Thalamic Cav3.1 T-type Ca2+ channel plays a crucial role in stabilizing sleep

It has long been suspected that sensory signal transmission is inhibited in the mammalian brain during sleep. We hypothesized that Cav3.1 T-type Ca2+ channel currents inhibit thalamic sensory transmission to promote sleep. We found that T-type Ca2+ channel activation caused prolonged inhibition (>9 s) of action-potential firing in thalamic projection neurons of WT but not Cav3.1 knockout mice. Inhibition occurred with synaptic transmission blocked and required an increase of intracellular Ca2+. Furthermore, focal deletion of the gene encoding Cav3.1 from the rostral-midline thalamus by using Cre/loxP recombination led to frequent and prolonged arousal, which fragmented and reduced sleep. Interestingly, sleep was not disturbed when Cav3.1 was deleted from cortical pyramidal neurons. These findings support the hypothesis that thalamic T-type Ca2+ channels are required to block transmission of arousal signals through the thalamus and to stabilize sleep.     

Theoretical investigation on the ground state properties of the hexaamminecobalt(iii) and nitro–nitrito linkage isomerism in pentaamminecobalt(iii) in vacuo

Nitro–nitrito isomerization in Co(NH₃)₅NO₂²⁺ linkage isomers was investigated with a focus on the geometries, relative stabilities and chemical bonding using ωB97XD/6-31+G(d,p) to elucidate the photo-salient effect in [Co(NH₃)₅NO₂]NO₃Cl. Different techniques like atoms in molecules (AIM), electron localization function (ELF) and natural bonding orbital (NBO) were used to gain insight into the chemical bonds of the isomers and to identify the key factors influencing their relative stabilities. The study of the ground-state potential energy surface of [Co(NH₃)₅NO₂]²⁺ reveals that the nitro/exo-nitrito isomerization reaction can proceed via the following two paths: (1) nitro → TS1 (38.16 kcal mol⁻¹) → endo-nitrito → TS2 (9.68 kcal mol⁻¹) → exo-nitrito and (2) nitro → TS3 (41.76 kcal mol⁻¹) → exo-nitrito. Pathway (1) through endo-nitrito is the most likely isomerization mechanism because of a lower energy barrier than pathway (2). The intramolecular-resonance-assisted hydrogen bonds (N–H⋯O and N–H⋯N), the orientation of NO₂, and the difference between Co–N and Co–O bond energies are identified as the key factors determining the relative stabilities of the linkage isomers. Co(NH₃)₆³⁺ is less stable compared to Co(NH₃)₅NO₂²⁺ and undergoes a slight geometrical distortion from D_3d to either D₃ or S₆ characterized by a stabilization energy of ∼750 cm⁻¹ at CCSD(T)/6-31+G(d,p).

Nitro–nitrito isomerization in Co(NH₃)₅NO₂²⁺ linkage isomers was investigated with a focus on the geometries, relative stabilities and chemical bonding using ωB97XD/6-31+G(d,p) to elucidate the photo-salient effect in [Co(NH₃)₅NO₂]NO₃Cl.     

Integrating medical and psychological treatment for sexual problems: the psyche and the soma

I approach the integration of medical and psychological treatment for sexual problems from the perspective of a medical graduate for 41 years, and as a specialist obstetrician, gynaecologist and sexologist I learned that medical practitioners do not have all the answers, but neither do psychologists or all the other ‘-ologists’, but that together we can get so many of the answers. The emergence of Psychosomatic Obstetrics & Gynaecology suited my developing thirst for knowledge in this area to try and make me more effective in managing among other things patients' psychosexual difficulties. Combining this with learning about the actual therapeutic process, what doctoring actually does and how in many instances we can be effective just with the counselling process, not prescribing a ‘silver bullet’ or using the scalpel along the way, as in the Balint model of being a medical instrument. Abnormal illness behaviour, its offshoot – pain behaviour and abnormal treatment behaviour, concepts still not covered in medical schools, will be discussed. A case will be made for using the biopsychological model rather than the traditional medical illness model in the management of sexual dysfunctions.     

Walks4work: Rationale and study design to investigate walking at lunchtime in the workplace setting

ABSTRACT: BACKGROUND: Following recruitment of a private sector company, an 8 week lunchtime walking intervention was implemented to examine the effect of the intervention on modifiable cardiovascular disease risk factors, and further to see if walking environment had any further effect on the cardiovascular disease risk factors. METHODS: For phase 1 of the study participants were divided into three groups, two lunchtime walking intervention groups to walk around either an urban or natural environment twice a week during their lunch break over an 8 week period. The third group was a waiting-list control who would be invited to join the walking groups after phase 1. In phase 2 all participants were encouraged to walk during their lunch break on self-selecting routes. Health checks were completed at baseline, end of phase 1 and end of phase 2 in order to measure the impact of the intervention on cardiovascular disease risk. The primary outcome variables of heart rate and heart rate variability were measured to assess autonomic function associated with cardiovascular disease. Secondary outcome variables (Body mass index, blood pressure, fitness, autonomic response to a stressor) related to cardiovascular disease were also measured. The efficacy of the intervention in increasing physical activity was objectively monitored throughout the 8-weeks using an accelerometer device. DISCUSSION: The results of this study will help in developing interventions with low researcher input with high participant output that may be implemented in the workplace. If effective, this study will highlight the contribution that natural environments can make in the reduction of modifiable cardiovascular disease risk factors within the workplace.     

Molecular Predictors of Prognosis in Lung Cancer

Lung carcinoma is the leading cause of cancer mortality worldwide. Currently, cancer staging and prognosis are determined using histopathology and clinical factors such as lymph node status. However, even the earliest stage of non-small cell lung carcinoma has a widely varying prognosis. In this review, the evolution and refinement of molecular predictors of prognosis in lung carcinoma are described.