NSF workshop report: Discovering general principles of nervous system organization by comparing brain maps across species

Efforts to understand nervous system structure and function have received new impetus from the federal Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Comparative analyses can contribute to this effort by leading to the discovery of general principles of neural circuit design, information processing, and gene‐structure‐function relationships that are not apparent from studies on single species. We here propose to extend the comparative approach to nervous system ‘maps' comprising molecular, anatomical, and physiological data. This research will identify which neural features are likely to generalize across species, and which are unlikely to be broadly conserved. It will also suggest causal relationships between genes, development, adult anatomy, physiology, and, ultimately, behavior. These causal hypotheses can then be tested experimentally. Finally, insights from comparative research can inspire and guide technological development. To promote this research agenda, we recommend that teams of investigators coalesce around specific research questions and select a set of ‘reference species' to anchor their comparative analyses. These reference species should be chosen not just for practical advantages, but also with regard for their phylogenetic position, behavioral repertoire, well‐annotated genome, or other strategic reasons. We envision that the nervous systems of these reference species will be mapped in more detail than those of other species. The collected data may range from the molecular to the behavioral, depending on the research question. To integrate across levels of analysis and across species, standards for data collection, annotation, archiving, and distribution must be developed and respected. To that end, it will help to form networks or consortia of researchers and centers for science, technology, and education that focus on organized data collection, distribution, and training. These activities could be supported, at least in part, through existing mechanisms at NSF, NIH, and other agencies. It will also be important to develop new integrated software and database systems for cross‐species data analyses. Multidisciplinary efforts to develop such analytical tools should be supported financially. Finally, training opportunities should be created to stimulate multidisciplinary, integrative research into brain structure, function, and evolution. J. Comp. Neurol. 522:1445–1453, 2014. © 2014 Wiley Periodicals, Inc.     

Respiratory and vasomotor effects of excitatory amino acid on ventral medullary surface

Three glutamic acid analogues, N-methyl-D-aspartic (NMDA), quisqualic (QQ), and kainic (KAI) acids were applied topically to the ventral surface of the medulla (VMS) in paralyzed, vagotomized and carotid sinus denervated cats hyperventilated to apnea. Respiratory and vasomotor effects were assessed by changes in phrenic nerve activity and systemic arterial blood pressure. All three agents to varying degrees raised systemic blood pressure, but only NMDA consistently initiated phrenic nerve activity at pCO2 levels below that observed in control trials. KAI and QQ raised blood pressure even in those animals in which they had little effect on initiating phrenic nerve activity. Furthermore, respiratory responses were obtained from localized areas on VMS, namely the intermedio-caudal zone (I-C areas); whereas blood pressure elevations could be obtained from wider VMS areas including the rostral zone (R areas). In addition, the effects of the three amino acids on blood pressure were quantitatively different with KAI causing much greater increases in blood pressure than QQ or NMDA. The respiratory and vasomotor effects of NMDA and QQ were blocked by the use of 2-amino-5-phosphonovaleric acid and L-glutamic acid diethylester, their respective antagonists. The results suggest that neurons in the VMS which cause respiratory and vasomotor responses are not identical. Cells containing receptors stimulated by NMDA predominantly increase respiration, whereas cells containing receptors excited by KAI are more effective in eliciting vasomotor responses.     

Real-World Treatment Patterns and Clinical Effectiveness of Palbociclib Plus an Aromatase Inhibitor as First-Line Therapy in Advanced/Metastatic Breast Cancer: Analysis from the US Syapse Learning Health Network

This retrospective single-arm study assessed real-world treatment patterns and clinical outcomes in patients with hormone receptor—positive/human epidermal growth factor receptor 2—negative (HR+/HER2−) advanced/metastatic breast cancer (A/MBC) who received palbociclib plus an aromatase inhibitor as first-line therapy in US community health systems. Using electronic health records from the Syapse Learning Health Network, 242 patients were identified as having received first-line palbociclib plus an aromatase inhibitor between 3 February 2015, and 31 July 2019 (data cutoff 1 February 2020) resulting in a minimum potential 6-month follow-up period. In total, 56.6% of patients had de novo A/MBC at initial breast cancer diagnosis, 50.8% had bone-only disease, and 32.2% had visceral disease. Median follow-up was 22.4 months. Disease progression (26.4%) and intolerance/toxicity (14.9%) were the main reasons for treatment discontinuation. The median (95% CI) real-world progression-free survival was 31.7 (27.9—not estimable (NE)) months and 2-year estimated overall survival (OS) rate was 78.0%. In total, 25.6% of patients died; however, OS data are limited by the small population size and insufficient follow-up time. These real-world effectiveness outcomes complement findings from other real-world studies and randomized controlled trials and support palbociclib plus an aromatase inhibitor as first-line therapy for HR+/HER2− A/MBC.     

Impact of body mass index on survival of patients with surgically treated renal cell carcinoma

PURPOSE: Population studies link increased BMI with an increased risk of cancer and cancer mortality and in particular a greater risk of RCC. We evaluated the impact of BMI and other clinical/pathological characteristics on survival in patients with RCC treated with radical or partial nephrectomy. MATERIALS AND METHODS: Between 1995 and 2003 patients undergoing radical (760) or partial (399) nephrectomy for RCC were entered into a database. BMI data were available on 1,137 of 1,159 (98%). Demographic and clinical/pathological parameters were analyzed. World Health Organization BMI definitions (normal-less than 25 kg/m(2), overweight-25 to 29.9 kg/m(2), obese-30 kg/m(2) or more) were used. RESULTS: A total of 75% of patients had greater than normal BMI with 472 (41.5%) overweight and 387 (34.0%) obese. Median followup was 33 months with a median overall survival of 110 months and a 5-year overall survival probability of 0.79. BMI categories were similar in age, gender, smoking status, presenting symptoms, tumor size, stage, and type of surgery. Significant increases in blood loss and operative time (p <0.05) were seen with increasing BMI. Although BMI 30 kg/m(2) or greater was associated with a higher proportion of clear cell histology (p = 0.002), it did not translate into an increased pathological stage, or incidence of metastasis. Multivariate analysis revealed age older than 65 years, systemic symptoms, surgery type, and pathological stage impacted overall survival (p <0.05). CONCLUSIONS: Although an increased BMI was associated with a greater proportion of clear cell histology, comorbidity, and surgical morbidity, BMI did not adversely impact overall or progression-free survival.     

New rat to mouse xenograft transplantation of endometrium as a model of human endometriosis

BackgroundEndometriosis can lead to infertility. Since there is no definitive treatment for endometriosis, animal modelling seems necessary to examine the possible treatments. Mouse endometrium cannot be separated for endometriosis induction. In addition, transplantation of uterus into the abdominal viscera to induce endometriosis causes organ damage. In this study, we defined a new model of endometriosis leading to separability of endometrium and a safe anatomical region for transplantation.MethodsForty female mice were allocated to 5 groups: 1, sham; 2, allograft uterus transplantation of mice to anterior abdominal wall of mice; 3, allograft uterus transplantation of mice to mesentery of mice; 4, xenograft endometrial transplantation of rat to anterior abdominal wall of mice; 5, xenograft endometrial transplantation of rat to mesentery of mice. Adult female rats with a previous pregnancy experience were selected and placed in the vicinity of male rats for 2 weeks to induce estrogen secretion and increase endometrial thickness.ResultsIn the 4th group of animals, compared to sham, the peritoneal concentrations of VEGF‐A, TNF‐α, NO, MDA, and serum levels of CA‐125 and IL‐37 were increased and total body weight was decreased, while weight and size of endometrial lesions were increased significantly (P < .05). Genes expression of HOXA10 and HOXA11 were decreased significantly (P < .05) in groups 2 and 4 compared to sham.ConclusionsXenograft transplantation of endometrium from rat to anterior abdominal wall of mice can potentially mimic human endometriosis morphologically, histologically, and genetically.     

Efficacy of Preprocedural Mouth Rinsing in Reducing Aerosol Contamination Produced by Ultrasonic Scaler: A Pilot Study

Background: The aerosol generated by an ultrasonic scaler contains microorganisms that can penetrate into the body through the respiratory system of dental surgeons and patients. The aim of this pilot study is to evaluate and compare the efficacy of commercially available preprocedural mouthrinses containing 0.2% chlorhexidine gluconate, an herbal mouthwash, and water in reducing the levels of viable bacteria in aerosols. Methods: This single‐center, double‐masked, placebo‐controlled, randomized, three‐group parallel design was conducted over a period of 45 days. Twenty‐four patients with chronic periodontitis were divided randomly into three groups (A, B, and C) of eight patients each to receive 0.2% chlorhexidine gluconate, herbal mouthwash, and water, respectively, as a preprocedural rinse. The aerosol produced by the ultrasonic unit was collected at patient's chest area, doctor's chest area, and assistant's chest area on blood agar plates in all three groups. The blood agar plates were incubated at 37°C for 48 hours, and the total number of colony‐forming units (CFUs) was counted and statistically analyzed. Results: The results showed that CFUs in groups A and B were significantly reduced compared with group C, P <0.001 (analysis of variance). Also, CFUs in group A were significantly reduced compared with group B, P <0.05 (independent t‐test). The numbers of CFUs were highest at the patient's chest area and lowest at the assistant's chest area. Conclusion: This study suggests that a routine preprocedural mouthrinse could eliminate the majority of bacterial aerosols generated by the use of an ultrasonic unit, and that 0.2% chlorhexidine gluconate is more effective than herbal mouthwash.     

基底动脉尖卒中

儿童卒中常见［１］,在过去２０年里,抗磷脂抗体（ＡＰＬＡ）一直被认为是缺血性卒中的一个重要原因。在所有缺血性卒中中,以大脑中动脉分布区最为常见,而后循环则最为罕见［２］．本文报告１例ＡＰＬＡ引起的儿童基底动脉尖卒中。ｌ 病例报告 患儿,男,８岁,因发热４天突发失明１２小时人院．无癫■、神志改变、头痛或呕吐史．无眼痛或幻视,入院时发热。全身周围血管搏动正常,血压正常．其他检查未见明显异常。患儿间歇出现嗜睡,双侧眼睑下垂伴完全失明。上视麻痹伴左视时水平震颤加重。瞳孔３ｍｍ,对光反射正常。眼底正常．躯干…