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As Earth's atmospheric temperatures and human populations increase, more people are becoming vulnerable to natural and human-induced disasters. This is particularly true in Central America, where the growing human population is experiencing climate extremes (droughts and floods), and the region is susceptible to geological hazards, such as earthquakes and volcanic eruptions, and environmental deterioration in many forms (soil erosion, lake eutrophication, heavy metal contamination, etc.). Instrumental and historical data from the region are insufficient to understand and document past hazards, a necessary first step for mitigating future risks. Long, continuous, well-resolved geological records can, however, provide a window into past climate and environmental changes that can be used to better predict future conditions in the region. The Lake Izabal Basin (LIB), in eastern Guatemala, contains the longest known continental records of tectonics, climate, and environmental change in the northern Neotropics. The basin is a pull-apart depression that developed along the North American and Caribbean plate boundary ∼ 12 Myr ago and contains > 4 km of sediment. The sedimentological archive in the LIB records the interplay among several Earth System processes. Consequently, exploration of sediments in the basin can provide key information concerning: (1) tectonic deformation and earthquake history along the plate boundary; (2) the timing and causes of volcanism from the Central American Volcanic Arc; and (3) hydroclimatic, ecologic, and geomicrobiological responses to different climate and environmental states. To evaluate the LIB as a potential site for scientific drilling, 65 scientists from 13 countries and 33 institutions met in Antigua, Guatemala, in August 2022 under the auspices of the International Continental Scientific Drilling Program (ICDP) and the US National Science Foundation (NSF). Several working groups developed scientific questions and overarching hypotheses that could be addressed by drilling the LIB and identified optimal coring sites and instrumentation needed to achieve the project goals. The group also discussed logistical challenges and outreach opportunities. The project is not only an outstanding opportunity to improve our scientific understanding of seismotectonic, volcanic, paleoclimatic, paleoecologic, and paleobiologic processes that operate in the tropics of Central America, but it is also an opportunity to improve understanding of multiple geological hazards and communicate that knowledge to help increase the resilience of at-risk Central American communities.

This work presents unprecedented, high-resolution palaeomagnetic data from the sedimentary record of Lake Levinson-Lessing, the deepest lake in northern central Siberia. Palaeomagnetic analyses were carried out on 730 discrete samples from the upper 38 m of the 46 m long core Co1401, which was recovered from the central part of the lake. Alternating field demagnetization experiments were carried out to obtain the characteristic remanent demagnetization. The relative palaeointensity is determined using the magnetic susceptibility, the anhysteretic remanent magnetization, and the isothermal remanent magnetization for normalization of the partial natural remanent magnetization. The chronology of Co1401 derives from correlation of the relative palaeointensity of 642 discrete samples with the GLOPIS-75 reference curve, accelerated mass spectrometer radiocarbon ages, and optically stimulated luminescence dating. This study focuses on the part > 10 ka but also presents preliminary results for the younger part of the core. The record includes the geomagnetic excursions Laschamps and Mono Lake and resolves sufficient geomagnetic features to establish a chronology that continuously covers the last ∼ 62 kyr. The results reveal continuous sedimentation at high rates between 45 and 95 cm kyr−1. The low variability of the magnetic record compared to datasets of reference records with lower sedimentation rates may be due to a smoothing effect associated with the lock-in depths. Because Co1401 was cored without core segment overlap the horizontal component of the characteristic remanent magnetization can only be used with caution. Nevertheless, the magnetic record of Co1401 is exceptional as it is the only high-resolution record of relative palaeointensity and palaeosecular variations from the Arctic tangent cylinder going back to ∼ 62 ka.

Os jalecos são um veículo potencial de transmissão microbiológica e seu uso inadequado traz riscos à saúde de profissionais e da população. O objetivo deste estudo foi o de conhecer as práticas de utiliza- ção e o perfil de contaminação dos jalecos brancos usados como uniforme por docentes e discentes do Centro Universitário Serra dos Orgãos (UNIFESO). Trata-se de um estudo quantitativo, transversal e exploratório. Respeitados os princípios éticos, aplicou-se questionário sobre o modo de uso e se realizou a análise microbiológica. Os dados foram analisados de forma manual, expressos em percentuais e demonstrados por meio de tabelas. Como resultado, 73 (setenta e três) jalecos estudados apresentaram variada flora, com predomínio de cocos Gram positivos. A região do punho, a mais contaminada, apresentou em média 23 UFC por campo. Quanto ao perfil de uso, a maioria, 42, (57%) tem idade entre 18 e 25 anos, 46 (63%) são do sexo feminino, 27 (37%) são acadêmicos de medicina do 3o período e apenas 13 (18%) são docentes. Sobre a frequência de troca do jaleco, 35 (48%) trocam uma vez por semana, entretanto com inadequado manuseio. Após uso, 36 (49%) não lavam o jaleco separadamente, 43 (58%) não usam produto desinfetante e 54 (73%) utilizam a passagem a ferro como medida complementar de contenção microbiológica. Conclui-se que há imperiosa necessidade de conscientização dos acadêmicos e docentes sobre adequados uso e manuseio do jaleco e importância da vestimenta na epidemiologia das infecções intra e extra-ambientes da saúde

Inflammation models with the proinflammatory cytokine interleukin-1β (IL-1β) are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis (OA). The aim of this study was to systematically analyze the influence of IL-1β in a 3D chondral pellet culture model. Bovine articular chondrocytes were cultured to passage 3 and then placed in pellet culture. Titration of IL-1β (100-0.1 ng/mL) was performed with both human and bovine recombinant protein in chondrocyte culture for 2 weeks. Gene expression of anabolic (collagen 2, aggrecan, cartilage oligomeric protein (COMP), proteoglycan-4 (PRG-4)), catabolic matrix metallo proteinases (MMP-3, MMP-13), dedifferentiation (collagen 1) markers and inflammatory cytokines IL-6 and IL-8 was determined. Analysis of the cell culture medium was performed for the inflammatory markers IL-6 and nitric oxide (NO). In general, the influence of IL-1β was shown by a decrease in the expression of anabolic markers (collagen 2, aggrecan, PRG-4), whereas the catabolic markers MMP-3 and MMP-13 as well as the inflammatory markers IL-6 and IL-8 were significantly increased. This was observed both at the early time point (day 4) and at the late time point (day 14). The described inflammatory effects were confirmed by increased concentration-dependent release of NO and IL-6. The threshold concentration for a detectable effect compared to control differed between groups, but was reached earlier by homologous application of IL-1β. This study provides a systematic evaluation of IL-1β-specific effects on chondrocytes in a 3D pellet culture model, which is highly relevant for comparisons of studies in OA-specific drug development.

Purpose: Assessing scapulothoracic kinematics typically involves visually observing patients during movement, which has limited inter- and intraobserver reliability. Dynamic rasterstereography (DRS) records, measures and visualizes surface structures in real time, using a curvature map to colour-code convex, concave and saddle-shaped structures on the body surface. This study aimed to evaluate the diagnostic efficacy of DRS-assisted observation in identifying dyskinetic scapulothoracic patterns., Methods: Thirty-seven healthy participants performed shoulder abduction/adduction and flexion/extension cycles without additional weight, recorded using both DRS and a conventional video camera. A metronome ensured consistent timing, and for DRS a grid of parallel light rays projected onto the back surface was captured using indirect optical measurement techniques. The mean surface curvature was converted into a colour scale. The diagnostic performance of conventional and DRS videos in detecting dyskinetic patterns, including static asymmetries, dynamic asymmetries, motion delays and rapid compensatory movements, were compared. Two investigators independently evaluated the videos twice in a blinded and randomized sequence to assess intra- and interrater reproducibility., Results: Analysis of 118 videos showed good-to-excellent intrarater and interrater reproducibility for both techniques (ICCs 0.727-0.949). Movement delays and dynamic asymmetries were observed more frequently when evaluating DRS videos rather than conventional videos ( p  = 0.0008 and p  = 0.0016). However, no differences were found in static asymmetry and rapid compensatory movement detection., Conclusions: DRS can create a real-time model of the trunk surface and allows observers to evaluate the scapular movements with good-to-excellent intrarater and interrater reproducibility; compared to clinical observation, some specific scapular motion alterations can be observed more frequently. Clinical Trial Registration: Part of the DRKS00022334 trial., Level of Evidence: Level II, prospective cohort study., Competing Interests: Author S. S. declares travel/accommodation reimbursements from Arthrex outside the presented work. Author D. C. declares travel/accommodation reimbursements from Lima outside the presented work. The remaining authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Background : Acetabular fractures continue to pose a major challenge in clinical practice, not least because of the growing geriatric population. While the influence of the force vectors on fracture formation is well established, the impact of anatomical factors on fracture morphology remains poorly understood. The aim of this study was to investigate patient-specific hip joint geometry, identify structural risk factors and correlate these with the resulting fracture patterns. Methods : This retrospective cohort analysis included 226 patients (Mdn age = 58 yrs.) with acetabular fracture categorized by Judet/Letournel and the AO/OTA classification. Computed tomography (CT) datasets of the injured and contralateral sides were analyzed using multiplanar reconstruction. Parameters included modified center-edge (CE) angle (Wiberg), rotation angles (Ullmann and Anda), acetabular sector angle (Anda), true caput-collum-diaphyseal (CCD) angle, femoral head diameter and volume, as well as femoral neck length, circumference, and diameter. In addition, intrarater reliability within a subcohort was assessed for the metric measurements and inter-rater analysis for the classification of the entire sample. Results : The primary analysis showed direct effects of femoral head diameter, femoral neck length and femoral head size on the fracture type according to AO/OTA (type A/B/C), whereby this effect was particularly seen between type A and type C fractures ( p = 0.001). Ordinal regression identified femoral head diameter as the only significant predictor ( p = 0.02), with a 25% increased likelihood of complex fractures per unit of change. Low-energy trauma doubled the risk of severe fractures. Specific findings include a higher acetabular anteversion in anterior column fractures. Age correlated positively with the cause of injury and fracture type. The inter-rater reliability for fracture classification was excellent, as was the intrarater reliability of the measurements. Conclusions : This study suggests that anatomical factors, particularly proximal femoral geometry, have an impact on acetabular fracture morphology-in addition to factors such as trauma type and patient demographics.

Background: Only a few cases of bilateral traumatic sternoclavicular dislocations have been reported in the literature. This injury is considered one of the rarest injuries of the human musculoskeletal system. Therefore, we present the first documented case of a cyclist with a third-degree open thoracic trauma (Gustilo-Anderson 3a) associated with a dislocated manubrium sterni fracture in the upper thoracic aperture, bilateral anterior dislocations of the sternoclavicular joints, rib fractures, and pleural ruptures., Case Presentation: The patient, a 27-year-old Caucasian male, incurred this injury while participating in a professional cycling race at Nürburgring, Germany and received immediate interdisciplinary surgical treatment and has encountered no complications. We conducted a 1-year follow-up and present the clinical findings of this follow up. Additionally, we conducted a comprehensive review of the existing literature on this injury., Conclusions: Immediate interdisciplinary intervention, including surgical repair and meticulous postoperative care, facilitated successful patient recovery. This underscores the critical role of comprehensive trauma management in complex polytrauma cases. In conclusion, this case report highlights the rarity and complexity of a traumatic injury involving bilateral sternoclavicular dislocation, with this case being the first case reported with concomitant open thorax trauma. Our patient benefited greatly from immediate air-bound transportation to an interdisciplinary care provider, which houses both thoracic and trauma surgery departments., (© 2024. The Author(s).)

The current gold standard to treat large cartilage defects is autologous chondrocyte transplantation (ACT). As a new surgical method of cartilage regeneration, minced cartilage implantation (MCI) is increasingly coming into focus. The aim of this study is to investigate the influence of chondrogenesis between isolated and cultured chondrocytes compared to cartilage chips in a standardized inflammation model with the proinflammatory cytokine TNFα. Articular chondrocytes from bovine cartilage were cultured according to the ACT method to passage 3 and transferred to spheroid culture. At the same time, cartilage was fragmented (<1 mm 3 ) to produce cartilage chips. TNFα (20 ng/mL) was supplemented to simulate an inflammatory process. TNFα had a stronger influence on the passaged chondrocytes compared to the non-passaged ones, affecting gene expression profiles differently between isolated chondrocytes and cartilage chips. MCI showed less susceptibility to TNFα, with reduced IL-6 release and less impact on inflammation markers. Biochemical and histological analyses supported these findings, showing a greater negative influence of TNFα on the passaged pellet cultures compared to the unpassaged cells and MCI constructs. This study demonstrated the negative influence of TNFα on chondrogenesis in a chondrocyte spheroid culture and cartilage fragment model. Passaged chondrocytes are more sensitive to cytokine influences compared to non-passaged cells and chondrons. This suggests that MCI may have superior regeneration potential in osteoarthritic conditions compared to ACT. Further investigations are necessary for the translation of these findings into clinical practice.

The biological enhancement of tissue regeneration and healing is an appealing perspective in orthopedics. We aimed to conduct a systematic review to describe the global distribution of studies investigating the use of adipose tissue derivates in orthopedics and to provide information on their quality and on the products available. The quality of the included studies was assessed using the modified Coleman Methodology Score (mCMS) and the Cochrane risk-of-bias tool for randomized trials. Eighty-two studies were included, with a total of 3594 patients treated. In total, 70% of the studies investigated the treatment of knee disorders, predominantly osteoarthritis; 26% of all studies dealt with expanded adipose-derived stem/stromal cells (ADSCs), 72% of which had stromal vascular fraction (SVF); 70% described the injection of adipose tissue derivates into the affected site; and 24% described arthroscopies with the addition of adipose tissue derivates. The mean mCMS for all studies was 51.7 ± 21.4 points, with a significantly higher score for the studies dealing with expanded ADSCs compared to those dealing with SVF ( p = 0.0027). Our analysis shows high heterogeneity in terms of the types of performed procedures as well as the choice and processing of adipose tissue derivates.

Introduction: Periprosthetic joint infections (PJI) are a major complication in joint-arthroplasty. Rifampicin is often used as an additional agent to treat PJI, because it penetrates bacterial biofilms. However, rifaximin, belonging to the same antibiotic class as rifampicin, is frequently used to prevent episodes of hepatic encephalopathy in patients with cirrhosis and may induce resistance to rifampicin. The aim of this study was to examine the microbial pattern of periprosthetic joint infections in cirrhotic patients and to test the hypothesis that intake of rifaximin increases the rate of resistance to rifampicin in periprosthetic joint infections., Methods: A cohort of cirrhotic patients and PJI (n = 25) was analysed on the characteristics of bacterial isolates from sonication and tissue analysis. In a second step a subgroup analysis on the development of rifampicin resistant bacterial specimens, depending on the intake of rifaximin (8 rifaximin intake patients vs. 13 non rifaximin intake patients) was performed., Results: Intestinal bacteria were found in 50% of the specimens, which was significantly more frequent than in a control cohort. By comparison of the single bacterial isolates, rifampicin resistance was detected in 69.2% (9/13) of the rifaximin-intake samples. In contrast, the non-rifaximin-intake isolates only were resistant to rifampicin in 22.2% (4/18) of the cases (p = 0.01). The odds ratio for developing a rifampicin-resistance through rifaximin intake was calculated as OR = 13.5., Conclusion: Periprosthetic joint infections have a high incidence of being caused by enteric bacteria in cirrhotic patients. Due to this change in microbial pattern and the innate resistance to rifampicin of most of gram-negative bacteria, the therapy with rifampicin should be carefully considered. The association between the use of rifaximin and developed resistance to rifampicin has a major impact on the treatment of PJI., (© 2022. The Author(s).)

The goal of this study was to compare operative outcomes after lesser toe deformity correction with either proximal interphalangeal (PIP) joint arthrodesis or PIP joint resection arthroplasty. A prospective randomized controlled trial was performed with 37 patients (48 toes) operated on with one of these two procedures. Evaluation of the numeric rating scale score, the American Orthopedic Foot and Ankle Society score, osseous consolidation, and clinical outcome was performed preoperatively and at 6 weeks and 6 months postoperatively. Both study groups showed significant improvement at 6 months postoperatively. Although osseous consolidation was significantly higher for the arthrodesis group ( P =.001), this difference did not affect clinical outcomes, and at 6 months postoperatively, pain on the numeric rating scale was 0 (range, 0-7) for the arthroplasty group and 0 (range, 0-5) for the arthrodesis group ( P =.669). The American Orthopedic Foot and Ankle Society score was 83 (range, 39-95) and 80 (range, 59-95), respectively ( P =.879). No difference was observed for signs of inflammation or axis correction. Even a direct comparison of toes with radiologically osseous fusion (n=16) with those without fusion (n=32) did not show any clinical differences. This randomized controlled study showed no clinical differences in outcome between PIP joint arthrodesis and PIP joint resection arthroplasty for correction of lesser toe deformities, with good to excellent outcomes for both groups. [ Orthopedics . 2022;45(2):86-90.].

Aseptic prosthetic loosening and periprosthetic joint infections (PJI) are among the most frequent complications after total knee/hip joint arthroplasty (TJA). Current research efforts focus on understanding the involvement of the immune system in these frequent complications. Different immune cell types have already been implicated in aseptic prosthetic loosening and PJI. The aim of this study was to systematically analyze aspirates from knee and hip joints, evaluating the qualitative and quantitative composition of soluble immunoregulatory markers, with a focus on co-inhibitory and co-stimulatory markers. It has been shown that these molecules play important roles in immune regulation in cancer and chronic infectious diseases, but they have not been investigated in the context of joint replacement. For this purpose, aspirates from control joints (i.e., native joints without implanted prostheses), joints with TJA (no signs of infection or aseptic loosening), joints with aseptic implant failure (AIF; i.e., aseptic loosening), and joints with PJI were collected. Fourteen soluble immunoregulatory markers were assessed using bead-based multiplex assays. In this study, it could be shown that the concentrations of the analyzed immunoregulatory molecules vary between control, TJA, AIF, and PJI joints. Comparing TJA patients to CO patients, sCD80 was significantly elevated. The marker sBTLA was significantly elevated in AIF joints compared to TJA joints. In addition, a significant difference for eight markers could be shown when comparing the AIF and CO groups (sCD27, sCTLA-4, sCD137, sCD80, sCD28, sTIM-3, sPD-1, sBTLA). A significant difference was also reached for nine soluble markers when the PJI and CO groups were compared (sLAG-3, sCTLA-4, sCD27, sCD80, sCD28, sTIM-3, sPD-1, IDO, sBTLA). In summary, the analyzed immunoregulatory markers could be useful for diagnostic purposes as well as to develop new therapeutic approaches for AIF and PJI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jubel, Randau, Becker-Gotot, Scheidt, Wimmer, Kohlhof, Burger, Wirtz and Schildberg.)

Operative treatment of ruptured pubic symphysis by plating is often accompanied by complications. Trans-obturator cable fixation might be a more reliable technique; however, have not yet been tested for stabilization of ruptured pubic symphysis. This study compares symphyseal trans-obturator cable fixation versus plating through biomechanical testing and evaluates safety in a cadaver experiment. APC type II injuries were generated in synthetic pelvic models and subsequently separated into three different groups. The anterior pelvic ring was fixed using a four-hole steel plate in Group A, a stainless steel cable in Group B, and a titan band in Group C. Biomechanical testing was conducted by a single-leg-stance model using a material testing machine under physiological load levels. A cadaver study was carried out to analyze the trans-obturator surgical approach. Peak-to-peak displacement, total displacement, plastic deformation and stiffness revealed a tendency for higher stability for trans-obturator cable/band fixation but no statistical difference to plating was detected. The cadaver study revealed a safe zone for cable passage with sufficient distance to the obturator canal. Trans-obturator cable fixation has the potential to become an alternative for symphyseal fixation with less complications.

Cells within the tumor stroma are essential for tumor progression. In particular, cancer-associated fibroblasts (CAF) and CAF precursor cells (resident fibroblasts and mesenchymal stromal cells) are responsible for the formation of the extracellular matrix in tumor tissue. Consequently, CAFs directly and indirectly mediate inflammation, metastasis, immunomodulation, angiogenesis, and the development of tumor chemoresistance, which is orchestrated by complex intercellular cytokine-mediated crosstalk. CAFs represent a strategic target in antitumor therapy but their heterogeneity hinders effective treatment regimes. In-depth understanding of CAF subpopulations and knowledge of specific functions in tumor progression will ultimately result in more specific and effective cancer treatments. This review provides a detailed description of CAFs and CAF precursor cells and summarizes possible treatment strategies as well as molecular targets of these cells in antitumor therapies.

Premise: TagSeq is a cost-effective approach for gene expression studies requiring a large number of samples. To date, TagSeq studies in plants have been limited to those with a high-quality reference genome. We tested the suitability of reference transcriptomes for TagSeq in non-model plants, as part of a study of natural gene expression variation at the Santa Rita Experimental Range National Ecological Observatory Network (NEON) core site., Methods: Tissue for TagSeq was sampled from multiple individuals of four species ( Bouteloua aristidoides and Eragrostis lehmanniana [Poaceae], Tidestromia lanuginosa [Amaranthaceae], and Parkinsonia florida [Fabaceae]) at two locations on three dates (56 samples total). One sample per species was used to create a reference transcriptome via standard RNA-seq. TagSeq performance was assessed by recovery of reference loci, specificity of tag alignments, and variation among samples., Results: A high fraction of tags aligned to each reference and mapped uniquely. Expression patterns were quantifiable for tens of thousands of loci, which revealed consistent spatial differentiation in expression for all species., Discussion: TagSeq using de novo reference transcriptomes was an effective approach to quantifying gene expression in this study. Tags were highly locus specific and generated biologically informative profiles for four non-model plant species., (© 2020 Marx et al. Applications in Plant Sciences published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

Before engaging with the already intensive and still increasing personal branding activities in many fields of practice, a scholarly approach would call for a more specific definition of the concept of personal branding processes and the resulting human brands. A multi-step analysis of the growing body of literature on personal branding is employed, integrating a framework that covers six key research streams of personal branding, (1) terminology and definition, (2) underlying theories, (3) classes and categories, (4) benefits, (5) antecedents, and (6) key ingredients and applications, complemented by challenges the domain of personal branding has to cope with. The analysis shows that personal branding is an interdisciplinary concern, which is still in its infancy and in which universally valid personal branding frameworks or even theories cannot be identified yet. Personal branding appears as a source for new academic impulses, as it may sensitize scholars to opportunities for intensifying collaboration with practitioners and with other academic domains to enrich and disseminate knowledge in their fields., (Copyright © 2020 Scheidt, Gelhard and Henseler.)

Prevalence of scapular dyskinesis varies across records, with overhead athletes being more frequently affected than non-overhead athletes A number of methods have been described to evaluate scapular kinematics and scapular dyskinesis. The "yes/no" and the "4-type" classification systems are widely accepted and diffusely used among orthopaedics and physical therapists. The inter-rater reliability for both the "yes/no" and the "4-type" classification systems may be different. Moreover, differences between physical therapists and orthopaedic surgeons may exist. Seven examiners (2 orthopaedic surgeons and 5 physical therapists) were asked to evaluate a mixed sequence of video recordings of healthy subjects and patients affected by shoulder, scapular or clavicular disorders and to assess scapular dyskinesis using the "yes/no" and the "4-type" classification systems. Cohen's kappa coefficient (κ) and weighted kappa were used to measure inter-rater reliability. Twenty-four subjects were enrolled. In general, the "4- type" system has higher κ values than ''yes/no'' classification system and orthopaedic surgeons achieve higher reliability than physical therapists for both systems. The clinical evaluation of active shoulder movements permits reproducible assessment and classification of scapular dyskinesis, in particular for the "4-type" classification system. The "4-type" classification system can be used to assess and classify scapular dyskinesis, especially among orthopaedic surgeons., (Copyright 2020 Biolife Sas. www.biolifesas.org.)

The history of the antithrombotic agents--aspirin, heparin, warfarin, and the thrombolytics--is a rich and lively odyssey of serendipity, perseverance, vision, and conflict involving a number of striking personalities. The history of aspirin spans ages and continents from Hippocrates' analgesic for women in labor to the rediscovery of the white willow bark by English country scholar Reverend Edward Stone. Bayer chemist Felix Hoffmann reinvented aspirin for his ailing father; suburban physician L.L. Craven pioneered the prophylactic antithrombotic uses of aspirin; and Sir John Vane elucidated aspirin's mechanism of action as the inhibition of prostaglandin synthetase. Heparin was discovered by McLean, working as a medical student in 1915 in search of a pure procoagulant in dog liver. His original impure material differed somewhat from today's heparin, but purified heparin was rapidly accepted for a myriad of clinical uses; to this day, diverse new properties of this complex glycosaminoglycan continue to be elucidated. The oral anticoagulants emerged from veterinary research in the 1920s on a hemorrhagic disorder afflicting cattle that consumed spoiled sweet clover hay. Several chance encounters led Karl Link and his University of Wisconsin team to the identification of dicumarol as the offending agent in 1939 and its widespread therapeutic use by Wright and others in the 1940s. Link later developed warfarin as a rodenticide, but its use in humans soon followed in the 1950s. Vitamin K was discovered in the 1930s; its involvement in the mechanism of the anticoagulant agents was not delineated until the 1970s. The intrinsic ability of clotted blood to liquify and the fibrinolytic properties of normal urine were noted in the 1800s. Tillett and Sherry's group stumbled on the fibrinolytic properties of streptokinase in the 1930s and pioneered the therapeutic use of streptokinase in the 1940s and of urokinase in the 1960s. Several teams found tissue-type plasminogen activator in various body sites beginning in the 1940s, leading to its cloning and widespread use in the 1980s; anisoylated plasminogen-streptokinase activator complex is an example of rational drug design. The discoverers of these diverse agents have not only provided physicians with a potent armamentarium of antithrombotic drugs but also helped elucidate much basic science and vividly demonstrated the merits of perseverance, independent thought, and adherance to the scientific method.

New York County physicians were surveyed by questionnaire concerning their attitudes and practices regarding continuing medical education (CME). There were 1,558 responders, and they included those practicing in shared health facilities (SHF) and random samples of academicians on the faculties of the four medical schools and of the entire physician population of Manhattan. Reading professional books and journals was regarded as by far the most important CME activity by all three groups of physicians, and this activity consumed about four hours per week. All physicians spent several days and often as much as two weeks per year attending professional meetings and formal postgraduate courses. The former were rated as not very useful and the latter as quite useful for CME. Major impediments to CME participation for all groups were time away from home and practice, expense, loss of income, and scheduling problems. Relevance, quality, and organization of CME courses were not major impediments. SHF physicians differed little from other physicians in their attitudes, perceptions, and practices concerning CME.

Rate-corrected left ventricular ejection time was measured from the aortic pressure tracings of 171 catheterised patients with aortic valve area less than or equal to 1.2 cm2. In 50 patients with pure aortic stenosis, left ventricular ejection time in increased with decreasing valve area and was significantly higher (468 +/- 5 ms, mean +/- SEM) than in 13 normal subjects (435 +/- 5 ms). Additional aortic regurgitation in 72 patients further increased the left ventricular ejection time to 484 +/- 4 ms. Significant mitral stenosis (mitral valve are less than or equal to 1.2 cm2) in 6 patients with aortic stenosis and 33 patients with aortic stenosis and regurgitation reduced the left ventricular ejection time to normal. Similarly, severe mitral regurgitation in 3 patients with aortic stenosis and regurgitation reduced left ventricular ejection time to normal, though slight or moderate mitral regurgitation in 4 of these patients did not. These data show that the prolonged left ventricular ejection time in aortic valve disease may be restored to normal in the presence of coexisting significant mitral disease.