Single-cell and spatial profiling identify three response trajectories to pembrolizumab and radiation therapy in triple negative breast cancer.

Strategies are needed to better identify patients that will benefit from immunotherapy alone or who may require additional therapies like chemotherapy or radiotherapy to overcome resistance. Here we employ single-cell transcriptomics and spatial proteomics to profile triple negative breast cancer biopsies taken at baseline, after one cycle of pembrolizumab, and after a second cycle of pembrolizumab given with radiotherapy. Non-responders lack immune infiltrate before and after therapy and exhibit minimal therapy-induced immune changes. Responding tumors form two groups that are distinguishable by a classifier prior to therapy, with one showing high major histocompatibility complex expression, evidence of tertiary lymphoid structures, and displaying anti-tumor immunity before treatment. The other responder group resembles non-responders at baseline and mounts a maximal immune response, characterized by cytotoxic T cell and antigen presenting myeloid cell interactions, only after combination therapy, which is mirrored in a murine model of triple negative breast cancer.

Fatty Acids: An Insight into the Pathogenesis of Neurodegenerative Diseases and Therapeutic Potential.

One of the most common lipids in the human body is palmitic acid (PA), a saturated fatty acid with essential functions in brain cells. PA is used by cells as an energy source, besides being a precursor of signaling molecules and protein tilting across the membrane. Although PA plays physiological functions in the brain, its excessive accumulation leads to detrimental effects on brain cells, causing lipotoxicity. This mechanism involves the activation of toll-like receptors (TLR) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, with the consequent release of pro-inflammatory cytokines, increased production of reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, and autophagy impairment. Importantly, some of the cellular changes induced by PA lead to an augmented susceptibility to the development of Alzheimer's and Parkinson´s diseases. Considering the complexity of the response to PA and the intrinsic differences of the brain, in this review, we provide an overview of the molecular and cellular effects of PA on different brain cells and their possible relationships with neurodegenerative diseases (NDs). Furthermore, we propose the use of other fatty acids, such as oleic acid or linoleic acid, as potential therapeutic approaches against NDs, as these fatty acids can counteract PA's negative effects on cells.

Rigidity coincides with reduced cognitive control to affective cues in children with autism.

The present study tested whether salient affective cues would negatively influence cognitive control in children with and without autism spectrum disorder (ASD). One hundred children aged 6-12 years who were either typically developing or had ASD performed a novel go/no-go task to cues of their interest versus cues of noninterest. Linear mixed-effects (LME) models for hit rate, false alarms, and the sensitivity index d' were used to test for group differences. Caregivers completed the Repetitive Behavior Scale-Revised to test associations between repetitive behaviors and task performance. Children with ASD had reduced cognitive control toward their interests compared with typically developing children. Further, children with ASD showed reduced cognitive control to interests compared with noninterests, a pattern not observed in typically developing children. Decreased cognitive control toward interests was associated with higher insistence on sameness behavior in ASD, but there was no association between sameness behavior and cognitive control for noninterests. Together, children with ASD demonstrated decreased cognitive flexibility in the context of increased affective salience related to interests. These results provide a mechanism for how salient affective cues, such as interests, interfere with daily functioning and social communication in ASD. Further, the findings have broader clinical implications for understanding how affective cues can drive interactions between restricted patterns of behavior and cognitive control. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Administer but Do Not Dispense: Effect of Change in Medication Handling by Nurses on Outcomes of Home Dialysis Patients.

BACKGROUND: To come into compliance with South Carolina statute, we changed how nurses handle medications (antibiotics, erythropoietin [EPO], calcitriol and heparin) in our outpatient home dialysis clinic. Nurses continued to administer medications in the clinic but no longer dispensed medications for patients to take home; instead, medications were dispensed from pharmacies to the patients by mail. We hypothesized that the abovementioned change in medication handling worsened clinical outcomes. There is very little medical literature on this topic. MATERIALS AND METHODS: A retrospective case series of quality and safety in 31 patients in a community-based, medical center-affiliated home dialysis program was performed. We compared laboratory values and adverse clinical events relevant to the medications mentioned above during 4-8 months before and during 5 months after September 1, 2014 (the day when medication handling was changed). RESULTS: We observed no changes in the incidences of dialysis access dysfunction, access infections, antibiotic inaccessibility to patients for access-related infections, infection outcomes, parathyroid hormone concentrations, hemoglobin concentrations, monthly EPO dose and missed monthly clinic visits after September 1, 2014. However, we noted significantly fewer subcutaneous EPO administrations per month and less time between phlebotomy and laboratory review with patients by their nephrologists at monthly clinic visits after September 1, 2014. CONCLUSIONS: The change in handling of medications by nurses in our outpatient home dialysis program to comply with the state statute did not worsen patient outcomes relevant to the affected medications and in fact caused several unexpected improvements.

Early results from a United States trial of prostatic artery embolization in the treatment of benign prostatic hyperplasia.

PURPOSE: To report early findings from a prospective United States clinical trial to evaluate the efficacy and safety of prostatic artery embolization (PAE) for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: From January 2012 to March 2013, 72 patients were screened and 20 patients underwent treatment. Patients were evaluated at baseline and selected intervals (1, 3, and 6 mo) for the following efficacy variables: American Urological Association (AUA) symptom score, quality of life (QOL)-related symptoms, International Index of Erectile Function score, peak urine flow rate, and prostate volume (on magnetic resonance imaging at 6 mo). Complications were monitored and reported per Society of Interventional Radiology guidelines. RESULTS: Embolization was technically successful in 18 of 20 patients (90%); bilateral PAE was successful in 18 of 19 (95%). Unsuccessful embolizations were secondary to atherosclerotic occlusion of prostatic arteries. Clinical success was seen in 95% of patients (19 of 20) at 1 month, with average AUA symptom score improvements of 10.8 points at 1 month (P < .0001), 12.1 points at 3 months (P = .0003), and 9.8 points at 6 months (P = .06). QOL improved at 1 month (1.9 points; P = .0002), 3 months (1.9 points; P = .003), and 6 months (2.6 points; P = .007). Sexual function improved by 34% at 1 month (P = .11), 5% at 3 months (P = .72), and 16% at 6 months (P = .19). Prostate volume at 6 months had decreased 18% (n = 5; P = .05). No minor or major complications were reported. CONCLUSIONS: Early results from this clinical trial indicate that PAE offers a safe and efficacious treatment option for men with BPH.

Neuropsychological assessment of decision making in alcohol-dependent commercial pilots.

BACKGROUND: The aim of this exploratory archival study was to discern the utility of the Iowa Gambling Task (IGT) in identifying adaptive decision-making capacities among pilots with a history of alcohol dependence both with and without Cluster B personality features. METHODS: Participants included 18 male airmen at the rank of captain with a history of receiving alcohol dependence treatment and subsequent referral for a fitness-for-duty evaluation. Data from prior comprehensive neuropsychological evaluations conducted in a private practice setting at the mandate of the FAA utilizing criteria outlined in the HIMS program was used. ANOVA was conducted to compare pilots with (N = 4) and without Cluster B personality features (N = 14) on measures of decisionmaking capacities, intelligence, and executive functioning. RESULTS: Pilots with Cluster B personality features were found to have a significantly lower Total Net T-Score on IGT (M = 35.00, SD = 9.27) than pilots without features of Cluster B (M = 56.36, SD = 9.55). Furthermore, with the exception of the first 20 cards (i.e., Net 1); the groups significantly differed in their Net scores. No statistically significant difference was found on airmen's intelligence and executive functioning. DISCUSSION: The present study found that alcohol-dependent airmen with Cluster B personality features evidenced significantly poorer decisionmaking capacities as measured by the ICT in comparison to alcohol dependent airman without Cluster B personality features. Implications and limitations of the study are discussed.

Emotional competence and behavior problems: Differences across Preschool Assessment of Attachment classifications.

This study examined attachment in association with preschoolers' emotional functioning among 54 predominantly low-income families living in Appalachia. Attachment was assessed at age 4 years using the Strange Situation (Ainsworth, Blehar, Waters, & Wall, 1978) and classified with the PAA (Crittenden, 2004). Emotional competence was measured via an interview about children's memories for six emotions, rated in terms of both emotion understanding and regulation. Parent-, teacher-, and self-reports of children's internalizing and externalizing symptoms were also completed. Questionnaires and interviews assessed socioeconomic risk and parental symptoms and negative childhood experiences. Children's PAA strategies were significantly associated with risks, emotion regulation and understanding, and symptoms. Children using highly coercive strategies showed the greatest difficulties. Emotion regulation and understanding also were associated with parent- and teacher-report of symptoms. These findings suggest that intervention efforts with at-risk youngsters should target not only attachment security, but also emotional competence skills.