Prognostic influence of mechanical cardiopulmonary resuscitation on survival in patients with out-of-hospital cardiac arrest undergoing ECPR on VA-ECMO.

Introduction: The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in extracorporeal cardiopulmonary resuscitation (ECPR) in selected patients after out-of-hospital cardiac arrest (OHCA) is an established method if return of spontaneous circulation cannot be achieved. Automated chest compression devices (ACCD) facilitate transportation of patients under ongoing CPR and might improve outcome. We thus sought to evaluate prognostic influence of mechanical CPR using ACCD in patients presenting with OHCA treated with ECPR including VA-ECMO. Methods: We retrospectively analyzed data of 171 consecutive patients treated for OHCA using ECPR in our cardiac arrest center from the years 2016 to 2022. A Cox proportional hazards model was used to identify characteristics related with survival. Results: Of the 171 analyzed patients (84% male, mean age 56 years), 12% survived the initial hospitalization with favorable neurological outcome. The primary reason for OHCA was an acute coronary event (72%) followed by primary arrhythmia (9%) and non-ischemic cardiogenic shock (6.7%). In most cases, the collapse was witnessed (83%) and bystander CPR was performed (83%). The median time from collapse to VA-ECMO was 81 min (Q1: 69 min, Q3: 98 min). No survival benefit was seen for patients resuscitated using ACCD. Patients in whom an ACCD was used presented with overall longer times from collapse to ECMO than those who were resuscitated manually [83 min (Q1: 70 min, Q3: 98 min) vs. 69 min (Q1: 57 min, Q3: 84 min), p = 0.004]. Conclusion: No overall survival benefit of the use of ACCD before ECPR is established was found, possibly due to longer overall CPR duration. This may arguably be because of the limited availability of ACCD in pre-clinical paramedic service at the time of observation. Increasing the availability of these devices might thus improve treatment of OHCA, presumably by providing efficient CPR during transportation and transfer.

Gender disparities in patients undergoing extracorporeal cardiopulmonary resuscitation.

Introduction: The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in extracorporeal cardiopulmonary resuscitation (eCPR) has emerged as a treatment option for selected patients who are experiencing refractory cardiac arrest (CA). In the light of increasing availability, the analyses of outcome-relevant predisposing characteristics are of growing importance. We evaluated the prognostic influence of gender in patients presenting with out-of-hospital cardiac arrest (OHCA) treated with eCPR. Methods: We retrospectively analysed the data of 377 consecutive patients treated for OHCA using eCPR in our cardiac arrest centre from January 2016 to December 2022. The primary outcome was defined as the survival of patients until they were discharged from the hospital, with a favourable neurological outcome [cerebral performance category (CPC) score of ≤2]. Statistical analyses were performed using baseline comparison, survival analysis, and multivariable analyses. Results: Out of the 377 patients included in the study, 69 (21%) were female. Female patients showed a lower prevalence rate of pre-existing coronary artery disease (48% vs. 75%, p < 0.001) and cardiomyopathy (17% vs. 34%, p = 0.01) compared with the male patients, while the mean age and prevalence rate of other cardiovascular risk factors were balanced. The primary reason for CA differed significantly (female: coronary event 45%, pulmonary embolism 23%, cardiogenic shock 17%; male: coronary event 70%, primary arrhythmia 10%, cardiogenic shock 10%; p = 0.001). The prevalence rate of witnessed collapse (97% vs. 86%; p = 0.016) and performance of bystander CPR (94% vs. 85%; p = 0.065) was higher in female patients. The mean time from collapse to the initiation of eCPR did not differ between the two groups (77 ± 39 min vs. 80 ± 37 min; p = 0.61). Overall, female patients showed a higher percentage of neurologically favourable survival (23% vs. 12%; p = 0.027) despite a higher prevalence of procedure-associated bleeding complications (33% vs. 16%, p = 0.002). The multivariable analysis identified a shorter total CPR duration (p = 0.001) and performance of bystander CPR (p = 0.03) to be associated with superior neurological outcomes. The bivariate analysis showed relevant interactions between gender and body mass index (BMI). Conclusion: Our analysis suggests a significant survival benefit for female patients who obtain eCPR, possibly driven by a higher prevalence of witnessed collapse and bystander CPR. Interestingly, the impact of patient age and BMI on neurologically favourable outcome was higher in female patients than in male patients, warranting further investigation.

Benzimidazole resistant Haemonchus contortus in a wildlife park.

INTRODUCTION: Anthelmintic resistance (AR) of ruminant gastrointestinal nematodes (GINs) constitutes a major problem worldwide. Among GINs, the abomasal blood-feeding parasite Haemonchus contortus is particularly pathogenic and may show resistance against all major anthelmintic substance classes. In the present study, the death of a 1,5 year-old European bison (Bison bonasus) from a German wildlife park due to haemonchosis despite frequent anthelmintic treatment of the herd with fenbendazole as well as doramectin prompted an investigation regarding AR. Pooled faecal samples were collected from four different bison groups as well as from mouflons (Ovis orientalis), elk (Alces alces), reindeer (Rangifer tarandus), sika deer (Cervus nippon), Persian fallow deer (Dama mesopotamica) and red deer (Cervus elaphus) housed by the wildlife park. After coproscopical examination, faecal larval cultures were established. Haemonchus contortus-positive larval cultures were further examined for genetic polymorphisms associated with benzimidazole resistance at codons 167 and 200 of the ß-tubulin isotype 1 gene by real-time pyrosequencing. Infections with H. contortus were detected in all four bison groups, as well as in mouflons. In five samples, representing two bison groups and the mouflons, the frequency of the resistance-associated single-nucleotide polymorphism (SNP) at codon 200 was 100%. In contrast, resistance-associated SNPs were not detected at codon 167. In addition, faecal egg counts from two bison before and 14 days after parenteral doramectin treatment indicated possible macrocyclic lactone resistance. Detection of anthelmintic resistant nematodes in these animals was especially concerning in the light of planned reintroduction into the wild. As helminth control in zoological gardens and wildlife parks relies mostly on anthelmintic treatment due to restricted possibilities regarding management practices such as rotational grazing, care should be taken to avoid underdosing or unnecessary frequent treatments facilitating the development of AR.

INTRODUCTION: La résistance aux anthelminthiques (RA) des nématodes gastro-intestinaux (NGI) des ruminants constitue un problème majeur dans le monde. Parmi les NGI, le parasite hématophage de la caillette Haemonchus contortus est particulièrement pathogène et peut montrer une résistance contre toutes les principales classes de substances anthelminthiques. Dans la présente étude, la mort d'un bison d'Europe de 1,5 ans (Bison bonasus) d'un parc animalier allemand en raison d'une hémonchose malgré un traitement anthelminthique fréquent du troupeau avec du fenbendazole ainsi que de la doramectine a incité une enquête sur la RA. Des échantillons de matières fécales regroupés ont été collectés auprès de quatre groupes de bisons différents ainsi que de mouflons (Ovis orientalis), de wapitis (Alces alces), de rennes (Rangifer tarandus), de cerfs sika (Cervus nippon), de daims de Perse (Dama mesopotamica) et de cerfs élaphes (Cervus elaphus) hébergés par le parc animalier. Après examen coproscopique, des cultures larvaires fécales ont été réalisées. Des cultures larvaires positives pour Haemonchus contortus ont été examinées plus avant pour les polymorphismes génétiques associés à la résistance au benzimidazole aux codons 167 et 200 du gène de l'isotype 1 de la ß-tubuline par pyroséquençage en temps réel. Des infections à H. contortus ont été détectées dans les quatre groupes de bisons, ainsi que chez les mouflons. Dans cinq échantillons, représentant deux groupes de bisons et les mouflons, la fréquence du polymorphisme mononucléotidique (SNP) associé à la résistance au codon 200 était de 100 %. En revanche, les SNP associés à la résistance n'ont pas été détectés au codon 167. De plus, le nombre d'œufs par gramme de fèces de deux bisons avant et 14 jours après le traitement parentéral à la doramectine a indiqué une possible résistance aux lactones macrocycliques. La détection de nématodes résistants aux anthelminthiques chez ces animaux était particulièrement préoccupante à la lumière de la réintroduction prévue dans la nature. Étant donné que le contrôle des helminthes dans les jardins zoologiques et les parcs animaliers repose principalement sur un traitement anthelminthique en raison des possibilités limitées concernant les pratiques de gestion telles que le pâturage en rotation, des précautions doivent être prises pour éviter un sous-dosage ou des traitements fréquents inutiles facilitant le développement de la RA.

Rising rates of hospital-onset Klebsiella spp. and Pseudomonas aeruginosa bacteraemia in NHS acute trusts in England: a review of national surveillance data, August 2020-February 2021.

Increases in hospital-onset Klebsiella spp. and Pseudomonas aeruginosa bacteraemia rates in England were observed between August 2020 and February 2021 to the highest levels recorded since the start of mandatory surveillance in April 2017. Cases were extracted from England's mandatory surveillance database for key Gram-negative bloodstream infections. Incidence rates for hospital-onset bacteraemia cases increased from 8.9 (N=255) to 14.9 (N=394) per 100,000 bed-days for Klebsiella spp. [incidence rate ratio (IRR) 1.7, P<0.001], and from 4.9 (N=139) to 6.2 (N=164) per 100,000 bed-days for P. aeruginosa (IRR 1.3, P<0.001) (August 2020-February 2021). These incidence rates were higher than the average rates observed during the same period in the previous 3 years. These trends coincided with an increase in the percentage of hospital-onset bacteraemia cases that were also positive for severe acute respiratory syndrome coronavirus-2.

Distribution of Borrelia burgdorferi s.l. and Borrelia miyamotoi in Ixodes tick populations in Northern Germany, co-infections with Rickettsiales and assessment of potential influencing factors.

To determine Borrelia spp. (Spirochaetales: Spirochaetaceae) prevalence and species distribution in Northern Germany, Ixodes ticks were sampled from April to October in 2018 and 2019 by the flagging method at three locations each in five regions. Analysis by quantitative real-time PCR of 3150 individual ticks revealed an overall prevalence of 30.6%, without significant differences between tick stages (31.7% positive adults, 28.6% positive nymphs). Significant differences were observed in seasonal infection rates, but not between regions, landscape types or sampling years. Analysis of co-infections with Rickettsiales indicated a negative association between Borrelia and Anaplasma phagocytophilum infection. The most frequent Borrelia species differentiated by Reverse Line Blot were B. afzelii and B. garinii/B. bavariensis, followed by B. valaisiana, B. burgdorferi sensu stricto, B. spielmanii and B. lusitaniae. Furthermore, B. miyamotoi was identified in 12.9% of differentiable samples. No effect of region nor landscape type on species composition was found, but significant variations in the distribution at the different sampling sites within a region were observed. The detected monthly fluctuations in prevalence and the differences in intra-regional Borrelia species distribution underline the importance of long-term and multi-location monitoring of Borrelia spp. in ticks as an essential part of public health assessment.

Treatment Algorithm for Pilon Fracture - Clinical and Radiological Results.

PURPOSE OF THE STUDY The aim of the present study was to evaluate the postoperative outcome of patients with pilon tibial fractures with a minimum follow-up of 24 months, treated according to a staged treatment algorithm. MATERIAL AND METHODS In total, 27 patients (mean age 43.6 ± 13 years, range 18-69) with a pilon tibial fracture and a minimum follow-up of 24 months were included in the study. Medical recordings (discharge documents and surgical reports) and radiographic examinations were analyzed. All enrolled patients were invited for a clinical and radiological follow-up examination (ROM, AOFAS hindfoot score, Kellgren score). The mean follow-up time was 44.5 ± 16 months (range 24-82). RESULTS In 21 cases a two-stage operative strategy with initial closed reduction and external fixation was necessary prior to definitive osteosynthesis. Overall, the patients scored 82.1 ± 20 points (range 30-100) in AOFAS hindfoot score, which represents a good clinical outcome. Patients with B-type fractures scored significantly better than those with C-type fractures. Patients with closed pilon tibial fractures reached significantly higher values in the AOFAS hindfoot score than those with open ones. Age and gender did not affect the functional outcome. Total ankle range of motion was 41° ± 10° for B-type fractures (range 20°-55°) and 35° ± 17° (range 0°-60°) for C-type fractures respectively (p > 0.05). Only five patients reached higher scores (Grade III) in Kellgren classification system. DISCUSSION Within the last decades, the therapeutic algorithm of pilon fractures underwent a paradigm shift; a two-stage protocol has prevailed today. However, the initial severity of the fracture in terms of initial absorbed energy, bony comminution and softtissue trauma still affects the outcome. Moreover, the necessity for bone grafting, as an indirect measurement of bone comminution and bone defects, resulted in higher degrees of osteoarthritis in the final follow-up. Higher initial soft-tissue injury also had an impact on the functional outcome of the patients, as patients with closed fractures scored better in AOFAS at the final follow-up. In order to counteract these risk factors and to reduce complications that define the outcome of these severe injuries, clearly defined surgical principles and standardized treatment protocols are needed. CONCLUSIONS The present study confirms the fact that meticulous planning, respect of the soft-tissues and choice of the optimal timepoint for the definitive osteosynthesis and overall treatment according to standardized protocols can optimize the outcome of this severe injury. Key words:pilon, distal tibia fracture, outcome, algorithm.

Barriers to participation in clinical trials: a physician survey.

Background: Clinical trials are vital for evidence-based cancer care. Oncologist engagement in clinical trials has an effect on patient recruitment, which in turn can affect trial success. Identifying barriers to clinical trial participation might enable interventions that could help to increase physician participation. Methods: To assess factors affecting physician engagement in oncology trials, a national survey was conducted using the online SurveyMonkey tool (SurveyMonkey, San Mateo, CA, U.S.A.; http://www.surveymonkey.com). Physicians associated with the Canadian Cancer Clinical Trials Network and the Canadian Cancer Trials Group were asked about their specialty, years of experience, barriers to participation, and motivating interventions, which included an open-ended question inviting survey takers to suggest interventions. Results: The survey collected 207 anonymous responses. Respondents were predominantly medical oncologists (46.4%), followed by radiation oncologists (24.6%). Almost 70% of the respondents had more than 10 years of experience. Significant time constraints included extra paperwork (77%), patient education (54%), and extended follow-up or clinic visits (53%). Timing of events within trials was also a barrier to participation (55%). Most respondents favoured clinical work credits (72%), academic credits (67%), a clinical trial alert system (75%), a regular meeting to review trial protocols (65%), and a screening log to aid in patient accrual (67%) as motivational strategies. Suggested interventions included increased support staff, streamlined regulatory burden, and provision of greater funding for trials and easier access to ancillary services. Conclusions: The present study confirms that Canadian oncologists are willing to participate in clinical research, but face multiple barriers to trial participation. Those barriers could be mitigated by the implementation of several interventions identified in the study.

A novel preventive therapy for paclitaxel-induced cognitive deficits: preclinical evidence from C57BL/6 mice.

Chemotherapy-induced central nervous system (CNS) neurotoxicity presents an unmet medical need. Patients often report a cognitive decline in temporal correlation to chemotherapy, particularly for hippocampus-dependent verbal and visuo-spatial abilities. We treated adult C57Bl/6 mice with 12 × 20 mg kg-1 paclitaxel (PTX), mimicking clinical conditions of dose-dense chemotherapy, followed by a pulse of bromodesoxyuridine (BrdU) to label dividing cells. In this model, mice developed visuo-spatial memory impairments, and we measured peak PTX concentrations in the hippocampus of 230 nm l-1, which was sevenfold higher compared with the neocortex. Histologic analysis revealed a reduced hippocampal cell proliferation. In vitro, we observed severe toxicity in slowly proliferating neural stem cells (NSC) as well as human neuronal progenitor cells after 2 h exposure to low nanomolar concentrations of PTX. In comparison, mature post-mitotic hippocampal neurons and cell lines of malignant cells were less vulnerable. In PTX-treated NSC, we observed an increase of intracellular calcium levels, as well as an increased activity of calpain- and caspase 3/7, suggesting a calcium-dependent mechanism. This cell death pathway could be specifically inhibited with lithium, but not glycogen synthase kinase 3 inhibitors, which protected NSC in vitro. In vivo, preemptive treatment of mice with lithium prevented PTX-induced memory deficits and abnormal adult hippocampal neurogenesis. In summary, we identified a molecular pathomechanism, which invokes PTX-induced cytotoxicity in NSC independent of cell cycle status. This pathway could be pharmacologically inhibited with lithium without impairing paclitaxel's tubulin-dependent cytostatic mode of action, enabling a potential translational clinical approach.

Worldwide prevalence of hypospadias.

INTRODUCTION: Hypospadias is a common congenital malformation. Surgical repair and management of the long-term consequences require a substantial amount of socioeconomic resources. It is generally accepted that genetic and environmental factors play a major role in the etiology of hypospadias. There have been contradictory reports on rising hypospadias rates, and regional and ethnical differences. The exact prevalence of hypospadias is of major interest for healthcare providers, clinical medicine, and research. OBJECTIVE: To review the literature regarding the worldwide prevalence of hypospadias. STUDY DESIGN: Pubmed, EMBASE and Google were systematically screened for: hypospadias, congenital malformation, anomaly, incidence, prevalence, and epidemiology. Exclusion criteria were surgical and risk-factor studies. To give an additional comprehensive overview, prevalence data were harvested from the Annual Report of the International Clearinghouse Centre for Birth Defects Surveillance and Research. Prevalence was reported as per 10,000 live births. RESULTS: Data were available from 1910 to 2013. The median study period was 9 years (range: 1-36 years). Approximately 90,255,200 births have been screened in all studies. The mean prevalence were: Europe 19.9 (range: 1-464), North America 34.2 (6-129.8), South America 5.2 (2.8-110), Asia 0.6-69, Africa 5.9 (1.9-110), and Australia 17.1-34.8. There were major geographical, regional, and ethnical differences, with an extreme heterogeneity of published studies. Numerous studies showed an increasing prevalence; on the other hand, there were a lot of contradictory data on the prevalence of hypospadias. The summary table shows contradictory data from the five largest international studies available. DISCUSSION: There was huge literature available on the prevalence of hypospadias. Most data derived from Europe and North America. Many methodological factors influenced the calculation of an accurate prevalence, and even more of the true changes in prevalence over time (no generally accepted and standardized definition of hypospadias, different monitoring systems, unclear efficiency of notification and data ascertainment, etc.). There was wide variation of prevalence according to countries and ethnicity, and there were conflicting data on the recent trends of prevalence. Moreover, there weren't any epidemiologic data available from many parts of the world. CONCLUSION: True prevalence of hypospadias and trends were difficult to estimate. For the future, to be able to assess the true prevalence of hypospadias and changes in prevalence collaboration of national and international prospective registers is recommended.

Induction of apoptosis in human cancer cells by targeting mitochondria with gold nanoparticles.

A major challenge in designing cancer therapies is the induction of cancer cell apoptosis, although activation of intrinsic apoptotic pathways by targeting gold nanoparticles to mitochondria is promising. We report an in vitro procedure targeting mitochondria with conjugated gold nanoparticles and investigating effects on apoptosis induction in the human breast cancer cell line Jimt-1. Gold nanoparticles were conjugated to a variant of turbo green fluorescent protein (mitoTGFP) harbouring an amino-terminal mitochondrial localization signal. Au nanoparticle conjugates were further complexed with cationic maltotriose-modified poly(propylene imine) third generation dendrimers. Fluorescence and transmission electron microscopy revealed that Au nanoparticle conjugates were directed to mitochondria upon transfection, causing partial rupture of the outer mitochondrial membrane, triggering cell death. The ability to target Au nanoparticles into mitochondria of breast cancer cells and induce apoptosis reveals an alternative application of Au nanoparticles in photothermal therapy of cancer.

Pre-injury neuro-psychiatric medication use, alone or in combination with cardiac medications, may affect outcomes in trauma patients.

BACKGROUND: Recent review of older (≥45-years-old) patients admitted to our trauma center showed that more than one-third were using neuro-psychiatric medications (NPMs) prior to their injury-related admission. Previously published data suggests that use of NPMs may increase patients' risk and severity of injury. We sought to examine the impact of pre-injury NPM use on older trauma patients' morbidity and mortality. MATERIALS AND METHODS: Retrospective record review included medication regimen characteristics and NPM use (antidepressants-AD, antipsychotics-AP, anxiolytics-AA). Hospital morbidity, mortality, and 90-day survival were examined. Comparisons included regimens involving NPMs, further focusing on their interactions with various cardiac medications (beta blocker - BB; angiotensin-converting enzyme inhibitor/angiotensin receptor blocker - ACE/ARB; calcium channel blocker - CCB). RESULTS: 712 patient records were reviewed (399 males, mean age 63.5 years, median ISS 8). 245 patients were taking at least 1 NPM: AD (158), AP (35), or AA (108) before injury. There was no effect of NPM monotherapy on hospital mortality. Patients taking ≥3 NPMs had significantly lower 90-day survival compared to patients taking ≤2 NPMs (81% for 3 or more NPMs, 95% for no NPMs, and 89% 1-2 NPMs, P < 0.01). Several AD-cardiac medication (CM) combinations were associated with increased mortality compared to monotherapy with either agent (BB-AD 14.7% mortality versus 7.0% for AD monotherapy or 4.8% BB monotherapy, P < 0.05). Combinations of ACE/ARB-AA were associated with increased mortality compared to ACE/ARB monotherapy (11.5% vs 4.9, P = 0.04). Finally, ACE/ARB-AD co-administration had higher mortality than ACE/ARB monotherapy (13.5% vs 4.9%, P = 0.01). CONCLUSIONS: Large proportion of older trauma patients was using pre-injury NPMs. Several regimens involving NPMs and CMs were associated with increased in-hospital mortality. Additionally, use of ≥3 NPMs was associated with lower 90-day survival.

Validated modeling for German white wine varietal authentication based on headspace solid-phase microextraction online coupled with gas chromatography mass spectrometry fingerprinting.

An untargeted analytical approach combined with chemometrics using the volatiles of German white wine was investigated regarding the usefulness for verifying botanical origin. A total of 198 wine samples of Riesling, Müller-Thurgau, Silvaner, Pinot Gris, and Pinot Blanc were examined applying headspace solid-phase microextraction online coupled with gas chromatography mass spectrometry. The resultant three-dimensional raw data were processed by available metabolomics software. After data treatment, a partial least-squares discriminant analysis (PLS-DA) model was validated. External samples were correctly classified for 97% Silvaner, 93% Riesling, 91% Pinot Gris/Blanc, and 80% Müller-Thurgau. This model was related to monoterpenoids, C13-norisoprenoids, and esters. Further, 100% prediction for a two-class model of Riesling versus Pinot Gris/Blanc was confirmed by 74 additional samples measured independently. Hence, the strategy applied was, in particular, reliable and relevant for white wine varietal classification. In addition, the superior classification performance of the Riesling class was revealed.

SU-E-I-29: Dose Rate and Image Quality Comparison Between Philips Veradius and GE OEC 9900 Elite Fluoroscopic C-Arms.

PURPOSE: The radiation dose rate and image quality were compared on GE OEC 9900 Elite Vas 8 and Philips Veradius fluoroscopic C-arms. METHODS: Plastic (PMMA) phantoms were used to simulate various thicknesses of soft tissues encountered during fluoroscopically-guided interventional procedures while aluminum and copper phantoms were used to simulate extremities of different sizes. An image quality test tool and an ionization chamber were included in the setup of each phantom. The phantoms were imaged in several fluoroscopy modes and at different dose levels. The entrance surface air KERMA rate (ESAKR) was measured for each phantom in each fluoroscopy mode. Simultaneously, the image quality was assessed by counting the number of low-contrast objects visible in the image quality test tool. For a given phantom type and thickness, the ESAKR was plotted versus the number of visible low-contrast objects to compare the dose rate required for a given level of image quality. Additionally, the mean ESAKR per number of objects was calculated and p-values were used to test for statistically significant differences between the C-arms. RESULTS: For comparable image quality with a given phantom type and thickness the ESAKR with the OEC was typically much higher than with the Veradius. One-tailed, unpaired t-tests confirm that the mean ESAKR per number of visible low-contrast objects was lower for the Veradius than for the OEC with all thicknesses of PMMA (p < 0.05). The differences for the aluminum and copper phantoms were much smaller and were not statistically significant (p-values ranged from 0.2 to 0.47). CONCLUSION: In general, the Veradius C-arm provided better low-contrast image quality during fluoroscopy, with lower ESAKR than the OEC 9900 Elite Vas 8. The differences were statistically significant only with PMMA phantoms. Funding support provided by Philips Healthcare (Bothell, WA).

Crosstalk of osteoblast and osteoclast precursors on mineralized collagen--towards an in vitro model for bone remodeling.

Bone remodeling and, therefore, integration of implant materials require the coordinated regulation of osteoblast and osteoclast activity. This is why the in vitro evaluation of biomaterials for bone regeneration should involve not only the analysis of osteoblast differentiation but also the formation and differentiation of osteoclasts. In the present study, we applied a material made of mineralized collagen I that mimics extracellular bone matrix to establish a culture system, which allows the cocultivation of human monocytes and human mesenchymal stem cells (hMSCs), which were differentiated into osteoclast-like cells and osteoblasts, respectively. Both cell types were cultivated on membrane-like structures from mineralized collagen. Transwell inserts were used to spatially separate the cell types but allowed exchange of soluble factors. The osteoclastogenesis and osteogenic differentiation were evaluated by analysis of gene expression, determination of alkaline phosphatase (ALP), and tartrate-resistant acidic phosphatase (TRAP) activity. Furthermore, cell morphology was studied using scanning electron and transmission electron microscopy. Osteogenically induced hMSC showed an increased specific ALP activity as well as increased gene expression of gene coding for alkaline phosphatase (ALPL), when cocultivated with differentiating osteoclasts. Adipogenic differentiation of hMSCs was suppressed by the presence of osteoclasts as indicated by a major decrease in adipocyte cell number and a decrease in gene expression of adipogenic markers. The formation of multinucleated osteoclasts seems to be decreased in the presence of osteogenically induced hMSC as indicated by electron microscopic evaluation and determination of TRAP activity. However, gene expression of osteoclast markers was not decreased in coculture with osteogenically induced hMSC.

Delayed referral despite appropriate knowledge in cryptorchidism as a cause of delayed orchidopexies in Austria.

AIM: Guidelines recommend early orchidopexy in cryptorchidism to decrease the risk of infertility and tumor formation. We aimed to asses if a delayed initial presentation for cryptorchidism was due to unawareness of these guidelines or for any other reasons. METHODS: A short questionnaire exploring timing and referral habits when assessing children with cryptorchidism was sent by email to all registered pediatricians in Austria. Comparatively, a chart review of performed orchidopexies was performed at our institution. RESULTS: Of 369 registered pediatricians, 102 (27.6%) returned valid questionnaires. The average maximum age at which pediatricians in Austria suggested treatment of cryptorchidism was the 21.2 (8.4 months standard deviation (SD)) month of life. Assessment of testicular descent was reported to be regularly performed until the 8.8 (3-18 years SD) year of life. In contrast, from 1997-2008, 730 boys were treated surgically for cryptorchidism at our department. The mean age at operation was 3.4 years (3.1 years SD). CONCLUSION: The majority of pediatricians in Austria know the correct timing for treatment of cryptorchidism. Nevertheless, orchidopexies are still carried out to later than suggested by international guidelines. Further studies and analysis to evaluate the reasons for these suboptimal referring patterns coupled with further communication improvements between pediatricians and surgeons are needed.

Causes and consequences of marine mammal population declines in southwest Alaska: a food-web perspective.

Populations of sea otters, seals and sea lions have collapsed across much of southwest Alaska over the past several decades. The sea otter decline set off a trophic cascade in which the coastal marine ecosystem underwent a phase shift from kelp forests to deforested sea urchin barrens. This interaction in turn affected the distribution, abundance and productivity of numerous other species. Ecological consequences of the pinniped declines are largely unknown. Increased predation by transient (marine mammal-eating) killer whales probably caused the sea otter declines and may have caused the pinniped declines as well. Springer et al. proposed that killer whales, which purportedly fed extensively on great whales, expanded their diets to include a higher percentage of sea otters and pinnipeds following a sharp reduction in great whale numbers from post World War II industrial whaling. Critics of this hypothesis claim that great whales are not now and probably never were an important nutritional resource for killer whales. We used demographic/energetic analyses to evaluate whether or not a predator-prey system involving killer whales and the smaller marine mammals would be sustainable without some nutritional contribution from the great whales. Our results indicate that while such a system is possible, it could only exist under a narrow range of extreme conditions and is therefore highly unlikely.