Association Between Diverse Diabetic Treatments and Duration of Diabetes Mellitus According to Progression of Diabetic Retinopathy: Experience From a Small Regional Hospital

Introduction: Research objectives of present study were to examine sex and age-related specifics of diabetic retinopathy according to the therapy approach and duration of diabetes mellitus. The study also aimed to determine the association between the presence of diabetic retinopathy and diabetes duration as a prognostic factor of retinopathy progression in such patients. Materials and Methods: The study was designed as a retrospective study and included 289 patients with diabetic retinopathy, who were treated at the Department of Ophthalmology of the General Hospital “Dr. Josip Benčević” in Slavonski Brod during the period from 2019 to 2020. Results: 176 patients were treated with oral antidiabetic drugs (OAD), while 113 patients were insulin-dependent. The median age of patients treated with OAD was 77 years. Diabetic retinopathy was present in 35 (19.9%) patients, of whom 33 (18.8%) had non-proliferative diabetic retinopathy, while 2 patients (1.1%) had proliferative diabetic retinopathy. The median age of the insulin-dependent patients was 79 years. Diabetic retinopathy was present in 54 patients (47.8%), non-proliferative diabetic retinopathy was diagnosed in 51 patients (45.1%), while proliferative diabetic retinopathy was diagnosed in only 3 (2.7%) patients. There was a significant difference between the presence of diabetic retinopathy and diabetes duration (P<0.001), as well as between the therapy approach and diabetes duration (⍺<0.001). Conclusion: Various hypotheses have been proposed to explain the worsening of diabetic retinopathy, and we assume that the therapy approach, duration of diabetes and HbA1c have a significant role in retinopathy progression. Hereby, we emphasize that, although there have been significant advances, there is still a pressing need for a better understanding of a new therapeutic modality, new tools for identifying high-risk patients and continued monitoring in order to intervene effectively before vision loss occurs. Further research is needed to identify and implement the best practices to increase diabetic eye screening rates in the long term

Tito's Bunker

Inclusion of Amoy Gardens (2003/07) in international group exhibition Tito's Bunker at Württembergischer Kunstverein, Stuttgart, curated by Iris Dressler and Hans D. Christ. The exhibition reconsiders the socio-political text of a nuclear bunker built between 1953 and 1979 in Konjic, Bosnia and Herzegovina, for Josip Broz Tito, former prime minister of Yugoslavia

Status Report and Beam Time Request for Experiment AD-4

Summary of current status and plans for October 200

Biological Effects of Antiprotons Are Antiprotons a Candidate for Cancer Therapy?

2009 Status Report of AD-4 Experimen

A Study On The Model Of Profit And Risk In Xiamen’s Commercial Banks

随着相对滞后的金融体制改革提上议事日程，金融业中的银行业的风险和效益的矛盾对立统一日益成为讨论的焦点、热点。加入WTO对金融业意味着拥有先进管理技术和经验的外资银行抢滩国内银行业务，其对国内中资银行的竞争和生存环境的影响是巨大且不可预测的。作者认为国内中资银行是缺乏效率的，为避免银行命脉被外资控制，国内中资银行不能讳疾忌医，而要以有容乃大、自省的态度积极寻求市场经济下的解决之道，最可取的莫过于解剖一只麻雀。 按照这一思路，本文选取了厦门8家经营较稳定的商业银行进行收益风险模式比较，为国内其他中资商业银行的经营管理提供实证参考。 第一章导言。对银行经营活动的一般特点进行描述。提出银行作为经济...Owing to the combination between banking and economics , influencing factor is increasingly complicated. Banker needs to design one macroanalysis model to logically judge different kinds of income chance and danger all banks faced with，through which banker may supply effective diagnose for banking operating management. The theses takes banking 'data in Xiamen as an example .It exists that huge c...学位：工商管理硕士院系专业：管理学院工商管理教育中心_工商管理硕士(MBA)学号：19981505

The Toronto prehospital hypertonic resuscitation-head injury and multi organ dysfunction trial (TOPHR HIT) - Methods and data collection tools

<p>Abstract</p> <p>Background</p> <p>Clinical trials evaluating the use of hypertonic saline in the treatment of hypovolemia and head trauma suggest no survival superiority over normal saline; however subgroup analyses suggest there may be a reduction in the inflammatory response and multiorgan failure which may lead to better survival and enhanced neurocognitive function. We describe a feasibility study of randomizing head injured patients to hypertonic saline and dextran vs. normal saline administration in the out of hospital setting.</p> <p>Methods/Design</p> <p>This feasibility study employs a randomized, placebo-controlled design evaluating normal saline compared with a single dose of 250 ml of 7.5% hypertonic saline in 6% dextran 70 in the management of traumatic brain injuries. The primary feasibility endpoints of the trial were: 1) baseline survival rates for the treatment and control group to aid in the design of a definitive multicentre trial, 2) randomization compliance rate, 3) ease of protocol implementation in the out-of-hospital setting, and 4) adverse event rate of HSD infusion.</p> <p>The secondary objectives include measuring the effect of HSD in modulating the immuno-inflammatory response to severe head injury and its effect on modulating the release of neuro-biomarkers into serum; evaluating the role of serum neuro-biomarkers in predicting patient outcome and clinical response to HSD intervention; evaluating effects of HSD on brain atrophy post-injury and neurocognitive and neuropsychological outcomes.</p> <p>Discussion</p> <p>We anticipate three aspects of the trial will present challenges to trial success; ethical demands associated with a waiver of consent trial, challenging follow up and comprehensive accurate timely data collection of patient identifiers and clinical or laboratory values. In addition all the data collection tools had to be derived de novo as none existed in the literature.</p> <p>Trial registration number</p> <p>NCT00878631</p

Delivery of a Chlamydial Adhesin N-PmpC Subunit Vaccine to the Ocular Mucosa Using Particulate Carriers

Trachoma, caused by the intracellular bacterium Chlamydia trachomatis (Ct), remains the world's leading preventable infectious cause of blindness. Recent attempts to develop effective vaccines rely on modified chlamydial antigen delivery platforms. As the mechanisms engaged in the pathology of the disease are not fully understood, designing a subunit vaccine specific to chlamydial antigens could improve safety for human use. We propose the delivery of chlamydia-specific antigens to the ocular mucosa using particulate carriers, bacterial ghosts (BGs). We therefore characterized humoral and cellular immune responses after conjunctival and subcutaneous immunization with a N-terminal portion (amino acid 1-893) of the chlamydial polymorphic membrane protein C (PmpC) of Ct serovar B, expressed in probiotic Escherichia coli Nissle 1917 bacterial ghosts (EcN BGs) in BALB/cmice. Three immunizations were performed at two-week intervals, and the immune responses were evaluated two weeks after the final immunization in mice. In a guinea pig model of ocular infection animals were immunized in the same manner as the mice, and protection against challenge was assessed two weeks after the last immunization. N-PmpC was successfully expressed within BGs and delivery to the ocularmucosa was well tolerated without signs of inflammation. N-PmpC- specific mucosal IgA levels in tears yielded significantly increased levels in the group immunized via the conjunctiva compared with the subcutaneously immunized mice. Immunization with N-PmpC EcN BGs via both immunization routes prompted the establishment of an N-PmpC-specific IFN gamma immune response. Immunization via the conjunctiva resulted in a decrease in intensity of the transitional inflammatory reaction in conjunctiva of challenged guinea pigs compared with subcutaneously and non-immunized animals. The delivery of the chlamydial subunit vaccine to the ocular mucosa using a particulate carrier, such as BGs, induced both humoral and cellular immune responses. Further investigations are needed to improve the immunization scheme and dosage

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.Peer reviewe

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Analysis of translocation of "ersinia outer proteins" into host cells viaYopE-Cre reporter system

Humanpathogene Yersinien unterlaufen die angeborene Immunabwehr des Wirtes, indem sie eine Gruppe von Virulenzfaktoren, die sogenannten Yersinia outer proteins (Yop) E, T, H, M, O und P mittels eines Typ III Sekretionssystems (TTSS) direkt in Wirtszellen translozieren. Diese Yops inhibieren Wirtszellfunktionen und nehmen so negativen Einfluss auf die Immunabwehr. In diversen Studien wurden zum besseren Verständnis, wie die Yop Translokation durch das TTSS von Yersinien funktioniert, verschiedene Reportersysteme entwickelt. Ziel der vorliegenden Arbeit war es ein Reportersystem, basierend auf einem Cre YopE Fusionsprotein und lox P flankiertem Reportergenkonstrukt zu entwickeln, um in Infektionsexperimenten zunächst von kultivierten Zellen diejenigen Zellen zu erkennen, in die die Yops transloziert werden. Langfristig sollte dieses System dazu dienen, Yop Translokation im Mausinfektionsmodell nachzuweisen. Das Prinzip des Systems ist es, einen Yersinien Stamm zu generieren, der nach Kontakt mit Zellen ein YopE Cre Fusionsprotein in die Zelle injiziert. Die translozierte Cre Rekombinase deletiert dann ein Genfragment, so dass ein konstitutiv aktiver Promotorbereich in die Nähe eines für Beta-Galaktosidase kodierenden Genabschnitts gebracht wird. Nach Expression von Beta-Galaktosidase kann diese durch Färbung mit X-Gal, wobei eine Blaufärbung entsteht, nachgewiesen werden kann. Es wurden Expressionsvektoren bestehend aus N-terminalen YopE Fragmenten (YopE138, YopE52) und einer C-terminalen NLSCre Domäne konstruiert. Durch transiente Transfektion von Zellen mit diesen Vektoren konnte gezeigt werden, dass die Funktionalität der Cre-Rekombinase durch die Fusion an die YopE Fragmente nicht beeinträchtigt wird. Die Yersinien-Stämme WA-P und WA-CpTTSS (Serotyp O:8, Typ III Sekretionssystem, aber keine Effektor-Yops) wurden mit den konstruierten Expressionsvektoren pACYC184yopE52Cre und pACYC184yopE138Cre transformiert und anschließend die Sekretion und Translokation der YopE-Cre Hybride beider Reporterstämme untersucht. Die Sekretion und Translokation der Fusionsproteine konnte für beide Reporterstämme nachgewiesen werden. Hierbei zeigte sich, dass der Reporterstamm WA-C(pTTSS) eine höhere Sekretions- und Translokationseffizienz aufweist als der Reporterstamm WA-P, der zusätzlich zum YopE-Cre Fusionsprotein weitere zytotoxische Effektor-Yops sekretiert. In vergleichenden Untersuchungen der Translokation der YopE-Cre Hybride konnte gezeigt werden, dass YopE52Cre besser transloziert wird als YopE138Cre. Dies entspricht den Untersuchungen von Feldmann et al mit YopE DHFR Hybriden. Zur quantitativen Auswertung der Translokation von YopE-Cre in Zellen nach Yersinien Infektion wurde weiterhin eine auf Druchflusszytometrie basierende Methode etabliert. Zusammenfassend lässt sich sagen, dass in der vorliegenden Arbeit ein Reportersystem etabliert werden konnte, das zur Untersuchung der Translokation von Yops prinzipiell geeignet ist. Allerdings ist der Anteil an Zellen, in denen Yop Translokation mit Hilfe des YopE-Cre Systems nach Infektion nachweisbar ist, mit weniger als 10 % relativ gering. In nachfolgenden Arbeiten konnte das System weiter optimiert werden, erwies sich aber für in vivo Untersuchungen als unzureichend. Auch Untersuchungen von Briones et al zum Proteintransfer über das TTSS von Salmonella enterica basierend auf einem SopE-Cre Reportersystem bestätigten retrospektiv, dass das Cre-System als Reportersystem zum Nachweis von Proteintranslokation durch TTSS-Systeme für in vivo Modelle wenig geeignet ist.Pathogenic yersiniae are able to resist the innate immune defense of their human host by injection of a set of anti-host proteins, called Yops via type III secretion (TTSS) mechanism into host cell. These proteins have the capacity to modulate or interfere with a variety of cellular functions. In several studies the transfer of proteins by the TTSS system has been monitored with a variety of reporter systems. In this study a reporter system based on a YopE-Cre fusion protein and a loxP flanked lacZ reporter gene was used to detect in cell culture experiments the cells, in which Yops have been injected. Based on long-term considerations this system was supposed to be used to detect Yop translocation in experimental mouse infection model. Principle of this system is to generate a Y. enterocolitica strain expressing a YopE-Cre fusion protein. The CV1 5B fibroblasts carry the reporter gene lacZ in which the expression of lacZ is conditional to the removal of a loxP flanked intervening sequence upon expression of the Cre recombinase. After cell contact Y. enterocolitica is injecting the YopE-Cre fusion protein directly into host cells, and depending on the Cre recombinase activity the lacZ gene is expressed. After lacZ expression beta-galactosidase activity can be detected by x-Gal staining, which forms an intense blue precipitate. Plasmids were constructed by fusing YopE fragments of Y. enterocolitica of the N-terminus (YopE138, YopE52) in frame with full length sequence of the P1 Cre recombinase. Transient transfection of these plasmids shows that YopE Cre retains efficient recombinase activity. Yersiniae strains WA-P and WA-CpTTSS (serovar O:8, typ III secretions¬system, but no effektor-Yops) were transformed with pACYC184yopE52Cre and pACYC184yopE138Cre and then secretion and translocation of YopE-Cre fusion proteins were tested. In both yersiniae strains secretion and translocation of YopE-Cre could be shown. The results indicated that strain WA-C(pTTSS) is more efficient in secretion and translocation compared to strain WA-P, which additional secrete further effector Yops. In line with analysis by Feldman et al with YopE-DHFR hybrid proteins, comparative experiments of translocation of YopE Cre fusion proteins indicate that YopE52Cre is better translocated than YopE138Cre. To quantify cell numbers of YopE-Cre translocation after Yersinia infection a flow cytometry based method was established. Taken together, in this study a reporter system in principle enable to detect Yop translocation could be established. Certainly the quantified fraction of cells in which Yops were translocated after infection using the YopE-Cre reporter system is with 10 % relatively low. Based on the studies performed here the YopE-Cre system was optimized, but the results indicated that it is not suitable for in vivo analysis. Also Briones et al affirmed with the study about monitoring protein transfer via TTSS by Salmonella enterica using a SopE-Cre reporter system that the Cre-system as a reporter system for quantitative detection of targeted cells in in vivo models is not suitable