Objective:To provide a comprehensive review on the existing literature on medical management of urolithiasis.Methods:A thorough literature review was performed using Medline,PubMed/PMC,Embase,and the Cochrane Database...Objective:To provide a comprehensive review on the existing literature on medical management of urolithiasis.Methods:A thorough literature review was performed using Medline,PubMed/PMC,Embase,and the Cochrane Database of Systematic Reviews up to December 2022 to identify publications on the medical management of urolithiasis.Studies that assessed dietary and pharmacologic management of urolithiasis were reviewed;studies on medical expulsive therapy were not included in this review.Results:Medical management of urolithiasis ranges from the prophylactic management of kidney stone disease to dissolution therapies.While most treatment concepts have been long established,large randomized controlled trials are scarce.Dietary modification and increased fluid intake remain cornerstones in the conservative management of urolithiasis.A major limitation for medical management of urolithiasis is poor patient compliance.Conclusion:Medical management of urolithiasis is more important in patients with recurrent urolithiasis and patients with metabolic abnormalities putting them at higher risk of developing stones.Although medical management can be effective in limiting stone recurrence,medical interventions often fail due to poor compliance.展开更多
Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the ...Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.展开更多
Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural regeneration.Both intrinsic and extrinsic factors ...Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural regeneration.Both intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following injury.At the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to regenerate.Recent works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of regeneration.The role of glia in neuron regeneration has long been studied.展开更多
BACKGROUND Healthcare professionals need to be prepared to promote healthy lifestyles and care for patients.By focusing on what students should be able to perform one day as clinicians,we can bridge the gap between me...BACKGROUND Healthcare professionals need to be prepared to promote healthy lifestyles and care for patients.By focusing on what students should be able to perform one day as clinicians,we can bridge the gap between mere theoretical knowledge and its practical application.Gender aspects in clinical medicine also have to be considered when speaking of personalized medicine and learning curricula.AIM To determine sets of intellectual,personal,social,and emotional abilities that comprise core qualifications in medicine for performing well in anamnesis-taking,in order to identify training needs.METHODS An analysis of training clinicians’conceptions with respect to optimal medical history taking was performed.The chosen study design also aimed to assess gender effects.Structured interviews with supervising clinicians were carried out in a descriptive study at the Medical University of Vienna.Results were analyzed by conducting a qualitative computer-assisted content analysis of the interviews.Inductive category formation was applied.The main questions posed to the supervisors dealt with(1)Observed competencies of students in medical history taking;and(2)The supervisor’s own conceptions of"ideal medical history taking".RESULTS A total of 33 training clinicians(n=33),engaged in supervising medical students according to the MedUni Vienna’s curriculum standards,agreed to be enrolled in the study and met inclusion criteria.The qualitative content analysis revealed the following themes relevant to taking an anamnesis:(1)Knowledge;(2)Soft skills(relationship-building abilities,trust,and attitude);(3)Methodical skills(structuring,precision,and completeness of information gathering);and(4)Environmental/contextual factors(language barrier,time pressure,interruptions).Overall,health care professionals consider empathy and attitude as critical features concerning the quality of medical history taking.When looking at physicians’theoretical conceptions,more general practitioners and psychiatrists mentioned attitude and empathy in the context of"ideal medical history taking",with a higher percentage of females.With respect to observations of students’history taking,a positive impact from attitude and empathy was mainly described by male health care professionals,whereas no predominance of specialty was found.Representatives of general medicine and internal medicine,when observing medical students,more often emphasized a negative impact on history taking when students lacked attitude or showed non-empathetic behavior;no gender-specific difference was detected for this finding.CONCLUSION The analysis reveals that for clinicians engaged in medical student education,only a combination of skills,including adequate knowledge and methodical implementations,is supposed to guarantee acceptable performance.This study’s findings support the importance of concepts like relationship building,attitude,and empathy.However,there may be contextual factors in play as well,and transference of theoretical concepts into the clinical setting might prove challenging.展开更多
The Kirsten rat sarcoma virus—son of sevenless 1(KRAS-SOS1)axis drives tumor growth preferentially in pancreatic,colon,and lung cancer.Now,KRAS G12C mutated tumors can be successfully treated with inhibitors that cov...The Kirsten rat sarcoma virus—son of sevenless 1(KRAS-SOS1)axis drives tumor growth preferentially in pancreatic,colon,and lung cancer.Now,KRAS G12C mutated tumors can be successfully treated with inhibitors that covalently block the cysteine of the switch II binding pocket of KRAS.However,the range of other KRAS mutations is not amenable to treatment and the G12C-directed agents Sotorasib and Adragrasib show a response rate of only approximately 40%,lasting for a mean period of 8 months.One approach to increase the efficacy of inhibitors is their inclusion into proteolysis-targeting chimeras(PROTACs),which degrade the proteins of interest and exhibit much higher antitumor activity through multiple cycles of activity.Accordingly,PROTACs have been developed based on KRAS-or SOS1-directed inhibitors coupled to either von Hippel-Lindau(VHL)or Cereblon(CRBN)ligands that invoke the proteasomal degradation.Several of these PROTACs show increased activity in vitro and in vivo compared to their cognate inhibitors but their toxicity in normal tissues is not clear.The CRBN PROTACs containing thalidomide derivatives cannot be tested in experimental animals.Resistance to such PROTACS arises through downregulation or inactivation of CRBN or factors of the functional VHL E3 ubiquitin ligase.Although highly active KRAS and SOS1 PROTACs have been formulated their clinical application remains difficult.展开更多
Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers worldwide.The main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma virus.Approved ...Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers worldwide.The main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma virus.Approved therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second primaries.The availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented pace.Initially,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk tumors.More recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within tumors.This review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.展开更多
Objective:Transurethral resection of bladder tumor is one of the most common everyday urological procedures.This kind of surgery demands a set of skills that need training and experience.In this review,we aimed to inv...Objective:Transurethral resection of bladder tumor is one of the most common everyday urological procedures.This kind of surgery demands a set of skills that need training and experience.In this review,we aimed to investigate the current literature to find out if simulators,phantoms,and other training models could be used as a tool for teaching urologists.Methods:A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement and the recommendations of the European Association of Urology guidelines for conducting systematic reviews.Fifteen out of 932 studies met our inclusion criteria and are presented in the current review.Results:The UroTrainer(Karl Storz GmbH,Tuttlingen,Germany),a virtual reality training simulator,achieved positive feedback and an excellent face and construct validity by the participants.The inspection of bladder mucosa,blood loss,tumor resection,and procedural time was improved after the training,especially for inexperienced urologists and medical students.The construct validity of UroSim®(VirtaMed,Zurich,Switzerland)was established.SIMBLA simulator(Samed GmbH,Dresden,Germany)was found to be a realistic and useful tool by experts and urologists with intermediate experience.The test objective competency model based on SIMBLA simulator could be used for evaluating urologists.The porcine model of the Asian Urological Surgery Training and Education Group also received positive feedback by the participants that tried it.The Simulation and Technology Enhanced Learning Initiative Project had an extraordinary face and content validity,and 60%of participants would like to use the simulators in the future.The 5-day multimodal training curriculum“Boot Camp”in the United Kingdom achieved an increase of the level of confidence of the participants that lasted months after the project.Conclusion:Simulators and courses or curricula based on a simulator training could be a valuable learning tool for any surgeon,and there is no doubt that they should be a part of every urologist's technical education.展开更多
Atrial fibrillation(AF)is a major public health problem and poses a substantial economic burden on healthcare systems worldwide.[1-4]The emergency department(ED)serves as the first point of contact with the healthcare...Atrial fibrillation(AF)is a major public health problem and poses a substantial economic burden on healthcare systems worldwide.[1-4]The emergency department(ED)serves as the first point of contact with the healthcare system and plays a key role in the management of patients with AF,which accounts for 3%-10%of all hospital admissions.[5]Treatment plans are often discussed and initiated at the ED.展开更多
Objective:To evaluate the feasibility and the safety of medial non-papillary percutaneous nephrolithotomy(npPCNL)for the management of large proximal ureteral stones.Methods:We evaluated prospectively collected data o...Objective:To evaluate the feasibility and the safety of medial non-papillary percutaneous nephrolithotomy(npPCNL)for the management of large proximal ureteral stones.Methods:We evaluated prospectively collected data of 37 patients with large proximal ureteral stones more than 1.5 cm in diameter treated by prone npPCNL.Depending on stone size,in-toto stone removal or lithotripsy using the Lithoclast®Trilogy(EMS Medical,Nyon,Switzerland)was performed.Perioperative parameters including operative time(from start of puncture to the skin suturing),stone extraction time(from the first insertion of the nephroscope to the extraction of all stone fragments),and the stone-free rate were evaluated.Results:Twenty-one males and 16 females underwent npPCNL for the management of large upper ureteral calculi.The median age and stone size of treated patients were 58(interquartile range[IQR]:51-69)years and 19.3(IQR:18.0-22.0)mm,respectively.The median operative time and stone extraction time were 25(IQR:21-29)min and 8(IQR:7-10)min,respectively.One case(2.7%)of postoperative bleeding and two cases(5.4%)of prolonged fever were managed conservatively.The stone-free rate at a 1-month follow-up was 94.6%.Conclusion:The npPCNL provides a straight route to the ureteropelvic junction and proximal ureter.Approaching from a dilated portion of the ureter under low irrigation pressure with larger diameter instruments results in effective and safe stone extraction within a few minutes.展开更多
Objective:Only a few numbers of studies have been published on the use of abobotulinumtoxinA(Dysport®)in idiopathic detrusor overactivity(IDO).This study reported the long-term follow-up of women with IDO who wer...Objective:Only a few numbers of studies have been published on the use of abobotulinumtoxinA(Dysport®)in idiopathic detrusor overactivity(IDO).This study reported the long-term follow-up of women with IDO who were treated with intravesical Dysport®injections.Methods:Two hundred and thirty-six patients with IDO who had failed first-line conservative and antimuscarinic therapy received 500-900 units of Dysport®between April 2014 and July 2015.All patients were followed up for 5 years after their initial injection and interviewed on the phone.Results:A total of 236 women with IDO aged from 18 years to 84 years(mean±standard deviation:49.6±15.9 years)were included in our study.The median follow-up time for patients was 36.5(range:10-70)months,and the median recovery time after injection was 18.5(range:0-70)months.A total of 83(35.2%)patients stated that they had subjective improvement of their symptoms whereas 84(35.6%)patients did not report any improvement in symptoms.The initial International Consultation on Incontinence Questionnaire Overactive Bladder mean score was 6.9(standard deviation 3.4).There was a positive association between the median recovery time and the components of the International Consultation on Incontinence Questionnaire Overactive Bladder questionnaire.Conclusion:In a sub-population of overactive bladder patients with IDO who have failed first-line therapy,a single intravesical Dysport®injection can resolve patient symptoms completely or reduce the symptoms to an acceptable level that can be controlled with antimuscarinics or re-injection on demands.展开更多
Objective: To analyze outcomes and complications of cytoreductive prostatectomy (CRP) for oligometastatic prostate cancer (PCa) in order to elucidate its role in this space.Methods: We performed a systematic literatur...Objective: To analyze outcomes and complications of cytoreductive prostatectomy (CRP) for oligometastatic prostate cancer (PCa) in order to elucidate its role in this space.Methods: We performed a systematic literature search using three databases (Medline, Scopus, and Web of Science). The primary endpoints were oncologic outcomes. The secondary endpoints were complication rates and functional results.Results: In all studies, overall survival was better or at least comparable variable in the groups with CRP compared to no local treatment. The greatest benefit from CRP in 5-year overall survival in one study was 67.4% for CRP versus 22.5% for no local treatment. Cancer-specific survival (CSS) showed the same trend. Several authors found significant benefits from CSS in the CRP group: from 79% vs. 46% to 100% vs. 61%. CRP was a predictor of better CSS (hazard ratio 0.264, p=0.004). Positive surgical margin rates differed widely from 28.6% to 100.0%. Urinary continence in CRP versus RP for localized PCa was significantly lower (57.4% vs. 90.8%, p<0.0001). Severe incontinence occurred seldom (2.5%-18.6%). Total complication rates after CRP differed widely, from 7.0% to 43.6%. Rates of grades 1 and 2 events prevailed. Patients on ADT alone also showed a considerable number of complications varying from 5.9% to 57.7%.Conclusion: CRP improves medium-term cancer control in patients with oligometastatic PCa. The morbidity and complication rates of this surgery are comparable with other approaches, but postoperative incontinence rate is higher compared with RP for localized disease.展开更多
Mesenchymal stem cells(MSCs)are considered as an attractive tool for tissue regeneration and possess a strong immunomodulatory ability.Dental tissuederived MSCs can be isolated from different sources,such as the denta...Mesenchymal stem cells(MSCs)are considered as an attractive tool for tissue regeneration and possess a strong immunomodulatory ability.Dental tissuederived MSCs can be isolated from different sources,such as the dental pulp,periodontal ligament,deciduous teeth,apical papilla,dental follicles and gingiva.According to numerous in vitro studies,the effect of dental MSCs on immune cells might depend on several factors,such as the experimental setting,MSC tissue source and type of immune cell preparation.Most studies have shown that the immunomodulatory activity of dental MSCs is strongly upregulated by activated immune cells.MSCs exert mostly immunosuppressive effects,leading to the dampening of immune cell activation.Thus,the reciprocal interaction between dental MSCs and immune cells represents an elegant mechanism that potentially contributes to tissue homeostasis and inflammatory disease progression.Although the immunomodulatory potential of dental MSCs has been extensively investigated in vitro,its role in vivo remains obscure.A few studies have reported that the MSCs isolated from inflamed dental tissues have a compromised immunomodulatory ability.Moreover,the expression of some immunomodulatory proteins is enhanced in periodontal disease and even shows some correlation with disease severity.MSC-based immunomodulation may play an essential role in the regeneration of different dental tissues.Therefore,immunomodulation-based strategies may be a very promising tool in regenerative dentistry.展开更多
The current World Health Organization classification system of primary brain tumors is solely based on morphologic criteria. However, there is accumulating evidence that tumors with similar histology have distinct mol...The current World Health Organization classification system of primary brain tumors is solely based on morphologic criteria. However, there is accumulating evidence that tumors with similar histology have distinct molecular signatures that significantly impact treatment response and survival. Recent practice-changing clinical trials have defined a role for routine assessment of O-6-methylguanine-DNA methyltransferase(MGMT) promoter methylation in glioblastoma patients, especially in the elderly, and 1p and 19q codeletions in patients with anaplastic glial tumors. Recently discovered molecular alterations including mutations in IDH-1/2, epidermal growth factor receptor(EGFR), and BRAF also have the potential to become targets for future drug development. This article aims to summarize current knowledge on the molecular biology of high-grade gliomas relevant to daily practice.展开更多
Substantial evidence exists that in addition to the well-known complications of diabetes, increased fracture risk is an important morbidity. This risk is probably due to altered bone properties in diabetes. Circulatin...Substantial evidence exists that in addition to the well-known complications of diabetes, increased fracture risk is an important morbidity. This risk is probably due to altered bone properties in diabetes. Circulating biochemical markers of bone turnover have been found to be decreased in type 2 diabetes (T2D) and may be predictive of fractures independently of bone mineral density (BMD). Serum sclerostin levels have been found to be increased in T2D and appear to be predictive of fracture risk independent of BMD. Bone imaging technologies, including trabecular bone score (TBS) and quantitative CT testing have revealed differences in diabetic bone as compared to non-diabetic individuals. Specifically, high resolution peripheral quantitative CT (HRpQCT) imaging has demonstrated increased cortical porosity in diabetic postmenopausal women. Other factors such as bone marrow fat saturation and advanced glycation endproduct (AGE) accumulation might also relate to bone cell function and fracture risk in diabetes. These data have increased our understanding of how T2D adversely impacts both bone metabolism and fracture risk.展开更多
Portal hypertension(PH),a common complication of liver cirrhosis,results in development of esophageal varices.When esophageal varices rupture,they cause significant upper gastrointestinal bleeding with mortality rates...Portal hypertension(PH),a common complication of liver cirrhosis,results in development of esophageal varices.When esophageal varices rupture,they cause significant upper gastrointestinal bleeding with mortality rates up to 20%despite state-of-the-art treatment.Thus,prophylactic measures are of utmost importance to improve outcomes of patients with PH.Several high-quality studies have demonstrated that non-selective beta blockers(NSBBs)or endoscopic band ligation(EBL)are effective for primary prophylaxis of variceal bleeding.In secondary prophylaxis,a combination of NSBB+EBL should be routinely used.Once esophageal varices develop and variceal bleeding occurs,standardized treatment algorithms should be followed to minimize bleeding-associated mortality.Special attention should be paid to avoidance of overtransfusion,early initiation of vasoconstrictive therapy,prophylactic antibiotics and early endoscopic therapy.Pre-emptive transjugular intrahepatic portosystemic shunt should be used in all Child C10-C13 patients experiencing variceal bleeding,and potentially in Child B patients with active bleeding at endoscopy.The use of carvedilol,safety of NSBBs in advanced cirrhosis(i.e.with refractory ascites)and assessment of hepatic venous pressure gradient response to NSBB is discussed.In the present review,we give an overview on the rationale behind the latest guidelines and summarize key papers that have led to significant advances in the field.展开更多
Studying physiological and pathophysiological mechanisms in the liver on a molecular basis is a challenging task.During two dimensional(2D) culture conditions hepatocytes dedifferentiate rapidly by losing metabolic fu...Studying physiological and pathophysiological mechanisms in the liver on a molecular basis is a challenging task.During two dimensional(2D) culture conditions hepatocytes dedifferentiate rapidly by losing metabolic functions and structural integrity.Hence,inappropriate 2D hepatocellular models hamper studies on the xenobiotic metabolism of the liver which strongly influences drug potency.Also,the lack of effective therapies against hepatocellular carcinoma shows the urgent need for robust models to investigate liver functions in a defined hepatic microenvironment.Here,we summarize and discuss three-dimensional cultures of hepatocytes,herein referred to as hepatospheres,which provide versatile tools to investigate hepatic metabolism,stemness and cancer development.展开更多
AIM: To investigate several complications like persistent radial head dislocation, forearm deformity, elbow stiffness and nerve palsies, associated with radial head fractures. METHODS: This study reviewed the clinical...AIM: To investigate several complications like persistent radial head dislocation, forearm deformity, elbow stiffness and nerve palsies, associated with radial head fractures. METHODS: This study reviewed the clinical records and trauma database of this level Ⅰ Trauma Center and identified all patients with fractures of the radial head and neck who where admitted between 2000 and 2010. An analysis of clinical records revealed 1047 patients suffering from fractures of the radial head or neck classified according to Mason. For clinical examination, range of motion, local pain and overall outcome were assessed. RESULTS: The incidence of one-sided fractures was 99.2% and for simultaneous bilateral fractures 0.8%. Non-operative treatment was performed in 90.4%(n = 947) of the cases, surgery in 9.6%(n = 100). Bony union was achieved in 99.8%(n = 1045) patients. Full satisfaction was achieved in 59%(n = 615) of the patients. A gender related significant difference(P = 0.035) in Mason type distribution-type Ⅲ fractures were more prominent in male patients vs type Ⅳ fractures in female patients-was observed in our study population. CONCLUSION: Mason typeⅠfractures can be treated safe conservatively with good results. In type Ⅱ to Ⅳ surgical intervention is usually considered to be indicated.展开更多
The aim of the present study was to assess if semen quality declines during in vitro fertilization (IVF) and whether or not this phenomenon is triggered by chronic male stress. In order to test this hypothesis, we f...The aim of the present study was to assess if semen quality declines during in vitro fertilization (IVF) and whether or not this phenomenon is triggered by chronic male stress. In order to test this hypothesis, we first investigated a retrospective cohort of 155 male IVF patients (testing cohort). Subsequently, we started a prospective cohort study in men undergoing their first IVF and assessed semen quality and subjective male chronic stress using a validated tool, i.e. the Fertility Problem Inventory (FPI) questionnaire. The association between stress and sperm quality decline measured 4-6weeks before the start of IVF (T1) and at the day of oocyte retrieval (T2) was the primary outcome. Live birth rate, first trimester abortion and rate of poor responders were secondary outcomes. In the testing cohort, mean progressive motility, but not mean sperm density significantly declined. There were 78/154 (51%) men who showed a decline in semen density and 50/154 (32%) men who showed a decline in progressive motility. In the validation cohort, progressive motility declined, whereas, sperm density increased from T1 to T2. Of 78 men, 27 men had increased stress (FPI-score 〉 146). Sperm density and progressive motility were not significantly different in men with and without stress. However, in the presence of male stress, couples had a higher rate of poor responders, miscarriages and a lower rate of live births. Subjective stress is not associated with a decline in semen quality observed during IVF but may be associated with adverse ore^nancv outcome.展开更多
Using two-colour flow cytometry>200 antibodies submitted to the 8^(th) International Workshop of Human Leukocyte Differentiation Antigens(HLDA8)have been analyzed for their reactivity with resting and activated CD2...Using two-colour flow cytometry>200 antibodies submitted to the 8^(th) International Workshop of Human Leukocyte Differentiation Antigens(HLDA8)have been analyzed for their reactivity with resting and activated CD203c^(+)basophils.Four antibodies either non-reactive or weakly reactive with resting basophils exhibited an increased reactivity with basophils activated by anti-IgE-mediated cross-linking of the high affinity IgE receptor(FcεRI).These include antibod-ies against CD164(WS-80160,clone N6B6 and WS-80162,clone 67D2),as well as two reagents with previously unknown specificities that were identified as CD13(WS-80274,clone A8)and CD107a(WS-80280,clone E63-880).The activation patterns followed either the“CD203c-like”or“CD63-like”activation profile.The CD203c profile is characterized by a rapid and significant upregulation(of CD13,CD164,and CD203c),reaching maximum levels after 5-15 min of stimulation.The phosphoinositide-3-kinase(PI3K)-specific inhibitor wortmannin inhibited the upregulation of these markers whereas 12-O-tetradecanoyl-phorbol-13-acetate(TPA)induced a rapid and FcεRI-independent upregulation within 1-2 min.In the CD63 profile,maximum upregulation(of CD63 and CD107a)was detected only after 20-40 min,and upregulation by TPA reached maximum levels after 60 min.In summary,our data identify CD13,CD107a,and CD164 as novel basophil-activation antigens.Based on time kinetics of upregulation,we hypothesize that molecules of the“CD203c group”and the“CD63 group”are linked to two different mechanisms of basophil activation.展开更多
AIM: To evaluate a possible association between thevarious levels of obesity and peri-operative characteristics of the procedure in patients who underwent endoprosthetic joint replacement in hip and knee joints. METHO...AIM: To evaluate a possible association between thevarious levels of obesity and peri-operative characteristics of the procedure in patients who underwent endoprosthetic joint replacement in hip and knee joints. METHODS: We hypothesized that obese patients were treated for later stage of osteoarthritis, that more conservative implants were used, and the intraand perioperative complications increased for such patients. We evaluated all patients with body mass index(BMI) ≥ 25 who were treated in our institution from January 2011 to September 2013 for a primary total hip arthroplasty(THA) or total knee arthroplasty(TKA). Patients were split up by the levels of obesity according to the classification of the World Health Organization. Average age at the time of primary arthroplasty, preoperative Harris Hip Score(HHS), Hospital for Special Surgery score(HSS), gender, type of implanted prosthesis, and intra-and postoperative complications were evaluated.RESULTS: Six thousand and seventy-eight patients with a BMI ≥ 25 were treated with a primary THA or TKA. Age decreased significantly(P < 0.001) by increasing obesity in both the THA and TKA. HHS and HSS were at significantly lower levels at the time of treatment in the super-obese population(P < 0.001). Distribution patterns of the type of endoprostheses used changed with an increasing BMI. Peri- and postoperative complications were similar in form and quantity to those of the normal population. CONCLUSION: Higher BMI leads to endoprosthetic treatment in younger age, which is carried out at significantly lower levels of preoperative joint function.展开更多
文摘Objective:To provide a comprehensive review on the existing literature on medical management of urolithiasis.Methods:A thorough literature review was performed using Medline,PubMed/PMC,Embase,and the Cochrane Database of Systematic Reviews up to December 2022 to identify publications on the medical management of urolithiasis.Studies that assessed dietary and pharmacologic management of urolithiasis were reviewed;studies on medical expulsive therapy were not included in this review.Results:Medical management of urolithiasis ranges from the prophylactic management of kidney stone disease to dissolution therapies.While most treatment concepts have been long established,large randomized controlled trials are scarce.Dietary modification and increased fluid intake remain cornerstones in the conservative management of urolithiasis.A major limitation for medical management of urolithiasis is poor patient compliance.Conclusion:Medical management of urolithiasis is more important in patients with recurrent urolithiasis and patients with metabolic abnormalities putting them at higher risk of developing stones.Although medical management can be effective in limiting stone recurrence,medical interventions often fail due to poor compliance.
基金supported by the Lorenz B?hler Fonds,#2/19 (obtained by the Neuroregeneration Group,Ludwig Boltzmann Institute for Traumatology)the City of Vienna project ImmunTissue,MA23#30-11 (obtained by the Department Life Science Engineering,University of Applied Sciences Technikum Wien)。
文摘Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.
文摘Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural regeneration.Both intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following injury.At the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to regenerate.Recent works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of regeneration.The role of glia in neuron regeneration has long been studied.
文摘BACKGROUND Healthcare professionals need to be prepared to promote healthy lifestyles and care for patients.By focusing on what students should be able to perform one day as clinicians,we can bridge the gap between mere theoretical knowledge and its practical application.Gender aspects in clinical medicine also have to be considered when speaking of personalized medicine and learning curricula.AIM To determine sets of intellectual,personal,social,and emotional abilities that comprise core qualifications in medicine for performing well in anamnesis-taking,in order to identify training needs.METHODS An analysis of training clinicians’conceptions with respect to optimal medical history taking was performed.The chosen study design also aimed to assess gender effects.Structured interviews with supervising clinicians were carried out in a descriptive study at the Medical University of Vienna.Results were analyzed by conducting a qualitative computer-assisted content analysis of the interviews.Inductive category formation was applied.The main questions posed to the supervisors dealt with(1)Observed competencies of students in medical history taking;and(2)The supervisor’s own conceptions of"ideal medical history taking".RESULTS A total of 33 training clinicians(n=33),engaged in supervising medical students according to the MedUni Vienna’s curriculum standards,agreed to be enrolled in the study and met inclusion criteria.The qualitative content analysis revealed the following themes relevant to taking an anamnesis:(1)Knowledge;(2)Soft skills(relationship-building abilities,trust,and attitude);(3)Methodical skills(structuring,precision,and completeness of information gathering);and(4)Environmental/contextual factors(language barrier,time pressure,interruptions).Overall,health care professionals consider empathy and attitude as critical features concerning the quality of medical history taking.When looking at physicians’theoretical conceptions,more general practitioners and psychiatrists mentioned attitude and empathy in the context of"ideal medical history taking",with a higher percentage of females.With respect to observations of students’history taking,a positive impact from attitude and empathy was mainly described by male health care professionals,whereas no predominance of specialty was found.Representatives of general medicine and internal medicine,when observing medical students,more often emphasized a negative impact on history taking when students lacked attitude or showed non-empathetic behavior;no gender-specific difference was detected for this finding.CONCLUSION The analysis reveals that for clinicians engaged in medical student education,only a combination of skills,including adequate knowledge and methodical implementations,is supposed to guarantee acceptable performance.This study’s findings support the importance of concepts like relationship building,attitude,and empathy.However,there may be contextual factors in play as well,and transference of theoretical concepts into the clinical setting might prove challenging.
文摘The Kirsten rat sarcoma virus—son of sevenless 1(KRAS-SOS1)axis drives tumor growth preferentially in pancreatic,colon,and lung cancer.Now,KRAS G12C mutated tumors can be successfully treated with inhibitors that covalently block the cysteine of the switch II binding pocket of KRAS.However,the range of other KRAS mutations is not amenable to treatment and the G12C-directed agents Sotorasib and Adragrasib show a response rate of only approximately 40%,lasting for a mean period of 8 months.One approach to increase the efficacy of inhibitors is their inclusion into proteolysis-targeting chimeras(PROTACs),which degrade the proteins of interest and exhibit much higher antitumor activity through multiple cycles of activity.Accordingly,PROTACs have been developed based on KRAS-or SOS1-directed inhibitors coupled to either von Hippel-Lindau(VHL)or Cereblon(CRBN)ligands that invoke the proteasomal degradation.Several of these PROTACs show increased activity in vitro and in vivo compared to their cognate inhibitors but their toxicity in normal tissues is not clear.The CRBN PROTACs containing thalidomide derivatives cannot be tested in experimental animals.Resistance to such PROTACS arises through downregulation or inactivation of CRBN or factors of the functional VHL E3 ubiquitin ligase.Although highly active KRAS and SOS1 PROTACs have been formulated their clinical application remains difficult.
文摘Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers worldwide.The main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma virus.Approved therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second primaries.The availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented pace.Initially,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk tumors.More recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within tumors.This review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.
文摘Objective:Transurethral resection of bladder tumor is one of the most common everyday urological procedures.This kind of surgery demands a set of skills that need training and experience.In this review,we aimed to investigate the current literature to find out if simulators,phantoms,and other training models could be used as a tool for teaching urologists.Methods:A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement and the recommendations of the European Association of Urology guidelines for conducting systematic reviews.Fifteen out of 932 studies met our inclusion criteria and are presented in the current review.Results:The UroTrainer(Karl Storz GmbH,Tuttlingen,Germany),a virtual reality training simulator,achieved positive feedback and an excellent face and construct validity by the participants.The inspection of bladder mucosa,blood loss,tumor resection,and procedural time was improved after the training,especially for inexperienced urologists and medical students.The construct validity of UroSim®(VirtaMed,Zurich,Switzerland)was established.SIMBLA simulator(Samed GmbH,Dresden,Germany)was found to be a realistic and useful tool by experts and urologists with intermediate experience.The test objective competency model based on SIMBLA simulator could be used for evaluating urologists.The porcine model of the Asian Urological Surgery Training and Education Group also received positive feedback by the participants that tried it.The Simulation and Technology Enhanced Learning Initiative Project had an extraordinary face and content validity,and 60%of participants would like to use the simulators in the future.The 5-day multimodal training curriculum“Boot Camp”in the United Kingdom achieved an increase of the level of confidence of the participants that lasted months after the project.Conclusion:Simulators and courses or curricula based on a simulator training could be a valuable learning tool for any surgeon,and there is no doubt that they should be a part of every urologist's technical education.
文摘Atrial fibrillation(AF)is a major public health problem and poses a substantial economic burden on healthcare systems worldwide.[1-4]The emergency department(ED)serves as the first point of contact with the healthcare system and plays a key role in the management of patients with AF,which accounts for 3%-10%of all hospital admissions.[5]Treatment plans are often discussed and initiated at the ED.
文摘Objective:To evaluate the feasibility and the safety of medial non-papillary percutaneous nephrolithotomy(npPCNL)for the management of large proximal ureteral stones.Methods:We evaluated prospectively collected data of 37 patients with large proximal ureteral stones more than 1.5 cm in diameter treated by prone npPCNL.Depending on stone size,in-toto stone removal or lithotripsy using the Lithoclast®Trilogy(EMS Medical,Nyon,Switzerland)was performed.Perioperative parameters including operative time(from start of puncture to the skin suturing),stone extraction time(from the first insertion of the nephroscope to the extraction of all stone fragments),and the stone-free rate were evaluated.Results:Twenty-one males and 16 females underwent npPCNL for the management of large upper ureteral calculi.The median age and stone size of treated patients were 58(interquartile range[IQR]:51-69)years and 19.3(IQR:18.0-22.0)mm,respectively.The median operative time and stone extraction time were 25(IQR:21-29)min and 8(IQR:7-10)min,respectively.One case(2.7%)of postoperative bleeding and two cases(5.4%)of prolonged fever were managed conservatively.The stone-free rate at a 1-month follow-up was 94.6%.Conclusion:The npPCNL provides a straight route to the ureteropelvic junction and proximal ureter.Approaching from a dilated portion of the ureter under low irrigation pressure with larger diameter instruments results in effective and safe stone extraction within a few minutes.
文摘Objective:Only a few numbers of studies have been published on the use of abobotulinumtoxinA(Dysport®)in idiopathic detrusor overactivity(IDO).This study reported the long-term follow-up of women with IDO who were treated with intravesical Dysport®injections.Methods:Two hundred and thirty-six patients with IDO who had failed first-line conservative and antimuscarinic therapy received 500-900 units of Dysport®between April 2014 and July 2015.All patients were followed up for 5 years after their initial injection and interviewed on the phone.Results:A total of 236 women with IDO aged from 18 years to 84 years(mean±standard deviation:49.6±15.9 years)were included in our study.The median follow-up time for patients was 36.5(range:10-70)months,and the median recovery time after injection was 18.5(range:0-70)months.A total of 83(35.2%)patients stated that they had subjective improvement of their symptoms whereas 84(35.6%)patients did not report any improvement in symptoms.The initial International Consultation on Incontinence Questionnaire Overactive Bladder mean score was 6.9(standard deviation 3.4).There was a positive association between the median recovery time and the components of the International Consultation on Incontinence Questionnaire Overactive Bladder questionnaire.Conclusion:In a sub-population of overactive bladder patients with IDO who have failed first-line therapy,a single intravesical Dysport®injection can resolve patient symptoms completely or reduce the symptoms to an acceptable level that can be controlled with antimuscarinics or re-injection on demands.
文摘Objective: To analyze outcomes and complications of cytoreductive prostatectomy (CRP) for oligometastatic prostate cancer (PCa) in order to elucidate its role in this space.Methods: We performed a systematic literature search using three databases (Medline, Scopus, and Web of Science). The primary endpoints were oncologic outcomes. The secondary endpoints were complication rates and functional results.Results: In all studies, overall survival was better or at least comparable variable in the groups with CRP compared to no local treatment. The greatest benefit from CRP in 5-year overall survival in one study was 67.4% for CRP versus 22.5% for no local treatment. Cancer-specific survival (CSS) showed the same trend. Several authors found significant benefits from CSS in the CRP group: from 79% vs. 46% to 100% vs. 61%. CRP was a predictor of better CSS (hazard ratio 0.264, p=0.004). Positive surgical margin rates differed widely from 28.6% to 100.0%. Urinary continence in CRP versus RP for localized PCa was significantly lower (57.4% vs. 90.8%, p<0.0001). Severe incontinence occurred seldom (2.5%-18.6%). Total complication rates after CRP differed widely, from 7.0% to 43.6%. Rates of grades 1 and 2 events prevailed. Patients on ADT alone also showed a considerable number of complications varying from 5.9% to 57.7%.Conclusion: CRP improves medium-term cancer control in patients with oligometastatic PCa. The morbidity and complication rates of this surgery are comparable with other approaches, but postoperative incontinence rate is higher compared with RP for localized disease.
基金Supported by Austrian Science Fund,No.Project 29440(to Andrukhov O)
文摘Mesenchymal stem cells(MSCs)are considered as an attractive tool for tissue regeneration and possess a strong immunomodulatory ability.Dental tissuederived MSCs can be isolated from different sources,such as the dental pulp,periodontal ligament,deciduous teeth,apical papilla,dental follicles and gingiva.According to numerous in vitro studies,the effect of dental MSCs on immune cells might depend on several factors,such as the experimental setting,MSC tissue source and type of immune cell preparation.Most studies have shown that the immunomodulatory activity of dental MSCs is strongly upregulated by activated immune cells.MSCs exert mostly immunosuppressive effects,leading to the dampening of immune cell activation.Thus,the reciprocal interaction between dental MSCs and immune cells represents an elegant mechanism that potentially contributes to tissue homeostasis and inflammatory disease progression.Although the immunomodulatory potential of dental MSCs has been extensively investigated in vitro,its role in vivo remains obscure.A few studies have reported that the MSCs isolated from inflamed dental tissues have a compromised immunomodulatory ability.Moreover,the expression of some immunomodulatory proteins is enhanced in periodontal disease and even shows some correlation with disease severity.MSC-based immunomodulation may play an essential role in the regeneration of different dental tissues.Therefore,immunomodulation-based strategies may be a very promising tool in regenerative dentistry.
文摘The current World Health Organization classification system of primary brain tumors is solely based on morphologic criteria. However, there is accumulating evidence that tumors with similar histology have distinct molecular signatures that significantly impact treatment response and survival. Recent practice-changing clinical trials have defined a role for routine assessment of O-6-methylguanine-DNA methyltransferase(MGMT) promoter methylation in glioblastoma patients, especially in the elderly, and 1p and 19q codeletions in patients with anaplastic glial tumors. Recently discovered molecular alterations including mutations in IDH-1/2, epidermal growth factor receptor(EGFR), and BRAF also have the potential to become targets for future drug development. This article aims to summarize current knowledge on the molecular biology of high-grade gliomas relevant to daily practice.
文摘Substantial evidence exists that in addition to the well-known complications of diabetes, increased fracture risk is an important morbidity. This risk is probably due to altered bone properties in diabetes. Circulating biochemical markers of bone turnover have been found to be decreased in type 2 diabetes (T2D) and may be predictive of fractures independently of bone mineral density (BMD). Serum sclerostin levels have been found to be increased in T2D and appear to be predictive of fracture risk independent of BMD. Bone imaging technologies, including trabecular bone score (TBS) and quantitative CT testing have revealed differences in diabetic bone as compared to non-diabetic individuals. Specifically, high resolution peripheral quantitative CT (HRpQCT) imaging has demonstrated increased cortical porosity in diabetic postmenopausal women. Other factors such as bone marrow fat saturation and advanced glycation endproduct (AGE) accumulation might also relate to bone cell function and fracture risk in diabetes. These data have increased our understanding of how T2D adversely impacts both bone metabolism and fracture risk.
基金Supported by the Austrian Science Fund FWF,No.J4396the Christian Doppler Society/Boehringer Ingelheim.
文摘Portal hypertension(PH),a common complication of liver cirrhosis,results in development of esophageal varices.When esophageal varices rupture,they cause significant upper gastrointestinal bleeding with mortality rates up to 20%despite state-of-the-art treatment.Thus,prophylactic measures are of utmost importance to improve outcomes of patients with PH.Several high-quality studies have demonstrated that non-selective beta blockers(NSBBs)or endoscopic band ligation(EBL)are effective for primary prophylaxis of variceal bleeding.In secondary prophylaxis,a combination of NSBB+EBL should be routinely used.Once esophageal varices develop and variceal bleeding occurs,standardized treatment algorithms should be followed to minimize bleeding-associated mortality.Special attention should be paid to avoidance of overtransfusion,early initiation of vasoconstrictive therapy,prophylactic antibiotics and early endoscopic therapy.Pre-emptive transjugular intrahepatic portosystemic shunt should be used in all Child C10-C13 patients experiencing variceal bleeding,and potentially in Child B patients with active bleeding at endoscopy.The use of carvedilol,safety of NSBBs in advanced cirrhosis(i.e.with refractory ascites)and assessment of hepatic venous pressure gradient response to NSBB is discussed.In the present review,we give an overview on the rationale behind the latest guidelines and summarize key papers that have led to significant advances in the field.
基金Supported by the Austrian Science Fund,FWF,NO.P19598-B13 and SFB F28,the"Hochschuljubilumsstiftung der Stadt Wien",the Herzfelder Family Foundationthe European Union,FP7 Health Research,NO.HEALTH-F4-2008-202047
文摘Studying physiological and pathophysiological mechanisms in the liver on a molecular basis is a challenging task.During two dimensional(2D) culture conditions hepatocytes dedifferentiate rapidly by losing metabolic functions and structural integrity.Hence,inappropriate 2D hepatocellular models hamper studies on the xenobiotic metabolism of the liver which strongly influences drug potency.Also,the lack of effective therapies against hepatocellular carcinoma shows the urgent need for robust models to investigate liver functions in a defined hepatic microenvironment.Here,we summarize and discuss three-dimensional cultures of hepatocytes,herein referred to as hepatospheres,which provide versatile tools to investigate hepatic metabolism,stemness and cancer development.
文摘AIM: To investigate several complications like persistent radial head dislocation, forearm deformity, elbow stiffness and nerve palsies, associated with radial head fractures. METHODS: This study reviewed the clinical records and trauma database of this level Ⅰ Trauma Center and identified all patients with fractures of the radial head and neck who where admitted between 2000 and 2010. An analysis of clinical records revealed 1047 patients suffering from fractures of the radial head or neck classified according to Mason. For clinical examination, range of motion, local pain and overall outcome were assessed. RESULTS: The incidence of one-sided fractures was 99.2% and for simultaneous bilateral fractures 0.8%. Non-operative treatment was performed in 90.4%(n = 947) of the cases, surgery in 9.6%(n = 100). Bony union was achieved in 99.8%(n = 1045) patients. Full satisfaction was achieved in 59%(n = 615) of the patients. A gender related significant difference(P = 0.035) in Mason type distribution-type Ⅲ fractures were more prominent in male patients vs type Ⅳ fractures in female patients-was observed in our study population. CONCLUSION: Mason typeⅠfractures can be treated safe conservatively with good results. In type Ⅱ to Ⅳ surgical intervention is usually considered to be indicated.
文摘The aim of the present study was to assess if semen quality declines during in vitro fertilization (IVF) and whether or not this phenomenon is triggered by chronic male stress. In order to test this hypothesis, we first investigated a retrospective cohort of 155 male IVF patients (testing cohort). Subsequently, we started a prospective cohort study in men undergoing their first IVF and assessed semen quality and subjective male chronic stress using a validated tool, i.e. the Fertility Problem Inventory (FPI) questionnaire. The association between stress and sperm quality decline measured 4-6weeks before the start of IVF (T1) and at the day of oocyte retrieval (T2) was the primary outcome. Live birth rate, first trimester abortion and rate of poor responders were secondary outcomes. In the testing cohort, mean progressive motility, but not mean sperm density significantly declined. There were 78/154 (51%) men who showed a decline in semen density and 50/154 (32%) men who showed a decline in progressive motility. In the validation cohort, progressive motility declined, whereas, sperm density increased from T1 to T2. Of 78 men, 27 men had increased stress (FPI-score 〉 146). Sperm density and progressive motility were not significantly different in men with and without stress. However, in the presence of male stress, couples had a higher rate of poor responders, miscarriages and a lower rate of live births. Subjective stress is not associated with a decline in semen quality observed during IVF but may be associated with adverse ore^nancv outcome.
基金This work was supported by a grant from the Deutsche Forschungsgemeinschaft,SFB 510-A1(F.H.and H.-J.B.),by the fortueneproject F1282700 of the univer-sity of Tuebingen(H.-J.B)by the Fonds zur Forderung der wissnschaflichen Forschung in Osterreich,SFB grant-project 018/09(P.V.).
文摘Using two-colour flow cytometry>200 antibodies submitted to the 8^(th) International Workshop of Human Leukocyte Differentiation Antigens(HLDA8)have been analyzed for their reactivity with resting and activated CD203c^(+)basophils.Four antibodies either non-reactive or weakly reactive with resting basophils exhibited an increased reactivity with basophils activated by anti-IgE-mediated cross-linking of the high affinity IgE receptor(FcεRI).These include antibod-ies against CD164(WS-80160,clone N6B6 and WS-80162,clone 67D2),as well as two reagents with previously unknown specificities that were identified as CD13(WS-80274,clone A8)and CD107a(WS-80280,clone E63-880).The activation patterns followed either the“CD203c-like”or“CD63-like”activation profile.The CD203c profile is characterized by a rapid and significant upregulation(of CD13,CD164,and CD203c),reaching maximum levels after 5-15 min of stimulation.The phosphoinositide-3-kinase(PI3K)-specific inhibitor wortmannin inhibited the upregulation of these markers whereas 12-O-tetradecanoyl-phorbol-13-acetate(TPA)induced a rapid and FcεRI-independent upregulation within 1-2 min.In the CD63 profile,maximum upregulation(of CD63 and CD107a)was detected only after 20-40 min,and upregulation by TPA reached maximum levels after 60 min.In summary,our data identify CD13,CD107a,and CD164 as novel basophil-activation antigens.Based on time kinetics of upregulation,we hypothesize that molecules of the“CD203c group”and the“CD63 group”are linked to two different mechanisms of basophil activation.
文摘AIM: To evaluate a possible association between thevarious levels of obesity and peri-operative characteristics of the procedure in patients who underwent endoprosthetic joint replacement in hip and knee joints. METHODS: We hypothesized that obese patients were treated for later stage of osteoarthritis, that more conservative implants were used, and the intraand perioperative complications increased for such patients. We evaluated all patients with body mass index(BMI) ≥ 25 who were treated in our institution from January 2011 to September 2013 for a primary total hip arthroplasty(THA) or total knee arthroplasty(TKA). Patients were split up by the levels of obesity according to the classification of the World Health Organization. Average age at the time of primary arthroplasty, preoperative Harris Hip Score(HHS), Hospital for Special Surgery score(HSS), gender, type of implanted prosthesis, and intra-and postoperative complications were evaluated.RESULTS: Six thousand and seventy-eight patients with a BMI ≥ 25 were treated with a primary THA or TKA. Age decreased significantly(P < 0.001) by increasing obesity in both the THA and TKA. HHS and HSS were at significantly lower levels at the time of treatment in the super-obese population(P < 0.001). Distribution patterns of the type of endoprostheses used changed with an increasing BMI. Peri- and postoperative complications were similar in form and quantity to those of the normal population. CONCLUSION: Higher BMI leads to endoprosthetic treatment in younger age, which is carried out at significantly lower levels of preoperative joint function.