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atient directly for prolonged period or his/her body fluids, materials or surfaces around him.Structure-based drug discovery (SBDD) is an indispensable approach for the design and optimization of new therapeutic agents. Here, we highlight the rapid progress that has turned cryo-electron microscopy (cryoEM) into an exceptional SBDD tool, and the wealth of new structural information it is providing for high-value pharmacological targets. We review key advantages of a technique that directly images vitrified biomolecules without the need for crystallization; both in terms of a broader array of systems that can be studied and the different forms of information it can provide, including heterogeneity and dynamics. We discuss near- and far-future developments, working in concert towards achieving the resolution and throughput necessary for cryoEM to make a widespread impact on the SBDD pipeline.

Pancreatic metastases from renal cell carcinoma (PRCC) often appear many years after treatment of the primary tumor, and differentiation from pancreatic neuroendocrine neoplasm (PanNEN) can be challenging due to their hypervascularity. Here, we investigated the utility of endoscopic ultrasound (EUS) for differentiation of these conditions.

A retrospective analysis was performed in 17 and 79 consecutive patients with pathologically proven PRCC and non-functional PanNEN who were examined by EUS. In cases examined by EUS elastography or contrast-enhanced harmonic EUS (CH-EUS), the lesions were classified as stiff or soft, or into three vascular patterns as hypoechoic, isoechoic, and hyperechoic. CH-EUS images at 20s, 40s, 60s, 3min and 5min were used for evaluation. EUS images were independently reviewed by two readers who were blinded to all clinical information.

The patients with PRCC were significantly older than those with PanNEN (median, 71 (range, 45-81) vs. 58 (22-76), P=0.001) and more often had multiple tumors (6/17 (35%) vs. 7/79 (9%), P=0.010). In EUS findings, PRCC lesions significantly more frequently had a marginal hypoechoic zone (MHZ) (11/17 (65%) vs. 27/79 (34%), P=0.028), being classified as soft (12/13 (92%) vs. 26/58 (45%), P=0.002), and showed sustained hyperechoic vascular patterns at 5min (7/8 (88%) vs. 4/59 (7%), P<0.001) compared to PanNEN lesions.

The presence of a MHZ, a soft lesion, and a sustained hyperechoic vascular pattern in EUS may be useful for differentiating PRCC from PanNEN.

The presence of a MHZ, a soft lesion, and a sustained hyperechoic vascular pattern in EUS may be useful for differentiating PRCC from PanNEN.

Our study aims to investigate dietary intake characteristics and their association with skeletal muscle mass in head and neck cancer patients treated with radiotherapy.

From March 2017 to August 2018, patients with head and neck cancer who received radiotherapy at our affiliated hospital were enrolled. Dietary intake was assessed through 24-hr dietary recall and skeletal muscle mass was evaluated by bioelectrical impedance analysis at three-time points. Appendicular skeletal muscle mass was adjusted for height squared defined sarcopenia and correlated with dietary intake by generalized estimating equations (GEE).

This study sample comprised 287 patients [median age 54 years; 187 (65.2%) men]. Median dietary intake at post-treatment was 14.95kcal/kg/day energy and 0.63g/kg/day protein. Skeletal muscle mass decreased significantly in all patients. The prevalence of sarcopenia increased from 24.4% before treatment to 46.7% at the end of treatment. Exploratory univariate GEE analysis revealed that radiotherapy time-point, male-gender, age ≥60 and decreased dietary energy intake significantly impacted on muscle loss represented by the appendicular skeletal muscle index. SGI-110 mouse After controlling covariates, dietary energy intake was only positively associated with muscle loss in women (P=0.013, 95% CI=0.003-0.027) but not in men (P=0.788, 95% CI=-0.007-0.009).

While the loss in skeletal muscle is more prevalent in men receiving radiotherapy, the effects of dietary energy intake were only associated with women. A prospective randomized clinical trial is required to identify the appropriate amount of dietary energy supplement by gender in cancer patients treated with radiotherapy.

While the loss in skeletal muscle is more prevalent in men receiving radiotherapy, the effects of dietary energy intake were only associated with women. A prospective randomized clinical trial is required to identify the appropriate amount of dietary energy supplement by gender in cancer patients treated with radiotherapy.

Micro-osteoperforation (MOP), a minimally invasive technique for accelerating the rate of orthodontic tooth movement has been research extensively, but with varied clinical results.

To compare the efficacy of one-time versus two-time micro-osteoperforation on the rate of maxillary canine retraction, its influence on anchorage loss, canine angulation and the levels of interleukin (IL-1β) in gingival crevicular fluid (GCF).

The split-mouth study included 16 patients in which the left and right sides were randomly allocated to the control side (one-time MOP) and experimental side (two-time MOP). MOP was performed on both sides distal to the maxillary canines and canine retraction was carried out using NiTi closed coil springs (150gm) and direct anchorage with miniscrew implants. The second MOP was performed on experimental side one month after the first MOP. The rate of canine movement was assessed using 3D model superimposition over a period of six months. The type of tooth movement, anchorage loss and levels of IL-1β were also evaluated.

Sixteen patients (mean age, 17.87±3.34 years) were analysed for a rate of canine retraction, anchorage loss, and type of tooth movement, while 15 patients were analysed for IL-1β. The rate was significantly higher on two-time MOP side after two months (P<0.001). No statistical difference was found in anchorage loss and controlled tipping of canines was observed. The IL-1β levels immediately after 2

MOP were significantly higher than 1

MOP (P<0.001).

The two-time intervention of MOP is more efficacious than one-time MOP in accelerating tooth movement.

The two-time intervention of MOP is more efficacious than one-time MOP in accelerating tooth movement.