Social determinants of health and surgical outcomes of minimally invasive radical prostatectomy: a national population-based study.

BACKGROUND: Socioeconomic determinants of health (SDOH) are often unvalued during surgery risk stratification; hence, they might be a major source of disparity that can jeopardize outcomes related to urological surgery. The aim of our study is to evaluate the impact of SDOH on postoperative outcomes following minimally invasive radical prostatectomy (MIRP). METHODS: Patients who underwent MIRP between 2011 and 2021 were retrospectively analyzed by using PearlDiver-Mariner, an all-payer insurance claims database. International Classification of Diseases diagnosis and procedure codes were used to identify patient's characteristics, postoperative complications and SDOH. Outcomes were compared using multivariable regression models. RESULTS: Overall, 100,035 patients (mean age = 63.24 ± 7.07) underwent MIRP. The 60-day postoperative complication rate was 18%. Approximately 6% of patients reported at least one SDOH at baseline. SDOH were associated with higher odds of 60-day postoperative complications (OR:1.24, 95% CI:1.15-1.34), including urinary tract infection (OR:1.32, 95% CI:1.20-1.45) and acute kidney injury (OR:1.31, 95% CI:1.00-1.39). Postoperative urethral stricture (OR:1.37, 95% CI:0.92-1.98) did not reach statistical significance at multivariable analysis. CONCLUSIONS: Patients with SDOH have a significantly higher risk of postoperative complications following MIRP, especially urinary infection and acute kidney injury. These findings are multifactorial and should prompt identifying measures that might help prevent this large-scale phenomenon.

Molecular Phylogenetics and Historical Biogeography of Subtribe Ecliptinae (Asteraceae, Heliantheae).

We present a molecular phylogeny for the subtribe Ecliptinae (Asteraceae, Heliantheae) based on three plastid (matK, psbA-trnH, and trnQ-rps16) and two nuclear (nrITS and nrETS) markers. The results of the phylogenetic reconstruction were utilised as a topological constraint for a subsequent divergence dating analysis and ancestral range reconstructions. We sampled 41 species and 40 genera (72%) of Ecliptinae and two species of Montanoa (as outgroups) to elucidate the generic relationships between the genera of this subtribe. The Bayesian inference (BI) and Maximum Likelihood (ML) analyses were performed for the combined molecular dataset. The divergence dating analysis was performed using a relaxed, uncorrelated molecular clock with BEAST v1.8.4 and calibrated using a single secondary calibration point from a recently published chronogram for the family. The ancestral range reconstructions focusing on continents (i.e., South America, North America, Africa, Asia, and Oceania) and biomes (Dry forests, Altitudinal grasslands, Savannas, and Rainforests) were performed on BioGeoBEARS. Our phylogenetic results indicate that the genera of Ecliptinae are grouped into five clades, informally named the Monactis, Oblivia, Blainvillea, Wedelia, and Melanthera clades. The most recent, common ancestor of Ecliptinae was widespread in the North and South American dry forests at 8.16 Ma and mainly radiated in these regions up to the Pleistocene. At least eight dispersal events to South America and four dispersal events from North America to Africa, Asia, and Oceania took place during this period in all five informal clades of Ecliptinae. At least 13 biome shifts from dry forests to rainforests were evidenced, in addition to ten biome shifts from dry forests to altitudinal grasslands and savannas. These results corroborate the mid-late Miocene to early Pleistocene radiation of Ecliptinae in tropical dry forests. Future studies should aim to sample the remaining 14 unsampled genera of Ecliptinae to position them in one of the five informal clades proposed in this study.

Optogenetic targeting of cortical astrocytes selectively improves NREM sleep in an Alzheimer's disease mouse model.

Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by memory impairments and distinct histopathological features such as amyloid-beta (Aß) accumulations. Alzheimer's patients experience sleep disturbances at early stages of the disease. APPswe/PS1dE9 (APP) mice exhibit sleep disruptions, including reductions in non-rapid eye movement (NREM) sleep, that contribute to their disease progression. In addition, astrocytic calcium transients associated with a sleep-dependent brain rhythm, slow oscillations prevalent during NREM sleep, are disrupted in APP mice. However, at present it is unclear whether restoration of circuit function by targeting astrocytic activity could improve sleep in APP mice. To that end, APP mice expressing channelrhodopsin-2 (ChR2) targeted to astrocytes underwent optogenetic stimulation at the slow oscillation frequency. Optogenetic stimulation of astrocytes significantly increased NREM sleep duration but not duration of rapid eye movement (REM) sleep. Optogenetic treatment increased delta power and reduced sleep fragmentation in APP mice. Thus, optogenetic activation of astrocytes increased sleep quantity and improved sleep quality in an AD mouse model. Astrocytic activity provides a novel therapeutic avenue to pursue for enhancing sleep and slowing AD progression.

Course-Skill Atlas: A national longitudinal dataset of skills taught in U.S. higher education curricula.

Higher education plays a critical role in driving an innovative economy by equipping students with knowledge and skills demanded by the workforce. While researchers and practitioners have developed data systems to track detailed occupational skills, such as those established by the U.S. Department of Labor (DOL), much less effort has been made to document which of these skills are being developed in higher education at a similar granularity. Here, we fill this gap by presenting Course-Skill Atlas - a longitudinal dataset of skills inferred from over three million course syllabi taught at nearly three thousand U.S. higher education institutions. To construct Course-Skill Atlas, we apply natural language processing to quantify the alignment between course syllabi and detailed workplace activities (DWAs) used by the DOL to describe occupations. We then aggregate these alignment scores to create skill profiles for institutions and academic majors. Our dataset offers a large-scale representation of college education's role in preparing students for the labor market. Overall, Course-Skill Atlas can enable new research on the source of skills in the context of workforce development and provide actionable insights for shaping the future of higher education to meet evolving labor demands, especially in the face of new technologies.

Telomere-to-telomere assemblies of cattle and sheep Y-chromosomes uncover divergent structure and gene content.

Reference genomes of cattle and sheep have lacked contiguous assemblies of the sex-determining Y chromosome. Here, we assemble complete and gapless telomere to telomere (T2T) Y chromosomes for these species. We find that the pseudo-autosomal regions are similar in length, but the total chromosome size is substantially different, with the cattle Y more than twice the length of the sheep Y. The length disparity is accounted for by expanded ampliconic region in cattle. The genic amplification in cattle contrasts with pseudogenization in sheep suggesting opposite evolutionary mechanisms since their divergence 19MYA. The centromeres also differ dramatically despite the close relationship between these species at the overall genome sequence level. These Y chromosomes have been added to the current reference assemblies in GenBank opening new opportunities for the study of evolution and variation while supporting efforts to improve sustainability in these important livestock species that generally use sire-driven genetic improvement strategies.

Efficacy of Gamified Digital Mental Health Interventions for Pediatric Mental Health Conditions: A Systematic Review and Meta-Analysis.

Importance: Anxiety, depression, and attention-deficit/hyperactivity disorder (ADHD) affect up to 20% of children and adolescents. Despite demonstrated efficacy, evidence-based treatments for these conditions are often inaccessible; innovative solutions are essential to meet the demand for pediatric mental health care. Objective: To examine the efficacy and moderators of gamified DMHIs for anxiety, depression, and ADHD in randomized clinical trials (RCTs) for children and adolescents. Data Sources: A systematic search of PubMed, PsycInfo, and Web of Science was conducted for RCTs published before March 20, 2024. Study Selection: RCTs that evaluated the efficacy of gamified DMHIs for treating pediatric ADHD, depression, or anxiety were included. Studies were excluded if they did not use a gamified DMHI, provide sufficient data for effect sizes, or were unavailable in English. Data Extraction and Synthesis: Efficacy data were extracted from rating scales for ADHD, depression, and anxiety. Extracted moderator variables included participant characteristics (eg, age and sex), intervention characteristics (eg, delivery modality and time limit), and trial design characteristics (eg, outcome measure and risk of bias). Main Outcomes and Measures: The primary outcome was change in ADHD, depression, or anxiety severity in the treatment group compared to the control group. Hedges g quantified treatment effects. Results: The search strategy identified 27 RCTs that included 2911 participants across ADHD, depression, and anxiety disorders. There were modest significant effects of gamified DMHIs on ADHD (g, 0.28; 95% CI, 0.09 to 0.48) and depression (g, 0.28; 95% CI, 0.08 to 0.47) but small, nonsignificant effects for anxiety disorders (g, 0.07; 95% CI, -0.02 to 0.17). Moderator analyses revealed that DMHIs for ADHD delivered on a computer and those RCTs that had a greater preponderance of male participants produced larger treatment effects. DMHIs for depressive disorders that used preset time limits for gamified DMHIs also exhibited larger treatment effects. Conclusions and Relevance: The findings suggest a benefit of gamified DMHIs for youth with ADHD or depressive disorder. Pediatricians and other health care professionals have new information about novel, accessible, and efficacious options for pediatric mental health care.

Positive Autism Screening Rates in Toddlers Born During the COVID-19 Pandemic.

Importance: Stress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Autism screening positivity for children born during the pandemic remains unknown. Objective: To examine associations between prenatal exposure to the pandemic milieu and maternal SARS-CoV-2 infection with rates of positive Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) screenings. Design, Setting, and Participants: Data for this cohort study were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. M-CHAT-R scores obtained from children aged 16 to 30 months during routine clinical care at Columbia University Irving Medical Center in New York City were abstracted from electronic health records (EHRs) for children born between January 2018 and September 2021 (COMBO-EHR cohort). Separately, the M-CHAT-R was administered at 18 months for children born between February 2020 and September 2021 through a prospective longitudinal study (COMBO-RSCH cohort). Prenatal pandemic exposure (birth after March 1, 2020) and maternal SARS-CoV-2 status during pregnancy was determined through EHRs. Data were analyzed from March 2022 to June 2024. Exposures: Prenatal exposures to the pandemic milieu and maternal SARS-CoV-2 infection. Main Outcomes and Measures: The primary outcome was rate of positive M-CHAT-R screenings. For all primary analyses, unadjusted χ2 tests and adjusted logistic regression models were performed. Results: The COMBO-EHR cohort included 1664 children (442 born before the pandemic and 1222 born during the pandemic; 997 SARS-CoV-2 unexposed, 130 SARS-CoV-2 exposed, and 95 with unknown SARS-CoV-2 exposure status), of whom 266 (16.0%) were Black, 991 (59.6%) were Hispanic, 400 (24.0%) were White, 1245 (74.8%) were insured through Medicaid, 880 (52.9%) were male, and 204 (12.3%) were born prematurely. The COMBO-RSCH cohort included 385 children (74 born before the pandemic and 311 born during the pandemic; 201 SARS-CoV-2 unexposed, 101 SARS-CoV-2 exposed, and 9 with unknown SARS-CoV-2 exposure status), of whom 39 (10.1%) were Black, 168 (43.6%) were Hispanic, 157 (40.8%) were White, 161 (41.8%) were insured through Medicaid, 222 (57.7%) were male, and 38 (9.9%) were born prematurely. Prenatal pandemic exposure was not associated with a higher positive M-CHAT-R screening rate in either the COMBO-EHR or COMBO-RSCH cohort. Prenatal exposure to maternal SARS-CoV-2 infection was associated with a lower rate of M-CHAT-R positivity in the COMBO-EHR cohort (12.3% [16 children] vs 24.0% [239 children]; adjusted odds ratio, 0.40; 95% CI, 0.22-0.68; P = .001), but no association was found in the COMBO-RSCH cohort (12.9% [13 children] vs 19.9% [40 children]; adjusted odds ratio, 0.51; 95% CI, 0.24-1.04; P = .07). Conclusions and Relevance: In this cohort study of 2 groups of children with prenatal pandemic exposure and/or exposure to maternal SARS-CoV-2 infection, neither exposure was associated with greater M-CHAT-R positivity.

Urinary tract infections: pathogenesis, host susceptibility and emerging therapeutics.

Urinary tract infections (UTIs), which include any infection of the urethra, bladder or kidneys, account for an estimated 400 million infections and billions of dollars in health-care spending per year. The most common bacterium implicated in UTI is uropathogenic Escherichia coli, but diverse pathogens including Klebsiella, Enterococcus, Pseudomonas, Staphylococcus and even yeast such as Candida species can also cause UTIs. UTIs occur in both women and men and in both healthy and immunocompromised patients. However, certain patient factors predispose to disease: for example, female sex, history of prior UTI, or the presence of a urinary catheter or other urinary tract abnormality. The current clinical paradigm for the treatment of UTIs involves the use of antibiotics. Unfortunately, the efficacy of this approach is dwindling as the prevalence of antimicrobial resistance rises among UTI isolates, and the immense quantity of antibiotics prescribed annually for these infections contributes to the emergence of resistant pathogens. Therefore, there is an urgent need for new antibiotics and non-antibiotic treatment and prevention strategies. In this Review, we discuss how recent studies of bacterial pathogenesis, recurrence, persistence, host-pathogen interactions and host susceptibility factors have elucidated new and promising targets for the treatment and prevention of UTIs.

Characterization and analysis of a Commiphora species germinated from an ancient seed suggests a possible connection to a species mentioned in the Bible.

A seed recovered during archaeological excavations of a cave in the Judean desert was germinated, with radiocarbon analysis indicating an age of 993 CE- 1202 calCE. DNA sequencing and phylogenetic analysis identified the seedling as belonging to the angiosperm genus Commiphora Jacq., sister to three Southern African Commiphora species, but unique from all other species sampled to date. The germinated seedling was not closely related to Commiphora species commonly harvested for their fragrant oleoresins including Commiphora gileadensis (L.) C.Chr., candidate for the locally extinct "Judean Balsam" or "Balm of Gilead" of antiquity. GC-MS analysis revealed minimal fragrant compounds but abundance of those associated with multi-target bioactivity and a previously undescribed glycolipid compound series. Several hypotheses are offered to explain the origins, implications and ethnobotanical significance of this unknown Commiphora sp., to the best of our knowledge the first identified from an archaeological site in this region, including identification with a resin producing tree mentioned in Biblical sources and possible agricultural relationship with the historic Judean Balsam.

Protection against influenza hospitalizations from enhanced influenza vaccines among older adults: A systematic review and network meta-analysis.

BACKGROUND: Influenza vaccines are available to help protect persons aged ≥65 years, who experience thousands of influenza hospitalizations annually. Because some influenza vaccines may work better than others, we sought to assess benefit of high-dose (HD), adjuvanted (ADJ), and recombinant (RIV) influenza vaccines ("enhanced influenza vaccines") compared with standard-dose unadjuvanted influenza vaccines (SD) and with one another for prevention of influenza-associated hospitalizations among persons aged ≥65 years. METHODS: We searched MEDLINE, Embase, CINAHL, Scopus, and Cochrane Library to identify randomized or observational studies published between January 1990 and October 2023 and reporting relative vaccine effectiveness (rVE) of HD, ADJ, or RIV for prevention of influenza-associated hospitalizations among adults aged ≥65 years. We extracted study data, assessed risk of bias, and conducted random-effects network meta-analysis and meta-regression. RESULTS: We identified 32 studies with 90 rVE estimates from five randomized and 27 observational studies (71,459,918 vaccinated participants). rVE estimates varied across studies and influenza seasons. Pooled rVE from randomized studies was 20% (95% CI -54 to 59) and 25% (95% CI -19 to 53) for ADJ and HD compared with SD, respectively; rVE was 6% (95% CI -109 to 58) for HD compared with ADJ; these differences were not statistically significant. In observational studies, ADJ, HD, and RIV conferred modestly increased protection compared with SD (rVE ranging from 10% to 19%), with no significant differences between HD, ADJ, and RIV. With enhanced vaccines combined, rVE versus SD was 18% (95% CI 3 to 32) from randomized and 11% (95% CI 8 to 14) from observational evidence. Meta-regression of observational studies suggested that those requiring laboratory confirmation of influenza reported greater benefit of enhanced vaccines. CONCLUSIONS: HD, ADJ, and RIV provided stronger protection than SD against influenza hospitalizations among older adults. No differences in benefit were observed in comparisons of enhanced influenza vaccines with one another.

Interventional radiology procedures, facilities, and workforce across England and Wales: a snapshot retrospective evaluation from 2017 to 2021.

AIMS: There is no comprehensive data collection outlining the numbers and types of interventional radiology (IR) procedures in the United Kingdom. Similarly, limited data are available on the IR facilities and workforce within the National Health Services (NHS) trusts. The purpose of this study is to evaluate the number/type of IR procedures, facilities, and workforces across England and Wales. MATERIALS AND METHODS: This retrospective study used the 2000 Freedom of Information Act to obtain information regarding the IR procedures performed in NHS trusts in England and Wales from 2017 to 2021. We collected additional information on IR workforce and facilities, including the number of IR consultants, nurses, trainees, and angiographic suites and day case units; analysed procedures by complexity; and performed data analysis by region. RESULTS: A total of 1,340,352 IR procedures were analysed. An increasing trend was observed in the number of IR procedures from 2017 to 2021 (p=0.07, R=0.93). There were more intermediate and complex procedures than simple ones (p=0.0001). Notable geographical variation was observed in terms of IR facilities including angiographic suites and day case units, and the number of IR consultants, nurses, and trainees. CONCLUSIONS: The IR field continues to grow as evidenced by increasing trends in the number and complexity of the procedures over the years. There is an uneven IR workforce, services, and facilities distribution across England and Wales. Therefore, there is a crucial need for centralised data collection to evaluate and monitor interventions besides comprehensive revision of UK IR service provision.

Pharmacist-Led Video Consultation to Identify and Mitigate Drug Interactions Among Patients Initiating Oral Anticancer Drugs.

PURPOSE: The past decade has seen an increase in oral anticancer drug (OACD) approvals. Polypharmacy and drug-drug interactions (DDIs) likely contribute to OACD toxicity. We assessed a one-time pharmacist-led video consultation to identify DDIs. METHODS: We conducted a single-arm telehealth intervention of a one-time 30-minute pharmacist-led video consultation among patients initiating OACDs. The visit focused on identifying polypharmacy and DDIs. Feasibility was defined as ≥50% completion of all study interventions. We determined the prevalence, characteristics, and severity of OACD-related potential DDIs. We also assessed the prevalence of medication list inaccuracies, polypharmacy, patient satisfaction, and patient perception of intervention acceptability, appropriateness, and feasibility. RESULTS: Of 58 eligible patients, 43 (74%) completed the intervention and 33 (57%) completed all evaluations. Median medication per patient was nine (range 4-21), and 98% of patients had at least five prescriptions. The median number of medication list errors was two (range 0-16), with at least one error for 76% and >1 for 52%. Pharmacists identified OACD-related interactions in 18 cases (42%), including change in drug metabolism (eight), elimination (one), and absorption (three). Interactions were classified as Lexicomp categories C (13), D (five), or X (one) requiring close monitoring or a change in treatment. All patients expressed high satisfaction with the intervention and agreed or completely agreed that it was acceptable, appropriate, and feasible. CONCLUSION: Polypharmacy, medication list errors, and DDIs are prevalent among patients initiating OACDs. A one-time remote pharmacist-led video consultation can address OACD-related DDIs, which may decrease medication complexity and improve adherence.

Evaluation of the Therapeutic Potential of Traditionally-Used Natural Plant Extracts to Inhibit Proliferation of a HeLa Cell Cancer Line and Replication of Human Respiratory Syncytial Virus (hRSV).

Traditional approaches employing natural plant products to treat a wide array of ailments have been documented and described for thousands of years. However, there remains limited scientific study of the therapeutic potential or effectiveness of ethnobotanical applications. Increases in the incidence of cancer and emerging infectious diseases demonstrate a growing need for advances in the development of therapeutic options. In this study, we evaluate the therapeutic potential of aqueous extracts prepared from four plants, purple aster (Symphyotrichum novae-angliae (L.) Nemsom), common sage (Salvia lyrata (L.)), northern spicebush (Lindera benzoin (L.) Blume), and lamb's ear (Stachys byzantina (K.) Koch)) traditionally used in Native American medicine in Indiana, USA. Using a combination of cytotoxicity assays, immunofluorescence microscopy, and antiviral assays, we found that sage and spicebush extracts exhibit cytotoxic and antiproliferative effects on HeLa cell proliferation and that sage, spicebush, and aster extracts were capable of significantly inhibiting human respiratory syncytial virus (hRSV), a major respiratory pathogen of infants and the elderly. Chemical analysis of the four extracts identified four major compounds which were subsequently evaluated to identify the responsible constituents in the extracts. While none of the identified compounds were shown to induce significant impacts on HeLa cell proliferation, two of the compounds, (1S)-(-)-Borneol and 5-(hydroxymethyl)-furfural, identified in sage and spicebush, respectively, were shown to have antiviral activities. Our data suggest that several of the extracts tested exhibited either anti-proliferative or antiviral activity supporting future further analysis.

Fungal Attachment-Resistant Polymers for the Additive Manufacture of Medical Devices.

This study reports the development of the first copolymer material that (i) is resistant to fungal attachment and hence biofilm formation, (ii) operates via a nonkilling mechanism, i.e., avoids the use of antifungal actives and the emergence of fungal resistance, (iii) exhibits sufficient elasticity for use in flexible medical devices, and (iv) is suitable for 3D printing (3DP), enabling the production of safer, personalized medical devices. Candida albicans (C. albicans) can form biofilms on in-dwelling medical devices, leading to potentially fatal fungal infections in the human host. Poly(dimethylsiloxane) (PDMS) is a common material used for the manufacture of medical devices, such as voice prostheses, but it is prone to microbial attachment. Therefore, to deliver a fungal-resistant polymer with key physical properties similar to PDMS (e.g., flexibility), eight homopolymers and 30 subsequent copolymers with varying glass transition temperatures (Tg) and fungal antiattachment properties were synthesized and their materials/processing properties studied. Of the copolymers produced, triethylene glycol methyl ether methacrylate (TEGMA) copolymerized with (r)-α-acryloyloxy-ß,ß-dimethyl-γ-butyrolactone (AODMBA) at a 40:60 copolymer ratio was found to be the most promising candidate by meeting all of the above criteria. This included demonstrating the capability to successfully undergo 3DP by material jetting, via the printing of a voice prosthesis valve-flap using the selected copolymer.

Arbuscular mycorrhizal diversity increases across a plant productivity gradient driven by soil nitrogen availability.

Arbuscular mycorrhizal fungi (AMF) are widespread obligate symbionts of plants. This dynamic symbiosis plays a large role in successful plant performance, given that AMF help to ameliorate plant responses to abiotic and biotic stressors. Although the importance of this symbiosis is clear, less is known about what may be driving this symbiosis, the plant's need for nutrients or the excess of plant photosynthate being transferred to the AMF, information critical to assess the functionality of this relationship. Characterizing the AMF community along a natural plant productivity gradient is a first step in understanding how this symbiosis may vary across the landscape. We surveyed the AMF community diversity at 12 sites along a plant productivity gradient driven by soil nitrogen availability. We found that AMF diversity in soil environmental DNA significantly increased along with the growth of the host plants Acer rubrum and A. saccharum., a widespread tree genus. These increases also coincided with a natural soil inorganic N availability gradient. We hypothesize photosynthate from the increased tree growth is being allocated to the belowground AMF community, leading to an increase in diversity. These findings contribute to understanding this complex symbiosis through the lens of AMF turnover and suggest that a more diverse AMF community is associated with increased host-plant performance.

Development of PainFace software to simplify, standardize, and scale up mouse grimace analyses.

ABSTRACT: Facial grimacing is used to quantify spontaneous pain in mice and other mammals, but scoring relies on humans with different levels of proficiency. Here, we developed a cloud-based software platform called PainFace ( http://painface.net ) that uses machine learning to detect 4 facial action units of the mouse grimace scale (orbitals, nose, ears, whiskers) and score facial grimaces of black-coated C57BL/6 male and female mice on a 0 to 8 scale. Platform accuracy was validated in 2 different laboratories, with 3 conditions that evoke grimacing-laparotomy surgery, bilateral hindpaw injection of carrageenan, and intraplantar injection of formalin. PainFace can generate up to 1 grimace score per second from a standard 30 frames/s video, making it possible to quantify facial grimacing over time, and operates at a speed that scales with computing power. By analyzing the frequency distribution of grimace scores, we found that mice spent 7x more time in a "high grimace" state following laparotomy surgery relative to sham surgery controls. Our study shows that PainFace reproducibly quantifies facial grimaces indicative of nonevoked spontaneous pain and enables laboratories to standardize and scale-up facial grimace analyses.

Epidermal growth factor augments the self-renewal capacity of aged hematopoietic stem cells.

Hematopoietic aging is associated with decreased hematopoietic stem cell (HSC) self-renewal capacity and myeloid skewing. We report that culture of bone marrow (BM) HSCs from aged mice with epidermal growth factor (EGF) suppressed myeloid skewing, increased multipotent colony formation, and increased HSC repopulation in primary and secondary transplantation assays. Mice transplanted with aged, EGF-treated HSCs displayed increased donor cell engraftment within BM HSCs and systemic administration of EGF to aged mice increased HSC self-renewal capacity in primary and secondary transplantation assays. Expression of a dominant negative EGFR in Scl/Tal1+ hematopoietic cells caused increased myeloid skewing and depletion of long term-HSCs in 15-month-old mice. EGF treatment decreased DNA damage in aged HSCs and shifted the transcriptome of aged HSCs from genes regulating cell death to genes involved in HSC self-renewal and DNA repair but had no effect on HSC senescence. These data suggest that EGFR signaling regulates the repopulating capacity of aged HSCs.

The dual role of a highly structured RNA (the S fragment) in the replication of foot-and-mouth disease virus.

Secondary and tertiary RNA structures play key roles in genome replication of single-stranded positive sense RNA viruses. Complex, functional structures are particularly abundant in the untranslated regions of picornaviruses, where they are involved in initiation of translation, priming of new strand synthesis and genome circularization. The 5' UTR of foot-and-mouth disease virus (FMDV) is predicted to include a c. 360 nucleotide-long stem-loop, termed the short (S) fragment. This structure is highly conserved and essential for viral replication, but the precise function(s) are unclear. Here, we used selective 2' hydroxyl acetylation analyzed by primer extension (SHAPE) to experimentally determine aspects of the structure, alongside comparative genomic analyses to confirm structure conservation from a wide range of field isolates. To examine its role in virus replication in cell culture, we introduced a series of deletions to the distal and proximal regions of the stem-loop. These truncations affected genome replication in a size-dependent and, in some cases, host cell-dependent manner. Furthermore, during the passage of viruses incorporating the largest tolerated deletion from the proximal region of the S fragment stem-loop, an additional mutation was selected in the viral RNA-dependent RNA polymerase, 3Dpol. These data suggest that the S fragment and 3Dpol interact in the formation of the FMDV replication complex.

Biomechanical Principles of Intramedullary Nails in Veterinary and Human Medicine.

Intramedullary nails are specialized metal rods inserted into the medullary cavity of a fractured bone and secured to reduce load on the fracture site, provide stability, and permit healing. The purpose of this review is to highlight the biomechanics of orthopaedic intramedullary nailing, as well as discuss the biomechanical considerations that have shaped implant design and fixation technique in veterinary and human medicine. Relevant studies were included from the PubMed database and Google Scholar for discussion on the basic science and nail design of intramedullary nails. Implant design and implementation continues to progress, with new innovative designs currently under investigation. A lack of consensus remains on the superior implant material. Recent studies, particularly in human populations, have supported the use of reaming based on reoperation rates, nonunion rates, and dynamization. Design modifications, such as the expandable intramedullary nails and angle-stable interlocking designs, have been investigated as methods of improving cortical contact and resisting torsional stress. Intramedullary nailing is a valuable stabilization technique for long bone fractures across a variety of species. The technology continues to undergo design improvements in both veterinary and human medicine.