Major-groove sequence-specific RNA recognition by LoaP, a paralog of transcription elongation factor NusG.

LoaP is a member of the universal NusG protein family. Previously, we reported that unlike other characterized homologs, LoaP binds RNA sequence-specifically, recognizing a stem-loop in the 5'-untranslated region of operons it regulates. To elucidate how this NusG homolog acquired this ability, we now determined the co-crystal structure of Thermoanaerobacter pseudethanolicus LoaP bound to its cognate 26-nucleotide dfn RNA element. Our structure reveals that the LoaP C-terminal KOW domain recognizes the helical portion of the RNA by docking into a broadened major groove, while a protruding ß-hairpin of the N-terminal NusG-like domain binds the UNCG tetraloop capping the stem-loop. Major-groove RNA recognition is unusual and is made possible by conserved features of the dfn hairpin. Superposition with structures of other NusG proteins implies that LoaP can bind concurrently to the dfn RNA and the transcription elongation complex, suggesting a new level of co-transcriptional regulation by proteins of this conserved family.

Myeloid AMPK signaling restricts fibrosis but is not required for metformin improvements during CDAHFD-induced NASH in mice.

Metabolic programming underpins inflammation and liver macrophage activation in the setting of chronic liver disease. Here, we sought to identify the role of an important metabolic regulator, AMP-activated protein kinase (AMPK), specifically within myeloid cells during the progression of non-alcoholic steatohepatitis (NASH) and whether treatment with metformin, a firstline therapy for diabetes and activator of AMPK could stem disease progression. Male and female Prkaa1fl/fl/Prkaa2fl/fl (Flox) control and Flox-LysM-Cre+ (MacKO) mice were fed a low-fat control or a choline-deficient, amino acid defined 45% Kcal high-fat diet (CDAHFD) for 8 weeks, where metformin was introduced in the drinking water (50 or 250 mg/kg/day) for the last 4 weeks. Hepatic steatosis and fibrosis were dramatically increased in response to CDAHFD-feeding compared to low-fat control. While myeloid AMPK signaling had no effect on markers of hepatic steatosis or circulating markers, fibrosis as measured by total liver collagen was significantly elevated in livers from MacKO mice, independent of sex. Although treatment with 50 mg/kg/day metformin had no effect on any parameter, intervention with 250 mg/kg/day metformin completely ameliorated hepatic steatosis and fibrosis in both male and female mice. While the protective effect of metformin was associated with lower final body weight, and decreased expression of lipogenic and Col1a1 transcripts, it was independent of myeloid AMPK signaling. These results suggest that endogenous AMPK signaling in myeloid cells, both liver-resident and infiltrating, acts to restrict fibrogenesis during CDAHFD-induced NASH progression but is not the mechanism by which metformin improves markers of NASH.

Design Optimization and Tradeoff Analysis of an Actuated Continuum Probe for Pulmonary Nodule Localization and Resection.

Pulmonary nodules are abnormal tissue masses in the lungs, typically less than 3.0 cm in diameter, commonly detected during imaging of the chest and lungs. While most pulmonary nodules are not cancerous, surgical resection may be required if growth is detected between scans. This resection is typically performed without the benefit of intraoperative imaging, making it difficult for surgeons to confidently provide appropriate margins. To enhance the efficacy of wedge resection, researchers have developed a modified ultrasound imaging approach that utilizes both multiple scattering (MS) and single scattering (SS) to enhance the accuracy of margin delineation. Clinical deployment of this novel ultrasound technology requires a highly maneuverable ultrasound probe, ideally one that could be deployed and actuated with minimal invasiveness. This study details the design optimization and tradeoff analysis of an actuated continuum probe for pulmonary nodule localization and resection. This device, deployed through intercostal ports, would enable the intraoperative imaging and precise mapping of nodules for improved margin delineation and patient outcomes. To achieve this objective, multiple objective genetic algorithms (MOGAs) and a design of experiments (DOE) study are used to explore the design space and quantify key dimensional relationships and their effects on probe actuation.

RETRACTED: Sixteen years of canine hepatic copper concentrations within normal reference ranges in dogs fed a broad range of commercial diets.

OBJECTIVE: To examine the effects of age, sex, breed, liver histopathology, and year of death/sample collection on liver copper concentrations in dogs fed various commercial dog foods throughout their lives. SAMPLE: During necropsy, 336 samples were collected between the years 2006 and 2022 from dogs that were fed a variety of commercial dog foods on the market. This study utilized all liver samples available and did not require specific criteria for sample selection. METHODS: Liver samples (n = 336) were analyzed as dry weight for copper concentration by inductively coupled plasma-optical emission spectrometry. The potential effects of animal age and year of death/collection (scatterplots and linear regression), sex, liver histopathology (t test), and breed (ANOVA) on liver copper concentration were assessed. RESULTS: Labrador Retrievers had lower liver copper concentrations than Beagles, but mixed breeds did not differ from Beagles or Labrador Retrievers. Analysis of year of death showed that liver copper concentrations decreased from 2006 through 2011, increased in 2012, decreased in 2013, and peaked in 2016, decreasing thereafter. Mean copper concentration of abnormal liver histopathology samples was lower than mean copper concentrations of normal liver histopathology samples. Age (12.9 ± 2.6 years) and sex had no effect on liver copper concentrations. Of note, some samples showed abnormal hepatic pathology. CLINICAL RELEVANCE: Liver copper concentrations varied significantly with breed and year of death; however, average liver copper concentrations of each year were within normal. However, this was a retrospective population study and diet histories of the dogs were unknown, requiring further investigation.

The MuSK-BMP pathway maintains myofiber size in slow muscle through regulation of Akt-mTOR signaling.

Myofiber size regulation is critical in health, disease, and aging. MuSK (muscle-specific kinase) is a BMP (bone morphogenetic protein) co-receptor that promotes and shapes BMP signaling. MuSK is expressed at all neuromuscular junctions and is also present extrasynaptically in the mouse soleus, whose predominantly oxidative fiber composition is akin to that of human muscle. To investigate the role of the MuSK-BMP pathway in vivo, we generated mice lacking the BMP-binding MuSK Ig3 domain. These ∆Ig3-MuSK mice are viable and fertile with innervation levels comparable to wild type. In 3-month-old mice, myofibers are smaller in the slow soleus, but not in the fast tibialis anterior (TA). Transcriptomic analysis revealed soleus-selective decreases in RNA metabolism and protein synthesis pathways as well as dysregulation of IGF1-Akt-mTOR pathway components. Biochemical analysis showed that Akt-mTOR signaling is reduced in soleus but not TA. We propose that the MuSK-BMP pathway acts extrasynaptically to maintain myofiber size in slow muscle by promoting protein synthetic pathways including IGF1-Akt-mTOR signaling. These results reveal a novel mechanism for regulating myofiber size in slow muscle and introduce the MuSK-BMP pathway as a target for promoting muscle growth and combatting atrophy.

BilR is a gut microbial enzyme that reduces bilirubin to urobilinogen.

Metabolism of haem by-products such as bilirubin by humans and their gut microbiota is essential to human health, as excess serum bilirubin can cause jaundice and even neurological damage. The bacterial enzymes that reduce bilirubin to urobilinogen, a key step in this pathway, have remained unidentified. Here we used biochemical analyses and comparative genomics to identify BilR as a gut-microbiota-derived bilirubin reductase that reduces bilirubin to urobilinogen. We delineated the BilR sequences from similar reductases through the identification of key residues critical for bilirubin reduction and found that BilR is predominantly encoded by Firmicutes species. Analysis of human gut metagenomes revealed that BilR is nearly ubiquitous in healthy adults, but prevalence is decreased in neonates and individuals with inflammatory bowel disease. This discovery sheds light on the role of the gut microbiome in bilirubin metabolism and highlights the significance of the gut-liver axis in maintaining bilirubin homeostasis.

Addressing Gaps and Saving Lives: Doulas' Role in Addressing Substance Use and Mental Health Challenges Among Pregnant and Postpartum Clients-A Scoping Review.

OBJECTIVES: Doulas are a potential resource for addressing substance use and mental health challenges that pregnant and postpartum individuals experience. We sought to review peer-reviewed literature that examines Doulas' role in addressing these challenges to highlight the need for more research in this area. METHODS: We conducted a scoping review (2001-2021) to identify articles that examine the way in which Doulas address maternal substance use and mental health challenges in their clients. The articles were reviewed by two members of the research team. RESULTS: Nine articles describing Doulas' role in addressing substance use and mental health challenges were identified. Six described Doulas' role in addressing mental health, five of which saw positive mental health outcomes due to Doula involvement. One additional article recommended Doulas be considered in the future to address mental health challenges. While the minority of articles addressed substance use (n = 2), it was reported that Doulas were a positive addition to interdisciplinary teams addressing substance use challenges with pregnant individuals. CONCLUSIONS: While the literature showed that Doulas can improve substance use and mental health outcomes among pregnant or postpartum individuals, a significant gap remains in research, practice, and peer-reviewed literature addressing this issue.

Postprandial triglycerides across the aging spectrum: A secondary analysis utilizing an abbreviated fat tolerance test.

BACKGROUND & AIMS: Elevated postprandial triglycerides are an independent cardiovascular disease risk factor and observed in older adults. However, differences in postprandial triglycerides across the spectrum of adulthood remain unclear. METHODS AND RESULTS: We performed a secondary analysis of six studies where adults (aged 18-84 years; N = 155) completed an abbreviated fat tolerance test (9 kcal/kg; 70% fat). Differences in postprandial triglycerides were compared in those ≥50 and <50 years and by decade of life, adjusting for sex and BMI. Compared to those <50 years, participants ≥50 years had higher fasting, 4 h, and Δ triglycerides from baseline (p's < 0.05). When examining triglyceride parameters by decade, no differences were observed for fasting triglycerides, but 50 s, 60 s, and 70s-80 s displayed greater 4 h and Δ triglycerides versus 20 s (p's ≤ 0.001). The frequency of adverse postprandial triglyceride responses (i.e., ≥220 mg/dL) was higher in participants ≥50 versus <50 years (p < 0.01), and in 60 s compared to all other decades (p = 0.01). CONCLUSION: Older age was generally associated with higher postprandial triglycerides, with no divergence across the spectrum of older adulthood. In our sample, postprandial triglyceride differences in older and younger adults were driven by those >50 years relative to young adults in their 20 s. REGISTRATION: N/A (secondary analysis).

Global patterns of plumage color evolution in island-living passeriform birds.

Island environments have the potential to change evolutionary trajectories of morphological traits in species relative to their mainland counterparts due to habitat and resource differences, or by reductions in the intensity of social or sexual selection. Latitude, island size, and isolation may further influence trait evolution through biases in colonization rates. We used a global dataset of passerine plumage color as a model group to identify selective pressures driving morphological evolution of island animals using phylogenetically-controlled analyses. We calculated chromaticity values from red and blue scores extracted from images of the majority of Passeriformes and tested these against the factors hypothesized to influence color evolution. In contrast to predictions based on sexual and social selection theory, we found consistent changes in island female color (lower red and higher blue chromaticity), but no change in males. Instead, island size and distance from mainland and other islands influenced color in both sexes, reinforcing the importance of island physiognomy in shaping evolutionary processes. Interactions between ecological factors and latitude also consistently influenced color for both sexes, supporting a latitudinal gradient hypothesis. Finally, patterns of color evolution varied among families, indicating taxon-specific microevolutionary processes in driving color evolution. Our results show island residency influences color evolution differently between sexes, but the patterns in both sexes are tempered by ecological, island characteristics, and phylogenetic effects that further vary in their importance among families. The key role of environmental factors in shaping bird plumage on islands further suggests a reduced importance of sexual and social factors in driving color evolution.

Impact of Geography and Rurality on Preconception Health Status in the United States.

Introduction: Maternal illness and death are largely preventable; however, the field of preconception health needs further study. Geographic region and rurality play a large role in maternal health, and an understanding of the effect of these 2 factors at the individual level could prevent future adverse maternal health outcomes. Methods: We developed an abbreviated index of preconception health risk (diabetes, hypertension, body weight, mental health, unintended pregnancy, HIV, alcohol and nicotine use, nutrition, physical activity, receipt of the influenza vaccine) by using data from the 2019 Behavioral Risk Factor Surveillance System (BRFSS). A score of 1 was assigned for each behavior factor classified as unhealthy and a score of 0 for each factor classified as healthy, for a total potential score of 11. Respondent women from the 37 states that included the BRFSS family planning supplemental module who were aged 18 to 44 years who could become pregnant (N = 25,999) were included. We used univariate and multivariate regression models to assess the relationship between sociodemographic factors (age, race or ethnicity, relationship status, insurance status, education, income, and rurality and region) and preconception health, with a primary focus on rurality and region. Results: The average preconception health risk index score among participants was 3.5, with higher average scores in rural areas than in urban areas. All factors were independently associated with preconception health. Compared with women living in the urban Northeast, women living in all rural and region groups, except the rural West, had increased preconception health risk. Conclusion: Preconception health scores from our study showed that, on average, a person had more than 3 risk factors or behaviors. Given the current state of reproductive health policy in the United States, increased efforts are needed to address preconception health.

Protease-Activated Receptor 2 Controls Vascular Smooth Muscle Cell Proliferation in Cyclic AMP-Dependent Protein Kinase/Mitogen-Activated Protein Kinase Kinase 1/2-Dependent Manner.

INTRODUCTION: Cardiovascular disorders are characterized by vascular smooth muscle (VSM) transition from a contractile to proliferative state. Protease-activated receptor 2 (PAR2) involvement in this phenotypic conversion remains unclear. We hypothesized that PAR2 controls VSM cell proliferation in phenotype-dependent manner and through specific protein kinases. METHODS: Rat clonal low (PLo; P3-P6) and high passage (PHi; P10-P15) VSM cells were established as respective models of quiescent and proliferative cells, based on reduced PKG-1 and VASP. Western blotting determined expression of cytoskeletal/contractile proteins, PAR2, and select protein kinases. DNA synthesis and cell proliferation were measured 24-72 h following PAR2 agonism (SLIGRL; 100 nM-10 µm) with/without PKA (PKI; 10 µm), MEK1/2 (PD98059; 10 µm), and PI3K (LY294002; 1 µm) blockade. RESULTS: PKG-1, VASP, SM22α, calponin, cofilin, and PAR2 were reduced in PHi versus PLo cells. Following PAR2 agonism, DNA synthesis and cell proliferation increased in PLo cells but decreased in PHi cells. Western analyses showed reduced PKA, MEK1/2, and PI3K in PHi versus PLo cells, and kinase blockade revealed PAR2 controls VSM cell proliferation through PKA/MEK1/2. DISCUSSION: Findings highlight PAR2 and PAR2-driven PKA/MEK1/2 in control of VSM cell growth and provide evidence for continued investigation of PAR2 in VSM pathology.

FoxO3 normalizes Smad3-induced arterial smooth muscle cell growth.

Transition of arterial smooth muscle (ASM) from a quiescent, contractile state to a growth-promoting state is a hallmark of cardiovascular disease (CVD), a leading cause of death and disability in the United States and worldwide. While many individual signals have been identified as important mechanisms in this phenotypic conversion, the combined impact of the transcription factors Smad3 and FoxO3 in ASM growth is not known. The purpose of this study was to determine that a coordinated, phosphorylation-specific relationship exists between Smad3 and FoxO3 in the control of ASM cell growth. Using a rat in vivo arterial injury model and rat primary ASM cell lysates and fractions, validated low and high serum in vitro models of respective quiescent and growth states, and adenoviral (Ad-) gene delivery for overexpression (OE) of individual and combined Smad3 and/or FoxO3, we hypothesized that FoxO3 can moderate Smad3-induced ASM cell growth. Key findings revealed unique cellular distribution of Smad3 and FoxO3 under growth conditions, with induction of both nuclear and cytosolic Smad3 yet primarily cytosolic FoxO3; Ad-Smad3 OE leading to cytosolic and nuclear expression of phosphorylated and total Smad3, with almost complete reversal of each with Ad-FoxO3 co-infection in quiescent and growth conditions; Ad-FoxO3 OE leading to enhanced cytosolic expression of phosphorylated and total FoxO3, both reduced with Ad-Smad3 co-infection in quiescent and growth conditions; Ad-FoxO3 inducing expression and activity of the ubiquitin ligase MuRF-1, which was reversed with concomitant Ad-Smad3 OE; and combined Smad3/FoxO3 OE reversing both the pro-growth impact of singular Smad3 and the cytostatic impact of singular FoxO3. A primary takeaway from these observations is the capacity of FoxO3 to reverse growth-promoting effects of Smad3 in ASM cells. Additional findings lend support for reciprocal antagonism of Smad3 on FoxO3-induced cytostasis, and these effects are dependent upon discrete phosphorylation states and cellular localization and involve MuRF-1 in the control of ASM cell growth. Lastly, results showing capacity of FoxO3 to normalize Smad3-induced ASM cell growth largely support our hypothesis, and overall findings provide evidence for utility of Smad3 and/or FoxO3 as potential therapeutic targets against abnormal ASM growth in the context of CVD.

Hip Strength Recovery After Anterior Cruciate Ligament Reconstruction.

Background: Return-to-play (RTP) assessment after anterior cruciate ligament reconstruction (ACLR) rarely includes hip strength. Hypothesis: It was hypothesized that (1) patients after ACLR will have weaker hip abduction (AB) and adduction (AD) strength compared with the contralateral limb, with larger deficits in women, (2) there will be a correlation between hip and thigh strength ratios and patient-reported outcomes (PROs), and (3) hip AB and AD strength will improve over time. Study Design: Descriptive laboratory study. Methods: Included were 140 patients (74 male, 66 female; mean age, 24.16 ± 10.82 years) who underwent RTP assessment at 6.1 ± 1.6 months after ACLR; 86 patients underwent a second assessment at 8.2 ± 2.2 months. Hip AB/AD and knee extension/flexion isometric strength were measured and normalized to body mass, and PRO scores were collected. Strength ratios (hip vs thigh), limb differences (injured vs uninjured), sex-based differences, and relationships between strength ratios and PROs were determined. Results: Hip AB strength was weaker on the ACLR limb (ACLR vs contralateral: 1.85 ± 0.49 vs 1.89 ± 0.48 N·m/kg; P < .001) and hip AD torque was stronger (ACLR vs contralateral: 1.80 ± 0.51 vs 1.76 ± 0.52 N·m/kg; P = .004), with no sex-by-limb interaction found. Lower hip-to-thigh strength ratios of the ACLR limb were correlated with higher PRO scores (r = -0.17 to -0.25). Over time, hip AB strength increased in the ACLR limb more than in the contralateral limb (P = .01); however, the ACLR limb remained weaker in hip AB at visit 2 (ACLR vs contralateral: 1.88 ± 0.46 vs 1.91 ± 0.45 N·m/kg; P = .04). In both limbs, hip AD strength was greater at visit 2 than visit 1 (ACLR: 1.82 ± 0.48 vs 1.70 ± 0.48 N·m/kg; contralateral: 1.76 ± 0.47 vs 1.67 ± 0.47 N·m/kg; P < .01 for both). Conclusion: The ACLR limb had weaker hip AB and stronger AD compared with the contralateral limb at initial assessment. Hip muscle strength recovery was not influenced by sex. Hip strength and symmetry improved over the course of rehabilitation. Although strength differences across limbs were minor, the clinical importance of these differences is still unknown. Clinical Relevance: The evidence provided highlights the need to integrate hip strength into RTP assessments to identify hip strength deficits that may increase reinjury or lead to poor long-term outcomes.

Comparison of Patient-Reported Outcomes, Strength, and Functional Performance in Primary Versus Revision Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Clinical outcomes after revision anterior cruciate ligament reconstruction (ACLR) are not well understood. HYPOTHESIS: Patients undergoing revision ACLR would demonstrate worse patient-reported outcomes and worse limb symmetry compared with a cohort undergoing primary ACLR. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: 672 participants (373 with primary ACLR, 111 with revision ACLR, and 188 uninjured) completed functional testing at a single academic medical center. Descriptive information, operative variables, and patient-reported outcomes (International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score, and Tegner Activity Scale score) were assessed for each patient. Quadriceps and hamstring strength tests were conducted using a Biodex System 3 Dynamometer. Single-leg hop for distance, triple hop test, and the 6-m timed hop test were also assessed. Limb symmetry index (LSI) between the ACLR limb and contralateral limb was calculated for strength and hop testing. Normalized peak torque (N·m/kg) was calculated for strength testing. RESULTS: No differences were found in group characteristics, excluding body mass (P < .001), or in patient-reported outcomes. There were no interactions between revision status, graft type, and sex. Knee extension LSI was inferior (P < .001) in participants who had undergone primary (73.0% ± 15.0%) and revision (77.2% ± 19.1%) ACLR compared with healthy, uninjured participants (98.8% ± 10.4%). Knee flexion LSI was inferior (P = .04) in the primary group (97.4% ± 18.4%) compared with the revision group (101.9% ± 18.5%). Difference in knee flexion LSI between the uninjured and primary groups, as well as between the uninjured and revision groups, did not reach statistical significance. Hop LSI outcomes were significantly different across all groups (P < .001). Between-group differences in extension in the involved limb (P < .001) were noted, as the uninjured group exhibited stronger knee extension (2.16 ± 0.46 N·m/kg) than the primary group (1.67 ± 0.47 N·m/kg) and the revision group (1.78 ± 0.48 N·m/kg). As well, differences in flexion in the involved limb (P = .01) were found, as the revision group exhibited stronger knee flexion (1.06 ± 0.25 N·m/kg) than the primary group (0.97 ± 0.29 N·m/kg) and the uninjured group (0.98 ± 0.24 N·m/kg). CONCLUSION: At 7 months postoperatively, patients who had undergone revision ACLR did not demonstrate inferior patient-reported outcomes, limb symmetry, strength, or functional performance compared with patients who had undergone primary ACLR. Patients who had undergone revision ACLR exhibited greater strength and LSI than their counterparts with primary ACLR, but these parameters were still inferior to those of uninjured controls.

Childhood Centeredness is a Broader Predictor of Young Adulthood Mental Health than Childhood Adversity, Attachment, and Other Positive Childhood Experiences.

This study introduced the novel concept of Centeredness, a measure of the emotional atmosphere of the family of origin and a target adult individual's perception of feeling safe, accepted, and supported from childhood primary caregivers and other family members. This study developed a Centeredness scale for adult respondents and tested hypotheses that higher levels of overall Centeredness would predict lower levels of depression and anxiety symptoms; suicidal thoughts and behaviors (STBs); and aggressive behavior; and higher levels of life satisfaction. Predictive effects of Centeredness were compared against attachment-related anxiety and avoidance, and adverse and benevolent childhood experiences (ACEs and BCEs). Participants were recruited via the Prolific-Academic (Pro-A) survey panel into two large independent samples of US young adults aged 19-35 years [Sample 1 (test sample), N = 548, 53.5% female, 2.2% gender non-conforming, 68.3% White, recruited before the pandemic; Sample 2 (replication sample), N = 1,198, 56.2% female, 2.3% gender non-conforming, 66.4% White; recruited during the pandemic]. Participants completed the novel Centeredness scale, which showed strong psychometric properties, and standardized, publicly available assessments of childhood experiences and mental health outcomes. Centeredness was the only variable that significantly predicted each mental health outcome across both samples. BCEs predicted all outcomes except aggressive behavior in the test sample. Centeredness and BCEs were also the only two variables that significantly predicted a dimensional mental health composite in both samples. Neither attachment-related anxiety and avoidance nor ACEs were as broadly predictive. The Centeredness scale assesses emotional aspects of childhood family relationships with individuals of diverse backgrounds and family compositions. Clinical and cultural implications are discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s42844-023-00089-x.

The MuSK-BMP pathway maintains myofiber size in slow muscle through regulation of Akt- mTOR signaling.

Myofiber size regulation is critical in health, disease, and aging. MuSK (muscle-specific kinase) is a BMP (bone morphogenetic protein) co-receptor that promotes and shapes BMP signaling. MuSK is expressed at all neuromuscular junctions and is also present extrasynaptically in the slow soleus muscle. To investigate the role of the MuSK-BMP pathway in vivo we generated mice lacking the BMP-binding MuSK Ig3 domain. These ΔIg3-MuSKmice are viable and fertile with innervation levels comparable to wild type. In 3-month-old mice myofibers are smaller in the slow soleus, but not in the fast tibialis anterior (TA). Transcriptomic analysis revealed soleus-selective decreases in RNA metabolism and protein synthesis pathways as well as dysregulation of IGF1-Akt-mTOR pathway components. Biochemical analysis showed that Akt-mTOR signaling is reduced in soleus but not TA. We propose that the MuSK-BMP pathway acts extrasynaptically to maintain myofiber size in slow muscle by promoting protein synthetic pathways including IGF1-Akt-mTOR signaling. These results reveal a novel mechanism for regulating myofiber size in slow muscle and introduce the MuSK-BMP pathway as a target for promoting muscle growth and combatting atrophy.

Short-Term and Textbook Surgical Outcomes During the Implementation of a Robotic Gastrectomy Program.

BACKGROUND: Whether gastric cancer patients derive greater benefit from robotic gastrectomy (RG), or open gastrectomy (OG) is unknown. We initiated a RG program in 2018, with prospective short-term outcome monitoring to ensure safety. We hypothesized that the RG program for gastric cancer can be safely implemented with equivalent safety and oncological textbook outcomes (TOs) to conventional open gastrectomy (OG). METHODS: The study included patients who underwent curative-intent OG or RG for gastric adenocarcinoma between January 2018 and December 2021. TO metrics were negative surgical margins, ≥ 15 lymph nodes examined, no severe (Clavien-Dindo grade ≥ IIIa) postoperative complications, no reinterventions within 90 days after surgery, no ICU admission, no prolonged length of stay (LOS; > 10 days), no 90-day postoperative mortality, and no readmission within 90 days after surgery. Overall TO was achieved when all these metrics were met. RESULTS: Of 161 patients, 120 underwent OG, and 41 underwent RG. The two groups' demographic and disease characteristics did not differ significantly. Compared with OG patients, RG patients had a longer median surgery time (348 vs. 282 min), smaller median blood loss volume (50 vs. 150 mL), lower mean prescribed opioid dose at discharge (12 vs. 45 mg), and shorter median LOS (4 vs. 7 days; all p < 0.001). The groups' postoperative complication rates (10% vs. 17%) did not differ significantly (p = 0.283). The overall TO rate of the RG group (73%) was higher than that of the OG group (60%), but the difference was not significant (p = 0.131). CONCLUSION: We were able to implement the RG program safely, without compromising safety or oncological outcomes.

Acceptance of a Novel, Highly Palatable, Calorically Dense, and Nutritionally Complete Diet in Dogs with Benign and Malignant Tumors.

Diminished appetite and poor eating behavior accompanied by weight loss or cachexia are often reported in dogs living with cancer. This study was conducted to determine the acceptance and eating enthusiasm in dogs with cancer for a new therapeutic, nutritionally balanced, and calorically dense food designed for dogs with cancer. Adult dogs with diagnosis of cancer were recruited from general and oncology practices and were fed the study food for 28 days. Evaluations included physical examination, body weight, food intake, caloric intake, hematology and serum biochemistry, and owner assessments, namely food evaluation, quality of life, and stool scores. The dogs transitioned smoothly and tolerated the food very well. The results showed high food acceptance within the first day, with continued eating enthusiasm over the 28 days. Significant increases in food and caloric intake were observed, with the study food having a positive impact on body weight in dogs that were losing weight and helping to maintain a high quality of life. Blood laboratory parameters remained within reference ranges. Thus, the therapeutic study food was well accepted and efficacious in supporting continued eating and required caloric intake, promoting a healthy weight gain and maintaining a high quality of life in dogs with cancer.

Determinants of Lung Cancer Screening in a Minnesota Urban Indigenous Community: A Community-Based, Participatory, Action-Oriented Study.

Although lung cancer screening (LCS) with annual low-dose chest CT has been shown to reduce lung cancer deaths, it remains underutilized. Northern Plains American Indian and Alaska Native (AI/AN) communities experience extreme lung cancer disparities, and little is known about the acceptance and adoption of LCS in these groups. We conducted interviews with healthcare professionals and focus groups with patients in an urban Minnesota community clinic serving AI/AN. Data collection took place during winter 2019-2020. Indigenous researchers collected and analyzed the data for emergent themes using simultaneous collaborative consensus with a LCS researcher. Participants reported some similar barriers to LCS as previous studies reported but also shared some new insights into traditional ways of knowing and recommendations for effectively implementing this evidence-based preventive care service. Lung screening is largely acceptable to patients and healthcare personnel in an AI/AN-serving community clinic. We identified barriers as previously reported in other populations but also identified some unique barriers and motivators. For example, the concept of the seven generations may provide motivation to maintain one's health for future generations while providing additional support during screening for persons traumatized by the Western medicine health system may facilitate increased screening uptake. PREVENTION RELEVANCE: Secondary prevention of lung cancer through screening is potentially lifesaving considering that overall survival of lung cancer is 20% at 5 years but curable if detected at an early stage. This work provides insight into culturally tailored approaches to implementing the service in individuals at high risk of the disease.