Anti-inflammatory properties of the short-chain fatty acids acetate and propionate:A study with relevance to inflammatory bowel disease

AIM: To compare the anti-inflammatory properties of butyrate with two other SCFAs,namely acetate and propionate,which have less well-documented effects on inflammation. METHODS: The effect of SCFAs on cytokine release from human neutrophils was studied with ELISA. SCFA-dependent modulation of NF-κB reporter activity was assessed in the human colon adenocarcinoma cell line,Colo320DM. Finally,the effect of SCFAs on gene expression and cytokine release,measured with RT-PCR and ELISA,respectively,was studied in mouse colon organ cultures established from colitic mice. RESULTS: Acetate,propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFα release from neutrophils,without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-κB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression,whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132,but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. CONCLUSION: In the present study propionate and butyrate were equipotent,whereas acetate was less effective,at suppressing NF-κB reporter activity,immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate,in addition to butyrate,could be useful in the treatment of inflammatory disorders,including IBD.

Advanced Phosphorus Removal and Needs for Recovery by Enhanced Filtration of Municipal Wastewater

The need for an advanced and even far reaching phosphorus removal at municipal WWTPs may soon get stipulations in relation to a reuse of phosphorus (P). This paper discusses the possible ways to remove phosphorous from municipal wastewater. This is already an established demand in many countries. However, as P is a limited raw material, this need for a reuse of P will become an example of what now is labelled “cyclic economy”. For instance, a national demand from the German state is already put in force. In this perspective the advanced filtration techniques will play an interesting role, and most possibly a crucial role. Examples are presented from several municipal WWTPs already in operation with a final polishing treatment step based on chemical precipitation and separation of phosphorus. Typical stable discharge P levels are found at these plants at levels < 0.05 to 0.10 ppm. The new demands on phosphorus recovery will also call for modified process concepts for the WWTP;for instance, a refined biological phosphorus removal (EBP) attains more attention and he needed very low discharge levels of P, where the enhanced P-removal will include different smart filtration techniques.

Optimizing aerosolization of a high-dose L-arginine powder for pulmonary delivery

In this study a carrier-free dry powder inhalation(DPI)containing L-arginine(ARG)was developed.As such,it is proposed that ARG could be used for adjunctive treatment of cystic fibrosis and/or tuberculosis.Various processing methods were used to manufacture highdose formulation batches consisting various amounts of ARG and excipients.The formulations were evaluated using several analytical methods to assess suitability for further investigation.Several batches had enhanced in vitro aerolization properties.Significant future challenges include the highly hygroscopic nature of unformulated ARG powder and identifying the scale of dose of ARG required to achieve the response in lungs.

A Survey of the Use of the Discrete-event Simulation in Manufacturing Industry

In this work, a survey of companies has been produc ed from a questionnaire and in-depth inter-views. The aimof the paper is to give a current view of the use of DES (Discrete- Event Simulation) in the indust ry. The companies have been selected in a wide range in e.g. size, capital turno ver and employees. The survey was restricted to Sweden, although the results may be applicable to other countries with similar industrial structure. Some of the companies investigated are also multinational with branches around the world. T o illustrate the differences in production systems different sectors have be en investigated, e.g. the manufacturing industry and energy sector. The manufact uring systems generally differ in that the energy sector is more known for high reliability in their systems and the manufacturing sector tends to work more wit h lean production. Previous surveys of manufacturing efficiency illustrate different aspects. Accor ding to one survey, more than one-third (34%) of the disturbances in two countr ies (the U.S. and Finland) were mainly caused by design-based errors and flaws. The survey also showed the scope of safety problems experienced in the implemen tation and use of flexible manufacturing systems (Jrvinen et al., 1996). Another survey in Germany reports a gap between users and non-users of DES. Man y companies that are not familiar with simulation are not aware of its benefits. The study suggested integrating simulation into the planning processes as a reg ular tool. So far, DES is mostly used in system planning, resource planning and scheduling and production planning (Hirschberg & Heitmann, 1997). The disposition of the accomplished questionnaire had been multiple-choice ques tions in a strict order. The respondents gave their views on what the interviewe r considered relevant for the survey. The questionnaire was mailed to 220 person s in May 2001; a second round for unanswered surveys was dispatched in August 20 01. Replies came from 114 respondents; thus, the reply rate to all questionnaire s sent out was 52%. The replies came in from 80 different companies. Questionswere raised regarding what kinds of decisions are taken from a simulation projec t and questions were also asked regarding the tool itself. Some common problems encountered based on the authors’ knowledge were asked in the questionnaire. The questions were sent to those who had reasonable knowledge of how to work with D ES. Supplementary in-depth interviews were also accomplished. On the question if DES facilitates the decision-making process 79% of totally 3 8 answered to a very large or a large extent. Regarding the question if DES is a useful tool for measuring the availability of equipment for example system verification 73% of 33 responded to a very large or a large extent. A majority o f the respondents genuinely see an advantage with the use of simulation, which i s an important result from the study. The cost reduction aspect of the productio n is also an advantage of DES. On the question eight answered to a very large ex tent and 23 to a large extent of total 39 replies. The question demonstrates tha t the results of a simulation model are indeed used in the real world. Finally, in the question of DES is used for staffing it is indicated that it is not so co mmonly used as for other functions asked for. The staffing issue requires good k nowledge about time measurement of manual labor. The option, however, to include manual work in a simulation model is in many programs extensive and must be a v aluable option to evaluate work intensive parts of production lines and their im provement. To conclude, it could be mentioned that DES is a tool with potential. The use is increasing and 12 of 80 companies investigated in Sweden 2001 are using it, an increase compared to previous stud-ies. Of those 12 companies, four are using t he tool to a large extent. The main advantage according to the survey beside the visualization part is that the knowledge about a system is investigated and doc umented.

Microstructure of Plasma Sprayed Al2O3-3wt%TiO2 Coating Using Freeze Granulated Powder

This study is aiming at controlling the microstructure of plasma sprayed Al2O3-TiO2 composite coatings using freeze granulated powders. As sprayed and sintered Al2O3 + 3wt%TiO2 powders were air plasma sprayed with industry process parameters and compared with a commercial powder. The resulting coatings were investigated with respect to powder flowability, porosity and microstructure of the granules. The results showed that microstructure and melting fraction in the coatings could be tailored with the freeze granulation process and heat treatment conditions.

人角膜移植术后上皮细胞与角膜干细胞的长期存活率

Purpose: To investigate the survival of donor-derived epithelial cells in con ventional penetrating keratoplasty (PKP) and in homologous penetrating central l imbal keratoplasty (HPCLK). Methods and patients: Epithelial cells from 26 eyes of 26 patients were analysed. All cases were sex-mismatched (i.e. the transplan t and patient were of different genders). At suture removal more than 1 year pos t surgery, epithelial cells were obtained by gently wiping the removed sutures o n glass slides. The cell samples were analysed using fluorescent in situ hybridi zation (FISH) of the sex chromosomes. This technique makes it possible to alloca te the origin of each cell nucleus to either the donor or the recipient. Results : All 19 conventional PKPs were clear and seven had donor-derived epithelial ce lls at suture removal. Five of the seven HPCLK grafts were clear at the time of investigation (365-1355 days post surgery), and donor-derived epithelial cells were found in two grafts. Conclusion: Harvesting cells from removed sutures in combination with FISH enables the clinical study of cell survival in corneal tra nsplants without jeopardizing functioning grafts. From the limited sample invest igated, the following tentative conclusions can be made. Donor-derived epitheli al cells can remain in conventional PKP for over 1 year. In combined stem cell a nd corneal grafts (HPCLK), donor-deriv- ed epithelial cells may also be retrieved at 1 year or beyond following surger y but the correlation between their presence and a remaining clear graft is unce rtain.

卵细胞内单精子注射受孕后出生儿童的眼部检查

Purpose: To investigate visual function and ocular morphology in children born after intracytoplasmic sperm injection (ICSI)-and compare them with visual function and ocular morphology in matched children born after spontaneous conception. Methods: A total of 137 children born after ICSI and 159 control children were examined at the age of 5 years in a blinded study. The two groups were matched for age, gender and maternal age. The children underwent a detailed ophthalmological investigation by an ophthalmologist and an orthoptist. Results: A total of 90.4% of the ICSI children had a visual acuity (VA) in the better eye of ≥ 0.8, compared with 93.7% of the controls (NS). No significant differences were found between ICSI children and controls with regard to hyperopia, myopia, astigmatism, heterotropia, stereoscopic vision and convergence. One child with Goldenhar syndrome and one with Marcus Gunn syndrome were observed in the ICSI group. One child in the ICSI group was treated for retinopathy of prematurity. Conclusion: In this limited study group, no significant differences in visual function and/or ocular morphology were found between children born after ICSI and matched control children at the age of 5 years.

心理因素作为胃灼热患者治疗反应的主要预测因素:一项临床试验的汇总分析

Objective.A pooled analysis,using data from three prospective,randomized,double-blind,placebo-controlled,clinical studies,was undertaken to determine the relationship between well-being and subsequent clinical response to acid suppressant therapy in 1887 adult patients with reflux symptoms(with/without endoscopically verified erosive esophagitis).Material and methods.Well-being was assessed at study entry using the Psychological General Well-Being(PGWB)Index.Patients were assessed for complete relief of heartburn(absence of symptoms in the preceding 7 days)after 4 weeks’treatment(omeprazole 10 or 20 mg once daily;ranitidine 150 mg twice daily).Results.Multiple logistic regression analysis identified baseline PGWB Index total score and anxiety score as independent prognostic indicators of treatment response in endoscopy-positive patients(n = 1333).Thus,the likelihood of achieving complete heartburn relief was impaired by high baseline levels of anxiety or a low total well-being score.In the endoscopy-negative group,high levels of depression and low vitality scores affected treatment response adversely.Furthermore,age(for endoscopy-positive patients only)and body mass index(for endoscopy-negative patients only)showed an association with treatment outcome.Gender seemed to have no prognostic value on treatment outcome.Conclusions.Patient well-being may be a useful prognostic indicator in patients presenting with reflux symptoms,with a high level of anxiety predicating against a response to acid suppressant therapy,particularly in those with normal endoscopic findings.

1型强直性肌营养不良患者的面部表情识别与CTG的重复扩增相关

Objective: To investigate the ability of patients with myotonic dystrophy type 1 to recognise basic facial emotions. We also explored the relationship between facial emotion recognition, neuropsychological data, personality, and CTG repeat expansion data in the DM-1 group. Methods: In total, 50 patients with DM-1 (28 women and 22 men) participated, with 41 healthy controls. Recognition of facial emotional expressions was assessed using photographs of basic emotions. A set of tests measured cognition and personality dimensions, and CTG repeat size was quantified in blood lymphocytes. Results: Patients with DM-1 showed impaired recognition of facial emotions compared with controls. A significant negative correlation was found between total score of emotion recognition in a forced choice task and CTG repeat size. Furthermore, specific cognitive functions (vocabulary, visuospatial construction ability, and speed) and personality dimensions (reward dependence and cooperativeness) correlated with scores on the forced choice emotion recognition task. Conclusion: These findings revealed a CTG repeat dependent facial emotion recognition deficit in the DM-1 group, which was associated with specific neuropsychological functions. Furthermore, a correlation was found between facial emotional recognition ability and personality dimensions associated with sociability. This adds a new clinically relevant dimension in the cognitive deficits associated with DM-1.

两种不同硅凝胶人工晶体植入后后囊浑浊形成的3年随访

Purpose: To compare posterior capsule opacification (PCO) after cataract surge ry with implantation of two silicone intraocular lenses (IOLs) with different de signs. Methods: We carried out a prospective, clinical study of 116 patients ran domized to standardized phacoemulsification with implantation of CeeOnEdge (n=57 ) or SI40NB (n=59) IOLs. The follow-up period was 3 years. To evaluate PCO morp hologically, digital images were obtained and analysed using evaluation of poste rior capsule opacification computer software (EPCO). The neodymium:YAG (Nd:YAG) capsulotomy rate was recorded. Results: At 2 and 3 years, the eyes with SI40NB I OLs had significantly more PCO than those with the CeeOn Edge IOLs (p=0.00014 an d p=0.002). Nine Nd:YAG capsulotomies were performed in the SI40NB group and non e in the CeeOn Edge group. This difference was statistically significant (p=0.00 3). In some patients a regression of PCO was noticed and confirmed usingEPCO. St atistically less PCO was noted when the capsulorhexis rim was placed so that it covered all 360 degrees of the optic of the IOL. Conclusions: A clinically and s tatistically significant difference in PCO development between CeeOn Edge and SI 40NB IOLs at 2 and 3 years postoperatively was found. These findings support earlier studies indicating that a sharp edge of the opt ic is a more important factor in IOL design than IOL material in the prevention of PCO.

海德堡视网膜断层扫描随访青光眼视盘改变的图像分析

Background:The Heidelberg Retina Tomograph(HRT)is a commercially available instrument for the detection of glaucomatous damage by analysis of optic nerve head topography.The main purpose of the study was to investigate the ability of HRT to detect changes in optic disc topography indicating progression of optic neuropathy in eyes with open-angle glaucoma or,in eyes with ocular hypertension,conversion to open-angle glaucoma.Methods:Fifty-nine subjects(34 with ocular hypertension,25 with glaucoma)from the glaucoma service at Sahlgrenska University Hospital were included in this study.One eye of each patient was selected.All participants underwent thorough clinical examination,including HRT,high-pass resolution perimetry(HRP),and optic disk photography.After a mean follow-up time of 50 months,patients were re-examined.Based on analyses of optic disc photographs and HRP,eyes were classified into one of two groups:progressive or stable.Methods:The differences between baseline and follow-up HRT parameters in the two groups were analysed.The topographic HRT change images were also compared after digital image processing.A pixel ratio was calculated defined as the ratio between the area of pixels representing deepening of the disc surface and the total disc area.Receiver operating characteristic(ROC)curves for HRT parameters and pixel ratio were compared.Results:In the group judged to have progressive optic neuropathy,a statistically significant change between baseline and follow-up examination was found for the following HRT parameters:cup shape measurement,classification index,the third moment in contour,cup/disc ratio,cup area,rim area,and area below reference.In the stable group no HRT parameters had changed significantly.A well-defined distinction between the two groups was found by comparing digitally processed HRT change images.The area under the ROC curve was larger for pixel ratio than for any of the HRT parameters.Conclusions:The HRT is a useful tool for long-term follow-up of glaucomatous optic neuropathy.Digital image processing of HRT change images could facilitate the detection of progressive change.

额颞型痴呆患者鞘内炎性反应增强的病理生理意义

Objective: Immunological mechanisms may be part of the pathophysiological mechanisms in frontotemporal dementia (FTD), but hitherto only vague evidence of such me chanisms has been presented. The aim of this study was to compare the cerebrospinal fluid (CSF) levels of the pro inflammatory cytokines interleukin (IL) 1β and tumour necrosis factor (TNF) α , and the anti inflammatory cytokine transforming growth factor (TGF) β in patients with FTD and normal controls. Furthermore, serum levels of TNF α , TGF β , and IL 1β were measured in FTD patients. Methods: The CSF levels of IL 1β , TNFα , and TGF β were measured using ELISA in 19 patients with FTD and 24 sex and age matched healthy controls. Results: The CSF levels of TNF α (FTD 0.6 pg/mL (median: lower, upper quartile 0.3, 0.7); controls: 0.0 pg/mL (0.0, 0.0); p = 0.008) and TGF β (FTD 266 pg/mL (157, 371), controls: 147 pg/mL (119, 156); p = 0.0001)were significantly increased in FTD patients compared with controls. No correlations were found between CSF and serum levels of the cytokines. In the controls, but not in the FTD patients, a positive correlation was found between the CSF levels of TGF β and age (r = 0.42, p < 0.05). No correlation was found between any of the cytokines and degree of brain atrophy or white matter changes. No differences between the groups were found for age, gender, or CSF/serum albumin ratio. Conclusions: The results suggest an increased intrathecal production of both pro and anti inflammatory cytokines in FTD. As no correlations were found with the albumin ratio, and no correlations between CSF and serum levels of the cytokines were found, these changes in the CSF cannot be explained by a systemic overproduction of cytokines.

重型颅脑创伤后脑室内脑脊液β-淀粉蛋白及其前体显著升高

Severe traumatic brain injury (TBI) may result in widespread damage to axons, termed diffuse axonal injury. Alzheimer’ s disease (AD) is characterised by synaptic and axonal degeneration together with senile plaques (SP). SP are mainly composed of aggregated β amyloid (Aβ ), which are peptides derived from the amyloid precursor protein (APP). Apart from TBI in itself being considered a risk factor for AD, severe head injury seems to initiate a cascade of molecular events that are also associated with AD. We have therefore analysed the 42 amino acid forms of Aβ (Aβ (1- 42)) and two soluble forms of APP (α sAPP and β sAPP) in ventricular cerebrospinal fluid (VCSF) andAβ (1 42) in plasma from 28 patients in a serial samples 0 11 days after TBI. The levels of α sAPP, β sAPP and Aβ (1- 42) were determined using ELISA assays. After TBI, there was a signi ficant stepwise increase in VCSF Aβ (1- 42) up to 1173 % from day 0- 1 to day 5 6and inVCSF α sAPP up to 2033% increase from day 0 1 to day 7- 11. There was also a slight but significant increase of VCSF β sAPP from day 0- 1 to day 5- 6 and day 7- 11. By contrast, the plasma Aβ (1- 42) level is unchanged after injury. The marked increase in VCSF Aβ (1- 42) implies that increased Aβ expression may occur as a secondary phenomenon after TBI with axonal damage. The unchanged level of plasma Aβ (1- 42) in contrast to the marked increase in VCSF Aβ (1- 42) after severe TBI, supports the suggestion that plasma Aβ (1- 42) does not reflect Aβ metabolism in the central nervous system (CNS).

17～18岁青少年的正常视力

Purpose: The aim of this work was to establish visual acuity norms in 17-18- year-olds. Methods: In a previous, populationbased study carried out in 1998, a total of 1046 12-13-year-old children were examined with a full eye examinat ion. In 2003, 25%(n=262) of these children were randomly selected and invited t o a re-examination; 147 subjects agreed to participate and 116 attended. The ex amined group did not significantly differ from the original sample in terms of t he prevalence of ocular and visual disorders. Best corrected monocular visual ac uity (VA) was assessed with the revised 2000 ETDRS logMAR chart. Results: Mean b est corrected VA was-0.10 logMAR across the examined group. There was no signif icant difference between right and left eyes. By excluding nine subjects who had significant ametropia and/or ocular or visual pathology, mean VA increased to- 0.12 logMAR (SD 0.07). The mean interocular difference in VA among normal subjec ts was 0.04 logMAR. Conclusions: Visual acuity in teenagers is signifi-cantly b etter than 0.0 logMAR and the interocular difference is low in healthy eyes.

When a 17-Year-Old Girl Is Diagnosed with Myalgic Encephalomyelitis: A Case Study from the Swedish Health Care System—A Parent Perspective

This case study presents different strategies that were explored by the patient’s mother (who is a researcher in music and medicine) when her 17-year-old daughter was diagnosed with ME (Myalgic Encephalomyelitis), also known as Chronic Fatigue Syndrome (CFS). ME is not widely recognized in the Global as well as the Swedish population at large, and within healthcare, there are no standardized recommended treatments, partly due to the lack of published evidence-based studies. This case study aims to provide insights into how the Swedish healthcare system works, how different clinics and hospitals within it operate and interconnect;and how these contribute to health outcomes after 15 months of treatment.

Energy harvesting textiles for a rainy day:woven piezoelectrics based on melt-spun PVDF microfibres with a conducting core

Recent advances in ubiquitous low-power electronics call for the development of light-weight and flexible energy sources.The textile format is highly attractive for unobtrusive harvesting of energy from e.g.,biomechanical movements.Here,we report the manufacture and characterisation of fully textile piezoelectric generators that can operate under wet conditions.We use a weaving loom to realise textile bands with yarns of melt-spun piezoelectric microfibres,that consist of a conducting core surrounded byβ-phase poly(vinylidene fluoride)(PVDF),in the warp direction.The core-sheath constitution of the piezoelectric microfibres results in a—for electronic textiles—unique architecture.The inner electrode is fully shielded from the outer electrode(made up of conducting yarns that are integrated in the weft direction)which prevents shorting under wet conditions.As a result,and in contrast to other energy harvesting textiles,we are able to demonstrate piezoelectric fabrics that do not only continue to function when in contact with water,but show enhanced performance.The piezoelectric bands generate an output of several volts at strains below one percent.We show that integration into the shoulder strap of a laptop case permits the continuous generation of four microwatts of power during a brisk walk.This promising performance,combined with the fact that our solution uses scalable materials and well-established industrial manufacturing methods,opens up the possibility to develop wearable electronics that are powered by piezoelectric textiles.

Insights into the present and future of cartilage regeneration and joint repair

Knee osteoarthritis is the most common joint disease.It causes pain and suffering for affected patients and is the source of major economic costs for healthcare systems.Despite ongoing research,there is a lack of knowledge regarding disease mechanisms,biomarkers,and possible cures.Current treatments do not fulfill patients’long-term needs,and it often requires invasive surgical procedures with subsequent long periods of rehabilitation.Researchers and companies worldwide are working to find a suitable cell source to engineer or regenerate a functional and healthy articular cartilage tissue to implant in the damaged area.Potential cell sources to accomplish this goal include embryonic stem cells,mesenchymal stem cells,or induced pluripotent stem cells.The differentiation of stem cells into different tissue types is complex,and a suitable concentration range of specific growth factors is vital.The cellular microenvironment during early embryonic development provides crucial information regarding concentrations of signaling molecules and morphogen gradients as these are essential inducers for tissue development.Thus,morphogen gradients implemented in developmental protocols aimed to engineer functional cartilage tissue can potentially generate cells comparable to those within native cartilage.In this review,we have summarized the problems with current treatments,potential cell sources for cell therapy,reviewed the progress of new treatments within the regenerative cartilage field,and highlighted the importance of cell quality,characterization assays,and chemically defined protocols.

A phase 1b randomized clinical trial of CT1812 to measure Aβoligomer displacement in Alzheimer’s disease using an indwelling CSF catheter

Trial Registration:May 11th,2018 ClinicalTrials.gov Identifier:NCT03522129 https://clini caltr ials.gov/ct2/show/NCT03522129.Investigational therapies for Alzheimer’s disease(AD)target a wide range of mechanisms,yet promising dis-ease-modifying therapies remain a huge unmet need.Much evidence indicates that the oligomeric form of amyloid-beta(Aβ)is a toxic species contributing to AD through synaptic damage and neuronal toxicity[1].