Inheritance of Biomass Yield and Tropane Alkaloid Content in Hyoscyamus muticus

The nature of gene action for biomass yield and tropane alkaloid content was ascertained through diallel analysis in Egyptian henbane, HYOSCYAMUS MUTICUS L. Dominance variation was preponderant over additive genetic variance, dominance being in the overdominance range for both traits. On an overall basis, recessive alleles had a positive (i.e. increasing) effect on both the characters. However, the positive or negative effects of recessive or dominant alleles were genotype-specific. Hence, transgressive breeding was suggested for isolating segregants with dominant alleles for herb yield and with recessives for alkaloid content so as to achieve overall high yields of tropane alkaloid per unit area.     

Within-subject behavioral analysis of recent memory in aging mice

Two experiments addressed the utility of a T-maze, delayed reversal paradigm for assessment of recent memory impairment in aging C57BL/6NNia mice. This paradigm involved acquisition of a learning set for identification of the correct arm choice in a daily multiple-trial discriminated avoidance session. During each session, the correct arm was always opposite that entered on an initial "information trial" and maximal performance thus required a reversal (or "lose-shift") strategy. Once the learning set had been acquired, retention performance was examined following delays of varying length which were introduced following the information trial during each session. In the first experiment, acquisition and retention components of delayed reversal were considered in a cross-sectional study involving separate groups of mice aged 7, 10, 15, or 27 months. Analysis of acquisition components suggested that relative to young mice, the old mice were slower to acquire both the first reversal and the learning set. Analysis of the retention phase suggested that memory decay gradients for goal arm discrimination became more pronounced with increasing age, whereas decay gradients for the avoidance response were similar among the age groups. Correlational analysis of data for the old mice suggested independence of age-related deficits in the acquisition and recent memory components of the delayed reversal paradigm. In the second experiment, survivors from the previous 7- and 10-month-old groups were retested when 27 months of age. The cross-sectional and longitudinal data led to the same conclusions with regard to the effect of age on recent memory function. Overall, these results suggest that the delayed reversal paradigm will be a valuable tool in the analysis and evaluation of interventions potentially affecting age-related cognitive impairment.     

Neurobehavioral biomarkers of aging: influence of genotype and dietary restriction

Because of the importance of central nervous system (CNS) functions to productive capacity and quality of life, biomarkers of these functions will play a key role in evaluating the success of interventions targeting aging processes. The CNS biomarkers may also be useful for predicting aging in other systems and in the organism as a whole. Age-related behavioral changes, the products of CNS aging, have content and predictive validity with respect to human functional capacities and may, therefore, represent important "neurobehavioral" markers of functional aging. This article presents a discussion of some behavioral paradigms which are currently being considered as neurobehavioral biomarkers of aging in mice and the experimental approaches being employed in the assessment of their validity. Studies conducted in the authors' laboratory using dietary restriction and genetic comparisons to evaluate the validity of neurobehavioral biomarkers have revealed several methodological concerns, and hypothetical and empirical examples of these pitfalls are described and discussed. In spite of those concerns, it is concluded that approaches to validity using genetic comparisons and dietary restriction can be successfully implemented and should ultimately lead to identification of valid and useful neurobehavioral biomarkers of aging.     

Favorable prognosis for patients 12 to 18 months of age with stage 4 nonamplified MYCN neuroblastoma: a Children's Cancer Group Study.

PURPOSE: The long-term survival of children between age 12 and 24 months with stage 4 neuroblastoma and nonamplified MYCN (MYCN-NA) has not been defined previously. PATIENTS AND METHODS: Survival for stage 4 MYCN-NA neuroblastoma patients enrolled onto Children's Cancer Group (CCG) protocols 321P2 (1986 to 1991) and 3891 (1991 to 1996) was analyzed. Treatment consisted of intensive alkylator-based induction chemotherapy with or without autologous bone marrow transplantation (ABMT) with or without 13 cis-retinoic acid. Survival was analyzed by age strata less than 12, 12 to 18, 18 to 24, and more than 24 months at diagnosis. Patients younger than 12 months were treated on the moderate-intensity CCG protocol 3881. RESULTS: Forty-three patients with stage 4 MYCN-NA disease enrolled onto CCG-321P2 (n = 17) or CCG-3891 (n = 26) were between 12 and 24 months of age at diagnosis. After a median follow-up of 94 months (range, 4 to 140 months), the 6-year event-free survival (EFS) for the 12- to 18-month age group was superior to that of the 18- to 24-month age group (74% +/- 8% v 31% +/- 12%; P = .008). The EFS for children older than 24 months with stage 4 MYCN-NA neuroblastoma was 23% +/- 3%, and for children younger than 12 months was 92% +/- 3%. CONCLUSION: Children diagnosed with stage 4 MYCN-NA neuroblastoma in the second year of life form a transitional group between infants and older children in terms of prognosis. Patients between 12 and 18 months of age have significantly better long-term survival than that of older children treated with intensive chemotherapy with or without ABMT. These patients may not benefit from additional intensification of therapy beyond that provided in earlier clinical trials and may even maintain this high survival rate with less intensive therapy.     

Synthesis and Structure-Activity Relationships of Vasicine Analogues as Bronchodilatory Agents

The series of vasicine (1) analogues, an alkaloid from Adhatoda vasica Nees., were synthesized with changes in A, B or C rings. Compounds 13-19 were evaluated for in vitro bronchodilatory activity using isolated guinea pig tracheal chain. Compounds 3-8 were also synthesized in good yields using microwave-mediated synthesis under solvent free conditions. Compounds 5 and 8 with seven-member C ring were more active than etofylline and caused 100% relaxation of both the histamine and acetycholine pre-contracted guinea pig tracheal chain. The structure-activity relationship studies showed that the quinazoline and oxo functionalities were essential for activity. The compounds without C ring and instead having aliphatic and phenyl substitutions in B ring showed relaxation against histamine pre-contracted tracheal chain only, 2-methyl substituted analogues, 12 and 13, being most active with 100% relaxation effect.     

Feasibility of Spotlight Consultations Tool in Routine Care: Real-World Evidence

Background:Burnout in people with diabetes and healthcare professionals (HCPs) is at an all-time high. Spotlight AQ, a novel “smart” adaptive patient questionnaire, is designed to improve consultations by rapidly identifying patient priorities and presenting these in the context of best-practice care pathways to aid consultations. We aimed to determine Spotlight AQ’s feasibility in routine care.Materials and Methods:The Spotlight prototype tool was trialed at three centers: two UK primary care centers and one US specialist center (June-September 2020). Participants with type 1 (T1D) or type 2 diabetes (T2D) completed the questionnaire prior to their routine consultations. Results were immediately available and formed the basis of the clinical discussion and decision-making within the clinic visit.Results:A convenience sample of 49 adults took part, n=31 T1D, (n=18 female); and n=18 T2D (n=10 male, n=4 female, n=4 gender unreported). Each identified two priority concerns. “Psychological burden of diabetes” was the most common priority concern (T1D n = 27, 87.1%) followed by “gaining more skills about particular aspects of diabetes” (T1D n=19, 61.3%), “improving support around me” (n=8, 25.8%) and “diabetes-related treatment issues” (n=8, 25.8%). Burden of diabetes was widespread as was lack of confidence around self-management. Similarly, psychological burden of diabetes was the primary concern for participants with T2D (n=18,100%) followed by “gaining more skills about aspects of diabetes” (n=7, 38.9%), “improving support around me” (n=7, 38.9%) and “diabetes-related treatment issues” (n=4; 22.2%).Conclusions:Spotlight AQ is acceptable and feasible for use in routine care. Gaining more skills and addressing the psychological burden of diabetes are high-priority areas that must be addressed to reduce high levels of distress.     

Investigating the Human Host—ssRNA Virus Interaction Landscape Using the SMEAGOL Toolbox

Viruses have evolved numerous mechanisms to exploit the molecular machinery of their host cells, including the broad spectrum of host RNA-binding proteins (RBPs). However, the RBP interactomes of most viruses are largely unknown. To shed light on the interaction landscape of RNA viruses with human host cell RBPs, we have analysed 197 single-stranded RNA (ssRNA) viral genome sequences and found that the majority of ssRNA virus genomes are significantly enriched or depleted in motifs for specific human RBPs, suggesting selection pressure on these interactions. To facilitate tailored investigations and the analysis of genomes sequenced in future, we have released our methodology as a fast and user-friendly computational toolbox named SMEAGOL. Our resources will contribute to future studies of specific ssRNA virus—host cell interactions and support the identification of antiviral drug targets.     

颈动脉粥样硬化疾病的处理——美国血管外科学会临床实践指南

美国血管外科学会（SVS）任命了一个专家委员会制定颈动脉狭窄处理的循证临床指南。在制定临床实践推荐意见过程中，该委员会使用系统评价对当前最佳的证据进行了总结，采用GRADE标准对推荐意见的强度（强烈推荐为GRADEI级，一般推荐为GRADEⅡ级）和证据的质量（高、中、低和极低）进行了分级。对于轻度颈动脉狭窄患者（有症状患者狭窄程度〈50％和无症状患者狭窄程度〈60％），推荐进行最佳的内科治疗而非血管重建术（I级推荐，高质量证据）。对于有症状中到重度狭窄患者（狭窄程度〉150％），推荐行颈动脉内膜切除术（CEA）＋最佳的内科治疗（I级推荐，高质量证据）。对于围手术期风险高的有症状中到重度狭窄患者（狭窄程度≥50％），建议采用颈动脉支架置入术作为其替代治疗手段（Ⅱ级推荐，低质量证据）。对于中到重度狭窄的无症状患者（狭窄程度≥60％），只要围手术期风险较低，就推荐行CEA＋内科治疗（I级推荐，高质量证据）。对于中到重度狭窄的无症状患者（狭窄程度≥60％），不推荐行颈动脉支架置入术（I级推荐，低质量证据）。颈动脉狭窄≥80％但存在CEA高危解剖学风险的患者可能是一个例外。     

Water-soluble optical sensors: keys to detect aluminium in biological environment

Metal ion plays a critical role from enzyme catalysis to cellular health and functions. The concentration of metal ions in a living system is highly regulated. Among the biologically relevant metal ions, the role and toxicity of aluminium in specific biological functions have been getting significant attention in recent years. The interaction of aluminium and the living system is unavoidable due to its high earth crust abundance, and the long-term exposure to aluminium can be fatal for life. The adverse Al³⁺ toxicity effects in humans result in various diseases ranging from cancers to neurogenetic disorders. Several Al³⁺ ions sensors have been developed over the past decades using the optical responses of synthesized molecules. However, only limited numbers of water-soluble optical sensors have been reported so far. In this review, we have confined our discussion to water-soluble Al³⁺ ions detection using optical methods and their utility for live-cell imaging and real-life application.

Aluminium ion plays a critical role in cellular health. Therefore, its detection in water is highly demanding.