Efficacy and tolerability of chitin-glucan combined with simethicone(GASTRAP^(■)DIRECT)in irritable bowel syndrome:A prospective,open-label,multicenter study

BACKGROUND Irritable bowel syndrome(IBS),defined according to the Rome IV diagnostic criteria,is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain related to altered bowel habits.First-line recommended treatments are limited to combining drugs targeting predominant symptoms,particularly pain(antispasmodics),constipation(laxatives),and diarrhea(loperamide),yielding only a limited therapeutic gain.GASTRAP^(■)DIRECT is a class IIa medical formulation composed of a combination of chitin-glucan and simethicone indicated for the symptomatic treatment of gas-related gastrointestinal disorders by combining different mechanisms of action.AIM To evaluate the efficacy,tolerability,and safety of 4-week GASTRAP^(■)DIRECT treatment in patients with IBS.METHODS In this prospective,multicenter,open-label trial,120 patients with IBS received three sticks of GASTRAP^(■)DIRECT(1.5 g/d of chitin-glucan and 0.75 mg/d of simethicone)per day for 4 weeks.The primary endpoint was the responder rate,defined as the number of patients whose abdominal pain score decreased by≥30%from baseline to week(W)4.The analysis was performed using the per-protocol set.Cardinal symptoms,impact of global symptoms on daily life,change in stool consistency,and improvement in defecatory disorders were evaluated.RESULTS Overall,100 patients were evaluated.At W4,67%(95%CI:57-75)showed improvement in abdominal pain(score:5.8±2.4 vs 2.9±2.0,P<0.0001).Similar improvements were observed for bloating[8.0±1.7 vs 4.7±2.9,P<0.0001;60%(95%CI:50-70)responders],abdominal distension[7.2±2.1 vs 4.4±3.1,P<0.0001;53%(95%CI:43-63)responders],and impact of global symptoms on daily life[7.1±2.0 vs 4.6±2.9,P<0.0001;54%(95%CI:44-64)responders].Stool consistency improved in most patients(90%and 57%for patients with liquid and hard stools,respectively).Overall,42%of patients with defecatory disorders reported very much/considerable improvements by W2.No severe adverse event occurred,and tolerability was rated“good”or“very good”by 93%of patients.CONCLUSION GASTRAP^(■)DIRECT is safe and well tolerated,alleviating IBS symptoms rapidly in 2 weeks.This open-label study suggests that the combination of chitin-glucan and simethicone could be beneficial in patients with IBS.

A hyaluronic acid granular hydrogel nerve guidance conduit promotes regeneration and functional recovery of injured sciatic nerves in rats

A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro,suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regeneration.However,in vivo experiments have not been conducted.In this study,we transplanted a hyaluronic acid granular hydrogel nerve guidance conduit to repair a 10-mm long sciatic nerve gap.The Basso,Beattie,and Bresnahan locomotor rating scale,sciatic nerve compound muscle action potential recording,Fluoro-Gold retrograde tracing,growth related protein 43/S100 immunofluorescence staining,transmission electron microscopy,gastrocnemius muscle dry/wet weight ratio,and Masson’s trichrome staining results showed that the nerve guidance conduit exhibited similar regeneration of sciatic nerve axons and myelin sheath,and recovery of the electrophysiological function and motor function as autologous nerve transplantation.The conduit results were superior to those of a bulk hydrogel or silicone tube transplant.These findings suggest that tissue-engineered nerve conduits containing hyaluronic acid granular hydrogels effectively promote the morphological and functional recovery of the injured sciatic nerve.The nerve conduits have the potential as a material for repairing peripheral nerve defects.

Uncoupling protein 2 deficiency of non-cancerous tissues inhibits the progression of pancreatic cancer in mice

Background: Pancreatic ductal adenocarcinoma(PDAC) is a disease of the elderly mostly because its development from preneoplastic lesions depends on the accumulation of gene mutations and epigenetic alterations over time. How aging of non-cancerous tissues of the host affects tumor progression, however, remains largely unknown. Methods: We took advantage of a model of accelerated aging, uncoupling protein 2-deficient( Ucp2 knockout, Ucp2 KO) mice, to investigate the growth of orthotopically transplanted Ucp2 wild-type(WT) PDAC cells(cell lines Panc02 and 6606PDA) in vivo and to study strain-dependent differences of the PDAC microenvironment. Results: Measurements of tumor weights and quantification of proliferating cells indicated a significant growth advantage of Panc02 and 6606PDA cells in WT mice compared to Ucp2 KO mice. In tumors in the knockout strain, higher levels of interferon-γ m RNA despite similar numbers of tumor-infiltrating T cells were observed. 6606PDA cells triggered a stronger stromal reaction in Ucp2 KO mice than in WT animals. Accordingly, pancreatic stellate cells from Ucp2 KO mice proliferated at a higher rate than cells of the WT strain when they were incubated with conditioned media from PDAC cells. Conclusions: Ucp2 modulates PDAC microenvironment in a way that favors tumor progression and implicates an altered stromal response as one of the underlying mechanisms.

Dental impact of anti-fibroblast growth factor 23 therapy in X-linked hypophosphatemia

Elevated fibroblast growth factor 23(FGF23)in X-linked hypophosphatemia(XLH)results in rickets and phosphate wasting,manifesting by severe bone and dental abnormalities.Burosumab,a FGF23-neutralizing antibody,an alternative to conventional treatment(phosphorus and active vitamin D analogs),showed significant improvement in the long bone phenotype.Here,we examined whether FGF23 antibody(FGF23-mAb)also improved the dentoalveolar features associated with XLH.Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg−1 of FGF23-mAb for 2 months and compared to wild-type(WT)and vehicle(PBS)treated Hyp mice(n=3–7 mice).Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice,the higher concentration resulting in a rescue similar to WT levels.FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones.Histology revealed improved mineralization of the dentoalveolar tissues,with a decreased amount of osteoid,predentin and cementoid.Better periodontal ligament attachment was also observed,evidenced by restoration of the acellular cementum.These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features.Taken together,our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment,heralding its benefit in clinics for dental abnormalities.

Development of a rapid test kit for SARS-CoV-2:an example of product design

We present an example of applying'need-driven'product design principle to the development of a rapid test kit to detect SARS-COV-2(COVID-19).The tests are intended for use in the field and,longer term,for home use.They detect whether a subject is currently infected with the virus and is infectious.The urgent need for large numbers of tests in field setting imposes constraints such as short test time and lack of access to specialist equipment,laboratories and skilled technicians to perform the test and interpret results.To meet these needs,an antigen test based on RT-LAMP with colorimetric readout was chosen.Direct use of swab sample with no RNA extraction was explored.After extensive experimental study(reported elsewhere),a rapid test kit has been fabricated to satisfy all design criteria.

他就是气雾剂，气雾剂就是他——献给伟大的美国科学家蒙迪先生

2004年4月26日，是我们多年的美国友人、世界首屈一指的气雾剂科学家蒙迪·约翰逊博士的80华诞。在这样一个值得祝贺的日子里，我要由衷地感谢上苍．感谢它在我的人生途中，能与如此伟大、完美的科学巨人相逢相识，这真是我生命里极大的荣耀!

降钙素原在儿童急性肾盂肾炎诊断中的应用

Background. -Acute pyelonephritis can induce parenchymal scarring. The aim of this study was to evaluate the usefulness of procalcitonin (PCT) to predict renal involvement in febrile children with urinary tract infection (UTI). Methods. -In a prospective study serum PCT was measured and compared with others commonly used inflammatory markers in children admitted to the emergency unit with acute pyelonephritis. Renal parenchymal involvement was assessed by a 99mTc-labeled dimercaptosuccinic acid (DMSA) renal scar performed in the first 3 days after the admission. Results. -Among 42 enrolled patients, 19 (45%) had acute renal involvement (Group A) ; 23 (55%) (Group B) had normal DMSA scan (n = 16), or old scarring (n = 4) or various anomalies related to uropathy (n = 3). In group A, the mean PCT level was significantly higher than in the group B (5,4 ng/ml, vs 0,4 ng /ml, p < 10-5). In these 2 groups, mean C reactive protein (CRP) levels were 99,1 mg/l and 44,6 mg/l respectively (p < 0,001). For a level of serum PCT ≥0,5 ng/ml, the sensitivity and specificity to predict the renal involvement were 100%and 87%respectively; for a level ≥20 mg/l CRP had a sensitivity of 94%but a specificity of 30%. Conclusion. -Serum PCT levels were significantly increased in febrile children with UTI when acute renal parenchymal involvement was present. PCT seems a better marker than CRP for the prediction of patients at risk of renal lesions.

MRI检查比较经腹或经阴道术式治疗生殖器脱垂对盆腔脏器解剖位置改变的影响

Purpose: The aim of this study was to determine whether or not abdominal or vaginal access is the best choice for treating genital prolapse in term of anatomical postoperative results, using an MRI pre and postoperative assessment. Materials and methods: Prospective study was conducted on 43 consecutive patients planned for surgery for genital prolapse from October 2001 to February 2002. The patients were studied with dynamic and static MRI sequence 4 months after surgery to indicate surgical effects on organ position. The position was evaluated with respect to the pubo coccygeal line in a dynamic sequence. Results: Fifteen patients had their prolapse corrected by laparotomy always associated with sub-total hysterectomy, anterior and posterior prosthetic mesh with promontory fixation to the prevertebral ligament. Sixteen others were subjected to vaginal route with vaginal hysterectomy, paravaginal suspension followed in all cases by suspension of the vaginal cuff using Richter’ s technique and myorraphy of the levators. Finally, 12 patients benefited from a suspension of a sacrospinous suspension and myorraphy of the levators, without paravaginal suspension. Measure of the MRI organ location showed no significant difference except for bladder position in vaginally operated women (P = 0.02). Vaginal length and axis were comparable in all groups. Conclusion: Our study confirmed the objective effectiveness of the anatomical prolapse corrections conducted by abdominal route using sacropexy or by vaginal route using sacrospinous fixation. The correction provided by vaginal route always results in a return of the bladder and the vaginal fundus to their normal positions, which clearly demonstrates the short-term effectiveness of these surgical suspensions. Prolapse corrections by vaginal route did not result in any shortening of the vagina or postoperative change in vaginal orientation. Further evaluations will be needed to assess the long-term results.

Impact of time to diagnosis on the occurrence of cardiogenic shock in MIS‑C post‑COVID-19 infection

Background In multisystem inflammatory syndrome in children(MIS-C),diagnostic delay could be associated with severity.This study aims to measure the time to diagnosis in MIS-C,assess its impact on the occurrence of cardiogenic shock,and specify its determinants.Methods A single-center prospective cohort observational study was conducted between May 2020 and July 2022 at a tertiary care hospital.Children meeting the World Health Organization MIS-C criteria were included.A long time to diagnosis was defined as six days or more.Data on time to diagnosis were collected by two independent physicians.The primary outcome was the occurrence of cardiogenic shock.Logistic regression and receiver operating characteristic curve analysis were used for outcomes,and a Cox proportional hazards model was used for determinants.Results Totally 60 children were assessed for inclusion,and 31 were finally analyzed[52%males,median age 8.8(5.7-10.7)years].The median time to diagnosis was 5.3(4.2-6.2)days.In univariable analysis,age above the median,time to diagnosis,high C-reactive protein,and high N-terminal pro-B-type natriuretic peptide(NT-proBNP)were associated with cardiogenic shock[odds ratio(OR)6.13(1.02-36.9),2.79(1.15-6.74),2.08(1.05-4.12),and 1.70(1.04-2.78),respectively].In multivariable analysis,time to diagnosis≥6 days was associated with cardiogenic shock[adjusted OR(aOR)21.2(1.98-227)].Time to diagnosis≥6 days had a sensitivity of 89% and a specificity of 77% in predicting cardiogenic shock;the addition of age>8 years and NT-proBNP at diagnosis≥11,254 ng/L increased the specificity to 91%.Independent determinants of short time to diagnosis were age<8.8 years[aHR 0.34(0.13-0.88)],short distance to tertiary care hospital[aHR 0.27(0.08-0.92)],and the late period of the COVID-19 pandemic[aHR 2.48(1.05-5.85)].Conclusions Time to diagnosis≥6 days was independently associated with cardiogenic shock in MIS-C.Early diagnosis and treatment are crucial to avoid the use of inotropes and limit morbidity,especially in older children.

Promise to electrically pumped colloidal quantum dot lasers

The laser has been recognized as one of the most successful and significant technological achievements of the 20th century.Undoubtedly,its applications are versatile,ranging from mundane tasks to cutting-edge scientific research,e.g.,displays,lighting,optical communications,remote sensing,and medical treatments.Thus,it is believed that laser technology will continue to shape the world and change our way of life.Among all laser technologies,solution-processed colloidal quantum dot(CQD)laser diodes have attracted intensive attention due to their low cost,flexibility,simple processing,and ease of integration.

Status of adult inpatient burn rehabilitation in Europe: are we neglecting metabolic outcomes?

Background:Hypermetabolism,muscle wasting and insulin resistance are challenging yet important rehabilitation targets in the management of burns.In the absence of concrete practice guidelines,however,it remains unclear how these metabolic targets are currently managed.This study aimed to describe the current practice of inpatient rehabilitation across Europe.Methods:An electronic survey was distributed by the European Burn Association to burn centres throughout Europe,comprising generic and profession-specific questions directed at therapists,medical doctors and dieticians.Questions concerned exercise prescription,metabolic management and treatment priorities,motivation and knowledge of burn-induced metabolic sequelae.Odds ratios were computed to analyse associations between data derived from the responses of treatment priorities and knowledge of burn-induced metabolic sequelae.Results:Fifty-nine clinicians with 12.3±9 years of professional experience in burns,representing 18 out of 91 burn centres(response rate,19.8%)across eight European countries responded.Resistance and aerobic exercises were only provided by 42%and 38%of therapists to intubated patients,87%and 65%once out-of-bed mobility was possible and 97%and 83%once patients were able to leave their hospital room,respectively.The assessment of resting energy expenditure by indirect calorimetry,muscle wasting and insulin resistance was carried out by only 40.7%,15.3%and 7.4%respondents,respectively,with large variability in employed frequency and methods.Not all clinicians changed their care in cases of hypermetabolism(59.3%),muscle wasting(70.4%)or insulin resistance(44.4%),and large variations in management strategies were reported.Significant interdisciplinary variation was present in treatment goal importance ratings,motivation and knowledge of burn-induced metabolic sequelae.The prevention of metabolic sequelae was regarded as the least important treatment goal,while the restoration of functional status was rated as the most important.Knowledge of burn-induced metabolic sequelae was linked to higher importance ratings of metabolic sequelae as a therapy goal(odds ratio,4.63;95%CI,1.50–14.25;p<0.01).Conclusion:This survey reveals considerable non-uniformity around multiple aspects of inpatient rehabilitation across European burn care,including,most notably,a potential neglect of metabolic outcomes.The results contribute to the necessary groundwork to formulate practice guidelines for inpatient burn rehabilitation.

空气污染和700万成人中的死亡率：荷兰环境纵向研究(DUELS)

[背景]一些城市队列研究已经表明空气污染长期暴露与死亡率相关联。但利用包括非城市人群的大规模人口登记数据分析这种关联的研究却很少。[目的]基于现有的国家数据库,评估荷兰空气污染长期暴露与非意外和死因别死亡率之间的关联。[方法]使用荷兰现有的有关死亡率、个体特征、居住历史、社区特征以及全国空气污染地图的数据库,其中全国空气污染地图是基于土地利用回归(LUR)技术,并针对空气动力学直径≤10μm(PM10)的颗粒物和二氧化氮(NO2)。使用这些数据库建立一个710万人的队列,且队列中研究对象的年龄均≥30岁。跟踪这一队列7年(2004—2011年),采用Cox比例风险模型校正潜在的个体和区域特定的混杂因素。[结果]校正个人和区域特定的混杂因素后,PM10和NO2每增加10μg/m3与非意外死亡[分别为危险比(HR)=1.08,95%CI:1.07~1.09;HR=1.03,95%CI:1.02~1.03]、呼吸系统死亡(分别为HR=1.13,95%CI:1.10~1.17;HR=1.02,95%CI:1.01~1.03)和肺癌死亡(分别为HR=1.26,95%CI:1.21~1.30;HR=1.10,95%CI:1.09~1.11)相关联。此外,PM_(10)与循环系统疾病死亡率(HR=1.06,95%CI:1.04~1.08)相关,但NO_2与其没有关联(HR=1.00,95%CI:0.99~1.01)。在校正了NO_2之后,PM_(10)的关联表现稳健;在校正了PM_(10)之后,NO^2与非意外死亡率和肺癌死亡率间的关联仍然存在。[结论]PM_(10)和NO_2长期暴露与荷兰30岁以上人群的非意外死亡率和死因别死亡率有关联。

The physical and physiological effects of vacuum massage on the different skin layers: a current status of the literature

Vacuum massage is a non-invasive mechanical massage technique performed with a mechanical device that lifts the skin by means of suction,creates a skin fold and mobilises that skin fold.In the late 1970s,this therapy was introduced to treat traumatic or burn scars.Although vacuum massage was invented to treat burns and scars,one can find very little literature on the effects of this intervention.Therefore,the aim of this review is to present an overview of the available literature on the physical and physiological effects of vacuum massage on epidermal and dermal skin structures in order to find the underlying working mechanisms that could benefit the healing of burns and scars.The discussion contains translational analysis of the results and provides recommendations for future research on the topic.An extended search for publications was performed using PubMed,Web of Science and Google Scholar.Two authors independently identified and checked each study against the inclusion criteria.Nineteen articles were included in the qualitative synthesis.The two most reported physical effects of vacuum massage were improvement of the tissue hardness and the elasticity of the skin.Besides physical effects,a variety of physiological effects are reported in literature,for example,an increased number of fibroblasts and collagen fibres accompanied by an alteration of fibroblast phenotype and collagen orientation.Little information was found on the decrease of pain and itch due to vacuum massage.Although vacuum massage initially had been developed for the treatment of burn scars,this literature review found little evidence for the efficacy of this treatment.Variations in duration,amplitude or frequency of the treatment have a substantial influence on collagen restructuring and reorientation,thus implying possible beneficial influences on the healing potential by mechanotransduction pathways.Vacuum massage may release the mechanical tension associated with scar retraction and thus induce apoptosis of myofibroblasts.Suggestions for future research include upscaling the study design,investigating the molecular pathways and dose dependency,comparing effects in different stages of repair,including evolutive parameters and the use of more objective assessment tools.

Short-term effects of vacuum massage on epidermal and dermal thickness and density in burn scars: an experimental study

Background:Vacuum massage is a non-invasive mechanical massage technique invented to treat burns and scars.To date,no effects of vacuum massage on thickness and density of human scar tissue have been reported.The process in which external stimuli are converted into biochemical responses in the cell is known as mechanotransduction.In the skin endothelial cells,fibroblasts and myofibroblasts embedded in the extracellular matrix(ECM)sense mechanical stimuli(created by vacuum massage)and may promote intracellular processes leading to matrix remodelling.Since mechanotransduction could be a plausible working mechanism for vacuum massage as an anti-scarring therapy,this study aims to investigate the short-term effects of vacuum massage on thickness and density of epidermis and dermis in burn scars in order to find proof of ECM remodelling.Methods:A one group experimental study was performed.Patients with burn scars on upper extremities,lower extremities,and trunk were recruited for participation in this study.The DUB?cutis 22 MHz ultrasound scanner was used to assess thickness and density of the epidermal and dermal skin layers.After baseline measurements,vacuum massage was performed according to a pre-defined protocol.Measurements were carried out at 5 min,30 min,1 h,and 2 h post-intervention.Results:Thirteen scar sites from 9 different patients were investigated.In 8 out of the 13 scar sites,a disruption of the epidermis was noticed after the vacuum massage.Five minutes after the intervention,epidermal density decreased statistically significantly(p=.022)and dermal thickness increased(p=.018).Both changes lasted for more than 1 h,but after 2 h,the changes were no longer statistically significant.Dermal density decreased significantly(p=.048)immediately after the intervention,and this decrease was still present after 2 h(p=.011).Conclusions:Preliminary results show that the disruption of the epidermis may indicate that vacuum massage could be able to actually breach the skin barrier.The statistically significant changes in the dermal layers could suggest an increased ECM production after vacuum massage.

Real-time mechanical characterization of DNA degradation under therapeutic X-rays and its theoretical modeling

The killing of tumor cells by ionizing radiation beams in cancer radiotherapy is currently based on a rather empirical understanding of the basic mechanisms and effectiveness of DNA damage by radiation.By contrast,the mechanical behaviour of DNA encompassing sequence sensitivity and elastic transitions to plastic responses is much better understood.A novel approach is proposed here based on a micromechanical Silicon Nanotweezers device.This instrument allows the detailed biomechanical characterization of a DNA bundle exposed to an ionizing radiation beam delivered here by a therapeutic linear particle accelerator(LINAC).The micromechanical device endures the harsh environment of radiation beams and still retains molecular-level detection accuracy.In this study,the first real-time observation of DNA damage by ionizing radiation is demonstrated.The DNA bundle degradation is detected by the micromechanical device as a reduction of the bundle stiffness,and a theoretical model provides an interpretation of the results.These first real-time observations pave the way for both fundamental and clinical studies of DNA degradation mechanisms under ionizing radiation for improved tumor treatment.

时尚词汇:重新编织美国时尚故事

纽约大都会艺术博物馆(METROPOLITAN MUSEUM OF ART)为了庆柷美国时尚成就,即将以双联展的形式举办展览:从2021年9月18日至2022年9月5曰,在vogue美版主编安娜·温图尔(Anna Wintour)的时装中心(Anna Wintour Costume Center)展出第一部分“在美国:时尚辞典”(In America:A Lexicon of Fashion);2022年5月5日到2022年9月5日在“美国之翼历史房间”(American Wing Period Rooms)展出更偏重于历史和空间叙事的第二部分“在美国:时尚选集”(In America:An Anthology of Fashion)。

柔美色调 童梦奇缘

正色调对于梦幻效果的照片来说是很重要的。具有童话般梦幻效果的照片,其色调要柔和、淡雅、粉嫩、甜蜜,并且给人一种朦朦胧胧的美感,仿如置身于梦境中般奇妙。此组照片在人物造型上采用了白色的短款蕾丝蓬蓬纱裙,打造出甜美的小公主的形象。人物饰品和卡通玩偶道具以粉红和粉蓝色调为主,都采用了糖果色系的颜色,打造出天真可爱的童真世界。后期调修时也是以粉红、粉蓝为主色调,令画面中的色彩更为柔美和协调,并添加了若隐若现的光斑效果,营造出安静、唯美的甜蜜梦境。

趣味照片合拼术

正合拼照片能让画面效果更加丰富多彩,生动有趣。合拼照片一般采用的技法有:用仿制图章进行复制,选定多张动作照片拖至一张图层中,建立蒙板一张一张地擦拭出来。合拼照片的要点1.照片风格要统一,比如时装片合拼或是妆容片合拼,时装片可以通过时装的变化来达到一定的效果,妆容片则着重于妆容的变化。2.选择动作相互呼应的照片,这样合拼在一起的图片才会有统一协调的感觉。但是,动作的选择上又需要有些差别,例如,