reduced levels of fasting glucose, insulin, TNF-α and IL-6; reduced activation of toll-like receptor 4 (TLR4), c-Jun N-terminal kinase (JNK), inhibitor of κ light polypeptide gene enhancer in B cells, kinase β (IKKβ) and phosphorylated IRS-1 Ser307; and consequently improved glucose tolerance and insulin tolerance and action in metabolically active tissues. In addition, there was an increase in portal levels of circulating acetate, which probably contributed to an increase in 5′-AMP-activated protein kinase (AMPK) phosphorylation in mice. We observed a striking reduction in crown-like structures (CLS) and F4/80
+
macrophage cells in the adipose tissue of antibiotic-treated mice.
Conclusions/interpretation
These results suggest that modulation of gut microbiota in obesity can improve insulin signalling and glucose tolerance by reducing circulating LPS levels and inflammatory signalling. Modulation also appears to increase levels of circulating acetate, which activates AMPK and finally leads to reduced macrophage infiltration.
Personalizing non-small-cell lung cancer (NSCLC) therapy toward oncogene addicted pathway inhibition is effective. Hence, the ability to determine a more comprehensive genotype for each case is ...becoming essential to optimal cancer care.
We developed a multiplexed PCR-based assay (SNaPshot) to simultaneously identify >50 mutations in several key NSCLC genes. SNaPshot and FISH for ALK translocations were integrated into routine practice as Clinical Laboratory Improvement Amendments-certified tests. Here, we present analyses of the first 589 patients referred for genotyping.
Pathologic prescreening identified 552 (95%) tumors with sufficient tissue for SNaPshot; 51% had ≥1 mutation identified, most commonly in KRAS (24%), EGFR (13%), PIK3CA (4%) and translocations involving ALK (5%). Unanticipated mutations were observed at lower frequencies in IDH and β-catenin. We observed several associations between genotypes and clinical characteristics, including increased PIK3CA mutations in squamous cell cancers. Genotyping distinguished multiple primary cancers from metastatic disease and steered 78 (22%) of the 353 patients with advanced disease toward a genotype-directed targeted therapy.
Broad genotyping can be efficiently incorporated into an NSCLC clinic and has great utility in influencing treatment decisions and directing patients toward relevant clinical trials. As more targeted therapies are developed, such multiplexed molecular testing will become a standard part of practice.
BACKGROUND: Sarcopenia is defined as a progressive and generalized loss of skeletal muscle mass and strength. The specific threshold of muscle weakness that leads to mobility limitations has not been ...identified. OBJECTIVES: To determine the best cutoff point of handgrip strength for identifying mobility limitation and to investigate the factors associated with muscle weakness and mobility limitation in community-dwelling older people. DESIGN: Transversal study. SETTING: Cities of Belo Horizonte, Barueri and Santa Cruz in Brazil. PARTICIPANTS: 1374 community-dwelling older people from the Frailty study in Brazilian older people (FIBRA Study). MEASUREMENTS: Outcomes included muscle weakness determined according to gender-specific handgrip strength cutoff points generated by Receiver Operating Characteristic curves, mobility limitation defined as a gait speed = 0.8 m/s; and a combination of both muscle weakness and mobility limitation. Associated factors included socio-demographic variables, lifestyle, anthropometrics, health conditions, use of health services and disability. RESULTS: The cutoff points of handgrip strength with the best balancing between sensitivity and specificity for mobility limitation were 25.8 kgf for men (sensitivity 69%, specificity 73%) and 17.4 kgf (sensitivity 60%, specificity 66%) for women. Age and disability in instrumental activities of daily living were associated with all outcomes. Women had greater odds of mobility limitation than men. Physical inactivity, body fat, diabetes, depression, sleeping disturbances, number of medications and occurrence of falls remained as significant associated factors in the final model. CONCLUSIONS: Handgrip strength can be a useful tool to identify mobility limitation in clinical practice. Interventions to prevent or minimize impacts of sarcopenia should stimulate physical activity and improvement of body composition in addition to the management of chronic diseases and disabilities.
We report the discovery and characterisation of a giant transiting planet orbiting a nearby M3.5V dwarf ( d = 80.4pc, G = 15.1 mag, K =11.2mag, R * = 0.358 ± 0.015 R ⊙ , M * = 0.340 ± 0.009 M ⊙ ). ...Using the photometric time series from TESS sectors 10, 36, 46, and 63 and near-infrared spectrophotometry from ExTrA, we measured a planetary radius of 0.77 ± 0.03 R J and an orbital period of 1.52 days. With high-resolution spectroscopy taken by the CFHT/SPIRou and ESO/ESPRESSO spectrographs, we refined the host star parameters (Fe/H = 0.27 ± 0.12) and measured the mass of the planet (0.273 ± 0.006 M J ). Based on these measurements, TOI-4860 b joins the small set of massive planets (>80 M E ) found around mid to late M dwarfs (<0.4 R ⊙ ), providing both an interesting challenge to planet formation theory and a favourable target for further atmospheric studies with transmission spectroscopy. We identified an additional signal in the radial velocity data that we attribute to an eccentric planet candidate ( e = 0.66 ± 0.09) with an orbital period of 427 ± 7 days and a minimum mass of 1.66 ± 0.26 M J , but additional data would be needed to confirm this.
We provide strong evidence that, up to 99.999% of extremality, Kerr-Newman black holes (KNBHs) are linear mode stable within Einstein-Maxwell theory. We derive and solve, numerically, a coupled ...system of two partial differential equations for two gauge invariant fields that describe the most general linear perturbations of a KNBH. We determine the quasinormal mode (QNM) spectrum of the KNBH as a function of its three parameters and find no unstable modes. In addition, we find that the lowest radial overtone QNMs that are connected continuously to the gravitational ℓ=m=2 Schwarzschild QNM dominate the spectrum for all values of the parameter space (m is the azimuthal number of the wave function and ℓ measures the number of nodes along the polar direction). Furthermore, the (lowest radial overtone) QNMs with ℓ=m approach Reω=mΩH(ext) and Imω=0 at extremality; this is a universal property for any field of arbitrary spin |s|≤2 propagating on a KNBH background (ω is the wave frequency and ΩH(ext) the black hole angular velocity at extremality). We compare our results with available perturbative results in the small charge or small rotation regimes and find good agreement.
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