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The aims of the present study were to (1) assess relationships between running performance and parasympathetic function both at rest and following exercise, and (2) examine changes in heart rate (HR)-derived indices throughout an 8-week period training program in runners. In 14 moderately trained runners (36 ± 7 years), resting vagal-related HR variability (HRV) indices were measured daily, while exercise HR and post-exercise HR recovery (HRR) and HRV indices were measured fortnightly. Maximal aerobic speed (MAS) and 10 km running performance were assessed before and after the training intervention. Correlations ( r  > 0.60, P  < 0.01) were observed between changes in vagal-related indices and changes in MAS and 10 km running time. Exercise HR decreased progressively during the training period ( P  < 0.01). In the 11 subjects who lowered their 10 km running time >0.5% (responders), resting vagal-related indices showed a progressively increasing trend (time effect P  = 0.03) and qualitative indications of possibly and likely higher values during week 7 [+7% (90% CI −3.7;17.0)] and week 9 [+10% (90% CI −1.5;23)] compared with pre-training values, respectively. Post-exercise HRV showed similar changes, despite less pronounced between-group differences. HRR showed a relatively early possible decrease at week 3 [−20% (90% CI −42;10)], with only slight reductions near the end of the program. The results illustrate the potential of resting, exercise and post-exercise HR measurements for both assessing and predicting the impact of aerobic training on endurance running performance.

Chemotherapy and radiotherapy are first-line treatments in the management of advanced solid tumors. Whereas these treatments are directed at eliminating cancer cells, they cause significant adverse effects that can be detrimental to a patient’s quality of life and even life-threatening. Diet is a modifiable risk factor that has been shown to affect cancer risk, recurrence, and treatment toxicity, but little information is known how diet interacts with cancer treatment modalities. Although dietary interventions, such as intermittent fasting and ketogenic diets, have shown promise in pre-clinical studies by reducing the toxicity and increasing the efficacy of chemotherapeutics, there remains a limited number of clinical studies in this space. This review surveys the impact of dietary interventions (caloric restriction, intermittent and short-term fasting, and ketogenic diet) on cancer treatment outcomes in both pre-clinical and clinical studies. Early studies support a complementary role for these dietary interventions in improving patient quality of life across multiple cancer types by reducing toxicity and perhaps a benefit in treatment efficacy. Larger, phase III, randomized clinical trials are ultimately necessary to evaluate the efficacy of these dietary interventions in improving oncologic or quality of life outcomes for patients that are undergoing chemotherapy or radiotherapy.

ObjectiveTo characterize and further compare the immune cell populations of the tumor microenvironment (TME) in both clear cell and papillary renal cell carcinoma (RCC) using heavy metal-labeled antibodies in a multiplexed imaging approach (imaging mass cytometry).Materials and methodsFormalin-fixed paraffin-embedded (FFPE) baseline tumor tissues from metastatic patients with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were retrospectively requisitioned from an institutional biorepository. Pretreated FFPE samples from 33 RCC patients (10 ccRCC, 23 pRCC) were accessioned and stained for imaging mass cytometry (IMC) analysis. Clinical characteristics were curated from an institutional RCC database. FFPE samples were prepared and stained with heavy metal-conjugated antibodies for IMC. An 11-marker panel of tumor stromal and immune markers was used to assess and quantify cellular relationships in TME compartments. To validate our time-of-flight (CyTOF) analysis, we cross-validated findings with The Cancer Genome Atlas Program (TCGA) analysis and utilized the CIBERSORTx tool to examine the abundance of main immune cell types in pRCC and ccRCC patients.ResultsPatients with ccRCC had a longer median overall survival than did those with pRCC (67.7 vs 26.8 mo, respectively). Significant differences were identified in the proportion of CD4+ T cells between disease subtypes (ccRCC 14.1%, pRCC 7.0%, p<0.01). Further, the pRCC cohort had significantly more PanCK+ tumor cells than did the ccRCC cohort (24.3% vs 9.5%, respectively, p<0.01). There were no significant differences in macrophage composition (CD68+) between cohorts. Our results demonstrated a significant correlation between the CyTOF and TCGA analyses, specifically validating that ccRCC patients exhibit higher levels of CD4+ T cells (ccRCC 17.60%, pRCC 15.7%, p<0.01) and CD8+ T cells (ccRCC 17.83%, pRCC 11.15%, p<0.01). The limitation of our CyTOF analysis was the large proportion of cells that were deemed non-characterizable.ConclusionsOur findings emphasize the need to investigate the TME in distinct RCC histological subtypes. We observed a more immune infiltrative phenotype in the TME of the ccRCC cohort than in the pRCC cohort, where a tumor-rich phenotype was noted. As practical predictive biomarkers remain elusive across all subtypes of RCC, further studies are warranted to analyze the biomarker potential of such TME classifications.

Introduction In a joint statement, Friends of Cancer Research and the American Society of Clinical Oncology affirmed the need for broadening clinical trial eligibility criteria to expand patient access to investigational treatments and enroll cohorts more representative of the general population. Our study aimed to characterize and analyze the prevalence of overly exclusionary eligibility criteria in contemporary clinical trials involving patients with locally advanced and metastatic urothelial cancer. Methods Utilizing MeSH query terms “(metastatic OR advanced OR stage IV OR unresectable) AND (bladder cancer OR upper tract urothelial carcinoma OR upper tract urothelial cancer)” in ClinicalTrials.gov, we identified 205 interventional urothelial cancer trials activated between June 30, 2012 through June 30, 2022. We investigated the prevalence of four potentially restrictive criteria: the presence of brain metastases, HIV infection, hepatitis B/C infection, and the presence of concurrent malignancies. Fisher's Exact test was utilized to ascertain significant associations between criteria and trial characteristics. Results Of 205 trials found initially, 37 (18%) contained sufficient data for analysis. Overall, HIV infection and Hepatitis B/C infection were most restrictive, with most trials completely excluding patients with these conditions (89.2%; 56.8%). Restrictiveness for HIV infection and type of therapy were significantly associated, with most exclusionary trials involving combination or immunotherapies (39.4%; 33.3%; p = 0.003). Brain metastases were totally excluded by 35.1% of trials and had 18.9% of trials provide no explicit criteria or guidelines. Most trials specified conditions for the inclusion of patients with concurrent malignancies (91.9%). Variant histology was also underrepresented, with most trials not specifying or totally excluding all variant histology (43.2%; 8.1%). Conclusion HIV infection and hepatitis B/C infection were commonly identified in exclusion criteria across these trials despite limited evidence suggesting these criteria significantly impact therapy efficacy and tolerability. Broadening and modernization of eligibility criteria will ensure more inclusive clinical trials.

Slip transmission across grain boundaries is an essential micromechanical processes during deformation of polycrystalline materials. Slip transmission processes can be characterized based on the geometrical arrangement of active slip systems in adjacent grains and the value of the critical resolved shear stress acting on the incoming and possible outgoing slip systems. We present a Matlab toolbox which enables quantification of grain boundary slip transfer properties and comparison with experiments. Using a graphical user interface, experimental grain boundary data can be directly exported as input files for crystal plasticity finite element simulation of bicrystal experiments.

Cognitive regulation of emotion develops from childhood into adulthood. This occurs in parallel with maturation of prefrontal cortical (PFC) regulation over the amygdala. The cellular substrates for this regulation may include PFC activation of inhibitory GABAergic elements in the amygdala. The purpose of this study was to determine whether PFC regulation over basolateral amygdala area (BLA) in vivo is immature in adolescence, and if this is due to immaturity of GABAergic elements or PFC excitatory inputs. Using in vivo extracellular electrophysiological recordings from anesthetized male rats we found that in vivo summation of PFC inputs to the BLA was less regulated by GABAergic inhibition in adolescents (postnatal day 39) than adults (postnatal day 72–75). In addition, stimulation of either prelimbic or infralimbic PFC evokes weaker inhibition over basal (BA) and lateral (LAT) nuclei of the BLA in adolescents. This was dictated by both weak recruitment of inhibition in LAT and weak excitatory effects of PFC in BA. The current results may contribute to differences in adolescent cognitive regulation of emotion. These findings identify specific elements that undergo adolescent maturation and may therefore be sensitive to environmental disruptions that increase risk for psychiatric disorders.

While much research has focused on the relationship between duration of untreated psychosis (DUP) and clinical outcomes in the first episode psychosis (FEP) patient population, little is known about the individual help-seeking episodes (HSE) that patients undergo before receiving appropriate care. The purpose of this project is to better understand how early referral to FEP-specific care and support system differences affect patients’ DUP and engagement with treatment. Data from 50 patients was analyzed at the Early Psychosis Intervention Clinic of New Orleans (EPIC-NOLA) using a modified version of the Pathways to Care Assessments and data captured during clinical care. Patients with their first HSE leading to a referral to EPIC-NOLA (M = 13.3, SD = 11.17) had shorter DUP compared to patients referred after two or more HSEs (M = 29.7, SD = 36. 7), t (38.6) = 2.31, p = .026, 95%CI = 2.0–30.7. One chi-square test revealed a significantly greater proportion of patients referred after one HSE stayed in treatment for 12 months or more. Cluster analysis and independent t-test analyses revealed that patients with hospital pathways (M = 35.00, SD = 39.36) had significantly longer DUP compared to those with self, other and hospital (M = 15.21, SD = 19.07) care pathways. This study supports existing literature that suggest early FEP treatment leads to shortened DUP and longer treatment engagement. Additionally, patients with support systems (people or services) assisting them with help-seeking reach EPIC-NOLA faster, have shorter DUP, and have better treatment engagement.

Nasotracheal intubation (NTI) is often required for oropharyngeal surgery to maximize surgical access, but epistaxis is a common complication. NTI using a nasotracheal tube (NTT) telescoped into a red rubber urinary catheter (RRC) to guide the NTT and protect the nasal mucosa has been described for adults and studied in children but has not been systematically evaluated in adults. This was a two-center, single-blinded, randomized controlled trial. 112 adults (mean age 57.1 ± 16.3 years, 61.6 % male) undergoing surgery requiring NTI were randomized 1: 1 to intubation with a thermosoftened, lubricated NTT, either alone or telescoped into an RRC to shield the beveled NTT tip. The primary outcome was incidence of epistaxis assessed at 5 min post-intubation by a blinded observer. Secondary outcomes included the severity of epistaxis, time to intubation, the rate of complications during nasotracheal intubation, and the degree of postoperative pain in PACU. Use of an RRC significantly reduced the likelihood of epistaxis (39.3 % vs. 62.5 %, Odds Ratio (OR) = 0.380, p = 0.0140; 95 % CI: 0.174 to 0.831, p = 0.0153; FDR = 0.0255) and the severity of epistaxis (OR for lower severity = 4.145; 95 % CI: 1.923 to 8.934, p = 0.0003; FDR = 0.0013), but was associated with a longer time to intubation (Least squares adjusted means 104.2 (SE = 6.87) seconds vs. 74.30 (SE = 6.86) seconds, p = 0.0005; FDR = 0.0015, d = 0.70). No difference was found in postoperative pain or in the rate of procedural complications. Use of the RRC significantly reduced the likelihood and severity of epistaxis following nasal intubation, at the cost of longer time to intubation. [Display omitted] •Epistaxis less frequent if red rubber urinary catheter used during nasal intubation.•Epistaxis less severe if red rubber urinary catheter used during nasal intubation.•Time to nasotracheal intubation longer when red rubber urinary catheter used.•No complications attributed to use of red rubber catheter technique.•No difference seen in number of intubation attempts required.

Radiation treatment (RT) is a mainstay treatment for many types of cancer. Recommendations for RT and the radiation plan are individualized to each patient, taking into consideration the patient’s tumor pathology, staging, anatomy, and other clinical characteristics. Information on germline mutations and somatic tumor mutations is at present rarely used to guide specific clinical decisions in RT. Many genes, such as ATM, and BRCA1/2, have been identified in the laboratory to confer radiation sensitivity. However, our understanding of the clinical significance of mutations in these genes remains limited and, as individual mutations in such genes can be rare, their impact on tumor response and toxicity remains unclear. Current guidelines, including those from the National Comprehensive Cancer Network (NCCN), provide limited guidance on how genetic results should be integrated into RT recommendations. With an increasing understanding of the molecular underpinning of radiation response, genomically-guided RT can inform decisions surrounding RT dose, volume, concurrent therapies, and even omission to further improve oncologic outcomes and reduce risks of toxicities. Here, we review existing evidence from laboratory, pre-clinical, and clinical studies with regard to how genetic alterations may affect radiosensitivity. We also summarize recent data from clinical trials and explore potential future directions to utilize genetic data to support clinical decision-making in developing a pathway toward personalized RT.