Gonzalezstiles4580

One potential benefit of neoadjuvant therapy (NAT) in node-positive, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) patients is axillary downstaging to avoid axillary dissection.

The aim of this study was to evaluate axillary response to NAT with chemotherapy (NCT) or endocrine therapy (NET) and identify potential predictors of response.

A prospectively collected database was queried for node-positive, ER+, HER2- breast cancer patients treated with NAT and surgery from January 2011 to September 2020. Axillary response was categorized into pathologic complete response (pCR) versus no pCR, and was correlated to demographic and clinicopathologic parameters in a logistic regression model.

A cohort of 176 eligible patients was identified and 178 breast cancers were included in the study. The overall axillary pCR rate was 12.3% (22/178). NCT and NET achieved response rates of 13.9% (19/137) and 7.3% (3/41), respectively (p=0.232). A significantly higher axillary pCR rate was identified in patients with clinical stage II at diagnosis (12/60, 20%) compared with stage III (10/118, 8.4%; p=0.03). NET patients with ypN0 were younger and were treated for a longer period of time (>6months). Completion axillary dissection was omitted in the majority (73.7%) of NCT patients achieving axillary pCR.

For patients with node-positive, ER+, HER2- breast cancer, a lower burden of disease at the time of diagnosis (stage II) is associated with a significantly higher axillary pCR, enabling those patients to be spared axillary dissection. Further studies are necessary to define the role of genomic profiling in predicting axillary response.

For patients with node-positive, ER+, HER2- breast cancer, a lower burden of disease at the time of diagnosis (stage II) is associated with a significantly higher axillary pCR, enabling those patients to be spared axillary dissection. Further studies are necessary to define the role of genomic profiling in predicting axillary response.

Long-term exposure to PM

(particulate matter with an aerodynamic diameter of ≤ 2.5μm) is associated with pulmonary injury and emphysema in patients with chronic obstructive pulmonary disease (COPD). We investigated mechanisms through which the long noncoding RNA lnc-IL7R contributes to cellular damage by inducing oxidative stress in COPD patients exposed to PM

.

Associations of serum lnc-IL7R levels with lung function, emphysema, and previous PM

exposure in COPD patients were analyzed. Reactive oxygen species and lnc-IL7R levels were measured in PM

-treated cells. The levels of lnc-IL7R and cellular senescence-associated genes, namely p16

and p21

, were determined through lung tissue section staining. The effects of p16

or p21

regulation were examined by performing lnc-IL7R overexpression and knockdown assays. The functions of lnc-IL7R-mediated cell proliferation, cell cycle, senescence, colony formation, and apoptosis were examined in cells treated with PM

. Chromatin immunoprecipitation assays were conducted to investigate the epigenetic regulation of p21

.

Lnc-IL7R levels decreased in COPD patients and were negatively correlated with emphysema or PM

exposure. Lnc-IL7R levels were upregulated in normal lung epithelial cells but not in COPD cells exposed to PM

. Lower lnc-IL7R expression in PM

-treated cells induced p16

and p21

expression by increasing oxidative stress. Higher lnc-IL7R expression protected against cellular senescence and apoptosis, whereas lower lnc-IL7R expression augmented injury in PM

-treated cells. Lnc-IL7R and the enhancer of zeste homolog 2 (EZH2) synergistically suppressed p21

expression through epigenetic modulation.

Lnc-IL7R attenuates PM

-mediated p21

expression through EZH2 recruitment, and its dysfunction may augment cellular injury in COPD.

Lnc-IL7R attenuates PM2.5-mediated p21CIP1/WAF1 expression through EZH2 recruitment, and its dysfunction may augment cellular injury in COPD.Hip fracture data were retrieved from electronical medical records for the years 2017-2019 in the State of Qatar and used to create a FRAX® model to facilitate fracture risk assessment. Hip fracture rates were comparable with estimates from Saudi Arabia, Abu Dhabi, and Kuwait but fracture probabilities varied due to differences in mortality.

This paper describes the epidemiology of osteoporotic fractures in the State of Qatar that was used to develop the country-specific fracture prediction FRAX® tool.

Hip fracture data were retrieved from electronic medical records for the years 2017-2019 in the State of Qatar. The age and sex specific incidence of hip fracture in Qatari residents and national mortality rates were used to create a FRAX® model. Fracture probabilities were compared with those from neighboring countries having FRAX models.

Hip fracture rates were comparable with estimates from Saudi Arabia, Abu Dhabi and Kuwait. In contrast, probabilities of a major osteoporotic fracture or hip fracture were lower in Qatar than in Kuwait but higher than those in Abu Dhabi and Saudi Arabia due to differences in mortality.

The FRAX model should enhance accuracy of determining fracture probability among the Qatari population and help guide decisions about treatment.

The FRAX model should enhance accuracy of determining fracture probability among the Qatari population and help guide decisions about treatment.

Monocentric, prospective, observational study.

The clinical relevance of bacterial colonization of intervertebral discs is controversial. This study aimed to determine a possible relationship between bacterial and viral colonization and low-grade infection of the discs.

We investigated 447 disc samples from 392 patients. Microbiological culture was used to examine the samples for bacterial growth, polymerase chain reaction (PCR) was used for detection of herpes simplex virus types 1 and 2 (HSV-1, HSV-2) and Cytomegalovirus (CMV), and histopathological analysis was used to detect signs of inflammation. The results were compared between subgroups organized according to gender, age, location of the samples, surgical approach, preoperative C-reactive protein (CRP), preoperative and 6 months postoperative Oswestry Disability Index (ODI) and Neck Disability Index (NDI), and Modic changes (MC) of the corresponding endplates. TJM20105 Also, we assessed the occurrence of postoperative infections within 6 months.

Microbf further investigations.

III.

The study was registered at ClinicalTrials.gov (ID NCT04712487, https//www.

gov/ct2/show/study/NCT04712487 ).

gov/ct2/show/study/NCT04712487 ).Tendon injuries positively correlate with patient age, as aging has significant effects on tendon homeostatic maintenance and healing potential after injury. Vascularity is also influenced by age, with both clinical and animal studies demonstrating reduced blood flow in aged tissues. However, it is unknown how aging effects vascularity following tendon injury, and if this vascular response can be modulated through the delivery of angiogenic factors. Therefore, the objective of this study is to evaluate the vascular response following Achilles tendon injury in adult and aged rats, and to define the alterations to tendon healing in an aged model following injection of angiogenic factors. It was determined that aged rat Achilles tendons have a reduced angiogenesis following injury. Further, the delivery of vascular endothelial growth factor, VEGF, caused an increase in vascular response to tendon injury and improved mechanical outcome in this aged population. This work suggests that reduced angiogenic potential with aging may be contributing to impaired tendon healing response and that the delivery of angiogenic factors can rescue this impaired response. This study was also the first to relate changes in vascular response in an aged model using in vivo measures of blood perfusion to alterations in healing properties.In this work we present a new physics-informed machine learning model that can be used to analyze kinematic data from an instrumented mouthguard and detect impacts to the head. Monitoring player impacts is vitally important to understanding and protecting from injuries like concussion. Typically, to analyze this data, a combination of video analysis and sensor data is used to ascertain the recorded events are true impacts and not false positives. In fact, due to the nature of using wearable devices in sports, false positives vastly outnumber the true positives. Yet, manual video analysis is time-consuming. This imbalance leads traditional machine learning approaches to exhibit poor performance in both detecting true positives and preventing false negatives. Here, we show that by simulating head impacts numerically using a standard Finite Element head-neck model, a large dataset of synthetic impacts can be created to augment the gathered, verified, impact data from mouthguards. This combined physics-informed machine learning impact detector reported improved performance on test datasets compared to traditional impact detectors with negative predictive value and positive predictive values of 88 and 87% respectively. Consequently, this model reported the best results to date for an impact detection algorithm for American football, achieving an F1 score of 0.95. In addition, this physics-informed machine learning impact detector was able to accurately detect true and false impacts from a test dataset at a rate of 90% and 100% relative to a purely manual video analysis workflow. Saving over 12 h of manual video analysis for a modest dataset, at an overall accuracy of 92%, these results indicate that this model could be used in place of, or alongside, traditional video analysis to allow for larger scale and more efficient impact detection in sports such as American Football.Coronary microvascular endothelial dysfunction is both a culprit and a victim of diabetes, and can accelerate diabetes-related microvascular and macrovascular complications by promoting vasoconstrictive, pro-inflammatory and pro-thrombotic responses. Perturbed mitochondrial function induces oxidative stress, disrupts metabolism and activates apoptosis in endothelial cells, thus exacerbating the progression of coronary microvascular complications in diabetes. The mitochondrial quality surveillance (MQS) system responds to stress by altering mitochondrial metabolism, dynamics (fission and fusion), mitophagy and biogenesis. Dysfunctional mitochondria are prone to fission, which generates two distinct types of mitochondria one with a normal and the other with a depolarized mitochondrial membrane potential. Mitochondrial fusion and mitophagy can restore the membrane potential and homeostasis of defective mitochondrial fragments. Mitophagy-induced decreases in the mitochondrial population can be reversed by mitochondrial biogenesis. MQS abnormalities induce pathological mitochondrial fission, delayed mitophagy, impaired metabolism and defective biogenesis, thus promoting the accumulation of unhealthy mitochondria and the activation of mitochondria-dependent apoptosis. In this review, we examine the effects of MQS on mitochondrial fitness and explore the association of MQS disorders with coronary microvascular endothelial dysfunction in diabetes. We also discuss the potential to treat diabetes-related coronary microvascular endothelial dysfunction using novel MQS-altering drugs.