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Background: This is the first known investigation to identify specific patient characteristics and the relationship to their understanding of laboratory test results. The study examined patient characteristics influencing their level of understanding of laboratory test results reported to them by physicians or health care professionals.Methods: Questionnaires were distributed to 143 patients.Results: The authors' findings suggest that patients want information on and an understanding of their laboratory results Demographic variables and who explained the results to the patients did not significantly influence the findings.Conclusion: Patients reported that understanding the purpose of their tests and their relationships to their conditions would increase their satisfaction with the health care system. [ABSTRACT FROM AUTHOR]

Human brain organoids equipped with complex cytoarchitecture and closed-loop feedback from virtual environments could provide insights into neural mechanisms underlying cognition. Yet organoids with certain cognitive capacities might also merit moral consideration. A precautionary approach has been proposed to address these ethical concerns by focusing on the epistemological question of whether organoids possess neural structures for morally-relevant capacities that bear resemblance to those found in human brains. Critics challenge this similarity approach on philosophical, scientific, and practical grounds but do so without a suitable alternative. Here, I introduce an architectural approach that infers the potential for cognitive-like processing in brain organoids based on the pattern of information flow through the system. The kind of computational architecture acquired by an organoid then informs the kind of cognitive capacities that could, theoretically, be supported and empirically investigated. The implications of this approach for the moral considerability of brain organoids are discussed., (© The Author(s) 2024. Published by Oxford University Press.)

Human cerebral organoids (HCOs) are model systems that enable researchers to investigate the human brain in ways that had previously been impossible. The emergence of HCOs was accompanied by both expert and layperson discussions concerning the possibility of these novel entities developing sentience or consciousness. Such concerns are reflected in deliberations about how to handle and regulate their use. This perspective article resulted from an international and interdisciplinary research retreat "Ethical, Legal and Social Aspects of Human Cerebral Organoids and their Governance in Germany, the United Kingdom and the United States", which took place in Tübingen, Germany, in August 2022. The retreat focused on whether HCO research requires new ethical and regulatory approaches. It addressed epistemic issues around the detection and theorisation of consciousness, ethical concerns around moral status and research conduct, difficulties for legislation and guidelines managing these entities, and public engagement., Competing Interests: JS is a member of Merck KGaA’s Ethics Advisory Panel and Stem Cell Research Oversight Committee; a member of IQVIA’s Ethics Advisory Panel; a member of Aspen Neurosciences Clinical Advisory Panel; and previously a member of a Merck Data Monitoring Committee and a consultant to Biogen. The other 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 © 2023 Pichl, Ranisch, Altinok, Antonakaki, Barnhart, Bassil, Boyd, Chinaia, Diner, Gaillard, Greely, Jowitt, Kreitmair, Lawrence, Lee, McKeown, Sachdev, Schicktanz, Sugarman, Trettenbach, Wiese, Wolff and Árnason.)

The brain is arguably the most powerful computation system known. It is extremely efficient in processing large amounts of information and can discern signals from noise, adapt, and filter faulty information all while running on only 20 watts of power. The human brain's processing efficiency, progressive learning, and plasticity are unmatched by any computer system. Recent advances in stem cell technology have elevated the field of cell culture to higher levels of complexity, such as the development of three-dimensional (3D) brain organoids that recapitulate human brain functionality better than traditional monolayer cell systems. Organoid Intelligence (OI) aims to harness the innate biological capabilities of brain organoids for biocomputing and synthetic intelligence by interfacing them with computer technology. With the latest strides in stem cell technology, bioengineering, and machine learning, we can explore the ability of brain organoids to compute, and store given information (input), execute a task (output), and study how this affects the structural and functional connections in the organoids themselves. Furthermore, understanding how learning generates and changes patterns of connectivity in organoids can shed light on the early stages of cognition in the human brain. Investigating and understanding these concepts is an enormous, multidisciplinary endeavor that necessitates the engagement of both the scientific community and the public. Thus, on Feb 22-24 of 2022, the Johns Hopkins University held the first Organoid Intelligence Workshop to form an OI Community and to lay out the groundwork for the establishment of OI as a new scientific discipline. The potential of OI to revolutionize computing, neurological research, and drug development was discussed, along with a vision and roadmap for its development over the coming decade., Competing Interests: TH is employed by, and inventor on a patent by Johns Hopkins University on the production of brain organoids, which is licensed to AxoSim, New Orleans, LA, USA, and receives royalty shares. TH also consults to AxoSim. LS is employed by Johns Hopkins University and consults to AxoSim, New Orleans, LA, USA. JS is employed by, and inventor on a patent by the University of Luxembourg on the production of midbrain organoids, which is licensed to OrganoTherapeutics SARL, Esch-sur-Alzette, Luxembourg. JLC and BC were employed by AxoSim Inc., New Orleans, LA, United States. JS is also co-founder and shareholder of OrganoTherapeutics SARL. AM is employed by the University of California, San Diego and is co-founder and has equity interest in TISMOO, a company dedicated to genetic analysis and human brain organogenesis, focusing on therapeutic applications customized for autism spectrum disorders and other neurological disorders origin genetics. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. BK is employed by Cortical Labs Pty Ltd., Melbourne, Australia, and is an inventor on patents for technology related this paper and holds shares in Cortical Labs Pty Ltd., Melbourne, Australia. No specific funding or other incentives were provided for involvement in this publication. The remaining 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 © 2023 Morales Pantoja, Smirnova, Muotri, Wahlin, Kahn, Boyd, Gracias, Harris, Cohen-Karni, Caffo, Szalay, Han, Zack, Etienne-Cummings, Akwaboah, Romero, Alam El Din, Plotkin, Paulhamus, Johnson, Gilbert, Curley, Cappiello, Schwamborn, Hill, Roach, Tornero, Krall, Parri, Sillé, Levchenko, Jabbour, Kagan, Berlinicke, Huang, Maertens, Herrmann, Tsaioun, Dastgheyb, Habela, Vogelstein and Hartung.)

Willie O'Ree, known as the "Jackie Robinson of hockey," was the first Black player in the National Hockey League (NHL), debuting with the Boston Bruins in 1958. From the moment the Canadian-born player stepped onto the ice, he changed the notion of hockey as a "White sport," and he has dedicated his career to making it more accessible, including working with the NHL Diversity Task Force initiative Hockey Is For Everyone (HIFE). HIFE supports nonprofit hockey programs around the country and gives kids from all backgrounds the opportunity to try out their skills on the ice. Since 1994, Willie O'Ree has introduced 50,000 children across North America to the sport. Nonetheless, in the NHL today, only approximately 5% of the players (43 of >700) are players of color. However, several aspects of hockey's history, and innovations in the game, can be traced back to communities of color. Established in 1895, the Black Hockey League (BHL) of the Maritimes in Canada grew out of local churches in small towns such as Africville, Nova Scotia. By the beginning of the 20th century, the BHL had grown from a 3-team league to include newly formed teams across the region. The league had its own championship at a time when Black players were not allowed to play for the Stanley Cup. The BHL was at its height between 1890 and 1930, with hundreds of players, 12 teams, and as many as 1,200 spectators. Unfortunately, the Canadian government did not provide equitable resources, and churches alone could not maintain these small Black communities. As the NHL developed, focus shifted away from regional leagues. In 2018, Willie O'Ree was inducted into the NHL Hall of Fame. Although he may have broken the color barrier in 1958, hockey is still a predominantly White sport, and society continues to grapple with systematic racism. NHL players have formed an independent group, the Hockey Diversity Alliance, to work to make the game more socioeconomically inclusive and to help eradicate racism and intolerance.

The management of knee ligament injuries continues to evolve, and much debate persists over the timing of surgery, repair versus reconstruction, surgical technique, postoperative rehabilitation, graft selection, and fixation. Surgeons should be aware of updates on the best management strategies of knee ligament injuries in 2018 and understand the important history and physical examination findings of the knee with ligamentous injury; the anterior cruciate ligament; the role of the anterolateral ligament and lateral extra-articular tenodesis; combined anterior cruciate ligament and medial collateral ligament injuries; the posterior cruciate ligament; medial collateral ligament repair versus reconstruction; posterolateral corner repair versus reconstruction; the role of coronal plane osteotomies, including high tibial osteotomy and distal femoral osteotomy; the role of sagittal plane osteotomies, including anterior closing wedge osteotomy and anterior opening wedge osteotomy; the initial management of the multiligament-injured knee; and five keys to avoiding complications in the multiligament-injured knee. The best available evidence and sample case presentations help guide surgical decision making and improve patient outcomes.

Background: Enhanced recovery pathways (ERPs) are thought to improve surgical outcomes by standardizing perioperative patient care established in evidence-based literature. The objective of this study was to determine the impact of a colorectal surgery ERP on hospital length of stay (LOS) and other patient outcomes., Methods: This is a comparative effectiveness study of patients undergoing elective colorectal surgery 2 years prior (pre-ERP group) and 2 years after (ERP group) implementation of an ERP program. The primary outcome was hospital LOS. Secondary outcomes included postoperative complications, 30-day readmissions, and 30-day reoperations. Multivariable regression analyses were utilized to control for patient factors, general health factors, diagnosis, surgeon, colon versus rectal operations, and open versus minimally invasive operations-laparoscopic and robotic. An ERP checklist was developed to track adherence to components of the pathway., Results: The study population included 1036 patients: 523 in the pre-ERP group and 513 in the ERP group. Unadjusted LOS was significantly shorter in the ERP group than the control pre-ERP group [3 (IQR 3.5) vs 5 days (IQR 4.6); p < 0.0001]. Multivariable regression analysis confirmed the reduction in LOS, controlling for age, colon/rectum procedure, open/laparoscopic/robotic approach, primary diagnosis, and alvimopan use. Postoperative outcomes were not significantly different between groups except for 30-day readmissions, which were unexpectedly higher in the ERP group (14.6 vs 8.7 %, p = 0.04)., Conclusions: A newly implemented ERP on a dedicated colorectal surgery service in an academic non-university hospital setting resulted in shorter hospital LOS, but increased readmissions, for patients undergoing elective open and minimally invasive colon and rectal surgery. Future multi-institutional studies are needed to understand the impact of ERP on postoperative complications and readmissions.

This study investigated whether increased loading (representing obesity) in the extended knee and flexed knee led to increased stresses in areas of typical medial and lateral osteoarthritis cartilage lesions, respectively. We created two paired sets of subject-specific finite element models; both sets included models of extended knees and of flexed knees. The first set represented normal loading; the second set represented increased loading. All other variables were held constant. The von Mises stresses and contact areas calculated on the tibial cartilage surfaces of the paired models were then compared. In the extended knee models, applying a larger load led to increased stress in the anterior and central regions of the medial tibial cartilage. These are the typical locations of medial osteoarthritis cartilage lesions. Therefore, the results support that increased loading in the extended knee may result in medial osteoarthritis. In the flexed knee models, applying a larger load increased stress in the anterior and central regions of the lateral tibial cartilage. Lateral osteoarthritis cartilage lesions typically occur centrally and posteriorly. Therefore, these results do not support our hypothesis. Shear stress was increased in areas of typical lateral lesions, however, and should be investigated in future studies., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background: Performance outcomes and return-to-play data have been reported after anterior cruciate ligament (ACL) injuries in professional football and basketball, but they have rarely been reported in professional hockey., Hypothesis: The hypothesis was that performance after ACL reconstruction would be comparable to prior levels of play in a series of National Hockey League (NHL) players., Study Design: Case series; Level of evidence, 4., Methods: The NHL Injury Surveillance System (ISS) was utilized to identify all players with an ACL injury between 2006 and 2010. Medical staff members for all NHL teams were surveyed regarding these injuries. The medical staff completed a questionnaire for each injury, and statistics were analyzed using multiple analyses of variance to compare outcomes, performance, and the complication rate. A control group was identified and matched based on performance, career length before injury, age, height, and weight., Results: There were 47 players identified by the NHL ISS. There were 3 goalies, 8 defensemen, and 36 wings or centers. The average age of these players was 27.69 years. The average length of time played after the injury was 2.8 years, which was less than that of the control group (4.4 years) (P = .004). The presence of a meniscal injury was associated with a decreased length of career compared with the control group (P = .012) and with patients with an isolated ACL injury (P = .002). For wings and centers, the number of games played decreased from 71.2 to 58.2 in the first full season after the injury (P = .05) and to 59.29 in the second season (P = .03). In the first season after the injury, for forwards and wings, assists and total points decreased from 20.3 and 35.2 to 13.8 (P = .005) and 25.9 (P = .018), respectively. In the second season after the injury, assists and goals decreased to 10.0 (P = .002) and 10.0 (P = .013), respectively. Compared with controls, the per-season averages of goals (P = .001), assists (P = .010), and total points (P = .004) decreased. Four players (8.5%) had subsequent failure of reconstruction, and there was a total reoperation rate of 20%. Five players (10.6%) did not return to play, and 4 (8.5%) were unable to return to play for a full season., Conclusion: Most players are able to return to play in the NHL after an ACL injury. However, career length and performance may be significantly decreased compared with controls. This may represent a more severe initial injury, and more focused return-to-play pathways may identify barriers to return to play., (© 2015 The Author(s).)

Purpose: Currently, there are no studies that clearly define a method for the placement of the fibular tunnel between the fibular collateral ligament (FCL) and popliteofibular ligament (PFL) insertions when performing an anatomic-based posterolateral corner reconstruction. The purpose of this study was to use magnetic resonance-based anatomic landmarks to describe the orientation of a fibular tunnel between the FCL and PFL insertions., Methods: Magnetic resonance imaging (MRI) of 105 patients with normal posterolateral corner knee anatomy was identified by a musculoskeletal radiologist, and the FCL and popliteofibular insertions were labelled. Three experienced providers independently evaluated the images. In the axial plane, the Cobb angle of a fibular tunnel from the FCL to the popliteofibular insertion was measured using the tibial tubercle as a reference. In the sagittal plane, the same tunnel was measured in reference to the lateral tibial plateau., Results: In the axial plane, the average Cobb angle for an anatomic-based fibular tunnel was 48.1° ± 10.7° (ICC(2,1) = 0.76, p < 0.01) externally rotated to the tibial tubercle. In the sagittal plane, the average Cobb angle for an anatomic-based fibular tunnel was 59.8° ± 11.9° (ICC(2,1) = 0.81, p < 0.01) cranial, referenced from the lateral tibial plateau. The average length of the fibular tunnel was 2.0 ± 0.4 cm (ICC(2,1) = 0.78, p < 0.01), at the point of the fibular insertion. The distance from the midpoint of the fibular tunnel to the posterolateral wall of the fibular head was 0.8 ± 0.2 cm (ICC(2,1) = 0.63, p < 0.01)., Conclusions: The results of this study suggest that MRI can be used to identify the orientation between the FCL and PFL insertions to create an anatomic-based fibular tunnel, which is 50° externally rotated from the tibial tubercle in the axial plane and placed in a cranial direction of 60° relative to the lateral joint line. The clinical relevance of this study is that this information may aid surgeons in placing a fibular tunnel connecting the FCL and PFL insertions., Level of Evidence: IV.

The human neocortex differs from that of other great apes in several notable regards, including altered cell cycle, prolonged corticogenesis, and increased size [1-5]. Although these evolutionary changes most likely contributed to the origin of distinctively human cognitive faculties, their genetic basis remains almost entirely unknown. Highly conserved non-coding regions showing rapid sequence changes along the human lineage are candidate loci for the development and evolution of uniquely human traits. Several studies have identified human-accelerated enhancers [6-14], but none have linked an expression difference to a specific organismal trait. Here we report the discovery of a human-accelerated regulatory enhancer (HARE5) of FZD8, a receptor of the Wnt pathway implicated in brain development and size [15, 16]. Using transgenic mice, we demonstrate dramatic differences in human and chimpanzee HARE5 activity, with human HARE5 driving early and robust expression at the onset of corticogenesis. Similar to HARE5 activity, FZD8 is expressed in neural progenitors of the developing neocortex [17-19]. Chromosome conformation capture assays reveal that HARE5 physically and specifically contacts the core Fzd8 promoter in the mouse embryonic neocortex. To assess the phenotypic consequences of HARE5 activity, we generated transgenic mice in which Fzd8 expression is under control of orthologous enhancers (Pt-HARE5::Fzd8 and Hs-HARE5::Fzd8). In comparison to Pt-HARE5::Fzd8, Hs-HARE5::Fzd8 mice showed marked acceleration of neural progenitor cell cycle and increased brain size. Changes in HARE5 function unique to humans thus alter the cell-cycle dynamics of a critical population of stem cells during corticogenesis and may underlie some distinctive anatomical features of the human brain., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Isolated injuries to the fibular collateral ligament (FCL) are rare. Although recent data suggest that operative and nonoperative treatment can both result in good functional outcomes, limited data exist on return to play for nonoperative treatment of FCL injuries and the value of magnetic resonance imaging in predicting prognosis. In this article, we present a review of the current literature and present a focused review regarding the diagnosis, treatment, and prognosis of FCL injuries, as well as the senior authors experience and a cohort of National Football League players. Magnetic resonance imaging can be useful to predict the length of disability in isolated FCL injuries, and both operative and nonoperative management of isolated FCL injuries successfully resulted in return to play in all players in several series of elite athletes; however, nonoperative management may result in faster return to play. Evaluation of potential concomitant injury is imperative in treatment of FCL injuries.

Astronauts experience Space Motion Sickness requiring treatment with an anti-motion sickness medication, scopolamine during space missions. Bioavailability after oral administration of scopolamine is low and variable, and absorption form transdermal patch is slow and prolonged. Intranasal administration achieves faster absorption and higher bioavailability of drugs that are subject to extrahepatic, first pass metabolism after oral dosing. We examined pharmacokinetics of 0.1, 0.2, and 0.4 mg doses of the Investigational New Drug formulation of intranasal scopolamine gel (INSCOP) in 12 healthy subjects using a randomized, double-blind cross-over study design. Subjects received one squirt of 0.1 g of gel containing either 0.1 mg or 0.2 mg/0.1 mL scopolamine or placebo in each nostril. Serial blood samples and total urine voids were collected after dosing and drug concentrations were determined using a modified LC-MS-MS method. Results indicate dose-linear pharmacokinetics of scopolamine with linear increases in Cmax and AUC within the dose range tested. Plasma drug concentrations were significantly lower in females than in males after administration of 0.4 dose. All three doses were well tolerated with no unexpected or serious adverse side effects reported. These results suggest that intranasal scopolamine gel formulation (INSCOP) offers a fast, reliable, and safe alternative for the treatment of motion sickness., (© 2014, The American College of Clinical Pharmacology.)

Purpose: To compare the accuracy and reliability of the anatomic and radiographic techniques for identifying the isometric point of the knee., Methods: Only four specimens were used; however, eight experienced multiligament knee injury surgeons were recruited to address this limitation. Surgeons estimated the isometric point (EIP) on the medial and lateral sides using an anatomic and radiographic method. The x and y coordinates of the EIP were compared to the true isometric point (TIP). T-tests and interclass correlation coefficients (ICC) were performed to determine the accuracy and reliability between the methods., Results: There was no difference in placement of the EIP on the medial side of the knee in the anterior/posterior (x; p = n.s.) and superior/inferior direction (y; p = n.s). The EIP was anterior (p = 0.001) to the TIP with the radiographic method on the lateral side and approached significance (p = 0.05) in the superior/inferior direction. The ICC (95% CI) for identifying the EIP on the medial side in the anterior/posterior direction using the anatomic method was 0.64 (0.28-0.96) and 0.11 (-0.06 to 0.77) in the superior/inferior direction. Using the radiographic method, the ICC in the anterior/posterior and superior/inferior direction was 0.49 (0.14-0.94) and 0.15 (-0.47 to 0.81), respectively. On the lateral side, the ICC for the anatomic method was 0.84 (0.56-0.99) in the anterior/posterior direction and 0.36 (0.05-0.90) in the superior/inferior direction. Using the radiographic method, the ICC in the anterior/posterior and superior/inferior direction was 0.61 (0.26-0.96) and 0.89 (0.67-0.99), respectively., Conclusions: There was no difference in accuracy on the medial side of the knee. On the lateral side, the anatomic method was more accurate in the anterior/posterior direction. Reliability was greater in the anterior/posterior direction on both sides of the knee. Surgeons were most likely to place the isometric point anterior and superior to the TIP on both the medial and lateral sides of the knee with either method which has the potential to cause graft lengthening. This should be taken into consideration during reconstruction/repair of the MCL/PMC and LCL/PLC.

In the past decade, there has been a major increase in the use of unicompartmental knee arthroplasty (UKA) as surgical techniques have been refined and patient selection has improved. UKAs now account for 8% to 10% of knee arthoplasty procedures. Recent studies have suggested excellent medium- and long-term results of UKA. Overall, results have shown 85% to 90% survivorship at 10 years, with 90% of patients reporting good to excellent subjective and objective outcomes. Recent studies suggest that unicompartmental arthroplasty allows a high percentage of patients to return to presurgical sport and activity participation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Previous work has shown that the hypersaline-adapted archaeon, Halobacterium salinarum NRC-1, is highly resistant to oxidative stress caused by exposure to hydrogen peroxide, UV, and gamma radiation. Dynamic alteration of the gene regulatory network (GRN) has been implicated in such resistance. However, the molecular functions of transcription regulatory proteins involved in this response remain unknown., Results: Here we have reanalyzed several existing GRN and systems biology datasets for H. salinarum to identify and characterize a novel winged helix-turn-helix transcription factor, VNG0258H, as a regulator required for reactive oxygen species resistance in this organism. This protein appears to be unique to the haloarchaea at the primary sequence level. High throughput quantitative growth assays in a deletion mutant strain implicate VNG0258H in extreme oxidative stress resistance. According to time course gene expression analyses, this transcription factor is required for the appropriate dynamic response of nearly 300 genes to reactive oxygen species damage from paraquat and hydrogen peroxide. These genes are predicted to function in repair of oxidative damage to proteins and DNA. In vivo DNA binding assays demonstrate that VNG0258H binds DNA to mediate gene regulation., Conclusions: Together these results suggest that VNG0258H is a novel archaeal transcription factor that regulates gene expression to enable adaptation to the extremely oxidative, hypersaline niche of H. salinarum. We have therefore renamed VNG0258H as RosR, for reactive oxygen species regulator.

Background: Syndesmotic sprains may be a significant source of missed playing time, especially in football players. Advanced imaging is frequently used to confirm the clinical diagnosis. Our purpose was to evaluate the prognostic ability of MRI in predicting time of disability., Methods: Training room records from 1993 to 2007 for three National Football League teams were reviewed. Forty-three players were diagnosed with syndesmotic ankle injuries and underwent radiographs and magnetic resonance imaging. A blinded musculoskeletal radiologist interpreted all images. Players with fractures were excluded., Results: Thirty-six professional football players were included in the final analysis. Twenty-three players had a positive squeeze test which was correlated with increased missed practices (p = 0.012) and increased missed games (p ≤ 0.01). The average number of games missed was 3.3 (range, 0 to 20) and the average number of practices missed was 16.7 (range, 0 to 114). Four players had isolated injury to the anterior tibio-fibular ligament (AITFL) (MRI Grade I). Five players had injury to the AITFL and interosseous ligament (MRI Grade II). Twenty-four players sustained injury to the AITFL, interosseous ligament, and posterior inferior tibio-fibular ligament (MRI Grade III). Three players had Grade III injuries with additional injury to the deltoid ligament (MRI Grade IV). Increasing grade of injury was positively correlated with increased number of missed games (p = 0.033) and missed practices (p = 0.002)., Conclusion: MRI can be useful to help delineate the injury pattern and associated injuries, and may be useful in predicting time of disability using a grading system. Positive squeeze test can also be useful to determine prognosis.

Objectives: To assess characteristics of high-risk populations tested for HIV at particular testing sites., Methods: BRFSS data (N=20,633) was used to quantify rates of HIV testing and identify specific racial/ethnic testing locations., Results: Analysis determined associations existing among high-risk individuals based on demographics. Testing differences were identified in racial/ ethnic groups among those at high-risk in the United States. HIV testing was more likely among high-risk African Americans (OR=1.62), other races (OR=1.42), and multiracial participants (OR=1.89) than whites., Conclusions: Minorities were more likely to be tested at locations such as hospitals and clinics supporting the need for alternative testing locations.

Purpose: The purpose of this study was to compare the costs associated with anterior cruciate ligament (ACL) reconstruction with either bone-patellar tendon-bone (BPTB) autograft or BPTB allograft., Methods: Surgical costs are reported, including supply costs, based on invoice costs per item used per procedure, and personnel costs calculated as cost per minute. All operations were performed at an ambulatory surgery center between March 2005 and March 2006. A total of 160 patients underwent primary ACL reconstruction with either BPTB autograft (n = 106) or BPTB allograft (n = 54). Procedure cost data were retrieved from a financial management database and divided into various categories for comparison of the 2 groups. Payment data were provided by the surgery center's billing office., Results: The total mean cost per case was $4,147 ± $943 in the allograft group compared with $3,154 ± $704 in the autograft group; this was statistically significant (P < .001). The mean operating room time was 12 minutes greater in autograft cases (P = .006). Supply costs comprised a mean of 58.7% of total expenses in the autograft group and 72.2% in the allograft group., Conclusions: Allograft reconstruction of the ACL was significantly more expensive than autograft reconstruction., Level of Evidence: Level II, economic analysis., (Published by Elsevier Inc.)

Combined anterior cruciate ligament, posterior cruciate ligament, and lateral-sided injuries of the knee most often occurs secondary to a forced varus moment or after knee dislocation. Management controversies include the optimal timing of surgery, operative techniques, and postoperative rehabilitation. Recent systematic literature reviews have demonstrated higher rates of failure with repair of the lateral and posterolateral corner structures, as opposed to reconstruction. However, the ideal ligament reconstruction techniques remain unclear. This chapter will review the combined anterior cruciate ligament/posterior cruciate ligament/lateral-sided injury pattern, including the physical examination findings, imaging, timing of surgery, graft selection, operative techniques, and postoperative rehabilitation protocols.

Efficacy and safety of medications used for the treatment of astronauts in space may be compromised by altered stability in space. We compared physical and chemical changes with time in 35 formulations contained in identical pharmaceutical kits stowed on the International Space Station (ISS) and on Earth. Active pharmaceutical content (API) was determined by ultra- and high-performance liquid chromatography after returning to Earth. After stowage for 28 months in space, six medications aboard the ISS and two of matching ground controls exhibited changes in physical variables; nine medications from the ISS and 17 from the ground met the United States Pharmacopeia (USP) acceptance criteria for API content after 28 months of storage. A higher percentage of medications from each flight kit had lower API content than the respective ground controls. The number of medications failing API requirement increased as a function of time in space, independent of expiration date. The rate of degradation was faster in space than on the ground for many of the medications, and most solid dosage forms met USP standard for dissolution after storage in space. Cumulative radiation dose was higher and increased with time in space, whereas temperature and humidity remained similar to those on the ground. Exposure to the chronic low dose of ionizing radiation aboard the spacecraft as well as repackaging of solid dosage forms in flight-specific dispensers may adversely affect stability of pharmaceuticals. Characterization of degradation profiles of unstable formulations and identification of chemical attributes of stability in space analog environments on Earth will facilitate development of space-hardy medications.

The ideal management of the dislocated knee remains controversial. These injuries often can be elusive; a significant number of dislocated knees spontaneously reduce and appear relatively benign on routine radiographs. A high index of suspicion, based on the mechanism of injury, soft-tissue assessment of the limb, and the level of knee instability should alert the physician to the possibility of a dislocated knee. Early recognition and appropriate neurovascular assessment is paramount to the successful treatment of these complex injuries. Controversies exist regarding surgical versus nonsurgical management, early versus delayed surgery, the use of allograft versus autograft tissue, the decision to repair versus reconstruct torn ligamentous structures, and the type of reconstruction technique and postoperative rehabilitation program. To achieve optimal patient care, it is important to be aware of the current evaluation and treatment strategies for complex knee ligament injuries, including modern anatomic reconstruction techniques. Current recommendations include measurement of the ankle-brachial indices in each patient, early surgical management, the use of autograft or allograft tissue, reconstruction as opposed to repair alone of the fibular collateral ligament/posterolateral corner structures, reconstruction of the anterior and posterior cruciate ligaments, and repair and/or reconstruction of the medial collateral ligament/posteromedial corner depending on the injury pattern and the quality of tissue.

An acute knee dislocation is an uncommon injury, with a high rate of associated vascular and neurologic injuries as well as potentially limb-threatening complications. High-energy trauma is the most common cause of an acute knee dislocation, although lower-energy injuries, such as those sustained during athletic competition, are increasing in incidence. Injuries to the popliteal artery and common peroneal nerve are relatively common, requiring a high index of suspicion and complete neurovascular examination in a timely fashion. All cases of suspected knee dislocation should have an ankle-brachial index performed, reserving arteriography for those with an abnormal finding. Initial management consists of closed reduction, if possible, and application of a hinged brace or external fixator. Definitive management remains an area of controversy, although anatomic surgical repair or reconstruction is favored by most surgeons to help optimize knee function. Most patients treated for a knee dislocation can expect to return to their daily activities, but with less predictable returns to sporting activities.

In an NASA ground study, two forms of cognitive tests were evaluated in terms of their sensitivity to sleepiness induced by the drug promethazine (PMZ). Performance for the two test modes (Y(1) and Y(2)), PMZ concentration, and a self-reported sleepiness using the Karolinska Sleepiness Scale (KSS) were monitored for 12 h post dose. A problem arises when using KSS to establish an association between true sleepiness and performance because KSS scores are discrete and also because they tend to concentrate on certain values. Therefore, we define a latent sleepiness measure X as an unobserved continuous random variable describing a subject's actual state of sleepiness. Under the assumption that drug concentration affects X, which then affects Y(1), Y(2), and KSS, we use Bayesian methods to estimate joint equations that permit unbiased comparison of the performance measures' sensitivity to X. The equations incorporate subject random effects and include a negativity constraint on subject-specific slopes of performance with respect to sleepiness.

Introduction: Scopolamine is an effective motion sickness prophylactic, but oral and transdermal formulations are slowly absorbed. To enhance absorption and potentially efficacy, an intranasal formulation of scopolamine (INSCOP) was tested., Method: There were 16 motion sickness susceptible subjects with an average age of 23.5 +/- 3.0 yr and an average score of 11.3 +/- 4.7 on the Modified Motion Sickness Susceptibility Questionnaire-Short Form who volunteered to participate in the study. Each subject was given 0.4 mg of INSCOP and a placebo in a randomized, double-blind crossover design and, at 40 min post-dose, experienced Coriolis cross-coupling in a staircase progression until moderate nausea. Efficacy data and cognitive, physiological, and alertness assessments were collected during baseline control and throughout experimental testing., Results: Intranasal scopolamine significantly increased the mean number of head movements tolerated [INSCOP 275.9 +/- 120.5, Placebo 230.7 +/- 76.4; t (15) = 2.21]. Estimation of medication absorption via plasma concentration indicated the drug was absorbed relatively rapidly to measurable levels by 15 min post-administration. Diastolic blood pressures and heart rate were significantly lower after administration of INSCOP compared to placebo. No significant cognitive or medication side effects were reported. Subjects reported no significant decrease in alertness as indicated by the Karolinska Sleepiness Scale., Conclusions: Results of the current study strongly suggest that intranasal scopolamine is efficacious for the treatment of motion sickness in susceptible individuals with no significant cognitive or sedative effects. Intranasal delivery offers a promising alternative for use in dynamic operational environments without cognitive detriment or increased side effects.

Objective: Although some research suggests that online eating disorder forums promote "pro-eating-disorder" lifestyles and discourage recovery, other research suggests that such forums are an important source of interpersonal support. The current study extends this research by exploring the positive and negative behaviors encouraged on these forums and by comparing forum members' perceptions of support received from online and offline relationships to support received in relationships of age-matched controls., Method: In a survey of 60 forum members, we assessed information exchanged and support provided on eating disorder forums. Further, we assessed perceptions of social support for general and specific life concerns in this group of forum members as well as 64 age-matched university controls., Results: Results show that both adaptive and maladaptive behaviors are encouraged on the forums, and that this encouragement has some influence on forum members trying out these behaviors. Overall, forum members reported receiving less support for their eating concerns as compared to their general life stressors, and they perceived less support for both their general concerns and eating concerns in their offline relationships as compared to their online forum relationships. Moreover, forum members reported receiving less support from their offline relationships as compared to support received in relationships by age-matched controls., Discussion: Forum members perceive less support in their important relationships than other peers do, and they seek out and participate in forums as a means of attaining greater social support. However, our research suggests that these forums also encourage dysregulated eating behaviors. Implications of online forum support and its impact on recovery are discussed further.

Purpose: The purpose of this systematic review was to address the treatment of multiligament knee injuries, specifically (1) surgical versus nonoperative treatment, (2) repair versus reconstruction of injured ligamentous structures, and (3) early versus late surgery of damaged ligaments., Methods: Two independent reviewers performed a search on PubMed from 1966 to August 2007 using the terms "knee dislocation," "multiple ligament-injured knee," and "multiligament knee reconstruction." Study inclusion criteria were (1) levels I to IV evidence, (2) "multiligament" defined as disruption of at least 2 of the 4 major knee ligaments, (3) measures of functional and clinical outcome, and (4) minimum of 12 months' follow-up, with a mean of at least 24 months., Results: Four studies compared surgical treatment with nonoperative treatment. There was a higher percentage of excellent/good International Knee Documentation Committee (IKDC) scores (58% v 20%) in surgically treated patients, as well as higher rates for return to work (72% v 52%) and return to full sport (29% v 10%). Two studies compared repair with reconstruction of damaged structures, with similar mean Lysholm scores (88 v 87) and excellent/good IKDC scores (51% v 48%). However, repair of the posterolateral corner had a higher failure rate (37% v 9%). Similarly, repair of the cruciates yielded decreased stability and range of motion and a lower return to preinjury activity levels (0% v 33%). There were 5 studies comparing early surgery (

The NASA Reduced Gravity Office (RGO) uses scopolamine (SCOP) alone and in combination with dextoamphetamine (DEX) to treat motion sickness symptoms during DC-9 parabolic flights. The medications are sometimes dispensed as custom dosage forms in gelatin capsules for convenience. Reports of treatment failure during flights by the flight surgeons suggest that these formulations may be less efficacious for the treatment of motion sickness due to unreliable and inadequate bioavailability. We estimated bioavailability of four different oral formulations used by the NASA RGO physicians for the treatment of motion sickness.

The team physician landscape is littered with political land mines. In the high-stakes world of professional sports, the politics of each encounter and medical decision--from figuring out how to get hired, to setting up a communication chain of command, to treating visiting players, to fending off the media--must be identified, assessed, and resolved. Key information must be communicated according to the expectations and unique personalities of each owner, general manager, coach, trainer, and athlete. The best team physicians manage relationships, competing agendas, and politically charged circumstances as adeptly as they wield a scalpel.

Most of the previously reported lumbosacral nerve root avulsions presented with pseudomeningoceles at the time of delayed initial imaging. We report a case of traumatic lumbosacral nerve root injury associated with an isolated femur fracture and demonstrate the evolution of pseudomeningoceles following nerve root avulsions and edema in the perineural fat identified on the initial MR imaging.

Gas-solid chromatography was used to obtain second gas-solid virial coefficients, B2s, in the temperature range 342-613 K for methane, ethane, propane, butane, 2-methylpropane, chloromethane, chlorodifluoromethane, dichloromethane, and dichlorodifluoromethane. The adsorbent used was Carbosieve S-III (Supelco), a carbon powder with fairly uniform, predominately 0.55 nm slit width pores and a N2 BET surface area of 995 m2/g. The temperature dependence of B2s was used to determine experimental values of the gas-solid interaction energy, E*, for each of these molecular adsorbates. MM2 and MM3 molecular mechanics calculations were used to determine the gas-solid interaction energy, E*(cal), for each of the molecules on various flat and nanoporous model surfaces. The flat model consisted of three parallel graphene layers with each graphene layer containing 127 interconnected benzene rings. The nanoporous model consisted of two sets of three parallel graphene layers adjacent to one another but separated to represent the pore diameter. A variety of calculated adsorption energies, E*(cal), were compared and correlated to the experimental E* values. It was determined that simple molecular mechanics could be used to calculate an attraction energy parameter between an adsorbed molecule and the carbon surface. The best correlation between the E*(cal) and E* values was provided by a 0.50 nm nanoporous model using MM2 parameters.

The interpretation of results measured by quantitative ultrasound (QUS) of the heel depends on the population studied. We measured estimated bone mineral density (BMD) of the heel using the Hologic Sahara sonometer. People were studied at county fairs, health fairs, and churches. Subjects were not on treatments that would affect bone density, other than calcium supplementation. This included 823 Caucasian women, 131 African American women, and 301 Caucasian men. In contrast to women, for Caucasian men the squared term for age was not significant, and a straight line of decline was the best fit for estimated BMD. African American women had a standard deviation larger than that reported by Hologic for Caucasian women. We compared a history of self-reported fractures with a subject's estimated BMD. An estimated BMD of 0.57 gm/cm2 included 75% of all fractures. This cutoff point was associated with increased fracture prevalence in subjects over age 50, relative risk of 1.4. This result corresponds to the Hologic data T-score of -0.2. When used as a screening tool for osteoporosis fracture risk, an estimated BMD of 0.57 gm/cm2 seems reasonable in those subjects over age 50.

Background: The ideal treatment for patients presenting with bilateral anterior cruciate ligament (ACL) deficiency remains controversial., Purpose: To evaluate cost and early functional results after bilateral ACL reconstruction at a single setting., Study Design: Retrospective review., Methods: Eleven patients (22 knees) who underwent bilateral ACL reconstruction at a single setting were compared with 33 patients (35 knees) who underwent unilateral ACL reconstruction during the same time period., Results: The mean time to full unrestricted activity between groups was 6.5 months for both groups (P = 0.92). There were no significant differences between groups at latest follow-up for complication rates or laxity as judged by Lachman test, pivot shift test, and KT 1000 arthrometry. The mean International Knee Documentation Committee subjective score at a mean 3.1-year follow-up was 91.9 for the bilateral ACL group compared to 92.0 for the unilateral ACL group (P = 0.95). There was a total cost savings per knee (based on 2001 dollars) of $3751.59 when performing bilateral ACL reconstruction at a single setting (P = 0.0001)., Conclusions: For patients presenting with bilateral ACL deficient knees, reconstruction of both knees at a single setting is safe, cost effective, and does not appear to compromise early functional results.

Optimal information that should be included in ultrasound (US) heel bone mineral density (BMD) reports is not known. If additional information about further evaluation of patients with low heel BMD were included in reports, would responses for treatment improve? We screened people at health fairs using the Sahara heel US machine. For those with a T-score of

Previously we identified 4-[1-(4-hydroxyphenyl)-2-phenylbuten-1-yl]phenoxy-n-butyric acid (4HBA) and its des-hydroxy analog (BA) as potential selective estrogen receptor modulators (SERMs) in the ovariectomized (OVX) rat. The aim of the present study was to characterize comprehensively the effects of 4HBA and BA in both the OVX rat and in estrogen-responsive cells. Thus, 4HBA was found to be an estrogen antagonist with partial agonist efficacy in estrogen-responsive reporter gene and estrogen-dependent proliferation assays (MVLN cells and MCF-7 human breast cancer cells, respectively). In the OVX rat, 4HBA and BA were equally effective and comparable to other known SERMs regarding (a) serum cholesterol reduction and suppression of serum markers of excessive bone metabolism, and (b) partial agonist efficacy in reproductive tissue relative to steroidal estrogens. Like steroidal estrogens, both compounds increased serum triglyceride levels, with BA being more effective in this regard. The maximal effects of 4HBA on all of these parameters except cholesterol lowering were seen at oral doses of 0.4 micromol/kg/day; maximal cholesterol lowering required doses of 10 micromol/kg/day. In OVX rat liver 9S fraction, BA was found to be efficiently converted to a single hydroxylated metabolite, 4HBA. These results suggest that the effects of BA in the OVX rat might, in part, be a consequence of biotransformation to 4HBA, and that those of 4HBA and BA in the OVX rat and in estrogen-responsive cells are qualitatively similar to those of SERMs such as tamoxifen and raloxifene.

Aims: Local prostaglandin (PG) production contributes to tachyphylaxis to angiotensin II (ANGII) in veins. Our aim was to assess the hypothesis that local nitric oxide (NO) generation is also, in part, responsible for tachyphylaxis to ANGII in veins, using the Aellig dorsal hand vein technique., Methods: Eight healthy male volunteers received 600 mg of aspirin (orally) to inhibit PG production. The venoconstrictor effects of ANGII and noradrenaline (NA) were then compared in dorsal hand veins during co-infusion of the NO synthase inhibitor L-NMMA or saline, on separate occasions., Results: ANGII and NA produced a similar degree of initial venoconstriction. However, the response to ANGII was significantly attenuated by 12 min compared with NA (AUC 147 +/- 38 vs 196 +/- 40, respectively; [95% confidence interval for difference: 7, 92], P = 0.02). Infusion of L-NMMA did not influence the response to ANGII or NA (P = 0.2 and P = 0.3, respectively)., Conclusions: Tachyphylaxis to ANGII in dorsal hand veins is not dependent on local NO release.

Previously, the estrogen receptor (ER) ligand 4-[1-(p-hydroxyphenyl)-2-phenylethyl]phenoxyacetic acid (5) was found to have differential bone loss suppressive effects in the ovariectomized (OVX) rat approaching those of selective ER modulators (SERMs) such as tamoxifen. In an effort to improve efficacy, analogues of this compound were prepared which incorporated features designed to reduce polarity/ionizability. Thus, the acetic acid side chain of 5 was replaced by n-butanoic acid and 1H-tetrazol-4-ylmethyl moieties, to give 8 and 10, respectively. Also, the phenolic hydroxyl of 5 was replaced, giving deoxy analogue 9. We also developed new methods for the synthesis of triarylethylene variants of 5 and 9, namely 4-([1-(p-hydroxyphenyl)-2-phenyl-1-butenyl]phenoxy)-n-butanoic acid (6) and its des-hydroxy counterpart (7), because the former of these had in vitro antiestrogenic effects characteristic of known SERMs. In the OVX rat, 6 and 7 were as effective as 17 beta-estradiol in suppressing serum markers of bone resorption/turnover, namely osteocalcin and deoxypyridinoline, but had only 30% of the uterotrophic efficacy of 17 beta-estradiol. This study has thus identified two triarylethylene oxybutyric acids, 6 and 7, that have differential bone/uterus effects like those of known SERMs.