Comparison of three techniques for decellularization of porcine bone-tendon-bone grafts.

Anterior cruciate ligament injuries are frequent afflictions related to sports or physical trauma. Autograft reconstruction strategies cause secondary injury to the patient. One alternative, supported by clinical evidence, is porcine xenografts. For clinical use, xenografts must be conditioned to avoid immune rejection. The most widely accepted procedure is tissue decellularization. We analyzed three decellularization strategies: the application of the anionic detergent sodium dodecyl sulfate (SDS), sonication, and freezing and thawing cycles. The treated tissues were evaluated histologically using H&E, Masson's trichrome, Verhoeff-van Gieson staining, and DAPI for fluorescent staining of nuclei. Finally, collagen fiber preservation was evaluated by quantifying this protein by colorimetry. The most efficient decellularization techniques were sonication and SDS. Collagen fibers were preserved in all experimental conditions.

A comparison of three techniques for the osteosynthesis after minimal invasive osteotomies for hallux valgus.

PURPOSE: Third and fourth-generation minimal invasive osteotomies (MIO) for the treatment of hallux valgus (HV) have become popular procedures worldwide with promising results due to the improvement in the fixation method. The tricortical cannulated screw placement remains a complex procedure that is technically challenging and requires a long skill learning curve with high radiation exposure mainly in the form of intensifier shots (IS) required for the MIO fixation. This study aims to compare the number of X-ray IS required using three different techniques for the cannulated guide placement. METHODS: A retrospective cross-sectional observational and comparative study was conducted to assess the number of X-rays IS required for correct cannulated screw guide placement using three different techniques: traditional perforator, the drill and joystick, and K-wire first techniques. RESULTS: A total of 53 MIS procedures from thirty-one patients in two different hospitals were included. IS X-rays were 155.1 ± 29.7 in the traditional technique (n = 14), 143.0 ± 43.2 in the drill and joystick technique (n = 22), and 85 ± 18.7 in the K-wires first technique (n = 17), p = < 0.001 using one-way ANOVA. CONCLUSIONS: The K-wire first technique statistically significantly decreases X-ray IS numbers p ≤ 0.001. There were no statistically significant differences between the traditional (after osteotomy K-wire placement) and the drill and joystick techniques (p = 0.36).

Socioeconomic Diversity in Admissions to MD-PhD Programs, 2014-2019.

This cohort study of applicants to US MD-PhD programs examines the association of application outcomes with family income.

Cerebral small vessel disease burden is associated with decreased abundance of gut Barnesiella intestinihominis bacterium in the Framingham Heart Study.

A bidirectional communication exists between the brain and the gut, in which the gut microbiota influences cognitive function and vice-versa. Gut dysbiosis has been linked to several diseases, including Alzheimer's disease and related dementias (ADRD). However, the relationship between gut dysbiosis and markers of cerebral small vessel disease (cSVD), a major contributor to ADRD, is unknown. In this cross-sectional study, we examined the connection between the gut microbiome, cognitive, and neuroimaging markers of cSVD in the Framingham Heart Study (FHS). Markers of cSVD included white matter hyperintensities (WMH), peak width of skeletonized mean diffusivity (PSMD), and executive function (EF), estimated as the difference between the trail-making tests B and A. We included 972 FHS participants with MRI scans, neurocognitive measures, and stool samples and quantified the gut microbiota composition using 16S rRNA sequencing. We used multivariable association and differential abundance analyses adjusting for age, sex, BMI, and education level to estimate the association between gut microbiota and WMH, PSMD, and EF measures. Our results suggest an increased abundance of Pseudobutyrivibrio and Ruminococcus genera was associated with lower WMH and PSMD (p values < 0.001), as well as better executive function (p values < 0.01). In addition, in both differential and multivariable analyses, we found that the gram-negative bacterium Barnesiella intestinihominis was strongly associated with markers indicating a higher cSVD burden. Finally, functional analyses using PICRUSt implicated various KEGG pathways, including microbial quorum sensing, AMP/GMP-activated protein kinase, phenylpyruvate, and ß-hydroxybutyrate production previously associated with cognitive performance and dementia. Our study provides important insights into the association between the gut microbiome and cSVD, but further studies are needed to replicate the findings.

Association of Racial and Ethnic Identity With Attrition From MD-PhD Training Programs.

This cohort study analyzes the attrition rates of students from MD-PhD training programs by race and ethnicity.

Acute Treatment with the M-Channel (Kv7, KCNQ) Opener Retigabine Reduces the Long-Term Effects of Repetitive Blast Traumatic Brain Injuries.

We investigated whether pharmacological increase of "M-type" (KCNQ, Kv7) K + channel currents by the M-channel opener, retigabine (RTG), acutely after repetitive traumatic brain injuries (rTBIs), prevents or reduces their long-term detrimental effects. rTBIs were studied using a blast shock air wave mouse model. Animals were monitored by video and electroencephalogram (EEG) records for nine months after the last injury to assess the occurrence of post-traumatic seizures (PTS), post-traumatic epilepsy (PTE), sleep-wake cycle architecture alterations, and the power of the EEG signals. We evaluated the development of long-term changes in the brain associated with various neurodegenerative diseases in mice by examining transactive response DNA-binding protein 43 (TDP-43) expression and nerve fiber damage ~ 2 years after the rTBIs. We observed acute RTG treatment to reduce the duration of PTS and impair the development of PTE. Acute RTG treatment also prevented post-injury hypersomnia, nerve fiber damage, and cortical TDP-43 accumulation and translocation from the nucleus to the cytoplasm. Mice that developed PTE displayed impaired rapid eye movement (REM) sleep, and there were significant correlations between seizure duration and time spent in the different stages of the sleep-wake cycle. We observed acute RTG treatment to impair injury-induced reduction of age-related increase in gamma frequency power of the EGG, which has been suggested to be necessary for a healthy aged brain. The data show that RTG, administered acutely post-TBI, is a promising, novel therapeutic option to blunt/prevent several long-term effects of rTBIs. Furthermore, our results show a direct relationship between sleep architecture and PTE.

Gender, Racial, and Ethnic and Inequities in Receipt of Multiple National Institutes of Health Research Project Grants.

Importance: Diversity in the biomedical research workforce is essential for addressing complex health problems. Female investigators and investigators from underrepresented ethnic and racial groups generate novel, impactful, and innovative research, yet they are significantly underrepresented among National Institutes of Health (NIH) investigators. Objective: To examine the gender, ethnic, and racial distribution of super NIH investigators who received 3 or more concurrent NIH grants. Design, Setting, and Participants: This cross-sectional study included a national cohort of NIH-funded principal investigators (PIs) from the NIH Information for Management, Planning, Analysis, and Coordination (IMPAC II) database from 1991 to 2020. Exposures: Self-identified gender, race and ethnicity, annual number of NIH grant receipt, career stage, and highest degree. Main Outcomes and Measures: Distribution of investigators receiving 3 or more research project grants, referred to as super principal investigators (SPIs), by gender, race, and ethnicity. Results: Among 33 896 investigators in fiscal year 2020, 7478 (22.01%) identified as Asian, 623 (1.8%) as Black, 1624 (4.8%) as Hispanic, and 22 107 (65.2%) as White; 21 936 (61.7%) identified as men; and 8695 (35.3%) were early-stage investigators. Between 1991 and 2020, the proportion of SPIs increased 3-fold from 704 (3.7%) to 3942 (11.3%). However, SPI status was unequal across gender, ethnic, and racial groups. Women and Black PIs were significantly underrepresented among SPIs, even after adjusting for career stage and degree, and were 34% and 40% less likely than their male and White colleagues, respectively, to be an SPI. Black women PIs were the least likely to be represented among SPIs and were 71% less likely to attain SPI status than White men PIs (adjusted odds ratio, 0.29; 95% CI, 0.21-0.41). Conclusions and Relevance: In this cross-sectional study of a national cohort of NIH-funded investigators, the gender, ethnic, and racial gaps in receipt of multiple research project grants among NIH investigators was clearly apparent and warrants further investigation and interventions.

Variation in Research Experiences and Publications During Medical School by Sex and Race and Ethnicity.

Importance: Diverse research teams are critical to solving complex health problems and producing high-quality medical research. Objective: To examine the associations of student sex and racial and ethnic identity with publication rates during medical school. Design, Setting, and Participants: This cohort study assessed individual-level data of US MD graduates from medical school who matriculated in academic years 2014 to 2015 and 2015 to 2016. Data were obtained from the Association of American Medical Colleges and analyzed from October 2021 to January 2022. Main Outcomes and Measures: Outcomes of interest included students' self-reported participation in unique research experiences, number of publications, and computed publications per research experience. Poisson regressions were constructed to determine the association of sex and racial and ethnic identity with research outcomes using adjusted rate ratios (aRRs). Results: Among 31 474 graduates, 15 159 (48.2%) identified as women and 4344 (13.8%) identified as underrepresented in medicine by race and ethnicity (URIM; including American Indian, Alaska Native, Black, Hawaiian Native, Hispanic/Latinx, and Pacific Islander individuals). Students who attended National Institutes of Health (NIH) top 40 research-ranked schools reported higher number of research experiences and publication counts, resulting in a higher publication rate compared with students from non-top 40 schools (median [IQR] 1.60 [1.00-3.00] vs 1.25 [0.50-2.33]; P < .001). Women reported a higher number of research experiences than men but a significantly lower number of publications (top 40 schools: aRR, 0.89; 95% CI, 0.87-0.90; non-top 40 schools: aRR, 0.93; 95% CI, 0.92-0.95). This resulted in a significantly lower publication rate among women (top 40 schools: aRR, 0.85; 95% CI, 0.83-0.86; non-top 40 schools: aRR, 0.91; 95% CI, 0.90-0.92). Compared with White students, Asian students had higher publication rates at both NIH top 40 schools (aRR, 1.10; 95% CI, 1.08-1.12) and non-top 40 schools (aRR, 1.07; 95% CI, 1.05-1.08), while lower publication rates were reported among Black students (top 40 schools: aRR, 0.83; 95% CI, 0.80-0.86; non-top 40 schools: aRR, 0.88; 95% CI, 0.85-0.95) and Hispanic students attending non-top 40 schools (aRR, 0.93; 95% CI, 0.90-0.95). Conclusions and Relevance: These findings illustrate that inequities in the physician-scientist workforce began early in training and highlight key areas for intervention, such as funding support and mentorship training during undergraduate medical education, that may promote the future success of a diverse physician-scientist workforce.

Inequity in National Institutes of Health Predoctoral Fellowships, 2001-2020.

This cross-sectional study examines trends in number of awards and funding of general and diversity F31 predoctoral fellowships from 2001 to 2020.

Preliminary tribological results of a new total temporary hip joint prosthesis spacer.

Temporary antibiotic-loaded cement spacers are widely used for treating chronic periprosthetic hip infections. The aim of this study is to evaluate the short-term tribological performance of ultra-high-molecular-weight polyethylene (UHMWPE) and (60Co) gamma-irradiated cross-linked UHMWPE (XLPE) self-mated systems as frictional pairs for temporary total hip spacers. A three-axial hip joint simulator, FIME II, was used to test the UHMWPE and XLPE self-mated systems under variable load profiles. A fetal bovine serum solution was used as a lubricant. After simulation tests, wear measurements of damaged coupled surfaces were made with a coordinate measuring machine. Finally, surfaces were characterized with scanning electron microscopy, Raman spectroscopy, Fourier transform infrared spectroscopy, and nanoindentation tests. The mass loss test results for UHMWPE were 11.91 ± 3.43 mg for the cups and 4.57 ± 0.92 mg for the heads. Whereas, the results for XLPE showed a significant reduction, with mean mass loss values of 6.59 ± 0.14 mg for the cups and 2.82 ± 0.59 mg for the heads, suggesting the viability of the self-mated XLPE contact pair for a temporary total hip spacer.

Glucose and leukocyte esterase levels are possible biomarkers for bacterial septic arthritis.

OBJECTIVE: The objective of the study was to determine the added value of synovial fluid (SF) glucose levels and other biochemical parameters as possible biomarkers of bacterial septic arthritis (SA). MATERIALS AND METHODS: We prospectively examined adult patients with SA. As a control group, adults with uninfected joints were enrolled. SF samples were obtained, and microbiological analyses were made. SF glucose levels, pH, and leukocyte esterase were measured using a glucometer and colorimetric test strips. Blood samples were collected from both groups to determine glucose levels. RESULTS: We included eight subjects with knee ligaments lesions, six with meniscus lesions, and five with osteoarthritis as the control group, as well as 20 patients with SA. SF culture was positive in 60%. SF glucose levels from patients were lower than the controls (p = 0.0018) with the lowest concentration in patients with a positive culture (p = 0.0004). Blood and SF glucose concentration from the positive culture patients were compared (p < 0.0001). Leukocyte esterase presented the highest values in patients with a positive culture (p < 0.0001) and a more acidic pH was found compared to the control group (p < 0.0001). CONCLUSION: These biochemical parameters might be a quick and inexpensive added value for distinguishing between infective and non-infective joint disease.

OBJETIVO: Evaluar el valor añadido de los niveles de glucosa en el líquido sinovial (LS) y otros parámetros bioquímicos en el diagnostico de artritis séptica (AS). MATERIAL Y MÉTODOS: Análisis prospectivo de pacientes adultos con AS. Pacientes con articulaciones no infectadas fueron incluidos como grupo control. Se tomaron muestras de LS y sangre para la realización de análisis microbiológicos y bioquímicos en los pacientes y controles. RESULTADOS: Incluimos 8 sujetos con lesión ligamentosa de rodilla, 6 con lesiones meniscales y 5 con osteoartritis como grupo control, así como 20 pacientes con AS. El cultivo de LS fue positivo en 60%. Los niveles de glucosa en LS de pacientes con AS fueron más bajos que los controles (P = 0.0018) con la concentración más baja en pacientes con cultivo positivo (p = 0.0004). La relación de glucosa en sangre y LS de pacientes con cultivo positivo se vio afectada (p < 0.0001). La esterasa leucocitaria presentó valores más altos en pacientes con cultivo positivo (p < 0.0001); se encontró un pH más ácido en comparación con el grupo control (p < 0.0001). CONCLUSIÓN: Estos parámetros bioquímicos podrían ser un valor agregado útil, rápido y económico para distinguir entre enfermedad articular infecciosa y no infecciosa.

Trends in U.S. MD-PhD Program Matriculant Diversity by Sex and Race/Ethnicity.

PURPOSE: To examine demographic characteristics of matriculants to U.S. MD-PhD programs by sex and race/ethnicity from academic years (AYs) 2009-2018 and explore the relationships between trends in the percentage of female and underrepresented minority (URM) matriculants to programs with and without Medical Scientist Training Program (MSTP) funding. METHOD: Linear regression and time trend analysis of the absolute percentage of matriculants into all U.S. MD-PhD programs was performed for self-reported sex and race/ethnicity, using Association of American Medical Colleges data for AYs 2009-2018, including an interaction for MSTP funding status (yes/no) and year. Linear regression of the percentage of programs matriculating no female or no URM students between AYs 2009 and 2018 was performed, focusing on programs in the top 3 quartiles by size (i.e., those matriculating 4 or more students per year). RESULTS: Between AYs 2009 and 2018, the percentage of matriculants to all MD-PhD programs who were female (38.0%-46.0%, 1.05%/year, P = .002) or URM (9.8%-16.7%, 0.77%/year, P < .001) increased. The annual percentage gains of URM matriculants were greater at MSTP-funded programs compared with non-MSTP-funded programs (0.50%/year, P = .046). Moreover, among MD-PhD programs in the top 3 quartiles by size, the percentage of programs with no female matriculants decreased by 0.40% per year ( P = .02) from 4.6% in 2009 to 1.6% in 2018, and the percentage of programs with no URM matriculants decreased by 3.41% per year ( P < .001) from 49% in 2009 to 22% in 2018. CONCLUSIONS: A consistent and sustained increase in the percentage of female and URM matriculants to MD-PhD programs from AYs 2009-2018 was observed, but the annual increases in the percentages across groups were small, and the demographics of the MD-PhD workforce still do not reflect the diversity of the U.S. general population.

Exploring reasons for MD-PhD trainees' experiences of impostor phenomenon.

BACKGROUND: Acceptance into U.S. MD-PhD dual-degree programs is highly competitive, and the lengthy training program requires transitioning between multiple phases (pre-clinical-, PhD-research-, and clinical-training phases), which can be stressful. Challenges faced during MD-PhD training could exacerbate self-doubt and anxiety. Impostor phenomenon is the experience of feeling like a fraud, with some high-achieving, competent individuals attributing their successes to luck or other factors rather than their own ability and hard work. To our knowledge, impostor phenomenon among MD-PhD trainees has not been described. This study examined impostor phenomenon experiences during MD-PhD training and reasons trainees attributed to these feelings. METHODS: Individuals in science and medicine fields participated in an online survey that included the 20-item Clance Impostor Phenomenon Scale (CIPS); higher scores (range 20-100) indicate more frequent impostor phenomenon. Some respondents who reported experiencing impostor phenomenon also voluntarily completed a semi-structured interview, sharing experiences during training that contributed to feelings of impostor phenomenon. Interview transcripts were coded and analysed using the constant comparative method and analytic induction to identify themes. RESULTS: Of 959 survey respondents (students and professionals in science and medicine), 13 MD-PhD students and residents completed the survey, nine of whom (five male, four female; four white, five other race-ethnicity) also completed an interview. These participants experienced moderate-to-intense scores on the CIPS (range: 46-96). Four themes emerged from the interview narratives that described participants' experiences of IP: professional identity formation, fear of evaluation, minority status, and, program-transition experiences. All reported struggling to develop a physician-scientist identity and lacking a sense of belonging in medicine or research. CONCLUSIONS: Impostor experiences that MD-PhD participants attributed to bias and micro-aggressions in social interactions with peers, faculty, and patients challenged their professional identity formation as physician-scientists. It is important to further examine how MD-PhD-program structures, cultures, and social interactions can lead to feelings of alienation and experiences of impostor phenomenon, particularly for students from diverse and underrepresented populations in medicine.

Effect of exogenous lipase on subcutaneous adipose tissue in a porcine animal model.

BACKGROUND: Topical exogenous lipase has been approved for cosmetic use and has been used to mobilize fat from adipocytes. The objective of this study was to determine the effects of exogenous lipase in the subcutaneous adipose tissue. METHODS: Three different concentrations of exogenous lipase 1× (2 Units per ml), 5× (10 units per ml), and 10× (20 units per ml) were applied in a porcine model. Normal saline (NS) solution (as negative control) and phosphatidylcholine (as positive control) were also injected. Skin and subcutaneous tissue biopsies, up to the fascia, were obtained from each injection site on the 3rd day after injection. The number of cells per 20× field was counted as an indirect measurement of the size of the adipocytes. RESULTS: For 1× lipase, the number of cells per field was 47.80 (±7.63) versus 27.26 (±4.93), and 34.66 (±6.84) for NS, and phosphatidylcholine, respectively. For 5× lipase, the count was 36.06 (±4.74) versus 24.13 (±5.18), and 33.2 (±9.34). For 10× lipase, it was 40.06 (±4.35) versus 29.26 (±2.34) and 32.66 (±6.30) (p < .05 for all groups). CONCLUSIONS: A higher number of cells per field were observed in the lipase samples, inferring a decreased volume of adipocytes. No inflammation and/or loss of cell architecture were evidenced in the exogenous lipase groups.

COVID-19 y Justicia Social. Un enfoque sindémico de la resistencia a la vacunación / COVID-19 i Justícia social: un enfocament sindèmic de la resistència a la vacunació / COVID-19 and Social Justice: A syndemic approach to vaccine hesitancy

The effects of COVID-19 pandemic depend on socio-cultural determinants that shield some individuals or groups from the most severe effects or make others more vulnerable to suffering harms to their health, social position, or economic stability. The case of vaccination is symptomatic of how specific groups suffer a higher degree of vulnerability due to socioeconomic inequalities and cultural determinants. Consequently, vaccine hesitancy among these groups might deepen the vulnerabilities, which is why it is necessary to design strategies that, while confronting vaccine hesitancy, do not ignore those structural inequalities which could continue feeding skepticism and resistance to vaccination, if unattended. In this work we claim that public health policies focused on promoting vaccination may benefit from a syndemic approach that considers the synergies between diseases and socioeconomic and cultural determinants. This implies introducing social justice issues into the planning of public health strategies. By critically analyzing the work of bioethicist Norman Daniels —who goes over the moral importance of public health from an interpretation of John Rawls’ theory of justice—we explore the criticism to justice as fairness made by the communitarian and the politics of difference standpoints (specifically, I. M. Young), to show that a syndemic approach to public health is essential to achieve complete vaccination: the design of strategies will have to consider the specific contexts of vaccine hesitant groups, to achieve efficiency vaccinating in the short, medium and long term.(AU)

Las afectaciones por la pandemia de COVID-19 dependen de determinantes socio-culturales que blindan a algunos individuos o grupos de los efectos más severos o vuelven a otros más susceptibles de sufrir daños a su salud, posición social o estabilidad económica. El caso de la vacunación es sintomático de cómo grupos específicos sufren mayor vulnerabilidad por inequidades socioeconómicas y determinantes culturales. Consecuentemente, la resistencia a la vacunación entre estos grupos puede profundizar la vulnerabilidad, por lo que es necesario diseñar estrategias que, al confrontar la resistencia a la vacunación, no dejen de lado aquellas inequidades estructurales que, de no atenderse, seguirán alimentando la suspicacia y renuencia a vacunarse. En este trabajo sostenemos que las políticas de salud pública enfocadas a promover la vacunación pueden beneficiarse de un enfoque sindémico que considere las sinergias entre enfermedades y determinantes socioeconómicas y culturales. Esto implica introducir problemas de justicia social en la planificación de estrategias de salud pública. Haciendo un análisis crítico del trabajo del bioeticista Norman Daniels —quien aborda la importancia moral de la salud pública desde una interpretación de la teoría de la justicia de John Rawls—retomamos las críticas a la justicia como imparcialidad de las posturas comunitarista y delas políticas de la diferencia (específicamente I. M. Young), para mostrar que un enfoque sindémico de la salud pública es indispensable para lograr una vacunación completa: el diseño de estrategias tendrá que considerar los contextos específicos de grupos renuentes a vacunarse para lograr eficiencia a corto, mediano y largo plazo.(AU)

Les afectacions per la pandèmia de COVID-19 depenen de determinants socioculturals que blinden a alguns individus o grups dels efectes més severs o tornen a uns altres més susceptibles de sofrir danys a la seva salut, posició social o estabilitat econòmica. El cas de la vacunació és simptomàtic de com grups específics sofreixen major vulnerabilitat per inequitats socioeconòmiques i determinants culturals. Conseqüentment, la resistència a la vacunació entre aquests grups pot aprofundir la vulnerabilitat, per la qual cosa és necessari dissenyar estratègies que, en confrontar la resistència a la vacunació, no deixin de costat aquelles inequitats estructurals que, de no atendre's, continuaran alimentant la suspicàcia i renuència a vacunar-se. En aquest treball sostenim que les polítiques de salut pública enfocades a promoure la vacunació poden beneficiar-se d'un enfocament sindèmic que consideri les sinergies entre malalties i determinants socioeconòmiques i culturals. Això implica introduir problemes de justícia social en la planificació d'estratègies de salut pública. Fent una anàlisi crítica del treball del bioeticista Norman Daniels —qui aborda la importància moral de la salut pública des d'una interpretació de la teoria de la justícia de John Rawls—reprenem les crítiques a la justícia com a imparcialitat de les postures comunitarista i de les polítiques de la diferència (específicament I. M. Young), per a mostrar que un enfocament sindèmic de la salut pública és indispensable per a aconseguir una vacunació completa: el disseny d'estratègies haurà de considerar els contextos específics de grups renuents a vacunar-se per a aconseguir eficiència a curt, mitjà i llarg termini.(AU)

Systemic and Local Cytokines Profile Determine Severity and Prognosis in Human Septic Arthritis.

BACKGROUND: Septic arthritis (SA) is a medical emergency. The most common etiological agents are bacteria, which activate the local immune response coordinated by cytokines; however, little is known about the cytokine profile in human SA. AIM: To determine the association of local and systemic cytokine profiles with the severity and prognosis of patients with SA. METHODS: Patients with clinical and laboratory diagnosed SA were enrolled as well as a control group. Serum and synovial fluid (SF) samples were obtained for determining cytokines and glucose levels; SF samples were used for histological analysis. Osteochondral damage and general health status and quality of life (SF-36) were evaluated during recruitment day. WOMAC osteoarthritis index score and SF-36 questionnaire were used a year after recruitment day as a follow up. RESULTS: A systemic and local proinflammatory cytokine profile was found in patients compared to the control group (p <0.05). IL-6 was 28 and 525 times higher than controls in sera and SF, respectively (p <0.0001). Systemic IL-6 correlated negatively with general mental health score (p = 0.0184) and was associated with a higher osteoarthritis index after one year follow-up in the patients (p = 0.0352). HMGB1 in SF was found higher in patients with SA (p <0.0001), and it was associated with osteochondral damage (p = 0.0042). TNF-α in SF correlated negatively with SF-36 questionnaire one year after patients' recruitment in role limitation score (p = 0.0318), body pain score (p = 0.0315), and general mental health score (p = 0.0197). CONCLUSION: Serum and SF cytokine signatures are associated with disease severity and prognosis in patients with SA.

Neuroprotective Roles of the Adenosine A3 Receptor Agonist AST-004 in Mouse Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) remains one of the greatest public health concerns with increasing morbidity and mortality rates worldwide. Our group reported that stimulation of astrocyte mitochondrial metabolism by P2Y1 receptor agonists significantly reduced cerebral edema and reactive gliosis in a TBI model. Subsequent data on the pharmacokinetics (PK) and rapid metabolism of these compounds suggested that neuroprotection was likely mediated by a metabolite, AST-004, which binding data indicated was an adenosine A3 receptor (A3R) agonist. The neuroprotective efficacy of AST-004 was tested in a control closed cortical injury (CCCI) model of TBI in mice. Twenty-four (24) hours post-injury, mice subjected to CCCI and treated with AST-004 (0.22 mg/kg, injected 30 min post-trauma) exhibited significantly less secondary brain injury. These effects were quantified with less cell death (PSVue794 fluorescence) and loss of blood brain barrier breakdown (Evans blue extravasation assay), compared to vehicle-treated TBI mice. TBI-treated mice also exhibited significantly reduced neuroinflammatory markers, glial-fibrillary acidic protein (GFAP, astrogliosis) and ionized Ca2+-binding adaptor molecule 1 (Iba1, microgliosis), both at the mRNA (qRT-PCR) and protein (Western blot and immunofluorescence) levels, respectively. Four (4) weeks post-injury, both male and female TBI mice presented a significant reduction in freezing behavior during contextual fear conditioning (after foot shock). AST-004 treatment prevented this TBI-induced impairment in male mice, but did not significantly affect impairment in female mice. Impairment of spatial memory, assessed 24 and 48 h after the initial fear conditioning, was also reduced in AST-004-treated TBI-male mice. Female TBI mice did not exhibit memory impairment 24 and 48 h after contextual fear conditioning and similarly, AST-004-treated female TBI mice were comparable to sham mice. Finally, AST-004 treatments were found to increase in vivo ATP production in astrocytes (GFAP-targeted luciferase activity), consistent with the proposed mechanism of action. These data reveal AST-004 as a novel A3R agonist that increases astrocyte energy production and enhances their neuroprotective efficacy after brain injury.

Anatomical variations of the sacro-iliac joint: a computed tomography study.

PURPOSE: To identify, describe, and compare the prevalence of sacroiliac joint anatomical variants. METHODS: A retrospective study was performed on computed tomography scans. Joint space was measured, and variants were classified as accessory joint, ileosacral complex, bipartite bony plate, semicircular defect, iliac bony plate, and ossification centers. RESULTS: 400 scans were analyzed. Mean age was 49 years, 180 men (45%), and 220 women (55%). 209 (52.2%) patients presented an anatomical variant with higher prevalence in women (65.4% vs 36.2%), and those older than 40 years of age (60% vs 40%). Mean joint space was similar bilaterally (right 2.41 ± 0.65 mm vs. left 2.37 ± 0.65 mm). Prevalence was: 19.8% accessory joint, 6.5% ileosacral complex, 12.3% bipartite bony plate, 8% semicircular defect, 5% iliac bony plate, and 0.8% for ossification centers. CONCLUSION: Prevalence of anatomical variants of the SIJ is higher in the Hispanic population, women, and those older than 40 years.