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11.

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Objectives

To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.

Methods

Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.

Results

Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.

Conclusions

These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.  相似文献   
12.
13.
Background The impact of various breast-cancer treatments on patients with a BRCA2 mutation has not been studied. We sought to estimate the impact of bilateral oophorectomy and other treatments on breast cancer-specific survival among patients with a germline BRCA2 mutation.Methods We identified 664 women with stage I–III breast cancer and a BRCA2 mutation by combining five different datasets (retrospective and prospective). Subjects were followed for 7.2 years from diagnosis to death from breast cancer. Tumour characteristics and cancer treatments were patient-reported and derived from medical records. Predictors of survival were determined using Cox proportional hazard models, adjusted for other treatments and for prognostic features.Results The 10-year breast-cancer survival for ER-positive patients was 78.9% and for ER-negative patients was 82.3% (adjusted HR = 1.23 (95% CI, 0.62–2.45, p = 0.55)). The 10-year breast-cancer survival for women who had a bilateral oophorectomy was 89.1% and for women who did not have an oophorectomy was 59.0% (adjusted HR = 0.45; 95% CI, 0.28–0.72, p = 0.001). The adjusted hazard ratio for chemotherapy was 0.83 (95% CI, 0.65–1.53: p = 0.56).Conclusions For women with breast cancer and a germline BRCA2 mutation, positive ER status does not predict superior survival. Oophorectomy is associated with a reduced risk of death from breast cancer and should be considered in the treatment plan.Subject terms: Targeted therapies, Breast cancer  相似文献   
14.
Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia, but the underlying mechanism has not yet been fully elucidated. Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment, and the phosphoinositide 3-kinase(PI3 K)/Akt signaling pathway plays an important role in autophagy regulation. To investigate the role played by the PI3 K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models, we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method. Starting at 2 hours after modeling, electroacupuncture was delivered at the Shenting(GV24) and Baihui(GV20) acupoints, with a dilatational wave(1–20 Hz frequency, 2 mA intensity, 6 V peak voltage), for 30 minutes/day over 8 consecutive days. Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury, increased the mRNA expression levels of the PI3 K/Akt signaling pathwayrelated factors Beclin-1, mammalian target of rapamycin(mTOR), and PI3 K, increased the protein expression levels of phosphorylated Akt, Beclin-1, PI3 K, and mTOR in the ischemic cerebral cortex, and simultaneously reduced p53 mRNA and protein expression levels. In the Morris water maze test, the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. In the spatial probe test, the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. Electroacupuncture stimulation applied to the Shenting(GV24) and Baihui(GV20) acupoints activated the PI3 K/Akt signaling pathway and improved rat learning and memory impairment. This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, China(approval No. 8150150901) on March 10, 2016.  相似文献   
15.
PurposeTo retrospectively report on safety, pain relief and local tumor control achieved with percutaneous ablation of sacral bone metastases.Materials and methodsFrom February 2009 to June 2020, 23 consecutive patients (12 women and 11 men; mean age, 60 ± 8 [SD] years; median, 60; range: 48-80 years) with 23 sacral metastases underwent radiofrequency (RFA) or cryo-ablation (CA), with palliative or curative intent at our institution. Patients’ demographics and data pertaining to treated metastases, procedure-related variables, safety, and clinical evolution following ablation were collected and analyzed. Pain was assessed with numerical pain rating scale (NPRS).ResultsSixteen (70%) patients were treated with palliative and 7 (30%) with curative intent. Mean tumor diameter was 38 ± 19 (SD) mm (median, 36; range: 11-76). External radiation therapy had been performed on five metastases (5/23; 22%) prior to ablation. RFA was used in 9 (39%) metastases and CA in the remaining 14 (61%). Thermo-protective measures and adjuvant bone consolidation were used whilst treating 20 (87%) and 8 (35%) metastases, respectively. Five (22%) minor complications were recorded. At mean 31 ± 21 (SD) (median, 32; range: 2-70) months follow-up mean NPRS was 2 ± 2 (SD) (median, 1; range: 0–6) vs. 5 ± 1 (median, 5; range: 4–8; P < 0.001) at the baseline. Three metastases out of 7 (43%) undergoing curative ablation showed local progression at mean 4 ± 4 (SD) (median, 2; range: 1-8) months follow-up.ConclusionPercutaneous ablation of sacral metastases is safe and results in significant long-lasting pain relief. Local tumor control seems sub-optimal; however, further investigations are needed to confirm these findings due to paucity of data.  相似文献   
16.
<正>Norepinephrine (NE; also known as noradrenaline) is the body's primary adrenergic neurotransmitter which belongs to the catecholamine family. Norepinephrine has pharmacologic effects on theα1 (Suita et al.,2015),α2 (Schwartz,1997),β1,β2 andβ3(Tsukada et al., 2003) adrenoceptors. In the brain, norepinephrine increases arousal and alertness, promotes vigilance, enhances formation and retrieval of memory, and focuses attention. It also increases restlessness and anxiety. In the remainder of the body,  相似文献   
17.

Objective

To compare perioperative and long-term outcomes in patients undergoing hemiarch and aggressive arch replacement for acute type A aortic dissection (ATAAD).

Methods

From 1996 to 2017, we compared outcomes of hemiarch (n = 322) versus aggressive arch replacements (zones 2 and 3 arch replacement with implantation of 2-4 arch branches, n = 150) in ATAAD. Indications for aggressive arch were arch aneurysm >4 cm or intimal tear in the aortic arch that was not resectable by hemiarch replacement, or dissection of arch branches with malperfusion.

Results

Patients in the aggressive arch group were significantly younger (mean age: 57 vs 61 years old) and had significantly longer hypothermic circulatory arrest, cardiopulmonary bypass, and aortic crossclamp times. There were no significant differences in perioperative outcomes between hemiarch and aggressive arch groups, including 30-day mortality (5.3% vs 7.3%, P = .38) and postoperative stroke rate (7% vs 7%, P = .96). Over 15 years, Kaplan–Meier survival was similar between hemiarch and aggressive arch groups (log-rank P = .55, 10-year survival 70% vs 72%). Given death as a competing factor, incidence rates of reoperation over 15 years (2.1% vs 2.0% per year, P = 1) and 10-year cumulative incidence of reoperation (14% vs 12%, P = .89) for arch and distal aorta pathology were similar between the 2 groups.

Conclusions

Both hemiarch and aggressive arch replacement are appropriate approaches for select patients with ATAAD. Aggressive arch replacement should be considered for an arch aneurysm >4 cm or an intimal tear at the arch unable to be resected by hemiarch replacement, or dissection of the arch branches with malperfusion.  相似文献   
18.

Context

Demoralization is a state of existential distress in patients with advanced illness, typically with coping difficulties, feelings of loss of sense, and purpose in life and despair, among other things. The New Demoralization Scale (DS-II) is an evaluation tool for this syndrome, which has recently been reformulated on a shorter scale.

Objectives

The objective of this study was to obtain a Spanish version of the DS-II and to assess its psychometric properties in advanced cancer patients in Spain and a number of Latin American countries.

Methods

Following a translation–back translation process, a validation study and a confirmatory analysis using structural equation models with their corresponding latent constructs were undertaken. Patients completed the DS-II in Spanish (DS-II (es)), the Hospital Anxiety and Depression Scale, and the Edmonton Symptom Assessment System–revised. Reliability was studied according to internal consistency; construct validity and concurrent validity with the Hospital Anxiety and Depression Scale and the Edmonton Symptom Assessment System–revised; discriminant validity using the Karnofsky Performance Status scale; and feasibility, with response ratio and required time. Cutoff points were established, and sensitivity and specificity were studied.

Results

The DS-II (es) was obtained. One hundred fifty patients completed the validation study. The confirmatory analysis showed coherence, and all items correlated positively with their subscales and with the overall scale. Cronbach's alpha for the DS-II (es) was 0.88, for the sense and purpose subscale 0.83, and for the coping ability 0.79. Demoralization correlated significantly with emotional distress (rho = 0.73, P < 0.001). The tool distinguished between patients with diverse functional levels (rho = ?0.319, P = 0.001). Cutoff points at 10 and 20 out of 32 were established. The scale showed high sensitivity (81.97%) and specificity (80.90%). The prevalence of demoralization was 33% in our sample.

Conclusion

The Spanish version of the new Kissane DS-II demoralization scale has shown to be valid, reliable, and feasible with adequate psychometric properties.  相似文献   
19.

Context

Quality of life (QoL) is increasingly recognized as an important outcome of cancer treatment. Previous studies have examined clinical predictors of QoL, but with the increasing prevalence of wearable sensors that monitor sleep and activity patterns, further investigation into whether these behaviors are predictive of post-treatment QoL is now feasible. Among patients receiving aggressive cancer treatment such as hematopoietic cell transplantation (HCT), analysis of circadian rhythms (24-hour patterns of sleep and activity) via wearable sensors is limited.

Objective

To evaluate the relationship between overall QoL and circadian rhythms in patients receiving allogeneic HCT.

Methods

Patients wore an ActiGraph GT3X (Pensacola, FL) activity monitor for at least 72 hours before the initiation of conditioning chemotherapy and transplantation and completed a QoL (Functional Assessment of Cancer Therapy-General [FACT-G]) assessment. QoL assessments were also completed 1, 3, and 6 months after HCT.

Results

Patients (n = 45, M age = 55) were mostly male (66%) with a total FACT-G score of 80.96 (SD = 16.05) before HCT. Mixed models revealed robust cross-sectional associations between overall QoL and multiple circadian rhythmicity parameters, including durations of high physical activity, overall circadian rhythmicity, and earlier starts of daily activity (P's < .01). Recovery of QoL after transplant was predicted by longer pre-transplant durations of high physical activity (P = .04) and earlier evening retirement (P = .04).

Conclusion

Our findings suggest that wearable sensor information is a promising method of predicting recovery of QoL after HCT. Additional studies are needed to confirm these findings in a larger sample.  相似文献   
20.

Statement of problem

Polymeric material for 3-dimensional printing can be used to fabricate occlusal devices. However, information about fracture resistance and wear is scarce.

Purpose

The purpose of this in vitro study was to investigate the fracture resistance and 2-body wear of 3-dimensional–printed (3DP) (FotoDent splint; Dreve Dentamid GmbH), milled polymethylmethacrylate (CAM) (Temp Basic; Transpa 95H16, Zirkonzahn GmbH), and conventionally fabricated polymethylmethacrylate (CAST) (Castdon; Dreve Dentamid GmbH) occlusal devices.

Material and Methods

A total of 96 occlusal devices were prepared according to the 3 different manufacturing techniques 3DP, CAM, and CAST (n=32). For each manufacturing technique, specimens were further divided into initial fracture resistance tests (n=16) and artificial aging in the mastication simulator (50 N, 37°C) with 2-body wear followed by fracture resistance tests (n=16). The fracture resistance was determined using a universal testing machine (1 mm/min). The wear was measured after 20?000 and 120?000 mastication cycles with the replica technique, mapped with a laser scanner, and quantified in R software. Data were analyzed using a 2-way ANOVA followed by a 1-way ANOVA with Scheffé or Games-Howell post hoc tests, repeated measures ANOVA with corrected Greenhouse-Geisser P values, and the Levene, Mann-Whitney, and paired t tests (α=.05).

Results

CAM presented higher initial fracture resistance than 3DP or CAST (P<.001). After mastication simulation, CAM followed by 3DP showed higher fracture resistance than CAST (P<.001). Mastication simulation decreased the fracture resistance for CAM and CAST (P<.001) but not for 3DP (P=.78). Three-dimensional–printed occlusal devices showed the highest material volume loss, followed by CAM and the lowest in CAST (P<.001).

Conclusions

Three-dimensional–printed occlusal devices showed lower wear resistance and lower fracture resistance than those milled or conventionally fabricated. Therefore, only short-term application in the mouth is recommended. Further developments of occlusal device material for 3-dimensional printing are necessary.  相似文献   
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