Ionized o-, m-, and p-Difluorobenzene Dissociate Through Ring-Opened Intermediates: A TPEPICO Investigation

Threshold photoelectron photoion coincidence (TPEPICO) experiments have shown that o-, m-, and p-difluorobenzene ions dissociate via a common, ring-opened intermediate and not via ionized p-difluorobenzene. Rice-Ramsperger-Kassel-Marcus (RRKM) modeling of the experimental breakdown curves yields activation energies for the initial isomerization of 4.48 ± 0.05, 4.55 ± 0.05, and 4.68 ± 0.05 eV for o-, m-, and p-difluorobenzene, respectively. These values place each ion at a similar absolute energy and thus similar transition states. A large positive ΔS‡ for each ion (ca 100 J K−1 mol−1) suggests a ring-opened structure for these transition states

Development of functional connectivity during adolescence:A longitudinal study using an action-observation paradigm

Successful interpersonal interactions rely on an ability to read the emotional states of others and to modulate one's own behavior in response. The actions of others serve as valuable social stimuli in this respect, offering the observer an insight into the actor's emotional state. Social cognition continues to mature throughout adolescence. Here we assess longitudinally the development of functional connectivity during early adolescence within two neural networks implicated in social cognition: one network of brain regions consistently engaged during action observation and another one associated with mentalizing. Using fMRI, we reveal a greater recruitment of the social-emotional network during the observation of angry hand actions in male relative to female adolescents. These findings are discussed in terms of known sex differences in adolescent social behavior

Inhibition of the \u3cem\u3edapE\u3c/em\u3e-Encoded \u3cem\u3eN\u3c/em\u3e-Succinyl- ʟ, ʟ-diaminopimelic Acid Desuccinylase from \u3cem\u3eNeisseria meningitidis\u3c/em\u3e by ʟ-Captopril

Binding of the competitive inhibitor ʟ-captopril to the dapE-encoded N-succinyl-ʟ, ʟ-diaminopimelic acid desuccinylase from Neisseria meningitidis (NmDapE) was examined by kinetic, spectroscopic, and crystallographic methods. ʟ-Captopril, an angiotensin-converting enzyme (ACE) inhibitor, was previously shown to be a potent inhibitor of the DapE from Haemophilus influenzae (HiDapE) with an IC50 of 3.3 μM and a measured Ki of 1.8 μM and displayed a dose-responsive antibiotic activity toward Escherichia coli. ʟ-Captopril is also a competitive inhibitor of NmDapE with a Ki of 2.8 μM. To examine the nature of the interaction of ʟ-captopril with the dinuclear active site of DapE, we have obtained electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) data for the enzymatically hyperactive Co(II)-substituted forms of both HiDapE and NmDapE. EPR and MCD data indicate that the two Co(II) ions in DapE are antiferromagnetically coupled, yielding an S = 0 ground state, and suggest a thiolate bridge between the two metal ions. Verification of a thiolate-bridged dinuclear complex was obtained by determining the three-dimensional X-ray crystal structure of NmDapE in complex with ʟ-captopril at 1.8 Å resolution. Combination of these data provides new insights into binding of ʟ-captopril to the active site of DapE enzymes as well as important inhibitor–active site residue interaction’s. Such information is critical for the design of new, potent inhibitors of DapE enzymes

Isobutyl acetate: electronic state spectroscopy by high-resolution vacuum ultraviolet photoabsorption, He(I) photoelectron spectroscopy and ab initio calculations

The high-resolution vacuum ultraviolet photoabsorption spectrum of isobutyl acetate, C6H12O2, is presented here and was measured over the energy range 4.3–10.8 eV (290–115 nm). Valence and Rydberg transitions with their associated vibronic series have been observed in the photoabsorption spectrum and are assigned in accordance with new ab initio calculations of the vertical excitation energies and oscillator strengths. The measured photoabsorption cross sections have been used to calculate the photolysis lifetime of this ester in the Earth’s upper atmosphere (20–50 km). Calculations have also been carried out to determine the ionization energies and fine structure of the lowest ionic state of isobutyl acetate and are compared with a photoelectron spectrum (from 9.5 to 16.7 eV), recorded for the first time. Vibrational structure is observed in the first photoelectron band of this molecule

Developing an Intervention for Fall-Related Injuries in Dementia (DIFRID): an integrated, mixed-methods approach

Background Falls in people with dementia can result in a number of physical and psychosocial consequences. However, there is limited evidence to inform how best to deliver services to people with dementia following a fall. The aim of the DIFRID study was to determine the feasibility of developing and implementing a new intervention to improve outcomes for people with dementia with fall-related injuries; this encompasses both short-term recovery and reducing the likelihood of future falls. This paper details the development of the DIFRID intervention. Methods The intervention was designed using an integrated, mixed-methods approach. This involved a realist synthesis of the literature and qualitative data gathered through interviews and focus groups with health and social care professionals (n=81). An effectiveness review and further interviews and observation were also conducted and are reported elsewhere. A modified Delphi panel approach with 24 experts was then used to establish a consensus on how the findings should translate into a new intervention. After feedback from key stakeholders (n=15) on the proposed model, the intervention was manualised and training developed. Results We identified key components of a new intervention covering three broad areas: • Ensuring that the circumstances of rehabilitation are optimised for people with dementia • Compensating for the reduced ability of people with dementia to self-manage • Equipping the workforce with the necessary skills and information to care for this patient group Consensus was achieved on 54 of 69 statements over two rounds of the Delphi surveys. The statements were used to model the intervention and finalise the accompanying manual and protocol for a feasibility study. Stakeholder feedback was generally positive and the majority of suggested intervention components were approved. The proposed outcome was a 12-week complex multidisciplinary intervention primarily based at the patient’s home. Conclusions A new intervention has been developed to improve outcomes for people with dementia following a fall requiring healthcare attention. The feasibility of this intervention is currently being tested. Trial registration ISRCTN41760734 (16/11/2015

IRS2 mutations linked to invasion in pleomorphic invasive lobular carcinoma

Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of invasive lobular breast cancer that is associated with poor clinical outcomes. Limited molecular data are available to explain the mechanistic basis for PILC behavior. To address this issue, targeted sequencing was performed to identify molecular alterations that define PILC. This sequencing analysis identified genes that distinguish PILC from classic ILC and invasive ductal carcinoma by the incidence of their genomic changes. In particular, insulin receptor substrate 2 (IRS2) is recurrently mutated in PILC, and pathway analysis reveals a role for the insulin receptor (IR)/insulin-like growth factor-1 receptor (IGF1R)/IRS2 signaling pathway in PILC. IRS2 mutations identified in PILC enhance invasion, revealing a role for this signaling adaptor in the aggressive nature of PILC

Editorial: Writing the field of equity

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Rapid tests and urine sampling techniques for the diagnosis of urinary tract infection (UTI) in children under five years: a systematic review

Background: Urinary tract infection (UTI) is one of the most common sources of infection in children under five. Prompt diagnosis and treatment is important to reduce the risk of renal scarring. Rapid, cost-effective, methods of UTI diagnosis are required as an alternative to culture. Methods: We conducted a systematic review to determine the diagnostic accuracy of rapid tests for detecting UTI in children under five years of age. Results: The evidence supports the use of dipstick positive for both leukocyte esterase and nitrite (pooled LR+ = 28.2, 95% CI: 17.3, 46.0) or microscopy positive for both pyuria and bacteriuria (pooled LR+ = 37.0, 95% CI: 11.0, 125.9) to rule in UTI. Similarly dipstick negative for both LE and nitrite (Pooled LR- = 0.20, 95% CI: 0.16, 0.26) or microscopy negative for both pyuria and bacteriuria (Pooled LR- = 0.11, 95% CI: 0.05, 0.23) can be used to rule out UTI. A test for glucose showed promise in potty-trained children. However, all studies were over 30 years old. Further evaluation of this test may be useful. Conclusion: Dipstick negative for both LE and nitrite or microscopic analysis negative for both pyuria and bacteriuria of a clean voided urine, bag, or nappy/pad specimen may reasonably be used to rule out UTI. These patients can then reasonably be excluded from further investigation, without the need for confirmatory culture. Similarly, combinations of positive tests could be used to rule in UTI, and trigger further investigation