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Using time to TKR as an endpoint, a study with an average follow-up time of three years requires approximately 3,000 to 18,000 subjects depending on effect size. Alternatively, a composite endpoint such as ‘time to TKR or severe pain or severely impaired functioning’, the required sample sizes ranged from approximately 2,000 to 11,000 for a three-year study.

The proposed concept endpoints can reliably and feasibly evaluate effectiveness of therapies for this unmet need. In particular, the composite endpoint approach can substantially reduce sample sizes (up to approximately 40%) compared to the use of TKR alone.

The proposed concept endpoints can reliably and feasibly evaluate effectiveness of therapies for this unmet need. In particular, the composite endpoint approach can substantially reduce sample sizes (up to approximately 40%) compared to the use of TKR alone.Conventional chemical approaches for synthesizing nanoparticles (NPs) may restrict their applicability as they are not eco-friendly, energetically efficient and often involve toxic reducing/capping agents; but phytonanotechnology enabled the synthesis of safe, inexpensive, highly biocompatible NPs. In this regard, thorough understanding of green components and the modulatory effects of different reaction conditions on the physicochemical parameters of green synthesized NPs would be a prerequisite, which is not depicted elsewhere. This review critically analyzes the relevant reaction conditions from their mechanistic viewpoints in plant-based synthesis of NPs arising fundamental issues which need to be determined carefully. The size, stability and surface chemistry of phytogenic NPs may be fabricated as a function of multiple interconnected reaction parameters and the plant species used. The therapeutic potential of phytogenic NPs may depend on the plant species used; and so the meticulous understanding of physicochemical parameters and the family wise shorting of elite plant species may potentially benefit the theranostic future of plant-based NPs.2D layered photodetectors have been widely researched for intriguing optoelectronic properties but their application fields are limited by the bandgap. Extending the detection waveband can significantly enrich functionalities and applications of photodetectors. For example, after breaking through bandgap limitation, extrinsic Si photodetectors are used for short-wavelength infrared or even long-wavelength infrared detection. Utilizing extrinsic photoconduction to extend the detection waveband of 2D layered photodetectors is attractive and desirable. However, extrinsic photoconduction has yet not been observed in 2D layered materials. Here, extrinsic photoconduction-induced short-wavelength infrared photodetectors based on Ge-based chalcogenides are reported for the first time and the effectiveness of intrinsic point defects are demonstrated. The detection waveband of room-temperature extrinsic GeSe photodetectors with the assistance of Ge vacancies is broadened to 1.6 µm. Extrinsic GeSe photodetectors have an excellent external quantum efficiency (0.5%) at the communication band of 1.31 µm and polarization-resolved capability to subwaveband radiation. Moreover, room-temperature extrinsic GeS photodetectors with a detection waveband to the communication band of 1.55 µm further verify the versatility of intrinsic point defects. This approach provides design strategies to enrich the functionalities of 2D layered photodetectors.The bacterium Enterococcus faecalis has increasingly attracted global attention as an important opportunistic pathogen due to its ability to form biofilms that are known to increase drug resistance. However, there are still no effective antibiofilm drugs in clinical settings. Here, by drug repurposing, we investigated the antibacterial activity of penfluridol (PF), an oral long-acting antipsychotic approved by the FDA, against E. faecalis type strain and its clinical isolates. It was found that PF inhibited the growth of E. faecalis planktonic cells with the MIC and MBC of 7.81 µg/ml and 15.63 ~ 62.50 µg/ml, respectively. Moreover, PF could significantly prevent the biofilm formation of E. faecalis at the concentration of 1 × MIC. Furthermore, PF significantly eradicated 24 h pre-formed biofilms of E. faecalis in a dose-dependent manner, with a concentration range of 1 × MIC to 8 × MIC. Here, through the checkerboard method with other tested conventional antibiotics, we also determined that gentamycin, penicillin G, and amikacin showed partial synergistic antibacterial effects with PF. Also, PF showed almost no hemolysis on human erythrocytes. In a mouse peritonitis model, a single dose of 20 mg/kg of PF treatment could significantly reduce the bacterial colonization in the liver (~5-fold reduction) and spleen (~3-fold reduction). In conclusion, these findings indicated that after structural optimization, PF has the potential as a new antibacterial agent against E. faecalis.

To estimate the number of patients in refractory out-of-hospital cardiac arrest (OHCA) potentially suitable for transport to an extracorporeal cardiopulmonary resuscitation (ECPR)-capable hospital in Brisbane, Queensland, Australia, based on outcome predictors for ECPR, ambulance geolocation and patient data.

A retrospective cohort study was performed using data from all patients in OHCA attended by Queensland Ambulance Service between 1 January 2014 and 31 December 2018. The number of refractory arrest patients who could potentially be transferred to an ECPR-capable centre within 45 min of the time of arrest was modelled using theoretical on-scene treatment times.

Of 25 518 ambulance-attended OHCA in Queensland during the study period, 540 (2%) patients met criteria of refractory arrest for study inclusion. Further age and arrest rhythm criteria for transport to an ECPR-capable hospital were met in 253 (47%) study patients, an average of 51 patients per year. In 2018, 72 patients met study criteria forrt logistics and economic implications of providing ECPR services for OHCA are required to better inform decisions around this intervention.

Since the normal, non-pathological facial growth in preschool children is not sufficiently reported, the aim was to follow growth changes of facial surface, sex differences and facial variability in preschool children using 3D stereophotogrammetry.

Mixed longitudinal sample of healthy Caucasian preschool children without head and facial trauma or craniofacial anomalies from 3.4 to 6.7years of age consisted of 25 girls and 17 boys.

136 3D facial models from optical scanner Vectra 3D were evaluated by geometric morphometrics (CPC-DCA, PCA, per-vertex t test).

In both sexes, the lower face was widened and elongated, and the prominences of the superciliary arches, lower orbital region, nose, lips and chin increased. Facial surface increments were more even in girls with a maximum between the fourth and fifth year of age, while in boys, there was the most intensive growth between fifth and sixth year of age. Sexual dimorphism was very stable during investigated period, only less statistically significant at the age of 3years. Boys had more prominent lateral lower part of forehead, nose and lips than girls in every age category.

The longitudinal growth of the face between third and sixth year of age was similar in both sexes, facial sex differences were found in terms of intensity, size and timing. Variability of facial form showed that boys’ faces were larger on average and facial shape did not differ. The knowledge of facial growth is essential for diagnostics and clinical practice.

The longitudinal growth of the face between third and sixth year of age was similar in both sexes, facial sex differences were found in terms of intensity, size and timing. Variability of facial form showed that boys’ faces were larger on average and facial shape did not differ. The knowledge of facial growth is essential for diagnostics and clinical practice.The effect of age on the pharmacokinetics and safety of chiglitazar was evaluated in patients less then 65 and ≥ 65 years with type 2 diabetes mellitus (T2DM). A total of 20 T2DM patients ( less then 65 vs ≥65 years 11) completed the study. Patients received multiple doses of 48 mg chiglitazar once daily for 7 days consecutively. After the first dosing, chiglitazar maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC) in patients ≥ 65 years were similar to those observed in patients less then 65 years, with the geometric mean ratio (GMR) for Cmax and AUC being 97.22% and 96.83%, respectively. No significant difference was observed in Cmax (GMR, 97.23%) in the steady state. Compared with the patients less then 65 years, a slight increase (8%-13%) of AUC was observed in the patients ≥ 65 years after multiple doses. Chiglitazar was generally well tolerated following multiple doses in both age groups. In conclusion, there were no significant clinical influences on the pharmacokinetic properties and safety profiles of chiglitazar between patients with T2DM less then 65 and ≥ 65 years, indicating that in the future it is not required to adjust the dosing regimen by age for T2DM patients ≥ 65 years.

Postoperative intracerebral haematomas represent a serious complication following stereotactic biopsy. We investigated the possible underlying causes – poor planning or poor execution – of postoperative intracerebral haematomas following stereotactic biopsies.

We performed a technical investigation using a retrospective single-centre consecutive series of robot-assisted stereotactic biopsies for a supratentorial diffuse glioma in adults. Each actual biopsy trajectory was reviewed to search for a conflict with an anatomical structure at risk.

From 379 patients, 12 (3.2%) presented with a postoperative intracerebral haematoma ≥20mm on postoperative CT-scan (3 requiring surgical evacuation); 11 of them had available intraoperative imaging (bi-planar stereoscopic teleangiography x-rays at each biopsy site). The actual biopsy trajectory was similar to the planned biopsy trajectory in these 11 cases. In 72.7% (8/11) of these cases, the actual biopsy trajectory was found to contact a structure at risk (blood vessel and cerebral sulcus) and identified as the intracerebral haematoma origin.

Robot-assisted stereotactic biopsy is an accurate procedure. Postoperative intracerebral haematomas mainly derive from human-related errors during trajectory planning.

Robot-assisted stereotactic biopsy is an accurate procedure. Postoperative intracerebral haematomas mainly derive from human-related errors during trajectory planning.High salt (HS) intake is usually considered as an aggravating factor to induce inflammatory renal injury. However, the changes in the renal levels of inflammatory cytokines during HS intake is not yet clearly defined. We hypothesize that HS increases renal levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) but decreases interleukin-10 (IL-10; anti-inflammatory cytokine) and these responses exacerbate in NO deficient conditions. Both wild-type (WT) and endothelial NO synthase knockout (eNOSKO) mice (~8 weeks old, n = 6 in each group) were given normal-salt (NS; 0.3% NaCl) and HS (4% NaCl) containing diets for 2 weeks. Systolic blood pressure (SBP) was determined by tail-cuff plethysmography and urine collections were made using metabolic cages. Basal SBP was higher in eNOSKO than WT mice (131 ± 7 vs 117 ± 3 mmHg; p less then .05). HS intake for 2 weeks increased SBP in eNOSKO (161 ± 5 mmHg) but not in WT mice. In NS groups, the cytokine levels in renal tissues (measured using ELISA kits and expressed in pg/mg protein) were significantly higher in eNOSKO than WT mice (TNF-α, 624 ± 67 vs.