Comparing MRI and arthroscopic appearances of common knee pathologies: A pictorial review.

Knee pathology, including anterior cruciate ligament (ACL) tears, meniscal tears, articular cartilage lesions, and intra-articular masses or cysts are common clinical entities treated by orthopedic surgeons with arthroscopic surgery. Preoperatively, magnetic resonance imaging (MRI) is now standard in confirming knee pathology, particularly detecting pathology less evident with history and physical examination alone. The radiologist's MRI interpretation becomes essential in evaluating intra-articular knee structures. Typically, the radiologist that interprets the MRI does not have the opportunity to view the same pathology arthroscopically. Thus, the purpose of this article is to illustratively reconcile what the orthopedic surgeon sees arthroscopically with what the radiologist sees on magnetic resonance imaging when viewing the same pathology. Correlating virtual and actual images can help better understand pathology, resulting in more accurate MRI interpretations. In this article, we present and review a series of MR and correlating arthroscopic images of ACL tears, meniscal tears, chondral lesions, and intra-articular masses and cysts. Short teaching points are included to highlight the importance of radiological signs and pathological MRI appearance with significant clinical and arthroscopic findings.

Electric-field-assisted proton coupling enhanced oxygen evolution reaction.

The discovery of Mn-Ca complex in photosystem II stimulates research of manganese-based catalysts for oxygen evolution reaction (OER). However, conventional chemical strategies face challenges in regulating the four electron-proton processes of OER. Herein, we investigate alpha-manganese dioxide (α-MnO2) with typical MnIV-O-MnIII-HxO motifs as a model for adjusting proton coupling. We reveal that pre-equilibrium proton-coupled redox transition provides an adjustable energy profile for OER, paving the way for in-situ enhancing proton coupling through a new "reagent"- external electric field. Based on the α-MnO2 single-nanowire device, gate voltage induces a 4-fold increase in OER current density at 1.7 V versus reversible hydrogen electrode. Moreover, the proof-of-principle external electric field-assisted flow cell for water splitting demonstrates a 34% increase in current density and a 44.7 mW/cm² increase in net output power. These findings indicate an in-depth understanding of the role of proton-incorporated redox transition and develop practical approach for high-efficiency electrocatalysis.

Evaluation of a therapist-guided virtual psychological pain management program when provided as routine care: a prospective pragmatic cohort study.

INTRODUCTION: Numerous randomized controlled trials have evaluated the outcomes of internet-delivered psychological pain management programs (PMPs) as a way of increasing access to care for people with chronic pain. However, there are few reports of the effectiveness of these PMPs when provided as part of routine care. METHODS: The present study sought to report the clinical and demographic characteristics of users (n = 1367) and examine the effectiveness of an established internet-delivered psychological PMP program in improving several pain-related outcomes, when offered at a national digital mental health service over a 5-year period. It also sought to comprehensively explore predictors of treatment commencement, treatment completion, and clinical improvement. RESULTS: Evidence of clinical improvements (% improvement; Hedges g) were found for all outcomes, including pain interference (18.9%; 0.55), depression (26.1%; 0.50), anxiety (23.9%; 0.39), pain intensity (12.8%; 0.41), pain self-efficacy (-23.8%; -0.46) and pain-catastrophizing (26.3%; 0.56). A small proportion of users enrolled but did not commence treatment (13%), however high levels of treatment completion (whole treatment = 63%; majority of the treatment = 75%) and satisfaction (very satisfied = 45%; satisfied = 37%) were observed among those who commenced treatment. There were a number of demographic and clinical factors associated with commencement, completion and improvement, but no decisive or dominant predictors were observed. DISCUSSION: These findings highlight the effectiveness and acceptability of internet-delivered psychological PMPs in routine care and point to the need to consider how best to integrate these interventions into the pathways of care for people with chronic pain.

Isotopically Enriched Layers for Quantum Computers Formed by 28Si Implantation and Layer Exchange.

28Si enrichment is crucial for production of group IV semiconductor-based quantum computers. Cryogenically cooled, monocrystalline 28Si is a spin-free, vacuum-like environment where qubits are protected from sources of decoherence that cause loss of quantum information. Currently, 28Si enrichment techniques rely on deposition of centrifuged SiF4 gas, the source of which is not widely available, or bespoke ion implantation methods. Previously, conventional ion implantation into naturalSi substrates has produced heavily oxidized 28Si layers. Here we report on a novel enrichment process involving ion implantation of 28Si into Al films deposited on native-oxide free Si substrates followed by layer exchange crystallization. We measured continuous, oxygen-free epitaxial 28Si enriched to 99.7%. Increases in isotopic enrichment are possible, and improvements in crystal quality, aluminum content, and thickness uniformity are required before the process can be considered viable. TRIDYN models, used to model 30 keV 28Si implants into Al to understand the observed post-implant layers and to investigate the implanted layer exchange process window over different energy and vacuum conditions, showed that the implanted layer exchange process is insensitive to implantation energy and would increase in efficiency with oxygen concentrations in the implanter end-station by reducing sputtering. Required implant fluences are an order of magnitude lower than those required for enrichment by direct 28Si implants into Si and can be chosen to control the final thickness of the enriched layer. We show that implanted layer exchange could potentially produce quantum grade 28Si using conventional semiconductor foundry equipment within production-worthy time scales.

Neutrophil-mediated fibroblast-tumor cell il-6/stat-3 signaling underlies the association between neutrophil-to-lymphocyte ratio dynamics and chemotherapy response in localized pancreatic cancer: A hybrid clinical-preclinical study.

Background: Partial/complete pathologic response following neoadjuvant chemotherapy (NAC) in pancreatic cancer (PDAC) patients undergoing pancreatectomy is associated with improved survival. We sought to determine whether neutrophil-to-lymphocyte ratio (NLR) dynamics predict pathologic response following chemotherapy in PDAC, and if manipulating NLR impacts chemosensitivity in preclinical models and uncovers potential mechanistic underpinnings underlying these effects. Methods: Pathologic response in PDAC patients (n=94) undergoing NAC and pancreatectomy (7/2015-12/2019) was dichotomized as partial/complete or poor/absent. Bootstrap-validated multivariable models assessed associations between pre-chemotherapy NLR (%neutrophils÷%lymphocytes) or NLR dynamics during chemotherapy (ΔNLR = pre-surgery-pre-chemotherapy NLR) and pathologic response, disease-free survival (DFS), and overall survival (OS). To preclinically model effects of NLR attenuation on chemosensitivity, Ptf1aCre/+; KrasLSL-G12D/+;Tgfbr2flox/flox (PKT) mice and C57BL/6 mice orthotopically injected with KrasLSL-G12D/+;Trp53LSL-R172H/+;Pdx1Cre(KPC) cells were randomized to vehicle, gemcitabine/paclitaxel alone, and NLR-attenuating anti-Ly6G with/without gemcitabine/paclitaxel treatment. Results: In 94 PDAC patients undergoing NAC (median:4 months), pre-chemotherapy NLR (p<0.001) and ΔNLR attenuation during NAC (p=0.002) were independently associated with partial/complete pathologic response. An NLR score = pre-chemotherapy NLR+ΔNLR correlated with DFS (p=0.006) and OS (p=0.002). Upon preclinical modeling, combining NLR-attenuating anti-Ly6G treatment with gemcitabine/paclitaxel-compared with gemcitabine/paclitaxel or anti-Ly6G alone-not only significantly reduced tumor burden and metastatic outgrowth, but also augmented tumor-infiltrating CD107a+-degranulating CD8+ T-cells (p<0.01) while dampening inflammatory cancer-associated fibroblast (CAF) polarization (p=0.006) and chemoresistant IL-6/STAT-3 signaling in vivo. Neutrophil-derived IL-1ß emerged as a novel mediator of stromal inflammation, inducing inflammatory CAF polarization and CAF-tumor cell IL-6/STAT-3 signaling in ex vivo co-cultures. Conclusions: Therapeutic strategies to mitigate neutrophil-CAF-tumor cell IL-1ß/IL-6/STAT-3 signaling during NAC may improve pathologic responses and/or survival in PDAC. Funding: Supported by KL2 career development grant by Miami CTSI under NIH Award UL1TR002736, Stanley Glaser Foundation, American College of Surgeons Franklin Martin Career Development Award, and Association for Academic Surgery Joel J. Roslyn Faculty Award (to J. Datta); NIH R01 CA161976 (to N.B. Merchant); and NCI/NIH Award P30CA240139 (to J. Datta and N.B. Merchant).

Pancreatic cancer presenting as bowel obstruction and role of next generation sequencing: A case report.

INTRODUCTION AND IMPORTANCE: Pancreatic adenocarcinoma is one of the leading causes of death. Presentation with colonic metastases is far less frequently reported in the literature and may be misdiagnosed as colonic adenocarcinoma. We report the case of a female patient with metastatic pancreatic adenocarcinoma that presented with a sigmoid obstruction. CASE PRESENTATION: A 66-year-old female presented with constipation and abdominal pain. She was found to have an obstructing sigmoid colon lesion, multiple metastatic lesions in the liver, and a pancreatic tail lesion. She underwent left hemicolectomy and ostomy placement. The gross pathology of the colon and needle biopsy of the liver was consistent of pancreatobiliary origin. Genomic screening performed, patient found to be KRAS G12R mutated. She was given one cycle of chemotherapy, thereafter was referred to hospice care. CLINICAL DISCUSSION: Primary metastatic pancreatic cancer is now the 2nd most diagnosed cancer in the United States after lung cancer. The prognosis for the malignancy is poor, patients are usually diagnosed late at the time that the tumor has metastasized to other organs. Colonic metastasis is a rarely seen and far less frequently reported in the literature. Next-generation-sequencing was performed at baseline to further characterize her tumor for any actionable mutations. CONCLUSION: Pancreatic adenocarcinoma is an aggressive malignancy with a poor prognosis. Next-generation-sequencing may offer targeted therapy if an actionable mutation is present such as our patient's, however due to late diagnosis, rapid clinical deterioration, and next-generation sequencing delay we were unable to alter the patient's outcome.

Potential benefit of treatment with MEK inhibitors and chemotherapy in BRAF-mutated KRAS wild-type pancreatic ductal adenocarcinoma patients: a case report.

This is the first case report of a 60-yr-old female who underwent therapy for metastatic pancreatic cancer with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX). Upon the progression of her disease, she was switched to gemcitabine and nab-paclitaxel. Per genomic sequencing, her tumor was found to be a KRAS wild-type and BRAF V600E mutation, which then warranted treatment with the MEK1 and MEK2 inhibitor, cobimetinib. The patient has achieved a complete response (CR) to a combination of gemcitabine, nab-paclitaxel, and cobimetinib. It has been 16 mo since the start of the treatment, and the patient continues to demonstrate a complete durable response both serologically and radiologically.

Fibrohistiocytic Variant of Hepatic Pseudotumor: An Antibiotic Responsive Tumefactive Lesion.

Inflammatory pseudotumor is a term used to designate inflammation-rich tumefactive lesions. Following the exclusion of specific entities such as IgG4-related disease and other neoplastic entities previously included in this entity, the majority of hepatic pseudotumors show a prominent fibrohistiocytic inflammatory reaction and have been previously categorized as fibrohistiocytic variant of hepatic pseudotumor (FHVHPT). The goal of this study was to examine the clinical, radiologic, histologic, and etiologic aspects of this entity. After excluding neoplastic diseases, we identified 30 patients with FHVHPT from 3 institutions between 2009 and 2019. We extracted demographic and clinical data, liver function tests as well as culture results and radiologic information. Hematoxylin and eosin-stained slides were reviewed for pattern of inflammation as well as its cellular composition. Immunohistochemistry for IgG4 and IgG was performed in all cases. The mean age of the 30 lesions characterized as FHVHPT was 56 years (range: 23 to 79 y). Nineteen patients showed solitary lesions; 11 were multiple. The mean size of the lesion was 3.8 cm (range: 1 to 7.5 cm). On imaging, a neoplastic process or metastasis was the leading diagnostic consideration (n=15, 50%). The most common symptom was abdominal pain (n=14/30); 8 patients presented with symptoms compatible with an infectious process, including fever. The inflammatory infiltrate was dominated by lymphocytes and plasma cells, and in most cases, a prominent histiocytic infiltrate (22/30). Neutrophils were identified in 12 cases, with microabscess noted in 8. Storiform pattern of fibrosis was seen in 14/30 cases; obliterative phlebitis was not identified. Culture identified a microorganism in 4 of 9 cases evaluated. The mean IgG4 count was 9.3 per HPF (range: 0 to 51) with 9 of the 26 (35%) biopsies showing >10 IgG4 positive plasma cells per HPF. The mean IgG4 to IgG ratio was 8% (range: 8% to 46%). A hepatectomy was performed in 4 cases. On broad spectrum antibiotics (n=14) the lesions either resolved or decreased in size. Eight patients did not receive specific therapy, nevertheless, the lesion(s) resolved spontaneously in 6 cases, remained stable or decreased in size in 2 cases. Notably, none of these patients showed evidence of a hepatic recurrence. FHVHPT, a tumefactive lesion that mimics hepatic neoplasia, is histologically characterized by a fibrohistiocytic infiltrate. In the majority of patients FHVHPT represents the organizing phase of hepatic abscess and can be successfully managed with antibiotic therapy.

Clear Cell Change in Reactive Angiogenesis: A Potential Diagnostic Pitfall.

Reactive angiogenesis is commonplace, occurs in many circumstances, and is important in the repair of injured tissue. Histologically, it is characterized by newly formed capillaries arranged in a lobular architecture and lined by plump endothelial cells. We have encountered a form of reactive angiogenesis not well described; composed of large endothelial cells with abundant clear cytoplasm that causes diagnostic challenges. The cohort includes 10 patients, aged 4 to 61, mean 40 years; 7 males, 3 females. One case involved bone (ilium), and 9 involved soft tissue: fingers (n=2), toes (n=2), hip joint (n=1), shoulder (n=1), thigh (n=2), and anal mucosa (n=1). Clinically, the patients had chronic ulcers, osteomyelitis, or localized infection. All cases exhibited a lobular proliferation of capillaries lined by large polyhedral endothelial cells that obscured the vessel lumens and were admixed with acute and chronic inflammation. The endothelial nuclei were vesicular with small nucleoli and the cytoplasm was abundant and clear or palely eosinophilic. The endothelial cells were stained with CD31 and ERG (7/7 cases), CD34 (6/6), FLI1 (4/4), and were negative for keratin and CD68 (6/6). Periodic acid-Schiff stain and periodic acid-Schiff stain-diastase on 3 cases did not demonstrate glycogen. Using a polymerase chain reaction, no Bartonella henselae was found in all 6 cases tested. Reactive angiogenesis with clear cell change unassociated with Bartonella spp. has not been described. It causes diagnostic challenges and the differential diagnosis includes benign and malignant tumors, as well as unusual infections. It is important to distinguish between these possibilities because of the significant impact on treatment and prognosis.

Unusual Presentation of Renal Medullary Carcinoma With Undiagnosed Sickle Cell Trait.

Renal medullary carcinoma (RMC) is an extremely rare malignancy that has been described in younger male patients of African descent with a history of sickle cell disease or trait. We describe a rather unique case of RMC in an older male patient who initially presented with acute on chronic urinary retention and concern for infection. Further investigation revealed a history of hematuria and long-standing microcytic anemia, and the patient was found to have sickle cell trait (SCT) as part of a workup for malignancy of unknown primary. Imaging findings initially interpreted as hydronephrosis later characterized a mass in the renal pelvis concerning for a genitourinary malignancy, later biopsy-proven RMC. RMC typically presents in its advanced stages, with associated poor prognosis, and treatment options are limited and have been extrapolated from standard regimens for other genitourinary malignancies. Therefore, early clinical suspicion in patients with microcytic anemia, flank pain, hematuria, and urinary symptoms, can aid in the diagnosis of RMC and allow for prompt intervention.

The Fallacy of Teaching and the Illusion of Learning: Improving Articulation of Basic Science in the Medical School Curriculum.

Despite calls from educators to re-engineer how faculty deliver medical student curricula with integrated basic science concepts, this content is still frequently disarticulated from other curricular components. We renewed our curriculum using evidence-based pedagogical and cognitive learning strategies to interleave basic science across the 4-year curriculum.

Determination of Dimension and Conformal Arsenic Doping Profile of a Fin Field Effect Transistors by Time-of-Flight Medium Energy Ion Scattering.

We have developed a methodology that analyzes the dimensions and conformal doping profiles in fin field effect transistors (FinFET) using time-of-flight medium energy ion scattering (TOF-MEIS). The structure of a 3D FinFET and As dopant profiles were determined by comprehensive simulations of TOF-MEIS measurements made in three different scattering geometries. The width and height of a FinFET and the As doping profiles in the top, side, and bottom of fin were analyzed simultaneously. The results showed the dimension and conformal doping profile of nanostructures with complex shape can be determined by TOF-MEIS nondestructively, quantitatively, and with subnm depth resolution without any sputtering and matrix effects.

Room temperature synthesis of HfO2/HfO x heterostructures by ion-implantation.

Implantation of Hf films with oxygen ions is shown to be an effective means of fabricating high-quality HfO2/HfO x heterostructures at room temperature, with the layer composition and thicknesses determined by the ion energy and fluence. Implantation with 3 keV O+ ions to a fluence of 1 × 1017 ions cm-2 produces a polycrystalline (monoclinic-) HfO2 layer extending from the surface to a depth of ∼12 nm, and an underlying graded HfO x layer extending an additional ∼7 nm, while implantation with 6 keV O to a similar fluence produces a near-stoichiometric surface layer of 7 nm thickness and a graded substoichiometric layer extending to depth of ∼30 nm. These structures are shown to be broadly consistent with oxygen range data but more detailed comparison with dynamic Monte Carlo simulations suggests that the near-surface region contains more oxygen than expected from collisional processes alone. The bandgap and dielectric strength of the HfO2 layer produced by 3 keV; 1 × 1017 ions cm-2 implant is shown to be indistinguishable from those of an amorphous film deposited by atomic layer deposition at 200 °C. The utility of these layers is demonstrated by studying the resistive switching properties of metal-oxide-metal test structures fabricated by depositing a top metal contact on the implanted film. These results demonstrate the suitability of ion-implantation for the synthesis of functional oxide layers at room temperature.

Temperature as a Circadian Marker in Older Human Subjects: Relationship to Metabolic Syndrome and Diabetes.

BACKGROUND: Circadian rhythms are characterized by approximate 24-hour oscillations in physiological and behavioral processes. Disruptions in these endogenous rhythms, most commonly associated with shift work and/or lifestyle, are recognized to be detrimental to health. Several studies have demonstrated a high correlation between disrupted circadian rhythms and metabolic disease. The aim of this study was to determine which metabolic parameters correlate with physiological measures of circadian temperature amplitude (TempAmp) and stability (TempStab). METHODS: Wrist skin temperature was measured in 34 subjects (ages 50 to 70, including lean, obese, and diabetic subjects) every 10 minutes for 7 consecutive days. Anthropometric measures and fasting blood draws were conducted to obtain data on metabolic parameters: body mass index, hemoglobin A1C, triglycerides, cholesterol, high-density lipoprotein, and low-density lipoprotein. A history of hypertension and current blood pressure was noted. RESULTS: Analysis of the data indicated a substantial reduction in TempAmp and TempStab in subjects with metabolic syndrome (three or more risk factors). To determine the impact of individual interdependent metabolic factors on temperature rhythms, stepwise multilinear regression analysis was conducted using metabolic syndrome measurements. Interestingly, only triglyceride level was consistently correlated by the analysis. Triglyceride level was shown to contribute to 33% of the variability in TempAmp and 23% of the variability in TempStab. CONCLUSION: Our results demonstrate that elevated triglycerides are associated with diminished TempAmp and TempStab in human subjects, and triglycerides may serve as a primary metabolic predictor of circadian parameters.

Risk Stratification in Patients with Stage II Colon Cancer.

BACKGROUND: The decision to receive adjuvant chemotherapy is far from evident and remains controversial in patients with American Joint Committee on Cancer stage II colon cancer. This study analyzes several pathological characteristics in order to assess their (combined) predictive value for outcomes in stage II colon cancer. METHODS: All stage II patients treated surgically for colon cancer at our tertiary care center (2004-2011) were extracted from a prospectively maintained, Institutional Review Board-approved data repository (n = 313). Mortality and metastasis were compared, including multivariable Cox regression adjusted for stage subdivisions (IIA/IIB/IIC) and potential confounders. RESULTS: Colon cancer-specific mortality was substage independently increased in patients with baseline carcinoembryonic antigen (CEA) >5 ng/L [hazard ratio (HR) 2.88; p = 0.022], large vessel invasion (LVI; HR 4.59; p < 0.001), perineural invasion (HR 3.08; p = 0.006), and extramural vascular invasion (EMVI; HR 4.96; p < 0.001). Overall mortality adjusted for substage, age, and comorbidity was also significantly higher in patients with high-grade disease (HR 2.54; p < 0.001), LVI (HR 1.74; p = 0.015), perineural (HR 2.42; p < 0.001), and EMVI (HR 2.79; p < 0.001). Metastatic recurrence adjusted for adjuvant chemotherapy status had substage-independent associations with baseline CEA >5 ng/L (HR 2.37; p = 0.046), LVI (HR 3.07; p = 0.001), perineural invasion (HR 2.57; p = 0.010), and EMVI (HR 2.83; p = 0.002). The number of high-risk features (0, 1, 2-3, 4+) was associated with a clear incremental increase in overall and disease-specific mortality and recurrence (p ≤ 0.001). The major inflection point is at two high-risk characteristics or more, whereas 5-year survival is almost halved from 77.4 % to 31.7 % (p < 0.001). CONCLUSIONS: The risk score introduced provides a prognostic tool based on readily available data extracted from baseline pathology and preoperative CEA, which provides an easy method to stratify risks of mortality and recurrence and may therefore help in treatment decisions after surgery in stage II patients.

Intrinsic muscle clock is necessary for musculoskeletal health.

KEY POINTS: The endogenous molecular clock in skeletal muscle is necessary for maintenance of phenotype and function. Loss of Bmal1 solely from adult skeletal muscle (iMSBmal1(-/-) ) results in reductions in specific tension, increased oxidative fibre type and increased muscle fibrosis with no change in feeding or activity. Disruption of the molecular clock in adult skeletal muscle is sufficient to induce changes in skeletal muscle similar to those seen in the Bmal1 knockout mouse (Bmal1(-/-) ), a model of advanced ageing. iMSBmal1(-/-) mice develop increased bone calcification and decreased joint collagen, which in combination with the functional changes in skeletal muscle results in altered gait. This study uncovers a fundamental role for the skeletal muscle clock in musculoskeletal homeostasis with potential implications for ageing. ABSTRACT: Disruption of circadian rhythms in humans and rodents has implicated a fundamental role for circadian rhythms in ageing and the development of many chronic diseases including diabetes, cardiovascular disease, depression and cancer. The molecular clock mechanism underlies circadian rhythms and is defined by a transcription-translation feedback loop with Bmal1 encoding a core molecular clock transcription factor. Germline Bmal1 knockout (Bmal1 KO) mice have a shortened lifespan, show features of advanced ageing and exhibit significant weakness with decreased maximum specific tension at the whole muscle and single fibre levels. We tested the role of the molecular clock in adult skeletal muscle by generating mice that allow for the inducible skeletal muscle-specific deletion of Bmal1 (iMSBmal1). Here we show that disruption of the molecular clock, specifically in adult skeletal muscle, is associated with a muscle phenotype including reductions in specific tension, increased oxidative fibre type, and increased muscle fibrosis similar to that seen in the Bmal1 KO mouse. Remarkably, the phenotype observed in the iMSBmal1(-/-) mice was not limited to changes in muscle. Similar to the germline Bmal1 KO mice, we observed significant bone and cartilage changes throughout the body suggesting a role for the skeletal muscle molecular clock in both the skeletal muscle niche and the systemic milieu. This emerging area of circadian rhythms and the molecular clock in skeletal muscle holds the potential to provide significant insight into intrinsic mechanisms of the maintenance of muscle quality and function as well as identifying a novel crosstalk between skeletal muscle, cartilage and bone.

Physical activity, and not fat mass is a primary predictor of circadian parameters in young men.

Circadian rhythms are ≈24 h oscillations in physiology and behavior, and disruptions have been shown to have negative effects on health. Wrist skin temperature has been used by several groups as a valid method of assessing circadian rhythms in humans. We tested the hypothesis that circadian temperature amplitude (TempAmp) and stability (TempStab) would significantly differ among groups of healthy young men of varying adiposities, and that we could identify physiological and behavioral measures that were significantly associated with these temperature parameters. Wrist skin temperatures taken at 10 min intervals for 7 consecutive days were determined in 18 optimal (OGroup), 20 fair (FGroup) and 21 poor (PGroup) %Fat grouped young men and subsequently analyzed using available validated software. Body composition, cardiorespiratory fitness, actigraphy, daily nutritional and sleep data, and fasting lipid, insulin and glucose concentration measures were also determined. Significant changes in TempAmp and TempStab parameters in subjects with a single metabolic syndrome (MetS) risk factor compared to those with no MetS factors was observed. In addition, stepwise multivariate regression analyses showed that 50% of the variance in TempAmp was explained by actigraphy (mean steps taken per day; MSTPD), cardiorespiratory fitness, and late night eating per week (#LNE); and 57% in TempStab by MSTPD, time spent in moderate-to-vigorous activity per day, fat mass, and #LNE. Overwhelmingly, physical activity was the most important measure associated with the differences in circadian rhythm parameters. Further research is warranted to determine the effects of increasing the amount and timing of physical activity on the status of the circadian system in a variety of populations.

Blunted hypertrophic response in aged skeletal muscle is associated with decreased ribosome biogenesis.

The ability of skeletal muscle to hypertrophy in response to a growth stimulus is known to be compromised in older individuals. We hypothesized that a change in the expression of protein-encoding genes in response to a hypertrophic stimulus contributes to the blunted hypertrophy observed with aging. To test this hypothesis, we determined gene expression by microarray analysis of plantaris muscle from 5- and 25-mo-old mice subjected to 1, 3, 5, 7, 10, and 14 days of synergist ablation to induce hypertrophy. Overall, 1,607 genes were identified as being differentially expressed across the time course between young and old groups; however, the difference in gene expression was modest, with cluster analysis showing a similar pattern of expression between the two groups. Despite ribosome protein gene expression being higher in the aged group, ribosome biogenesis was significantly blunted in the skeletal muscle of aged mice compared with mice young in response to the hypertrophic stimulus (50% vs. 2.5-fold, respectively). The failure to upregulate pre-47S ribosomal RNA (rRNA) expression in muscle undergoing hypertrophy of old mice indicated that rDNA transcription by RNA polymerase I was impaired. Contrary to our hypothesis, the findings of the study suggest that impaired ribosome biogenesis was a primary factor underlying the blunted hypertrophic response observed in skeletal muscle of old mice rather than dramatic differences in the expression of protein-encoding genes. The diminished increase in total RNA, pre-47S rRNA, and 28S rRNA expression in aged muscle suggest that the primary dysfunction in ribosome biogenesis occurs at the level of rRNA transcription and processing.