Rosarosales9827

Functional performance tests provide quantitative information on specialized sport movements and are important for documenting training and fatigue. The single leg, medial countermovement jump provides objective measures of frontal plane force, velocity and power, and is relevant for ice hockey players given the similar lateral movement to ice skating. This study measured normative single leg, medial countermovement jump parameters (i.e., vertical and lateral maximum force, average concentric power and average concentric power during the last 100 ms) amongst male youth ice hockey players and assessed interlimb asymmetry in these healthy athletes. Ninety-one elite youth players participated in the study. Participants completed three right and three left jumps. Non-parametric tests were performed to evaluate between-jump and between-group comparisons. Many differences in jump force and power parameters were observed between the 10U/11U and 12U/13U age groups, and the 12U/13U and 14U/15U age groups, but differences were not as consistent between older or younger players. The average asymmetry index for each age group was less than 15% for force parameters, while the power parameters had larger asymmetry indices (between 9% and 22%). Our results provide age-specific reference values and asymmetry indices for male elite youth ice hockey players aged 10-18 years performing the single leg, medial countermovement jump.Small-sided games (SSGs) are common drills used in various team sports, but the exercise intensity in ultimate Frisbee SSG has not yet been investigated. To clarify the physical, physiological, and technical demands of ultimate Frisbee SSG, we investigated the influence of pitch size on exercise intensity during SSG. Nine male college ultimate Frisbee players played (3 vs. 3) SSG on small (SSGS 30 × 15 m) and large (SSGL 40 × 20 m) pitches; both SSGs comprised of four 4 min periods, interspersed by 5 min of passive recovery. Players' mean heart rate (170 ± 8 and 171 ± 7 bpm), peak heart rate (184 ± 7 and 184 ± 5 bpm), and blood lactate concentration (11.3 ± 4.7 and 11.8 ± 4.6 mmol/L) were similar in SSGS and SSGL, respectively. The total distance covered (1984 ± 166 m and 1702 ± 80 m) and the distance covered during quick (860 ± 112 m and 696 ± 69 m) and high-intensity running (439 ± 95 and 255 ± 44) in SSGL were significantly longer than those in SSGS (p less then 0.05). Conversely, the number of accelerations (45 ± 3 and 41 ± 3) and decelerations (44 ± 3 and 40 ± 4), catching errors (2 ± 1 and 1 ± 1), and turnovers (8 ± 2 and 6 ± 2) in SSGS were significantly greater than those in SSGL (p less then 0.05). This study suggests that ultimate Frisbee SSG provides high-intensity training, which stimulates the glycolytic pathway. Furthermore, manipulating SSG pitch size effectively modulates the physical demands of SSG.Introduction A thorough understanding of skull base anatomy is imperative to perform safely and effectively any skull base approach. In this article, we examine the microsurgical anatomy of the skull base by proposing a modular topographic organization in the median, paramedian, and lateral surgical corridors in relation to transcranial and endoscopic approaches. Methods Five dry skulls were studied focusing on the intracranial and exocranial skull base. Two lines were drawn parallel to the lateral border of the cribriform plate of the ethmoid bone and foramen lacerum, respectively. Lines 1 and 2 delimited the median, paramedian and lateral corridors of the skull base. The bony structures that formed each corridor were carefully reviewed in relation to the planning and execution of the skull base transcranial and endoscopic approaches. Results The midline corridor involves the crista galli, cribriform plate, planum and jugum sphenoidale, chiasmatic sulcus, tuberculum sellae, sellar region, dorsum sellae, clivus, and foramen magnum. The paramedian corridor includes the fovea ethmoidalis, the root of the lesser and greater sphenoid wing, anterior clinoid process, foramen lacerum, the upper half of the petro-occipital suture, and jugular tubercle. The lateral corridors include the orbital plates, sphenoid wings, squamosal and petrous parts of the temporal bone, caudal aspect of the petro-occipital suture, internal auditory canal, jugular foramen, the sulcus of the sigmoid sinus. Conclusion In-depth three-dimensional knowledge of skull base anatomy based on the modular concept of the surgical corridors is critical for the planning and execution of the transcranial and endoscopic approaches.Introduction Treatment of cranial neurovascular pathology requires a detailed understanding of the brain, head, and neck vasculature. This study aims at a comprehensive overview of the microsurgical anatomy of the anterior cerebral circulation. Methods Five formalin-fixed adult cadaveric heads were used. Common carotid arteries, vertebral arteries, and internal jugular veins were injected with colored latex (red for arteries and blue for veins). The heads were dissected under a surgical microscope with magnifications ranging between 3× to 40× focusing on the anterior circulation. A synoptic approach was used to describe in detail the segments, branches, perforating arteries, veins, and vascular territories of the cerebral arteries and veins. Results The anterior arterial circulation of the brain is provided by the internal carotid artery (ICA), anterior cerebral artery (ACA), middle cerebral artery (MCA), anterior communicating artery (ACoA), and perforating arteries. Perforating arteries of the anterior circulation arise from the ICA, ACA, MCA, ACoA, and posterior communicating artery (PCoA). The distal segments and collateral branches of the ICA, ACA, and MCA give the arterial supply to the largest part of the forebrain, whereas perforating arteries of the anterior circulation are related to the striatum, thalamus, and basal ganglia. The ACoA is the core functional anastomosis between the left and right ICA systems. The external carotid artery provides the vascular supply to the region of the face, head, and neck, and most of the meninges. The internal jugular venous system is composed of the internal and external jugular veins, which constitutes the outflow of the cerebral and facial venous system, respectively. Conclusion Thorough knowledge of the topographic, cisternal, and functional anatomy of the anterior circulation of the brain is critical for surgery of the supratentorial lesions.Introduction Vascular complications of posterior fossa surgery are often deadly although widely preventable through in-depth knowledge of the microsurgical neurovascular anatomy of the infratentorial region and careful surgical planning. The target of this study is to provide a synoptic overview of the normal anatomy and anatomic variants of the infratentorial neurovascular system, critical to safely operate tumors and neurovascular pathologies of the posterior fossa. Methods Two fresh-frozen and five formalin-fixed cadaveric heads were used. Cervical arteries and internal jugular veins were injected with red and blue latex, respectively. The heads were dissected under a surgical microscope, with magnifications ranging between 3× to 40×, focusing on the infratentorial region. The infratentorial arteries, their collaterals and perforating branches, the brainstem and cerebellar veins, the tentorial venous sinuses, and the relative vascular territories were summarized according to a synoptic approach. Results Thl region is vital for the planning and execution of the whole range of posterior fossa approaches.

Antibiotics represent the most widely prescribed drugs in children worldwide, both in hospital and community settings. A comprehensive approach to understanding the reasons and determinants of antibiotic prescription in the pediatric age is needed. This study aimed to assess parents' attitudes and perspectives about antibiotic use.

Prospective observational study was conducted in all Italian Regions between February 1 and April 30, 2020, using a standardized questionnaire.

Six thousand six hundred twenty-five parents from all Italian regions completed the survey. Seventy-six percent of parents were aware that only bacteria are the target of antibiotics, but 92.9% knew that the antibiotic has no direct effect on fever. Antibiotic self-prescription (10.4%) or by remote consultation by phone call (19.9%) or message (9.6%) were relatively common. Ninety-three percent of parents were aware that excessive use of antibiotics could select resistant bacteria and 84.7% of them knew that they could actively fight ilies from low-income settings or those born abroad have significantly more misconceptions about important antibiotic practices.Bleeding remains a major source of morbidity associated with veno-venous extracorporeal membrane oxygenation (VV-ECMO). Moreover, there remains significant controversy, and a paucity of data regarding the ideal anticoagulation strategy for VV-ECMO patients. All patients undergoing isolated, peripheral VV-ECMO between January 2009 and December 2014 at our institution were retrospectively reviewed. Patients (n = 123) were stratified into one of three sequential eras of anticoagulation strategies activated clotting time (ACT 160-180 seconds, n = 53), high-partial thromboplastin time (H-PTT 60-80 seconds, n = 25), and low-PTT (L-PTT 45-55 seconds, n = 25) with high-flow (>4 L/min). Pre-ECMO APACHE II scores, SOFA scores, and Murray scores were not significantly different between the groups. Patients in the L-PTT group required less red blood cell units on ECMO than the ACT or H-PTT group (2.1 vs. 1.3 vs. 0.9; p less then 0.001) and patients in the H-PTT and L-PTT group required less fresh frozen plasma than the ACT group (0.33 vs. 0 vs. 0; p = 0.006). Overall, major bleeding events were significantly lower in the L-PTT group than in the ACT and H-PTT groups. There was no difference in thrombotic events. In this single-institution experience, a L-PTT, high-flow strategy on VV-ECMO was associated with fewer bleeding and no difference in thrombotic events than an ACT or H-PTT strategy.Acute respiratory distress syndrome (ARDS) secondary to influenza in adults is associated with a high rate of morbidity and mortality. Extracorporeal membrane oxygenation (ECMO) is a supportive alternative for severe and refractory cases. This study aimed to perform a hospital-based case-control study between February 2018 and February 2020 for determining the factors associated with 30 day survival in adults with severe ARDS caused by influenza infection who are provided ECMO support. A total of 17 adults received ECMO support, mostly veno-venous for hypoxemic respiratory failure, with a 30 day survival rate of 65%. The cohort of patients who did not survive at 30 days compared with the cohort of those who did survive had higher body mass index (34 vs. 31), higher Sequential Organ Failure Assessment score (9.5 vs. 7) and lower Respiratory ECMO Survival Prediction score (2 vs. 4). This study shows the importance of evaluating the severity scores of patients before ECMO support initiation, which offers an acceptable survival in patients with severe ARDS, making it a feasible alternative in critical patients who are refractory to conventional management.Long-term continuous-flow left ventricular assist device (CFLVAD) therapy is limited by complications. Compared with stroke and renal dysfunction, post-CFLVAD bowel ischemia is poorly characterized. Adult patients who underwent first-time durable CFLVAD implantation at our institution between 2008 and 2018 were identified and screened for bowel ischemia using Current Procedural Terminology codes for abdominal surgical exploration and International Classification of Disease codes for intestinal vascular insufficiency. Patients who developed biopsy-proven bowel ischemia (cases) were matched to controls (11, nearest neighbor, caliper = 0.29) based on preoperative characteristics. Incidences of postoperative right heart failure and renal replacement therapy were compared using McNemar's test. One year survival was estimated using the Kaplan-Meier method. Overall, 711 patients underwent CFLVAD implantation. Nineteen (2.7%) developed bowel ischemia (cases) median 17 days postimplantation (IQR 8-71). The majority of cases were male (78.9%), Black (63.2%), received HeartMate II (57.9%), treated as destination therapy (78.9%), and had a history of hypertension (89.5%), chronic kidney disease (84.2%), hyperlipidemia (84.2%), smoking (78.9%), and atrial fibrillation (57.9%). Post-LVAD, case patients were more likely to develop moderate-severe right heart failure (89.5% vs. 68.4%, p = 0.005), require renal replacement therapy (21.1% vs. 0%, p less then 0.001), and less likely to survive to discharge (52.6% vs. 89.5%, p = 0.02) compared with controls. Case subjects demonstrated worse 1 year survival. While less common than stroke and renal dysfunction, post-CFLVAD bowel ischemia is associated with high 1 year mortality. Multi-institutional registries should consider reporting abdominal complications such as bowel ischemia as an adverse event to further investigate these trends and identify predictors of this complication to reduce patient mortality.

Most of the current orthopaedic residents are considered Millennials (born between 1981 and 1996) and are often trained by attending surgeons who are from Generation X (born between 1965 and 1980) or the Baby Boomer generation (born between 1946 and 1964). The Generation X orthopaedic surgeons were largely trained by Baby Boomers who were very demanding of their trainees and expected excellence. The Baby Boomers had been inspired, mentored, and trained by the Greatest Generation (born between 1901 and 1927). Baby Boomers took nothing for granted and nothing was given to them on a silver platter. Generation X was trained under these premises and was expected to abide by similar values. Regarding the next generation of residents, current faculty hope to instill the same qualities that had been instilled in them during their training. This value transference sometimes presents a challenge because of the differences in attitudes and perspectives that may exist between Millennial residents and their predecessors Baby Boomers took nothing for granted and nothing was given to them on a silver platter. Generation X was trained under these premises and was expected to abide by similar values. Regarding the next generation of residents, current faculty hope to instill the same qualities that had been instilled in them during their training. This value transference sometimes presents a challenge because of the differences in attitudes and perspectives that may exist between Millennial residents and their predecessors regarding work-life balance, teaching styles, the regulation of duty hours, and feedback assessments. These differences require an evolution in the methods of surgical education to optimize the educational benefit and ensure good will and rapport between the generations. Trainees and faculty alike have a responsibility to understand each other's differences and come together to ensure that knowledge, experience, values, and skill sets are effectively passed on to a new generation of orthopaedic surgeons.This article describes the staged restructure of the rapid response program into a dedicated 24/7 proactive rapid response system in a quaternary academic medical center in the southern United States. Rapid response nurses (RRNs) completed clinical leadership training on artificial intelligence, electronic risk stratification alerts, expert nurse rounding, emergency response, teamwork, closed-loop communication, and outcome measurement. The program goal was to reduce preventable deaths and resuscitation events outside the intensive care unit (ICU). Program outcomes between 2017 and 2019 included a 65% decrease in cardiac arrests outside the ICU, a 27% decrease of cardiac arrests inside the ICU, a 4.7% decrease in patients admitted to the ICU from inpatient beds, and a 27% reduction in the risk-adjusted mortality index for patients with expert proactive rounding encounters. Hospital peer group ranking on the Hospital Survey of Patient Safety improved in the areas of events reported, actions promoting patient safety, and continuous improvement suggesting a positive cultural shift. Implementation of a dedicated 24/7 RRN model of care integrating proactive rounding, technology, and ART can improve outcomes for patients and staff.Critically ill patients usually experience a significant level of pain during rest or during routine care such as turning, wound care, and endotracheal suctioning. Pain assessment is the cornerstone of pain management. Adequate pain assessment and management are major responsibilities of critical care nurses. The purpose of this study was to evaluate the nurses' knowledge, attitudes, and practices toward pain assessment and management of the intensive care unit (ICU) patients who are unable to communicate verbally. A descriptive cross-sectional design was used in this study. The study was conducted at ICUs in 5 hospitals from the north, middle, and south areas of Jordan. A self-administered questionnaire developed by Rose was used in this study. The most important finding in this study was that a large number of ICU nurses do not use assessment tools to evaluate the level of pain in patients who are unable to communicate verbally. Moreover, the nurses have inadequate knowledge about pain assessment and management. As perceived by the nurses, "restlessness" was the highest rated routine indicator of pain (25.1%), followed by "not following commands" (24%). Half of the participants (50%) answered that nurses were the persons who provide the most accurate rating of pain intensity. However, the participants showed positive attitude toward pain assessment and management.Adequate safety precautions and proper use of personal protective equipment (PPE) in hospitalized patients with health care-associated infections (HAIs) are the most effective preventions in their spread. Observational study was conducted in one inpatient facility in the Czech Republic before the COVID-19 pandemic (April 2019 to February 2020). Data were analyzed using Minitab at a significance level of .05. The execution of preventative measures in patients hospitalized with a HAI (n = 44) and the use of PPE by health care workers (n = 514) have been observed. The presence of defined PPE items usage differs on the basis of the department type (P = .0004). The correctness of PPE use differs on the basis of profession (P less then .001), hand disinfection before PPE use (P less then .001), use of all PPE (P less then .001), and hand hygiene after PPE use (P less then .001). General nurses had a higher observed frequency of hand hygiene (53.3%) than physicians (42.4%). The correct order of operations when using PPE differs on the basis of the department type (P less then .001) and their architecture arrangement (open, semiopen, box) (P less then .001). Critical preventative measures shortage was found at all units. Insufficient execution of the correct procedure of actions in the use of PPE was observed among health care workers. The best results have been observed among nurses.Delirium is an indicator of morbidity and mortality in intensive care unit (ICU) patients. It can lead to negative outcomes and longer hospital stays, thus increasing hospital costs. Despite national recommendations for daily assessment of delirium, it remains underdiagnosed. Many studies point to a lack of knowledge among health care professionals to accurately detect and manage ICU delirium. The aim of our study was to assess the knowledge, attitudes, and practices of Palestinian health care professionals regarding ICU delirium. The results of a cross-section observational study revealed that delirium appears to be often underrecognized or misdiagnosed in ICUs in Palestine. Therefore, it is critical to further educate the medical and nursing teams and to promote the use of validated tools that can aid in the assessment of this condition. In this way, the length of hospital stays and related health care costs can be reduced.The objective of this study was to determine the experience of the nurses who provide health care in the final stages of life in the intensive care unit for adults. The authors report the results of their study, which used a qualitative design with a phenomenological approach. Eighteen adults participated by being interviewed using semistructured questions. The nurses expressed that health care at the end of life represents an emotional and psychological burden for them. They also recognized that health care was given based on the empiricism achieved through clinical experience. In this regard, they emphasize the importance of having the proper education in this area to provide comprehensive care to the patient, the family, and the nurse.The number of patients with chronic diseases requiring invasive mechanical ventilation at home is increasing. Thus, identifying the challenges of this valuable type of care can be an elective step for achieving health-related goals. This study was conducted to determine the challenges faced by home health care providers. Three themes emerged from the data analysis (1) hospital-based challenges with 2 subthemes the family unpreparedness for home care and the lack of continuous education; (2) home health care agency challenges with 2 subthemes home health care workers and the deficiency in organizational policies; and (3) economic challenges. Three themes of hospital-related challenges, home health care agency challenges, and economic challenges that emerged in the study showed that support from the insurance system, improvement of home care agency policies, and holistic care for patients through a multidisciplinary team approach are essential for addressing the current challenges of care for patients under invasive mechanical ventilation at home.Determining the treatment plan and how to successfully manage a patient suffering from an acute ischemic stroke can be challenging for a registered nurse (RN) in the emergency department. Using a mnemonic in the treatment process assists in reducing medical errors and increases the likelihood of making positive clinical outcomes. Mnemonics sum up complex strategies into relevant information that can be comprehensible for users. The authors have created a mnemonic strategy to provide RNs in the emergency department with a structured approach to the pharmacotherapeutic strategies used in treating patients with an acute ischemic stroke. All guidelines used throughout the article are in concurrence.Social media has changed the way individuals communicate and recently multiple articles have been published highlighting the utilization of social media for education. To our knowledge, cross-discipline education utilizing these platforms has not been evaluated. The purpose of this study was to implement a pharmacist-led, social media-based nursing education program and evaluate the perceived value. A curriculum of pharmacy-related issues was developed and topics were posted to the neurocritical care unit (NCCU) Facebook group or emailed to non-Facebook users weekly. A pre- and posteducation survey was sent out evaluating the program's effectiveness. Thirty-seven nurses were members of the NCCU Facebook group and 33 received the education via email. A total of 29% and 19% of nurses completed the pre- and posteducation survey, respectively. Of those who completed the survey, 36% received education via Facebook. As compared with the preeducation survey, there were no statistically significant differences in nursing performance on fact-based questions (P value > .05 on all assessment questions); however, 100% of respondents wanted to continue this education delivery. Utilizing social media as a means of cross-discipline education was well-received; however, the solitary utilization should be used cautiously, as performance did not improve on assessment questions.

We investigated the relationship between the loaded pressure and flow rate in various catheters and the entire infusion line including the catheters, in several infusion solutions and packed red blood cells.

We connected the infusion line and catheter to the infusion solution and used an outer pressure bag or a compressor to pressurize the infusion solution bag to a pressure within the clinical (up to 450 mm Hg) or higher range (up to 1050 mm Hg). We approximated the relationship between the loaded pressure and flow rate in the entire infusion line including the catheter, versus the catheter alone, as a power function and compared the power numbers.

In the clinical pressure range of normal saline, the power numbers of the entire infusion line for the 24-, 22-, 20-, and 18-gauge catheters were 0.76, 0.82, 0.81, and 0.86, respectively, while those for the catheter alone were 0.67, 0.63, 0.56, and 0.44, respectively. In the higher pressure range of normal saline, the power numbers of the entire infusion lipressure range (up to 450 mm Hg), the relationship between the flow rate and pressure in the entire infusion line was almost linear and proportional.

The American Academy of Orthopaedic Surgeons American Joint Replacement Registry (AJRR) is the largest registry of total hip and knee arthroplasty (THA and TKA) procedures performed in the United States. The purpose of this study was to examine whether AJRR data are representative of the national experience with hip and knee arthroplasty as represented in the National (Nationwide) Inpatient Sample (NIS).

All patients undergoing a THA or TKA procedure between 2012 to 2018 (AJRR) and 2012 to 2016 (NIS) were identified. Cohen d effect sizes were computed to ascertain the magnitude of differences in demographics, hospital volume (in 50 patient increments), and geographic characteristics between the AJRR and NIS databases.

The study included (NIS 2,316,345 versus AJRR 557,684) primary THA and (NIS 3,417,700 versus AJRR 809,494) TKA procedures. The magnitude of distribution, as determined by the Cohen d effect size, showed that the proportions of AJRR and NIS patients were similar based on overall sex (THAs [d = 0.03] and TKAs [d = 0.02]) and age (THAs [d = 0.17] and TKAs [d = 0.12]). Similarly, only small differences (d = 0.34 or less) were identified between databases considering hospital volume and geography. The AJRR was underrepresented in Southern regions and hospitals with low procedure volume and overrepresented in Northern hospitals and those with larger volume. Both the NIS and the AJRR followed a similar overall trend, with most procedures performed at hospitals with <50 cases per year.

Distributions across hospital volume, age, and geography were proportionally similar between the AJRR and NIS databases, supporting the generalizability of AJRR findings to the larger US cohort.

Distributions across hospital volume, age, and geography were proportionally similar between the AJRR and NIS databases, supporting the generalizability of AJRR findings to the larger US cohort.

Cutibacterium acnes is a common pathogen associated with surgical site infection after shoulder surgery; current standard of care products are largely ineffective at reducing C acnes bacterial burden before surgery. The purpose of this systematic meta-analysis was to assess the efficacy of peroxide-containing solutions (PCS) in decreasing the C acnes burden on the shoulder.

This was a systematic review of all level I and II studies investigating the effect of peroxidase-containing products for skin preparation. We extracted data regarding demographics, treatment details and timing, study methodology, and culture positivity. Forest plots were used to determine the pooled efficacy of peroxide solutions versus control.

Seven studies with 412 patients were eligible for inclusion. Notable heterogeneity was observed in the manner and timing of peroxide application. Two studies applied PCS at the time of surgery; four studies applied PCS in the 24- to 72-hour period leading up to culture acquisition. Compared with the placebo, peroxide significantly diminished C acnes culture positivity (Hazard Ratio 0.174, P = 0.009). When considering using peroxide-containing products in the period leading up to surgery or at the time of surgery, in addition to standard preparation, the addition of peroxide significantly diminished C acnes culture positivity (HR 0.467, P = 0.004). Owing to study heterogeneity, we could not make notable comparisons based on the timing or duration of benzoyl peroxides application.

Despite heterogeneity in study design, pooled results of high-quality data suggest that the addition of PCS can markedly reduce C acnes bioburden. This review was not able to identify the ideal regimen for the utilization of PCS for reduction of C acnes burden.

Level II.

Level II.

Current guidelines recommend shared surgical decision-making, yet it is unclear whether shared decision-making improves health outcomes in patients who are considering knee and hip replacement. The purpose of the present study was to examine whether patients who made high-quality, informed, patient-centered (IPC) decisions had better health outcomes, higher satisfaction, and less decision regret compared with those who made lower-quality decisions.

A multisite, randomized study of 2 decision aids for patients with hip and knee osteoarthritis was utilized to collect data on decision-making and health outcomes at 2 time points shortly after the initial surgical evaluation and about 6 months after treatment. We calculated the percentage of patients who made an IPC decision and examined the a priori hypotheses that IPC decisions would be associated with better health outcomes, satisfaction, and less regret at 6 months. Linear and logistic regression models were utilized to examine the relationships.

The anaatisfaction and were associated with more regret.

Higher-quality decisions predicted small improvements in health outcomes, as well as greater satisfaction and less regret for patients with knee osteoarthritis, but not for patients with hip osteoarthritis.

Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.Neuropathic arthropathy of the knee (Charcot knee) is a rare pathology defined by progressive destruction of bone and soft tissue in a patient with underlying peripheral neuropathy. Historically, Charcot knee was associated with neurosyphilis, but it has been increasingly described as a late stage of diabetes. The pathophysiology of the disease is not completely understood, but theories include repetitive microtrauma and an abnormal neurovascular response. Patients present with a warm, swollen, and unstable joint and have rapid bone resorption and characteristic findings on pathology. Nonsurgical options for pain and dysfunction include total contact casting and bracing treatment. Pharmacologic management includes diphosphonates, although this use is considered off-label. Surgical management historically included knee fusion. However, recent case series have suggested that newer prostheses allow for successful arthroplasty in this cohort, although complications are higher when compared with joint arthroplasty in patients with normal neurologic function.

Orthopaedics pioneered the expansion of gene therapy beyond its traditional scope of diseases that are caused by rare single-gene defects. Orthopaedic applications of gene therapy are most developed in the areas of arthritis and regenerative medicine, but several additional possibilities exist.

Invossa, an ex vivo gene therapeutic for osteoarthritis, was approved in South Korea in 2017, but its approval was retracted in 2019 and remains under appeal; a Phase-III clinical trial of Invossa has restarted in the U.S.

There are several additional clinical trials for osteoarthritis and rheumatoid arthritis that could lead to approved gene therapeutics for arthritis.

Bone-healing and cartilage repair are additional areas that are attracting considerable research; intervertebral disc degeneration and the healing of ligaments, tendons, and menisci are other applications of interest. Orthopaedic tumors, genetic diseases, and aseptic loosening are additional potential targets.

If successful, these endeavors will expand the scope of gene therapy from providing expensive medicines for a few patients to providing affordable medicines for many.

If successful, these endeavors will expand the scope of gene therapy from providing expensive medicines for a few patients to providing affordable medicines for many.

This study systematically investigated circulating and retinal tissue lipid determinants of human diabetic retinopathy (DR) to identify underlying lipid alterations associated with severity of DR.

Retinal tissues were retrieved from postmortem human eyes including 19 individuals without diabetes, 20 with diabetes but without DR, and 20 with diabetes and DR for lipidomic study. In a parallel study, serum samples from 28 American Indians with type 2 diabetes from the Glia River Indian Community including 12 without DR, 7 with mild non-proliferative DR (NPDR), and 9 with moderate NPDR were selected. A mass-spectrometry-based lipidomic platform was used to measure serum and tissue lipids.

In the postmortem retinas, we found a graded decrease of long chain acylcarnitines, longer chain fatty acid ester of hydroxyl fatty acids, diacylglycerols, triacylglycerols, phosphatidylcholines, and Ceramide[NS] in central retina from no diabetes to diabetes with DR. The American Indians' sera also exhibited a graded decrease in circulating long-chain acylcarnitines and a graded increase in the intermediate length saturated and monounsaturated triacylglycerols from no DR to moderate NPDR.

These findings suggest diminished synthesis of complex lipids and impaired mitochondrial β-oxidation of fatty acids in retinal DR with parallel changes in circulating lipids.TRIALREGISTRION. ClinicalTrials.gov NCT00340678FUNDING. Supported by NIH grants K08DK106523, R03DK121941, P30DK089503, P30DK081943, P30DK020572, P30 EY007003, The Thomas Beatson Foundation, and JDRF Center for Excellence (5-COE-2019-861-S-B).

These findings suggest diminished synthesis of complex lipids and impaired mitochondrial β-oxidation of fatty acids in retinal DR with parallel changes in circulating lipids.TRIALREGISTRION. ClinicalTrials.gov NCT00340678FUNDING. Supported by NIH grants K08DK106523, R03DK121941, P30DK089503, P30DK081943, P30DK020572, P30 EY007003, The Thomas Beatson Foundation, and JDRF Center for Excellence (5-COE-2019-861-S-B).Multisystem Inflammatory Syndrome in Children (MIS-C) manifests as a severe and uncontrolled inflammatory response with multiorgan involvement, occurring weeks after SARS-CoV-2 infection. Here we utilized proteomics, RNA sequencing, autoantibody arrays and B-cell receptor (BCR) repertoire analysis to characterize MIS-C immunopathogenesis and identify factors contributing to severe manifestations and intensive care unit admission. Inflammation markers, humoral immune responses, neutrophil activation, complement and coagulation pathways were highly enriched in MIS-C patient serum, with a more hyperinflammatory profile in severe than in mild MIS-C cases. We identified a strong autoimmune signature in MIS-C, with autoantibodies targeted to both ubiquitously expressed and tissue-specific antigens, suggesting autoantigen release and excessive antigenic drive may result from systemic tissue damage. We further identified a cluster of patients with enhanced neutrophil responses as well as high anti-spike IgG and autoantibody titers. BCR sequencing of these patients identified a strong imprint of antigenic drive with substantial BCR sequence connectivity and usage of autoimmunity-associated immunoglobulin heavy chain variable region (IGHV) genes. This cluster was linked to a TRBV11-2 expanded T cell receptor (TCR) repertoire, consistent with previous studies indicating a superantigen-driven pathogenic process. Overall, we identify a combination of pathogenic pathways that culminate in MIS-C and may inform treatment.Myosin Binding Protein-C slow (sMyBP-C) comprises a subfamily of cytoskeletal proteins encoded by MYBPC1 that is expressed in skeletal muscles where it contributes to myosin thick filament stabilization and actomyosin cross-bridge regulation. Recently, our group described the causal association of dominant missense pathogenic variants in MYBPC1 with an early-onset myopathy characterized by generalized muscle weakness, hypotonia, dysmorphia, skeletal deformities, and myogenic tremor occurring in the absence of neuropathy. To mechanistically interrogate the etiologies of this MYBPC1-associated myopathy in vivo, we generated a knock-in mouse model carrying the E248K pathogenic variant. Using a battery of phenotypic, behavioral, and physiological measurements spanning neonatal to young adult life, we find that heterozygous E248K mice faithfully recapitulate the onset and progression of generalized myopathy, tremor occurrence, and skeletal deformities seen in human carriers. Moreover, using a combination of biochemical, ultrastructural, and contractile assessments at the level of the tissue, cell, and myofilaments, we show that the loss-of-function phenotype observed in mutant muscles is primarily driven by disordered and misaligned sarcomeres containing fragmented and out-of-register internal membranes that result in reduced force production and tremor initiation. Collectively, our findings provide mechanistic insights underscoring the E248K-disease pathogenesis and offer a relevant preclinical model for therapeutic discovery.Avian H7N9 influenza viruses cause sporadic outbreaks of human infections and threaten to cause a major pandemic. The breadth of B cell responses to natural infection and the dominant antigenic sites recognized during first exposure to H7 HA following infection are incompletely understood. Here, we studied the B cell response to H7 HA of two individuals who had recovered from natural H7N9 virus infection. We used competition-binding, hydrogen-deuterium mass spectrometry, and single-particle negative stain electron microscopy to identify the patterns of molecular recognition of the antibody responses to H7 hemagglutinin. We found that circulating H7-reactive B cells recognized a diverse antigenic landscape on the HA molecule, including HA head domain epitopes in antigenic Sites A, B, and the trimer interface-II region and epitopes in the stem region. Most H7 antibodies exhibited little heterosubtypic breadth, but many recognized a wide diversity of unrelated H7 strains. We tested the antibodies for functional activity and identified clones with diverse patterns of inhibition, including neutralizing, hemagglutination or egress inhibiting, or HA trimer-disrupting activities. Thus, the human B cell response to primary H7 natural infection is diverse, highly functional, and broad for recognition of diverse H7 strains.Evidence links osteoporosis and cardiovascular disease but the cellular and molecular mechanisms are unclear. Here we identify skeleton-derived platelet-derived growth factor (PDGF)-BB as a key mediator of arterial stiffening in response to aging and metabolic stress. Aged mice and those fed high-fat diet (HFD), relative to young mice and those fed normal chow food diet, had higher serum PDGF-BB and developed bone loss and arterial stiffening. Mononuclear RANK+TRAP+ preosteoclasts in bone/bone marrow secrete excessive amount of PDGF-BB in aged mice and HFD mice. Conditioned medium prepared from preosteoclasts stimulated proliferation and migration of the vascular smooth muscle cells. Conditional transgenic mice, in which PDGF-BB is overexpressed in preosteoclasts, had 3 times the serum PDGF-BB concentration of controls and developed simultaneous bone loss and arterial stiffening at young age. Conversely, in conditional knockout mice, in which PDGF-BB is deleted selectively in preosteoclasts, HFD did not affect serum PDGF-BB concentration. Whereas wild-type mice fed HFD had augmented arterial stiffness, this effect was attenuated in conditional knockout mice. These studies confirm that preosteoclasts are a main source of excessive PDGF-BB in blood circulation during aging and metabolic stress and establish the role of skeleton-derived PDGF-BB as an important mediator of vascular stiffening.

Problematic social media use (PSMU) has received growing attention in the last fifteen years. Even though PSMU has been extensively studied, its internal structure is not fully understood. We used network analysis to evaluate which symptoms and associations between symptoms are most central to PSMU - as assessed by the Generalized Problematic Internet Use Scale-2 adapted for PSMU - among undergraduates.

Network analysis was applied to a large gender-balanced sample of undergraduates (n = 1344 participants; M = 51.9%; mean age = 22.50 ± 2.20 years).

The most central nodes in the network were the difficulty of controlling one's own use of social media, the tendency to think obsessively about going online, the difficulties in resisting the urge to use social media and the preference for communicating with people online rather than face-to-face. This last element was strongly associated with a general preference for online social interactions and the feeling of being more comfortable online. The network was robust to stability and accuracy tests. The mean levels of symptoms and symptom centrality were not associated.

Deficient self-regulation and preference for online communication were the most central symptoms of PSMU, suggesting that these symptoms should be prioritized in theoretical models of PSMU and could also serve as important treatment targets for PSMU interventions.

Deficient self-regulation and preference for online communication were the most central symptoms of PSMU, suggesting that these symptoms should be prioritized in theoretical models of PSMU and could also serve as important treatment targets for PSMU interventions.

Esports betting is an emerging gambling activity where individuals place bets on an organized video gaming competition. It represents only one of several gambling activities commonly endorsed by adolescents. To date, limited research has explored the relationship between esports betting and mental health among adolescents and its convergence with both problem gambling (PG) and problem video gaming (PVG). The present study examined the relation between esports betting, PG and PVG, and both externalizing and internalizing problems among adolescents while accounting for adolescents' video gaming intensity (i.e., how often they play 2 h or more in a day) and engagement in other gambling activities.

Data was collected from 6,810 adolescents in Wood County, Ohio schools. A subset of 1,348 adolescents (Mage = 14.67 years, SD = 1.73, 64% male) who had gambled and played video games during the past year were included in the analyses.

Approximately 20% (n = 263) of the included sample had bet on esports during the past year. Esports betting was positively correlated with other forms of gambling, both PG and PVG, and externalizing behaviors. Mediation analyses revealed esports betting was associated to both internalizing and externalizing problems through PVG and not PG.

Esports betting may be particularly appealing to adolescents who are enthusiastic video gamers. As such, regulators must be vigilant to ensure codes of best practices are applied to esports betting operators specifically for underaged individuals.

Esports betting may be particularly appealing to adolescents who are enthusiastic video gamers. As such, regulators must be vigilant to ensure codes of best practices are applied to esports betting operators specifically for underaged individuals.

Compulsive Sexual Behavior Disorder (CSBD) is characterized by increased reactivity to erotic reward cues. Cue-encoded reward parameters, such as type (e.g. erotic or monetary) or probability of anticipated reward, shape reward-related motivational processes, increase the attractiveness of cues and therefore might enhance maladaptive behavioral patterns in CSBD. Studies on the neural patterns of cue processing in individuals with CSBD have been limited mainly to ventral striatal responses. Therefore, here we aimed to examine the cue reactivity of multiple key structures in the brain's reward system, taking into account not only the type of predicted reward but also its probability.

Twenty Nine men seeking professional help due to CSBD and 24 healthy volunteers took part in an fMRI study with a modified Incentive Delay Task with erotic and monetary rewards preceded by cues indicating a 25%, 50%, or 75% chance of reward. Analyses of functional patterns of activity related to cue type and probability were conducted on the whole-brain and ROI levels.

Increased anticipatory response to cues predictive of erotic rewards was observed among CSBD participants when compared to controls, in the ventral striatum and anterior orbitofrontal cortex (aOFC). The activity in aOFC was modulated by reward probability.

Type of anticipated reward (erotic vs monetary) affects reward-related behavioral motivation in CSBD more strongly than reward probability. We present evidence of abnormal aOFC function in CSBD by demonstrating the recruitment of additional subsections of this region by erotic reward cues.

Type of anticipated reward (erotic vs monetary) affects reward-related behavioral motivation in CSBD more strongly than reward probability. We present evidence of abnormal aOFC function in CSBD by demonstrating the recruitment of additional subsections of this region by erotic reward cues.Understanding the pathways and time scales underlying electrically driven insulator-metal transitions is crucial for uncovering the fundamental limits of device operation. Using stroboscopic electron diffraction, we perform synchronized time-resolved measurements of atomic motions and electronic transport in operating vanadium dioxide (VO2) switches. We discover an electrically triggered, isostructural state that forms transiently on microsecond time scales, which is shown by phase-field simulations to be stabilized by local heterogeneities and interfacial interactions between the equilibrium phases. This metastable phase is similar to that formed under photoexcitation within picoseconds, suggesting a universal transformation pathway. Our results establish electrical excitation as a route for uncovering nonequilibrium and metastable phases in correlated materials, opening avenues for engineering dynamical behavior in nanoelectronics.The structure of animal social networks influences survival and reproductive success, as well as pathogen and information transmission. However, the general mechanisms determining social structure remain unclear. Using data from 73,767 social interactions among wild spotted hyenas collected over 27 years, we show that the process of social inheritance determines how offspring relationships are formed and maintained. Relationships between offspring and other hyenas bear resemblance to those of their mothers for as long as 6 years, and the degree of similarity increases with maternal social rank. Mother-offspring relationship strength affects social inheritance and is positively correlated with offspring longevity. These results support the hypothesis that social inheritance of relationships can structure animal social networks and be subject to adaptive tradeoffs.Spatial memory in vertebrates requires brain regions homologous to the mammalian hippocampus. Between vertebrate clades, however, these regions are anatomically distinct and appear to produce different spatial patterns of neural activity. We asked whether hippocampal activity is fundamentally different even between distant vertebrates that share a strong dependence on spatial memory. We studied tufted titmice, food-caching birds capable of remembering many concealed food locations. We found mammalian-like neural activity in the titmouse hippocampus, including sharp-wave ripples and anatomically organized place cells. In a non-food-caching bird species, spatial firing was less informative and was exhibited by fewer neurons. These findings suggest that hippocampal circuit mechanisms are similar between birds and mammals, but that the resulting patterns of activity may vary quantitatively with species-specific ethological needs.Piezoelectric biomaterials are intrinsically suitable for coupling mechanical and electrical energy in biological systems to achieve in vivo real-time sensing, actuation, and electricity generation. However, the inability to synthesize and align the piezoelectric phase at a large scale remains a roadblock toward practical applications. We present a wafer-scale approach to creating piezoelectric biomaterial thin films based on γ-glycine crystals. The thin film has a sandwich structure, where a crystalline glycine layer self-assembles and automatically aligns between two polyvinyl alcohol (PVA) thin films. The heterostructured glycine-PVA films exhibit piezoelectric coefficients of 5.3 picocoulombs per newton or 157.5 × 10-3 volt meters per newton and nearly an order of magnitude enhancement of the mechanical flexibility compared with pure glycine crystals. With its natural compatibility and degradability in physiological environments, glycine-PVA films may enable the development of transient implantable electromechanical devices.Changes in the crystal system of an ionic nanocrystal during a cation exchange reaction are unusual yet remain to be systematically investigated. In this study, chemical synthesis and computational modeling demonstrated that the height of hexagonal-prism roxbyite (Cu1.8S) nanocrystals with a distorted hexagonal close-packed sulfide anion (S2-) sublattice determines the final crystal phase of the cation-exchanged products with Co2+ [wurtzite cobalt sulfide (CoS) with hexagonal close-packed S2- and/or cobalt pentlandite (Co9S8) with cubic close-packed S2-]. Thermodynamic instability of exposed planes drives reconstruction of anion frameworks under mild reaction conditions. Other incoming cations (Mn2+, Zn2+, and Ni2+) modulate crystal structure transformation during cation exchange reactions by various means, such as volume, thermodynamic stability, and coordination environment.Catalytic conversion of methane to methanol remains an economically tantalizing but fundamentally challenging goal. Current technologies based on zeolites deactivate too rapidly for practical application. We found that similar active sites hosted in different zeolite lattices can exhibit markedly different reactivity with methane, depending on the size of the zeolite pore apertures. Whereas zeolite with large pore apertures deactivates completely after a single turnover, 40% of active sites in zeolite with small pore apertures are regenerated, enabling a catalytic cycle. Detailed spectroscopic characterization of reaction intermediates and density functional theory calculations show that hindered diffusion through small pore apertures disfavors premature release of CH3 radicals from the active site after C-H activation, thereby promoting radical recombination to form methanol rather than deactivated Fe-OCH3 centers elsewhere in the lattice.