Structural studies of some heterocyclic and organometallic compounds

Single crystal X-ray work was carried out for four heterocyclic compounds: prior to this, definitive structures could not be written for any of these. The heterocyclic compounds reported are: 5,6-dihydro-1-thiobenzoylmethylene-1H-thiazolo[2,3-c][1,2,4] thiadiazole, (I); 4-N-(4'-bromophenylamino)-3-butylfuroxan, (II); 4,4'-methylenebis(1,3,5-trimethyl-4-imidazolin-2-one), (III), and 4-phenyl-3-phenylamino-1,2,4-thiadiazoline-5-one, (IV). These are then discussed, along with work which has been carried out for similar compounds. Trithiapentalenes and analogues having linear multisulphur systems are mentioned as criteria for deciding whether the NSS skeleton in (I) is best considered as N-S...S or N-S-S. Following this, the X-ray structure determinations of bis(4-methylpyridine)hydrogen(I) tetraphenylborate, (V), and bis(triphenylarsineoxide)hydrogen(I) tetrafluoroborate, (VI), arereported. Both (V) and (VI) are bis-cations which have strong hydrogen bonding. Other compounds with short 0...H...0 and N...H...N distances are mentioned, stabilities of such bis-cations compared to those of the monocations, and (amine-halogen-amine)⁺ complexes discussed. The final two X-ray structure determinations are for the compounds 1,1,1,3,3,3-hexaphenyldisilazane and µ-nitrido-bis (triphenylphosphorus)((I) thiocyanate. MNDO was used to calculate force constants for bending of linear molecular pseudohalides. The aim of such work was to rationalise 'unusual' geometries in some silicon-containing compounds via Second Order Jahn-Teller distortions, postulating that such compounds are easily distorted along a "soft' normal vibration coordinate

Prevalence of preterm, low birthweight, and small for gestational age delivery after breast cancer diagnosis: a population-based study

Abstract Background Black-white disparities in breast cancer incidence rates and birth outcomes raise concerns about potential disparities in the reproductive health of premenopausal breast cancer survivors. We examined the prevalence of preterm birth (PTB), low birthweight (LBW), and small for gestational age (SGA) by breast cancer history and effect modification by race. Methods We analyzed linked North Carolina birth records and Central Cancer Registry files from 1990 to 2009 (n = 2,325,229). We used multivariable negative log-binomial regression to calculate prevalence ratios (PRs) and 95% confidence intervals (CIs) for the association between breast cancer history and PTB, LBW, and SGA. Results Of 1,912,269 eligible births, 512 births were to mothers with a previous breast cancer diagnosis history. Average age at breast cancer diagnosis was 31.8 years (SD = 4.7). Mean time from diagnosis to delivery was 3.3 years (SD = 2.8). After multivariable adjustment, the PR was 1.67 (95% CI, 1.42–1.97) for PTB, 1.50 (95% CI, 1.23–1.84) for LBW, and 1.30 (95% CI, 1.05–1.61) for SGA comparing women with a breast cancer history to the general population. Among black mothers, the PRs associated with breast cancer history for PTB, LBW, and SGA were 1.31 (95% CI, 1.00–1.72), 1.49 (95% CI, 1.14–1.94), and 1.44 (95% CI, 1.11–1.87), respectively. The corresponding PRs among white mothers were 2.06 (95% CI, 1.67–2.54), 1.53 (95% CI, 1.12–2.08), and 1.10 (95% CI, 0.77–1.58), respectively. The interaction between breast cancer history and race was statistically significant for associations with PTB, but not for LBW or SGA. Conclusions In our data, women with a breast cancer history were at higher risk of delivering a PTB, LBW, or SGA infant, especially if they received chemotherapy or gave birth within 2 years of their breast cancer diagnosis date

Childhood-Diagnosed ADHD, Symptom Progression, and Reversal Learning in Adulthood

Objective: ADHD persists in up to 60% into adulthood, and the reasons for persistence are not fully understood. The objective of this study was to characterize the neurofunctional basis of decision making in those with a childhood diagnosis of ADHD with either persistent or remitted symptoms in adulthood versus healthy control participants. Method: Thirty-two adults diagnosed with ADHD as children were split into persistent (n = 18) or remitted (n = 14) ADHD groups. Their neural activity and neurofunctional connectivity during a probabilistic reversal learning task were compared with 32 healthy controls. Results: Remitters showed significantly higher neural connectivity in final reversal error and probabilistic error conditions, and persisters depict higher neural connectivity in reversal errors than controls at a family-wise error (FWE) corrected whole-brain corrected threshold. Conclusion: Remitters may have utilized higher neural connectivity than controls to make successful decisions. Also, remitters may have utilized compensatory strategies to override any potential underlying ADHD deficits

Subject benchmark statement: healthcare programmes, phase 2: Arts Therapy, QAA 05909/04

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Comparing traditional and participatory dissemination of a shared decision making intervention (ADAPT-NC): a cluster randomized trial

BackgroundAsthma is a common disease that affects people of all ages and has significant morbidity and mortality. Poor outcomes and health disparities related to asthma result in part from the difficulty of disseminating new evidence and care delivery methods such as shared decision making (SDM) into clinical practice.This 3-year study explores the ideal framework for rapid dissemination of an evidence-based SDM toolkit for asthma management. The study leverages a partnership between the North Carolina (NC) statewide Medicaid network and the NC Network Consortium of practice-based research networks (PBRNs).Methods/designThis non-blinded study will randomize 30 primary care clinics in NC stratified by four PBRNs. We will test dissemination across these practices using a facilitator-led participatory approach to dissemination (FLOW), a novel method of participatory dissemination involving key principles of community-based participatory research, and a more typical “lunch and learn” dissemination method. Specifically, we will use cluster randomization to assign each of the 30 practices to one of three arms: (1) control, no dissemination; (2) traditional dissemination, one didactic session a year and distribution of educational material; and (3) FLOW dissemination. We hypothesize that at the unit of randomization, the clinic, patients in the FLOW dissemination arm will be more likely to share in their treatment decisions compared to patients in the traditional dissemination or control arms. All outcomes will be measured at the level of the clinic. Adoption of the SDM approach will be evaluated by 1) asthma exacerbations, 2) level of patient involvement in the decision making process, and 3) qualitative assessments from patients and providers.The research question is: What dissemination strategy most effectively increases practice level adoption of a shared decision making approach to asthma management? This study will provide important data to support best practices in dissemination of an evidence-based toolkit and implementation of shared decision making into primary care practices.Trial registrationThe trial was registered on January 27, 2014 through the United States National Institutes of Health’s ClinicalTrials.gov NCT02047929 and funded by the Patient-Centered Outcomes Research Institute (PCORI)

Response to the editorial by Dr Geraghty

This article is written in response to the linked editorial by Dr Geraghty about the adaptive Pacing, graded Activity and Cognitive behaviour therapy; a randomised Evaluation (PACE) trial, which we led, implemented and published. The PACE trial compared four treatments for people diagnosed with chronic fatigue syndrome. All participants in the trial received specialist medical care. The trial found that adding cognitive behaviour therapy or graded exercise therapy to specialist medical care was as safe as, and more effective than, adding adaptive pacing therapy or specialist medical care alone. Dr Geraghty has challenged these findings. In this article, we suggest that Dr Geraghty’s views are based on misunderstandings and misrepresentations of the PACE trial; these are corrected

Cu-II(atsm) Attenuates Neuroinflammation

Background: Neuroinflammation and biometal dyshomeostasis are key pathological features of several neurodegenerative diseases, including Alzheimer's disease (AD). Inflammation and biometals are linked at the molecular level through regulation of metal buffering proteins such as the metallothioneins. Even though the molecular connections between metals and inflammation have been demonstrated, little information exists on the effect of copper modulation on brain inflammation. Methods: We demonstrate the immunomodulatory potential of the copper bis(thiosemicarbazone) complex Cu-II(atsm) in an neuroinflammatory model in vivo and describe its anti-inflammatory effects on microglia and astrocytes in vitro. Results: By using a sophisticated in vivo magnetic resonance imaging (MRI) approach, we report the efficacy of Cu-II(atsm) in reducing acute cerebrovascular inflammation caused by peripheral administration of bacterial lipopolysaccharide (LPS). Cu-II(atsm) also induced anti-inflammatory outcomes in primary microglia [significant reductions in nitric oxide (NO), monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor (TNF)] and astrocytes [significantly reduced NO, MCP-1, and interleukin 6 (IL-6)] in vitro. These anti-inflammatory actions were associated with increased cellular copper levels and increased the neuroprotective protein metallothionein-1 (MT1) in microglia and astrocytes. Conclusion: The beneficial effects of Cu-II(atsm) on the neuroimmune system suggest copper complexes are potential therapeutics for the treatment of neuroinflammatory conditions.Peer reviewe