Fostering effective and sustainable scientific collaboration and knowledge exchange: a workshop-based approach to establish a national ecological observatory network (NEON) domain-specific user group.

The decision to establish a network of researchers centers on identifying shared research goals. Ecologically specific regions, such as the USA's National Ecological Observatory Network's (NEON's) eco-climatic domains, are ideal locations by which to assemble researchers with a diverse range of expertise but focused on the same set of ecological challenges. The recently established Great Lakes User Group (GLUG) is NEON's first domain specific ensemble of researchers, whose goal is to address scientific and technical issues specific to the Great Lakes Domain 5 (D05) by using NEON data to enable advancement of ecosystem science. Here, we report on GLUG's kick off workshop, which comprised lightning talks, keynote presentations, breakout brainstorming sessions and field site visits. Together, these activities created an environment to foster and strengthen GLUG and NEON user engagement. The tangible outcomes of the workshop exceeded initial expectations and include plans for (i) two journal articles (in addition to this one), (ii) two potential funding proposals, (iii) an assignable assets request and (iv) development of classroom activities using NEON datasets. The success of this 2.5-day event was due to a combination of factors, including establishment of clear objectives, adopting engaging activities and providing opportunities for active participation and inclusive collaboration with diverse participants. Given the success of this approach we encourage others, wanting to organize similar groups of researchers, to adopt the workshop framework presented here which will strengthen existing collaborations and foster new ones, together with raising greater awareness and promotion of use of NEON datasets. Establishing domain specific user groups will help bridge the scale gap between site level data collection and addressing regional and larger ecological challenges.

Goals of Care Discussions in Orthopaedic Surgery: Geriatric Hip Fractures.

BACKGROUND: Due to the severity of hip fracture complications in the geriatric population, including major morbidity and mortality, it is crucial to establish treatment goals and manage expectations as a patient-centered multidisciplinary team. Goals of care (GOC) are personalized treatment programs designed to align with the individual patient's values and preferences. There is a paucity of literature on the topic of GOC discussions, especially regarding orthopaedic injuries. Therefore, this narrative review aims to provide an account of GOC discussions related to geriatric hip fractures. METHODS: We reviewed articles published on GOC between 1978 and 2024. The articles were identified by searching PubMed and Google Scholar. We utilized the search terms GOC discussions and hip fracture, with additional descriptors including arthroplasty and geriatric. RESULTS: There were 11 articles that met the selection criteria and were published between 1978 and 2024. Five articles were published on GOC discussions in orthopaedic surgery, while the remaining 6 articles were published in non-orthopaedic fields. There was one systematic review, 2 narrative reviews, 6 observational studies, and 2 descriptive studies. Supplemental commentary from non-orthopaedic specialties and the fields of law and medical ethics was included to assist in highlighting barriers to GOC discussions and to explore potential strategies to enhance GOC discussions. CONCLUSIONS: Goals of care discussions provide a framework for treatment decisions based on an individual patient's values and cultural beliefs; however, these conversations may be limited by perceived time constraints, patient health care literacy, and physicians' misconceptions of what is most important to discuss. While no clear consensus was identified regarding strategies for improving GOC discussions in geriatric patients who have hip fractures, the authors recommend standardized training programs, expedited family meetings, multidisciplinary team involvement, assistive technology such as Outcome Prioritization Tool, and the incorporation of GOC discussions into institutional hip fracture pathways.

Disease-associated astrocyte epigenetic memory promotes CNS pathology.

Disease-associated astrocyte subsets contribute to the pathology of neurologic diseases, including multiple sclerosis and experimental autoimmune encephalomyelitis1-8 (EAE), an experimental model for multiple sclerosis. However, little is known about the stability of these astrocyte subsets and their ability to integrate past stimulation events. Here we report the identification of an epigenetically controlled memory astrocyte subset that exhibits exacerbated pro-inflammatory responses upon rechallenge. Specifically, using a combination of single-cell RNA sequencing, assay for transposase-accessible chromatin with sequencing, chromatin immunoprecipitation with sequencing, focused interrogation of cells by nucleic acid detection and sequencing, and cell-specific in vivo CRISPR-Cas9-based genetic perturbation studies we established that astrocyte memory is controlled by the metabolic enzyme ATP-citrate lyase (ACLY), which produces acetyl coenzyme A (acetyl-CoA) that is used by histone acetyltransferase p300 to control chromatin accessibility. The number of ACLY+p300+ memory astrocytes is increased in acute and chronic EAE models, and their genetic inactivation ameliorated EAE. We also detected the pro-inflammatory memory phenotype in human astrocytes in vitro; single-cell RNA sequencing and immunohistochemistry studies detected increased numbers of ACLY+p300+ astrocytes in chronic multiple sclerosis lesions. In summary, these studies define an epigenetically controlled memory astrocyte subset that promotes CNS pathology in EAE and, potentially, multiple sclerosis. These findings may guide novel therapeutic approaches for multiple sclerosis and other neurologic diseases.

Analysis of Changing Practice Trends in Anterior Cruciate Ligament Reconstruction: A Multicenter, Single-Institution Database Analysis.

PURPOSE: To identify trends in anterior cruciate ligament reconstruction (ACLR), including graft choice, femoral tunnel drilling techniques, and augmentation techniques, and to assess how various surgeon factors impact these trends. METHODS: A retrospective review of primary ACLRs performed between 2014 and 2022 was completed using a multicenter institutional database. Patient demographic characteristics, graft type, femoral drilling technique, use of extra-articular tenodesis, and use of suture augmentation were recorded from the medical record. Surgeon fellowship training (sports trained vs non-sports trained), experience (high [minimum of 15 years in practice] vs low), and volume (high [minimum of 15 ACLRs/year] vs low) were used to stratify technique utilization. The z test for proportions was used to compare categorical variables. Pearson correlation analyses identified trends and assessed statistical significance, defined as P < .05. RESULTS: Our cohort consisted of 2,032 ACLRs performed in 2,006 patients. The average patient age was 28.3 ± 11.6 years, with more procedures performed in male patients (67.3%). The average length of surgeon experience was 19.7 ± 11.4 years, with an average annual procedural volume of 4.0 ± 5.4 ACLRs. Most surgeons were sports trained (n = 55, 64.7%), high experience (n = 44, 57.1%), and low volume (n = 80, 94.1%). There was an increasing annual proportion of ACLRs performed by sports-trained surgeons (R = 0.748, P = .020) and low-experience surgeons (R = 0.940, P < .001). Autograft reconstructions were most often performed by sports-trained (71.2%), low-experience (66.1%), and high-volume (76.9%) surgeons. There was an increasing proportion of autograft ACLRs that used quadriceps tendon among sports-trained (R = 0.739, P = .023), high-experience (R = 0.768, P = .016), and low-volume (R = 0.785, P = .012) surgeons. Independent drilling techniques were used in an increasing proportion of ACLRs performed by non-sports-trained (R = 0.860, P = .003) and high-volume (R = 0.864, P = .003) surgeons. Augmentation of ACLR with concomitant suture augmentation (n = 24, 1.2%) or extra-articular tenodesis (n = 6, 0.3%) was rarely performed. CONCLUSIONS: In our multicenter institution, the quadriceps tendon autograft has been increasingly used in ACLR by sports-trained, low-volume, and high-experience surgeons. Independent drilling techniques have been increasingly used by non-sports-trained and high-volume surgeons. CLINICAL RELEVANCE: Surgeons must stay current with the literature that affects their procedures to ensure that evidence-based medicine is being practiced.

Community perspectives on the magnitude of Xeroderma pigmentosum and care-seeking practices in Micheweni district, Pemba: a mixed-methods cross-sectional study.

OBJECTIVES: To determine the community's perception on the magnitude of Xeroderma pigmentosum (XP) disease and healthcare-seeking practices in Micheweni, Pemba in response to the public widespread information on the increased burden of the disease. DESIGN: Mixed-methods cross-sectional study. SETTING: Micheweni district, Pemba. PARTICIPANTS: 211 male and female adults in the household survey, three caretakers/parents of patients with XP in the case study, 20 key community leaders/influential people and health workers in in-depth interviews and 50 community members and other leaders in six focus groups. RESULTS: This study has revealed that XP disease exists in few families of which some of them have more than one child affected. The record review showed that there were a total of 17 patients who were diagnosed with the disease for the past 3 years, however only 10 were alive during the time of the survey. Findings from the community members revealed that several patients were believed to have XP disease and perceived causes include inheritance, food types, beliefs and other sociocultural practices. Stigma and discrimination were reported by caretakers and religious leaders. However, some cases believed to be XP were identified as other skin conditions when clinical examination was performed by the team of our researchers. There is a great confusion about XP and other skin diseases. CONCLUSION: The study has shown that XP affects only few families, hence termed as concentrated rather than a generalised disease. Due to the rareness of the disease, majority of people in the district are unaware of the disease, hence confusing it with other skin conditions. There is a need for the government in collaboration with other stakeholders to provide educational programme to community members about the disease to address the misconception about the magnitude of the disease.

Opportunities for Pharmacogenetic Testing to Guide Dosing of Medications in Youths With Medicaid.

Importance: There are an increasing number of medications with a high level of evidence for pharmacogenetic-guided dosing (PGx drugs). Knowledge of the prevalence of dispensings of PGx drugs and their associated genes may allow hospitals and clinical laboratories to determine which pharmacogenetic tests to implement. Objectives: To investigate the prevalence of outpatient dispensings of PGx drugs among Medicaid-insured youths, determine genes most frequently associated with PGx drug dispenses, and describe characteristics of youths who were dispensed at least 1 PGx drug. Design, Setting, and Participants: This serial cross-sectional study includes data from 2011 to 2019 among youths aged 0 to 17 years in the Marketscan Medicaid database. Data were analyzed from August to December 2022. Main Outcomes and Measures: PGx drugs were defined as any medication with level A evidence as determined by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The number of unique youths dispensed each PGx drug in each year was determined. PGx drugs were grouped by their associated genes for which there was CPIC level A evidence to guide dosing, and a dispensing rate (No. of PGx drugs/100 000 youths) was determined for each group for the year 2019. Demographics were compared between youths dispensed at least 1 PGx drug and those not dispensed any PGx drugs. Results: The number of Medicaid-insured youths queried ranged by year from 2 078 683 youths in 2011 to 4 641 494 youths in 2017, including 4 126 349 youths (median [IQR] age, 9 [5-13] years; 2 129 926 males [51.6%]) in 2019. The proportion of Medicaid-insured youths dispensed PGx drugs increased from 289 709 youths (13.9%; 95% CI, 13.8%-14.0%) in 2011 to 740 072 youths (17.9%; 95% CI, 17.9%-18.0%) in 2019. Genes associated with the most frequently dispensed medications were CYP2C9, CYP2D6, and CYP2C19 (9197.0 drugs [95% CI, 9167.7-9226.3 drugs], 8731.5 drugs [95% CI, 8702.5-8759.5 drugs], and 3426.8 drugs [95% CI, 3408.1-3443.9 drugs] per 100 000 youths, respectively). There was a higher percentage of youths with at least 1 chronic medical condition among youths dispensed at least 1 PGx drug (510 445 youths [69.0%; 95% CI, 68.8%-69.1%]) than among 3 386 277 youths dispensed no PGx drug (1 381 544 youths [40.8%; 95% CI, 40.7%-40.9%) (P < .001) in 2019. Conclusions and Relevance: In this study, there was an increasing prevalence of dispensings for PGx drugs. This finding suggests that pharmacogenetic testing of specific drug-gene pairs should be considered for frequently prescribed PGx drugs and their implicated genes.

Land use change and forest management effects on soil carbon stocks in the Northeast U.S.

BACKGROUND: In most regions and ecosystems, soils are the largest terrestrial carbon pool. Their potential vulnerability to climate and land use change, management, and other drivers, along with soils' ability to mitigate climate change through carbon sequestration, makes them important to carbon balance and management. To date, most studies of soil carbon management have been based at either large or site-specific scales, resulting in either broad generalizations or narrow conclusions, respectively. Advancing the science and practice of soil carbon management requires scientific progress at intermediate scales. Here, we conducted the fifth in a series of ecoregional assessments of the effects of land use change and forest management on soil carbon stocks, this time addressing the Northeast U.S. We used synthesis approaches including (1) meta-analysis of published literature, (2) soil survey and (3) national forest inventory databases to examine overall effects and underlying drivers of deforestation, reforestation, and forest harvesting on soil carbon stocks. The three complementary data sources allowed us to quantify direction, magnitude, and uncertainty in trends. RESULTS: Our meta-analysis findings revealed regionally consistent declines in soil carbon stocks due to deforestation, whether for agriculture or urban development. Conversely, reforestation led to significant increases in soil C stocks, with variation based on specific geographic factors. Forest harvesting showed no significant effect on soil carbon stocks, regardless of place-based or practice-specific factors. Observational soil survey and national forest inventory data generally supported meta-analytic harvest trends, and provided broader context by revealing the factors that act as baseline controls on soil carbon stocks in this ecoregion of carbon-dense soils. These factors include a range of soil physical, parent material, and topographic controls, with land use and climate factors also playing a role. CONCLUSIONS: Forest harvesting has limited potential to alter forest soil C stocks in either direction, in contrast to the significant changes driven by land use shifts. These findings underscore the importance of understanding soil C changes at intermediate scales, and the need for an all-lands approach to managing soil carbon for climate change mitigation in the Northeast U.S.

A new early-diverging probainognathian cynodont and a revision of the occurrence of cf. Aleodon from the Chañares Formation, northwestern Argentina: New clues on the faunistic composition of the latest Middle-?earliest Late Triassic Tarjadia Assemblage Zone.

The Chañares Formation (Ischigualasto-Villa Unión Basin) is worldwide known by its exquisitely preserved fossil record of latest Middle-to-early Late Triassic tetrapods, including erpetosuchids, "rauisuchians," proterochampsids, gracilisuchids, dinosauromorphs, pterosauromorphs, kannemeyeriiform dicynodonts, and traversodontid, chiniquodontid and probainognathid cynodonts, coming from the Tarjadia (bottom) and Massetognathus-Chanaresuchus (top) Assemblage Zones of its lower member. Regarding cynodonts, most of its profuse knowledge comes from the traditional layers discovered by Alfred Romer and his team in the 1960s that are now enclosed in the Massetognathus-Chanaresuchus Assemblage Zone (AZ). In this contribution we focus our study on the probainognathian cynodonts discovered in levels of the Tarjadia Assemblage Zone. We describe a new chiniquodontid cynodont with transversely broad postcanine teeth (Riojanodon nenoi gen. et sp. nov.) which is related to the genus Aleodon. In addition, the specimen CRILAR-Pv 567 previously referred to cf. Aleodon is here described, compared, and included in a phylogenetic analysis. It is considered as an indeterminate Aleodontinae nov., a clade here proposed to included chiniquodontids with transversely broad upper and lower postcanines, by having a cuspidated sectorial labial margin and a lingual platform that is twice broader than a lingual cingulum. Cromptodon mamiferoides, from the Cerro de Las Cabras Formation (Cuyo Basin), was also included in the phylogenetic analysis and recovered as an Aleodontinae. The new cynodont and the record of Aleodontinae indet. reinforce the faunal differentiation between the Tarjadia and Massetognathus-Chanaresuchus Assemblage Zones, in the lower member of the Chañares Formation, and inform on the diverse chiniquodontid clade with both sectorial and transversely broad postcanine teeth.

Disease-associated astrocyte epigenetic memory promotes CNS pathology.

Astrocytes play important roles in the central nervous system (CNS) physiology and pathology. Indeed, astrocyte subsets defined by specific transcriptional activation states contribute to the pathology of neurologic diseases, including multiple sclerosis (MS) and its pre-clinical model experimental autoimmune encephalomyelitis (EAE) 1-8 . However, little is known about the stability of these disease-associated astrocyte subsets, their regulation, and whether they integrate past stimulation events to respond to subsequent challenges. Here, we describe the identification of an epigenetically controlled memory astrocyte subset which exhibits exacerbated pro-inflammatory responses upon re-challenge. Specifically, using a combination of single-cell RNA sequencing (scRNA-seq), assay for transposase-accessible chromatin with sequencing (ATAC-seq), chromatin immunoprecipitation with sequencing (ChIP-seq), focused interrogation of cells by nucleic acid detection and sequencing (FIND-seq), and cell-specific in vivo CRISPR/Cas9-based genetic perturbation studies we established that astrocyte memory is controlled by the metabolic enzyme ATP citrate lyase (ACLY), which produces acetyl coenzyme A (acetyl-CoA) used by the histone acetyltransferase p300 to control chromatin accessibility. ACLY + p300 + memory astrocytes are increased in acute and chronic EAE models; the genetic targeting of ACLY + p300 + astrocytes using CRISPR/Cas9 ameliorated EAE. We also detected responses consistent with a pro-inflammatory memory phenotype in human astrocytes in vitro ; scRNA-seq and immunohistochemistry studies detected increased ACLY + p300 + astrocytes in chronic MS lesions. In summary, these studies define an epigenetically controlled memory astrocyte subset that promotes CNS pathology in EAE and, potentially, MS. These findings may guide novel therapeutic approaches for MS and other neurologic diseases.

Seventy Percent of Abstracts Presented at the AANA Annual Meeting Are Later Published.

Purpose: To assess the future publication rates of abstracts presented at AANA annual meetings between 2015 and 2019. Methods: Abstracts presented at the 2015-2019 AANA annual meetings were identified. The PubMed and Google Scholar databases were searched for a corresponding manuscript for each abstract using the name of the first author, abstract title, and keywords. A level of evidence and anatomic category were assigned to each abstract. For each corresponding manuscript identified, the authors, journal of publication, journal impact factor (IF), time to publication, and number of citations were recorded. Results: Overall, 70.5% of abstracts presented at the 2015-2019 AANA annual meetings (275 of 390) went on to future publication, with 63.6% (248 of 390) achieving publication within 3 years. The median time to publication from presentation was 12.8 months. Arthroscopy (29.8%) was the most frequent journal of publication. The average IF of publishing journals was 4.92 ± 3.41, with 61.8% of manuscripts (170 of 275) published in journals with an IF of at least 4.00. Published manuscripts received an average of 36.30 ± 47.6 citations per manuscript. A stronger level of evidence was associated with an increased likelihood of future publication (P = .008). Conclusions: Pre-publication literature presented at the AANA annual meetings has continued to be associated with a strong likelihood of future publication in Arthroscopy and Arthroscopy, Sports Medicine, and Rehabilitation, as well as other respected peer-reviewed journals. Clinical Relevance: Exposure to pre-publication literature may have an impact on clinical management. It is important to understand the quality of research presented in abstracts from AANA annual meetings. Knowing how many abstracts are ultimately published in peer-reviewed journals provides an indicator of the quality and reliability of the research.

The quantum maxima for the basic graphs of exclusivity are not reachable in Bell scenarios.

A necessary condition for the probabilities of a set of events to exhibit Bell non-locality or Kochen-Specker contextuality is that the graph of exclusivity of the events contains induced odd cycles with five or more vertices, called odd holes, or their complements, called odd antiholes. From this perspective, events whose graph of exclusivity are odd holes or antiholes are the building blocks of contextuality. For any odd hole or antihole, any assignment of probabilities allowed by quantum theory can be achieved in specific contextuality scenarios. However, here we prove that, for any odd hole, the probabilities that attain the quantum maxima cannot be achieved in Bell scenarios. We also prove it for the simplest odd antiholes. This leads us to the conjecture that the quantum maxima for any of the building blocks cannot be achieved in Bell scenarios. This result sheds light on why the problem of whether a probability assignment is quantum is decidable, while whether a probability assignment within a given Bell scenario is quantum is, in general, undecidable. This also helps to understand why identifying principles for quantum correlations is simpler when we start by identifying principles for quantum sets of probabilities defined with no reference to specific scenarios. This article is part of the theme issue 'Quantum contextuality, causality and freedom of choice'.

Robotic-assisted TKA is Not Associated With Decreased Odds of Early Revision: An Analysis of the American Joint Replacement Registry.

BACKGROUND: Robotic-assisted TKA continues to see wider clinical use, despite limited knowledge of its impact on patient satisfaction and implant survival. Most studies to date have presented small cohorts and came from single-surgeon or single-center experiences. Therefore, a population-level comparison of revision rates between robotic-assisted and conventional TKA in the registry setting may help arthroplasty surgeons better define whether robotic assistance provides a meaningful advantage compared with the conventional technique. QUESTIONS/PURPOSES: (1) After controlling for confounding variables, such as surgeon, location of surgery, and patient comorbidity profile, were robotic-assisted TKAs less likely than conventional TKAs to result in revision for any reason at 2 years? (2) After again controlling for confounding variables, were robotic-assisted TKAs less likely to result in any specific reasons for revision than the conventional technique at 2 years? METHODS: The American Joint Replacement Registry was used to identify patients 65 years or older who underwent TKA between January 2017 and March 2020 with a minimum of 2 years of follow-up. Patients were limited to age 65 yeas or older to link TKAs to Medicare claims data. Two retrospective cohorts were created: robotic-assisted TKA and conventional TKA. Patient demographic variables included in the analysis were age, gender, BMI, and race. Additional characteristics included the Charlson comorbidity index, anesthesia type, year of the index procedure, and length of stay. A total of 10% (14,216 of 142,550) of TKAs performed during this study period used robotics. Patients with robotic-assisted TKA and those with conventional TKA were similar regarding age (73 ± 6 years versus 73 ± 6 years; p = 0.31) and gender (62% [8736 of 14,126] versus 62% [79,399 of 128,334] women; p = 0.34). A multivariable, mixed-effects logistic regression model was created to analyze the odds of all-cause revision as a factor of robot use, and a logistic regression model was created to investigate specific revision diagnoses. RESULTS: After controlling for potentially confounding variables, such as surgeon, location of surgery, and Charlson comorbidity index, we found no difference between the robotic-assisted and conventional TKAs in terms of the odds of revision at 2 years (OR of robotic-assisted versus conventional TKA 1.0 [95% CI 0.8 to 1.3]; p = 0.92). The reasons for revision of robotic-assisted TKA did not differ from those of conventional TKA, except for an increased odds of instability (OR 1.6 [95% CI 1.0 to 2.4]; p = 0.04) and pain (OR 2.1 [95% CI 1.4 to 3.0]; p < 0.001) in the robotic-assisted cohort. CONCLUSION: In light of these findings, surgeons should not assume that robotic assistance in TKA will lead to improved early implant survival. Our findings do not support an improvement over conventional TKA with robotic assistance with regards to common causes of early revisions such malalignment, malposition, stiffness, pain, and instability, and in some cases, suggest there is a benefit to conventional TKA. Differences in the mid-term and long-term revision risk with conventional versus robotic-assisted TKA remain unknown. Appropriate informed consent around the use of robotic assistance should not imply decreased early revision risk. LEVEL OF EVIDENCE: Level III, therapeutic study.

Effect of Parenteral Supplementation of Minerals and Vitamins on Oxidative Stress Biomarkers and Hepatic Fatty Acid Metabolism in Dairy Cows During the Transition Period.

In the present work we aimed to study the effects of parenteral vitamin and mineral supplementation on hepatic fatty acid metabolism as well as on the oxidative stress biomarkers in biological samples of transition cows. The supplemented group (SG, n = 11) received a subcutaneous injection of 5 mL of vitamin A palmitate 35 mg/mL, vitamin E acetate 50 mg/mL plus other injection of 5 mL of copper edetate 10 mg/mL, zinc edetate 40 mg/mL, manganese edetate 10 mg/mL, and sodium selenite 5 mg/mL on days - 60, - 30, and 7 (± 3) relative to calving. The control group (CG, n = 11) received two subcutaneous injections of 5 mL of 9 mg/mL sodium chloride at the same times of the SG. Blood, urine, and liver biopsies were sampled 21 (± 3) days before the expected calving date and 7 and 21 (± 3) days after calving. Results revealed that supplemented animals had higher glutation peroxidase (GSH-Px) activity, lower and higher concentration of 3-nitrotyrosine (3-NT) in the liver and plasma, respectively, higher expression of the mitochondrial beta-oxidation enzyme carnitine palmitoyltransferase 1 in the liver, and lower content of hepatic triacylglycerol, mirroring plasma liver function parameters. No differences between groups were found in the superoxide dismutase activity, MDA concentrations, the protein abundance of peroxisomal acyl-CoA oxidase 1, diacylglycerol O-acyltransferase 1, and peroxisome proliferator-activated receptor alpha. These results suggest that the vitamin and mineral supplementation provided to dairy cows had a beneficial effect on GSH-Px activity, hepatic 3-NT concentration, and on the metabolic adaptation during the peripartum period.

Cholic acid increases plasma cholesterol in Smith-Lemli-Opitz syndrome: A pilot study.

Background: Smith-Lemli-Opitz syndrome (SLOS) is an inherited disorder of cholesterol biosynthesis associated with congenital malformations, growth delay, intellectual disability and behavior problems. SLOS is caused by bi-allelic mutations in DHCR7, which lead to reduced activity of 7-dehydrocholesterol reductase that catalyzes the last step in cholesterol biosynthesis. Symptoms of SLOS are thought to be due to cholesterol deficiency and accumulation of its precursor 7-dehydrocholesterol (7-DHC) and 8-dehydrocholesterol (8-DHC), and toxic oxysterols. Therapy for SLOS often includes dietary cholesterol supplementation, but lipids are poorly absorbed from the diet, possibly due to impaired bile acid synthesis. We hypothesized that bile acid supplementation with cholic acid would improve dietary cholesterol absorption and raise plasma cholesterol levels. Methods: Twelve SLOS subjects (10 M, 2F, ages 2-27 years) who had plasma cholesterol ≤125 mg/dL were treated with cholic acid (10 mg/kg/day) divided twice daily for 2 months. Plasma cholesterol, 7-DHC and 8-DHC were measured by GC-MS. Oxysterols were measured by ultra-high-performance LC-MS/MS. Data were analyzed using paired t-tests. Results: At baseline, plasma cholesterol was 75 ± 24 mg/dL (mean ± SD; range 43-125, n = 12). After 2 months on cholic acid, mean plasma cholesterol increased to 97 ± 29 mg/dL (p = 0.011). Eleven of 12 subjects showed an increase in plasma cholesterol that varied from 3.8% to 85.7% (mean 38.7 ± 23.3%). 7-Hydroxycholesterol decreased by 20.6% on average (p = 0.013) but no significant changes were seen in 7-DHC or 8-DHC. Mean body weight tended to increase (3.6% p = 0.069). Subjects tolerated cholic acid well and experienced no drug-related adverse events. Conclusions: In this pilot study, cholic acid supplementation was well tolerated and safe and resulted in an increase in plasma cholesterol in most SLOS subjects. Further controlled longitudinal studies are needed to look for the sustainability of the biochemical effect and possible clinical benefits.

Linking microbiome and stress hormone responses in wild tropical treefrogs across continuous and fragmented forests.

The amphibian skin microbiome is an important component of anti-pathogen defense, but the impact of environmental change on the link between microbiome composition and host stress remains unclear. In this study, we used radiotelemetry and host translocation to track microbiome composition and function, pathogen infection, and host stress over time across natural movement paths for the forest-associated treefrog, Boana faber. We found a negative correlation between cortisol levels and putative microbiome function for frogs translocated to forest fragments, indicating strong integration of host stress response and anti-pathogen potential of the microbiome. Additionally, we observed a capacity for resilience (resistance to structural change and functional loss) in the amphibian skin microbiome, with maintenance of putative pathogen-inhibitory function despite major temporal shifts in microbiome composition. Although microbiome community composition did not return to baseline during the study period, the rate of microbiome change indicated that forest fragmentation had more pronounced effects on microbiome composition than translocation alone. Our findings reveal associations between stress hormones and host microbiome defenses, with implications for resilience of amphibians and their associated microbes facing accelerated tropical deforestation.

Phylogenetic relationship between Contracaecum spp. (Nematoda, Anisakidae) parasitizing cormorants (Aves, Phalacrocoracidae) in Argentina.

Species of the genus Contracaecum (Family Anisakidae) exhibit a broad host and geographical distribution, parasitizing aquatic organisms such as piscivorous birds and mammals as their definitive hosts. Several Contracaecum species have been reported parasitizing cormorants (Family: Phalacrocoracidae) in South America. The objective of this study was to highlight phylogenetic relationships between Contracaecum species parasitizing cormorants based on both molecular analyses and the papillae arrangement on the male tail. Some Contracaecum species parasitizing Red-legged cormorants from the Ría Deseado (RD), and other nematodes parasitizing eight Neotropic cormorants from San Miguel del Monte lagoon (SMML), Argentina, were collected and analyzed. Both morphological and phylogenetic analyses allowed us to recognize two species: Contracaecum chubutensis parasitizing Phalacrocorax gaimardi, and Contracaecum australe parasitic in Phalacrocorax brasilianus. According to the obtained sequences (mtDNA cox2, ITS1, ITS2, and SSrRNA), Contracaecum sp. parasitizing P. gaimardi exhibited concordance with the previously reported C. chubutensis parasitizing P. atriceps from Bahía Bustamante, Chubut province. Likewise, Contracaecum sp. isolates parasitizing P. brasilianus showed concordance with C. australe from Chile. Besides, the papillae arrangement on the male tail allowed us to understand the interspecific and genetic relationships between the Contracaecum species. The analyses confirm that C. chubutensis specimens parasitizing P. gaimardi from RD present a new host record for the species, whereas, those C. australe specimens parasitizing P. brasilianus from SMML provide a new geographical record for the species and the extension of its distribution range. Present results also confirm the inland and marine distribution of C. australe and C. chubutensis, respectively.

Cytotoxic, antioxidant, and cytoprotective properties of polyphenol-enriched extracts from pecan nutshells in MDA-MB-231 breast cancer cells.

Phenolic compounds present in plants have demonstrated several biological properties such as antioxidant, antitumor, cardioprotective, and antiproliferative. On the other hand, doxorubicin, a chemotherapeutic widely used to treat breast cancer, usually exhibits chronic cardiotoxicity associated with oxidative stress. Therefore, we aimed to study the effects of phenolic compound-enriched extract (PCEE) with doxorubicin in breast cancer. To achieve this, after an SPE-C18 -column purification process of crude extracts obtained from pecan nutshells (Carya illinoinensis), the resulting PCEE was used to evaluate the cytotoxicity and antioxidant properties against the human breast cancer cell line MDA-MB-231 and the normal-hamster ovary cell line CHO-K1. PCEE was selectively cytotoxic against both cell lines, with an IC50 value (≈26.34 mg/L) for MDA-MB-231 lower than that obtained for CHO-K1 (≈55.63 mg/L). As a cytotoxic mechanism, PCEE inhibited cell growth by G2/M cell cycle arrest in MDA-MB-231 cells. Simultaneously, the study of the antioxidant activity showed that PCEE had a cytoprotective effect, evidenced by reduced ROS production in cells with oxidative stress caused by doxorubicin. The results highlight PCEE as a potential antitumor agent, thus revaluing it as an agro-industrial residue.

Neuroinflammation: An astrocyte perspective.

Astrocytes are abundant glial cells in the central nervous system (CNS) that play active roles in health and disease. Recent technologies have uncovered the functional heterogeneity of astrocytes and their extensive interactions with other cell types in the CNS. In this Review, we highlight the intricate interactions between astrocytes, other CNS-resident cells, and CNS-infiltrating cells as well as their potential therapeutic value in the context of inflammation and neurodegeneration.

Publication Rates of Abstracts Presented at American Orthopaedic Society for Sports Medicine Annual Meetings From 2016 to 2019.

Background: Research in the form of poster and podium abstracts is disseminated at subspecialty society meetings. The quality of this research can be defined by exploring the ultimate publication rate of the presented abstracts. Purpose: To investigate (1) the manuscript publication rate of abstracts presented at the American Orthopaedic Society for Sports Medicine (AOSSM) annual meeting; (2) whether abstract format (poster vs podium) influences overall or 2-year publication rates and time to publication; (3) the abstract factors that are associated with increased publication rate; and (4) whether publication quality as measured by journal of publication, level of evidence (LOE), and number of citations differs between posters and podiums. Study Design: Cross-sectional study. Methods: Poster and podium abstracts that were presented at the AOSSM annual meetings between January 1, 2016, and December 31, 2019, were included. The PubMed and GoogleScholar databases were searched by abstract title and authors to determine whether the related manuscript had been published. For published manuscripts, the journal, journal impact factor (IF), time to publication, authors, and LOE were recorded. Results: The manuscripts of 664 abstracts (341 poster, 323 podium presentations) were published during the study period. The overall publication rate was 52.4%. Publication within 2 years of the meeting was found to be higher in podium abstracts (45.8%) compared with poster abstracts (37.8%) (P = .0366). Podium abstracts had a shorter time to publication (P < .001), higher LOE (P = .0166), more citations (P < .0001), and were published in higher IF journals (P = .0028). Poster presentations were more likely to undergo a change in first author between the time of the conference and future publication (P = .0300). The most common journal of publication was the American Journal of Sports Medicine (36.8%). Conclusion: Abstracts presented at the AOSSM annual meeting had a high rate of publication within 2 years. There was no difference in publication rates between podium and poster abstracts, but podium abstracts had a shorter time to publication and more future citations and were published in journals with higher IFs.

Personality correlates of dispositional forgiveness: a direct comparison of interpersonal and self-forgiveness using common transgression scenarios.

Although the personality correlates of dispositional interpersonal forgiveness (forgiveness of others) have been well characterized, those of dispositional self-forgiveness are less well understood. Moreover, when the personality correlates are examined for both types of forgiveness, the comparison has been based on participants' self-report ratings on questionnaires. The current study sought to address these gaps in the literature by adopting a scenario-based approach, which has been used less frequently, especially in self-forgiveness research. A total of 160 participants read six fictional scenarios, each describing a severe transgression, from the perspective of the transgressor (self-forgiveness, n = 78) or the victim (interpersonal forgiveness, n = 82) of the transgression, and then responded to several items assessing different facets of forgiveness (avoidance, revenge, and benevolence). Participants' personality (Big Five) and explanatory style were also assessed. Consistent with prior literature, agreeableness and neuroticism generally predicted different facets of interpersonal forgiveness. These two personality traits also predicted facets of self-forgiveness, but, additionally, conscientiousness and one's tendency to internalize failure (the personal component of explanatory style) uniquely predicted self-forgiveness, especially avoidance motivations. These results point to both similarities and differences in the personality correlates of interpersonal and self-forgiveness. As a secondary, more exploratory aim, the current study compared the results from our scenario-based assessment of forgiveness to those based on a commonly used questionnaire, the Other and Self subscales of the Heartland Forgiveness Scale (HFS). As expected, the Other subscale of the HFS were associated with levels of interpersonal forgiveness assessed with our transgression scenarios, but, surprisingly, the HFS Self subscale was more strongly related to interpersonal than self-forgivess assessed with scenarios. Moreover, the Self subscale was not associated with levels of self-forgiveness assessed with transgression scenarios, except for avoidance motivations. These results suggest that scenario-based and questionnaire-based methods may capture different facts of forgiveness and cannot be used interchangeably, especially for the assessment of self-forgiveness. More generally, the current study illustrates the importance of conducting direct within-study comparisons of interpersonal and self-forgiveness as well as of different assessment methods to better understand the similarities and differences between the two types of forgiveness.