Melatonin Supplementation for Cancer-Related Fatigue in Patients With Early Stage Breast Cancer Receiving Radiotherapy: A Double-Blind Placebo-Controlled Trial.

BACKGROUND: Fatigue is common in patients undergoing radiotherapy (RT) and can significantly impact quality of life. Melatonin, a safe inexpensive natural supplement, may improve symptoms and attenuate the side effects of RT. The purpose of this randomized double-blind placebo-controlled phase III trial was to assess the effects of melatonin for preventing fatigue and other symptoms in patients with breast cancer undergoing RT. METHODS: Female early stage or Ductal carcinoma in situ patients with breast cancer ≥18 years of age with Eastern Cooperative Oncology Group (ECOG) performance status <3, hemoglobin ≥9 g/dL, planned for outpatient RT treatment with curative intent, were randomized 1:1 to melatonin 20 mg or placebo, orally, starting the night before RT initiation until 2 weeks post-RT. Randomization was stratified according to treatment duration (<3 weeks, ≥3 weeks) and prior chemotherapy. The primary endpoint was the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue scale), and secondary endpoints were FACIT-F subscales, Edmonton Symptom Assessment Scale (ESAS), and Patient-Reported Outcomes Measurement Information System (PROMIS) scores obtained at baseline, and 2 and 8 weeks post-RT. A 2-sided ANOVA F-test at a 4.5% significance level for the primary endpoint was used. Secondary analyses were reported using an F-test at a 5% significance level. The goal was to recruit approximately 140 patients with interim analysis planned mid-recruitment. RESULTS: Eighty-five patients were screened for eligibility; 79 patients were randomized: 40 to melatonin and 39 to placebo; 78 patients were treated and included in the interim analysis at the mid-recruitment point. Baseline patient characteristics of age, race, and ECOG performance status were similar in both arms. The treatment effect was studied using a longitudinal mixed effects model with the effect of treatment over time (treatment × time) as the primary outcome parameter. The treatment × time for FACIT-Fatigue did not demonstrate statistical significance (P-value .83) in the melatonin group compared to placebo. In addition, secondary analyses of FACIT physical, social, emotional, and functional well-being scores did not demonstrate statistical significance (P-values of .35, .06, .62, and .71, respectively). Total PROMIS scores, collected as secondary outcome reported by patients, did not demonstrate statistically significant change over time either (P-value is .34). The other secondary scale, ESAS, was analyzed for each individual item and found to be nonsignificant, anxiety (P = .56), well-being (.82), drowsiness (.83), lack of appetite (.35), nausea (.79), pain (.50), shortness of breath (.77), sleep (.45), and tiredness (.56). Depression was the only item demonstrating statistical significance with a decrease of 0.01 unit in the placebo group, a change not considered clinically significant. Melatonin was well-tolerated with no grade 3 or 4 adverse events reported. The most common side effects were headache, somnolence, and abdominal pain. No patients died while participating in this study. Two patients died within a year of study completion from breast cancer recurrence. Sixteen patients withdrew prior to study completion for various reasons including adverse events, hospitalizations unrelated to study drug, RT discontinuation, and COVID-19 precautions. CONCLUSIONS: In this double-blind placebo-controlled phase III trial, melatonin did not prevent or significantly improve fatigue and other symptoms in patients with early stage breast cancer undergoing RT. The analysis, showing little evidence of an effect, at mid-recruitment, assured early termination of the trial.

Concordant care in sentinel lymph node omission following Choosing Wisely® recommendations at a comprehensive cancer center.

BACKGROUND: In 2016, the SSO and ABIM released a Choosing Wisely® guideline stating SLNB can be safely omitted in women ≥70 with HR â€‹+ â€‹HER-invasive breast cancer. No study evaluating concordance of care with this guideline has been performed within a comprehensive cancer center. METHODS: From 2005 to 2020, there were 382 patients with cT1-2N0 invasive carcinoma ER+/PR+ and HER2-identified as having undergone SLNB. These patients were then separated into two groups; those in the pre-guideline concordance cohort (2005-2015) and those in the post-guideline concordance (2016-2020) cohort. Axillary management concordance was trended over time. RESULTS: 382 patients from 2005 to 2020 with HR â€‹+ â€‹HER- IBC were identified. No difference was seen in SLNB pre-versus post-guidelines (p â€‹= â€‹0.35). Increased concordance was noted as age increased (p â€‹= â€‹0.0068) and adjuvant radiation therapy exclusion (p â€‹< â€‹0.0001) post-guideline release. Concordance improved over the years post-guideline release (R2 â€‹= â€‹0.45). CONCLUSIONS: Surgical guideline adoption occurs over time but may also be affected by outside decisions and factors. Further study into patterns of guideline adoption may facilitate improving adherence to guidelines.

Negative associations between folate and bacterial vaginosis in the NHANES 2001 to 2004.

BACKGROUND: Bacterial vaginosis (BV) is one of the most common infections among women of reproductive age and accounts for 15-50% of infections globally. The role played by folate in the pathogenesis and progression of BV is poorly understood. The aim of this study was to investigate the association between serum folate, red blood cell (RBC) folate, and BV in American women. METHODS: 1,954 participants from the 2001-2004 National Health and Nutrition Examination Survey (NHANES) program were included in this study. Multiple logistic regression was used to analyze the association between serum folate, RBC folate, and BV, and covariates including race, age, education level, and body mass index were used to construct adjusted models. Stratified analysis was used to explore the stability of the above associations in different populations. RESULTS: In the present cross-sectional study, we found that serum folate and RBC folate were inversely associated with the risk of BV. In the fully adjusted model, the risk of BV was reduced by 35% (OR=0.65, 95% CI: 0.51~0.83, p=0.0007) in the highest serum folate group and 32% (OR=0.68, 95% CI: 0.53~0.87, p=0.0023) in the highest RBC folate group compared to the lowest group. CONCLUSIONS: The results of this study indicated that serum folate and RBC folate were inversely associated with the risk of BV folate supplementation may play an important role in the prevention and management of BV.

Patient Survival With and Without Radiation Therapy for Early-Stage Diffuse Large B-Cell Lymphoma in the Era of PET and Rituximab.

Purpose: The benefit of radiation therapy (RT) becomes uncertain in the treatment of early stage diffuse large B-cell lymphoma (DLBCL) in the era of rituximab, positron emission topography (PET), and computed tomography (CT). We sought to retrospectively review modern patients with early stage I-II DLBCL treated with rituximab and staged by PET-CT to better define which patients benefit from consolidative RT. Methods and Materials: Patients with early stage I-II DLBCL from 1998 to 2017 were reviewed coinciding with our institutional utilization of rituximab with the standard regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone and PET-CT. Relevant clinical information was used to calculate National Comprehensive Cancer Network international prognostic index (IPI) scores. Kaplan-Meier survival analysis and a Cox proportional hazards model were used for overall survival (OS). Results: Seventy-seven patients received chemoimmunotherapy alone, and 41 received chemoimmunotherapy plus RT. Median follow-up time was 9.5 years. On univariate analysis, extranodal disease (P = .04) and National Comprehensive Cancer Network IPI (P < .001) were significantly correlated with OS. Five-year OS was 87% versus 67%, and 10-year OS was 67% versus 58%, numerically higher favoring RT (P = .16). On multivariate Cox regression analysis of OS controlling for IPI and extranodal disease, the addition of RT was associated with improved OS (hazard ratio of 0.4, P = .01). Conclusions: The current analysis supports the use of consolidative RT in early stage DLBCL given an OS benefit on multivariate analysis. Further prospective randomized data are needed to confirm these findings.

[Pharmacodynamics and intestinal flora research on different processed products of Puerariae Lobatae Radix and Puerariae Thomsonii Radix].

This study aims to explore the pharmacodynamic differences of Puerariae Lobatae Radix(PLR), Puerariae Thomsonii Radix(PTR) and their different processed products and the influences of these medical materials on the diversity of intestinal flora. The Sennae Folium-induced diarrhea model, streptozotocin(STZ)-induced diabetes model and L-nitro-arginine methyl ester(L-NAME)-induced hypertension model were used to compare the pharmacodynamic differences in anti-diarrhea, blood glucose reduction and blood pressure lowering among raw, roasted and vinegar-processed PLR and PTR. The effects of raw and processed PLR and PTR on intestinal flora diversity of rats were evaluated by 16 S rDNA high-throughput sequencing. The roasted PLR and PTR performed better in anti-diarrhea, especially the former. PLR and its processed products all presented the efficacy of reducing blood glucose, and the vinegar-processed PLR was the most outstanding. The raw PTR was not that effective in reducing blood glucose, whereas its efficacy was improved after roasting and vinegar processing. Both PLR and PTR were capable of lowering blood pressure to a certain extent, and PLR is superior to PTR in this aspect. Further, the vinegar-processed PLR showed the best effect. The diversity of intestinal flora was different among rats to which different products of PLR and PTR were administered. The roasted PLR led to the highest abundance of Lactobacillus, which was closely related to its best antidiarrheal effect. The highest abilities of vinegar-processed PLR to lower blood glucose and blood pressure were associated with the high abundance of Blautia and Prevotella_9. This study lays a foundation for elucidating the processing mechanisms of PLR and PTR and provides a basis for their further development and application.

An Ultrahigh Sensitive Paper-Based Pressure Sensor with Intelligent Thermotherapy for Skin-Integrated Electronics.

Porous microstructure pressure sensors that are highly sensitive, reliable, low-cost, and environment-friendly have aroused wide attention in intelligent biomedical diagnostics, human-machine interactions, and soft robots. Here, an all-tissue-based piezoresistive pressure sensor with ultrahigh sensitivity and reliability based on the bottom interdigitated tissue electrode and the top bridge of a microporous tissue/carbon nanotube composite was proposed. Such pressure sensors exhibited ultrahigh sensitivity (≈1911.4 kPa-1), fast response time (<5 ms), low fatigue of over 2000 loading/unloading cycles, and robust environmental degradability. These enabled sensors can not only monitor the critical physiological signals of the human body but also realize electrothermal conversion at a specific voltage, which enhances the possibility of creating wearable thermotherapy electronics for protecting against rheumatoid arthritis and cervical spondylosis. Furthermore, the sensor successfully transmitted wireless signals to smartphones via Bluetooth, indicating its potential as reliable skin-integrated electronics. This work provides a highly feasible strategy for promoting high-performance wearable thermotherapy electronics for the next-generation artificial skin.

Altered anxiety and social behaviors in a mouse model of Fragile X syndrome treated with hyperbaric oxygen therapy.

Fragile X syndrome (FXS) is a common mental retardation syndrome. Anxiety and abnormal social behaviors are prominent features of FXS in humans. To better understand the effects of hyperbaric oxygen therapy (HBOT) on these behaviors, we analyzed anxiety-related and social behaviors in Fmr1 knockout mice treated by HBOT. In the open field test, HBOT group mice preferred the periphery to central areas and tended to run or walk along the wall. The results suggested that thigmotaxis was significantly increased in the HBOT group compared with the control group. In the elevated plus maze test, the percentage of distance traveled was significantly increased in the open arm and significantly decreased in the closed arm for HBOT group mice compared with control group mice. These results suggested that HBOT group mice displayed enhanced motor activity in the open arm and exhibited fewer anxiety-related behaviors. In the three-chambered social approach test, the HBOT group mice made more approaches to the wire cup containing an acquaintance mouse than control group mice in the sociability test and made more approaches to the wire cup containing a stranger mouse than control group mice in the social novelty preference test. The results suggested that HBOT group mice showed increased levels of social interaction and decreased "social anxiety" than the control group to partner mice in this test. Our findings indicated that HBOT resulted in altered anxiety and social behavior in Fmr1 knockout mice and could possibly be used as a treatment for FXS.

Comparison of acupuncture and other drugs for chronic constipation: A network meta-analysis.

The objective of this study was to compare the efficacy and side effects of acupuncture, sham acupuncture and drugs in the treatment of chronic constipation. Randomized controlled trials (RCTs) assessing the effects of acupuncture and drugs for chronic constipation were comprehensively retrieved from electronic databases (such as PubMed, Cochrane Library, Embase, CNKI, Wanfang Database, VIP Database and CBM) up to December 2017. Additional references were obtained from review articles. With quality evaluations and data extraction, a network meta-analysis (NMA) was performed using a random-effects model under a frequentist framework. A total of 40 studies (n = 11032) were included: 39 were high-quality studies and 1 was a low-quality study. NMA showed that (1) acupuncture improved the symptoms of chronic constipation more effectively than drugs; (2) the ranking of treatments in terms of efficacy in diarrhoea-predominant irritable bowel syndrome was acupuncture, polyethylene glycol, lactulose, linaclotide, lubiprostone, bisacodyl, prucalopride, sham acupuncture, tegaserod, and placebo; (3) the ranking of side effects were as follows: lactulose, lubiprostone, bisacodyl, polyethylene glycol, prucalopride, linaclotide, placebo and tegaserod; and (4) the most commonly used acupuncture point for chronic constipation was ST25. Acupuncture is more effective than drugs in improving chronic constipation and has the least side effects. In the future, large-scale randomized controlled trials are needed to prove this. Sham acupuncture may have curative effects that are greater than the placebo effect. In the future, it is necessary to perform high-quality studies to support this finding. Polyethylene glycol also has acceptable curative effects with fewer side effects than other drugs.

Reduced deformability of parasitized red blood cells as a biomarker for anti-malarial drug efficacy.

BACKGROUND: Malaria remains a challenging and fatal infectious disease in developing nations and the urgency for the development of new drugs is even greater due to the rapid spread of anti-malarial drug resistance. While numerous parasite genetic, protein and metabolite biomarkers have been proposed for testing emerging anti-malarial compounds, they do not universally correspond with drug efficacy. The biophysical character of parasitized cells is a compelling alternative to these conventional biomarkers because parasitized erythrocytes become specifically rigidified and this effect is potentiated by anti-malarial compounds, such as chloroquine and artesunate. This biophysical biomarker is particularly relevant because of the mechanistic link between cell deformability and enhanced splenic clearance of parasitized erythrocytes. METHODS: Recently a microfluidic mechanism, called the multiplexed fluidic plunger that provides sensitive and rapid measurement of single red blood cell deformability was developed. Here it was systematically used to evaluate the deformability changes of late-stage trophozoite-infected red blood cells (iRBCs) after treatment with established clinical and pre-clinical anti-malarial compounds. RESULTS: It was found that rapid and specific iRBC rigidification was a universal outcome of all but one of these drug treatments. The greatest change in iRBC rigidity was observed for (+)-SJ733 and NITD246 spiroindolone compounds, which target the Plasmodium falciparum cation-transporting ATPase ATP4. As a proof-of-principle, compounds of the bisindole alkaloid class were screened, where cladoniamide A was identified based on rigidification of iRBCs and was found to have previously unreported anti-malarial activity with an IC50 lower than chloroquine. CONCLUSION: These results demonstrate that rigidification of iRBCs may be used as a biomarker for anti-malarial drug efficacy, as well as for new drug screening. The novel anti-malarial properties of cladoniamide A were revealed in a proof-of-principle drug screen.

Microfluidic cell-phoresis enabling high-throughput analysis of red blood cell deformability and biophysical screening of antimalarial drugs.

Changes in red blood cell (RBC) deformability are associated with the pathology of many diseases and could potentially be used to evaluate disease status and treatment efficacy. We developed a simple, sensitive, and multiplexed RBC deformability assay based on the spatial dispersion of single cells in structured microchannels. This mechanism is analogous to gel electrophoresis, but instead of transporting molecules through nano-structured material to measure their length, RBCs are transported through micro-structured material to measure their deformability. After transport, the spatial distribution of cells provides a readout similar to intensity bands in gel electrophoresis, enabling simultaneous measurement on multiple samples. We used this approach to study the biophysical signatures of falciparum malaria, for which we demonstrate label-free and calibration-free detection of ring-stage infection, as well as in vitro assessment of antimalarial drug efficacy. We show that clinical antimalarial drugs universally reduce the deformability of RBCs infected by Plasmodium falciparum and that recently discovered PfATP4 inhibitors, known to induce host-mediated parasite clearance, display a distinct biophysical signature. Our process captures key advantages from gel electrophoresis, including image-based readout and multiplexing, to provide a functional screen for new antimalarials and adjunctive agents.

[The effect of rhubarb ethanol-extract on hyperlipidemia and liver fatty in rabbits].

AIM: To observe the effect of rhubarb ethanol-extract on hyperlipidemia and liver fatty in rabbits. METHODS: Thirty healthy male white rabbits were divided randomly into five groups, six rabbits in each group. The rabbits in control group were fed with common forage. The rabbits in model group were fed with high lipid forage. The rabbits in three different rhubarb groups were fed with high lipid forage and treated with different level rhubarb ethanol-extract (REE). In the process of experiment, periodically measured serology index of the rabbits and observed common physiology index. The rabbits were killed at the end of tenth week, liver fatty degeneration degree and liver coefficient were measured and compared. RESULTS: REE could decrease serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), and increase serum high density lipoprotein cholesterol (HDL-C), and reduce liver fatty de generation and protect liver cell function. And the dose-effect relation was showed among different dose REE groups. CONCLUSION: REE can significantly reduce blood lipid, prevent and treat hyperlipidemia and liver fatty.

[Effects of extracts from different parts of Folium perillae (L.) Britt. on Hemorrheological parameters in rats].

In order to provide experimental data for the development and application of drug in clinic, we determined the effects of extracts from different parts of folium perillae (L. ) Britt. on hemorheological parameters, extracted from leaves (folium perillae), seeds (fructus perillae) and peduncles (caulis perillae). The results showed that all extracts from different parts of folium perillae (L. ) Britt. can significantly reduce the whole blood viscosity at low shear rate (10 s(-1)), erythrocyte aggregation index, erythrocyte electrophoresis index (P<0.05), and the whole blood reductive viscosity at low shear rate (10 s(-1)) (P<0.01). Extracts from folium perillae and caulis perillae can significantly decrease erythrocyte deformation index (P<0.05), whereas extracts from fructus perillae can not. Extracts from fructus perillae and caulis perillae can significantly decrease plasma viscosity at low shear rate(10 s(-1)), but extracts of folium perillae can not. Aspirin can only decrease the whole blood reductive viscosity at low shear rate and plasma viscosity (P<0.05). All extracts from different parts of folium perillae (L. ) Britt. had no significant effects on hematocrit, erythrocyte rigidity index, fibrinogen concentration , the whole blood viscosity and the whole blood reductive viscosity at middle and high shear rate (60 s(-1),120 s(-1)).