Regioselective Partial Hydrogenation and Deuteration of Tetracyclic (Hetero)aromatic Systems Using a Simple Heterogeneous Catalyst.

The introduction of added '3-dimensionality' through late-stage functionalisation of extended (hetero)aromatic systems is a powerful synthetic approach. The abundance of starting materials and cross-coupling methodologies to access the precursors allows for highly diverse products. Subsequent selective partial reduction can alter the core structure in a manner of interest to medicinal chemists.

Meeting the challenges of rising premature mortality in people with severe mental illness.

People with severe mental illness are 4.5 times more likely to die prematurely than the general UK population. We review the drivers of poorer physical health across mental health conditions and propose some practical approaches to addressing this in the clinic.

Understanding and managing psychological disorders in patients with inflammatory bowel disease: a practical guide.

Mood disturbances such as anxiety and depression are common in patients with inflammatory bowel disease (IBD), and impact negatively on their quality of life and disease course. An integrated multidisciplinary IBD team, which includes access to psychology and psychiatry opinion, makes possible the prompt recognition and management of psychological disturbance in patients with IBD. Based on our experience and existing literature, including systematic reviews of the effectiveness of available treatment modalities, a stepwise approach to the maintenance and restoration of psychological well-being is recommended, evolving upwards from lifestyle advice, through behavioural therapies to pharmacotherapy.

Gastrointestinal symptoms and nutritional issues in patients with hypermobility disorders: assessment, diagnosis and management.

Patients diagnosed with hypermobile Ehlers-Danlos syndrome and hypermobile spectrum disorders are increasingly presenting to secondary and tertiary care centres with gastrointestinal (GI) symptoms and nutritional issues. Due to the absence of specific guidance, these patients are investigated, diagnosed and managed heterogeneously, resulting in a growing concern that they are at increased risk of iatrogenic harm. This review aims to collate the evidence for the causes of GI symptoms, nutritional issues and associated conditions as well as the burden of polypharmacy in this group of patients.

Premature mortality of people with severe mental illness: a renewed focus for a new era.

This perspective article applies public health principles to improve the physical health of selected populations with mental disorders. Two preventable adverse outcomes, poorer physical health and premature mortality, are described across mental disorders. Evidence of the lifetime effects of adverse childhood experiences and inequalities is presented: these are the 'causes of the causes'.

Competition between N and O: use of diazine -oxides as a test case for the Marcus theory rationale for ambident reactivity.

The preferred site of alkylation of diazine -oxides by representative hard and soft alkylating agents was established conclusively using the H-N HMBC NMR technique in combination with other NMR spectroscopic methods. Alkylation of pyrazine -oxides ( and ) occurs preferentially on nitrogen regardless of the alkylating agent employed, while -methylation of pyrimidine -oxide () is favoured in its reaction with MeOTf. As these outcomes cannot be explained in the context of the hard/soft acid/base (HSAB) principle, we have instead turned to Marcus theory to rationalise these results.

Nucleophilicities and Nucleofugalities of Thio- and Selenoethers.

Rate constants for the reactions of dialkyl chalcogenides with laser flash photolytically generated benzhydrylium ions have been measured photometrically to integrate them into the comprehensive benzhydrylium-based nucleophilicity scale. Combining these rate constants with the previously reported equilibrium constants for the same reactions provided the corresponding Marcus intrinsic barriers and made it possible to quantify the leaving group abilities (nucleofugalities) of dialkyl sulfides and dimethyl selenide. Due to the low intrinsic barriers, dialkyl chalcogenides are fairly strong nucleophiles (comparable to pyridine and N-methylimidazole) as well as good nucleofuges; this makes them useful group-transfer reagents.

Management of functional gastrointestinal disorders.

Functional gastrointestinal (GI) disorders (eg irritable bowel syndrome and functional dyspepsia) are very common conditions which are associated with very poor quality of life and high healthcare utilisation. They are caused by disorders of GI functioning, namely altered gut sensitivity, motility, microbiota, immune functioning and central nervous system processing. They cause chronic symptoms throughout the gut (eg pain, dyspepsia and altered bowel habit), all of which are made worse by maladaptive patient behaviours, stress and psychological comorbidity.

Pressure-induced Pb-Pb bonding and phase transition in PbSnO.

High-pressure single-crystal to 20 GPa and powder diffraction measurements to 50 GPa, show that the structure of PbSnO strongly distorts on compression with an elongation of one axis. A structural phase transition occurs between 10 GPa and 12 GPa, with a change of space group from Pbam to Pnam. The resistivity decreases by more than six orders of magnitude when pressure is increased from ambient conditions to 50 GPa.

Placing poverty-inequality at the centre of psychiatry.

We examine epidemiological evidence for the central role of inequalities (principally economic) in driving the onset of mental disorders, physical ill health and premature mortality. We locate the search for solutions in current UK contexts, and include known and likely effects of the COVID-19 pandemic. Prevention of mental disorders and adverse outcomes such as premature mortality must begin with efforts to mitigate rising poverty-inequality.

Off-the-shelf DFT-DISPersion methods: Are they now "on-trend" for organic molecular crystals?

Organic molecular crystals contain long-range dispersion interactions that can be challenging for solid-state methods such as density functional theory (DFT) to capture, and in some industrial sectors are overlooked in favor of classical methods to calculate atomistic properties. Hence, this publication addresses the critical question of whether dispersion corrected DFT calculations for organic crystals can reproduce the structural and energetic trends seen from experiment, i.e.

Addiction care in crisis: evidence should drive progressive policy and practice.

Addictions are challenging health and social problems that need to be addressed to preserve and promote good mental health and ensure that individuals within society lead healthy and productive lives. Tackling addictions is complex and requires communities, public health, specialist services, and local and national government to act in unison and implement evidence-based interventions. This editorial raises systemic issues that need attention and proposes a range of systemic options.

Acute appendicitis presenting as a complicated inguinal hernia: a case of left-sided Amyand's hernia in an elderly man.

Amyand's hernia (AH) is characterized by the presence of the vermiform appendix in an inguinal hernia sac. Typically presenting on the right side and with manifestations similar to those seen in complicated hernias, it presents a diagnostic challenge and is frequently only diagnosed intraoperatively. We present the case of a left-sided AH on a 75-year-old man treated with appendicectomy, orchidectomy and hernioplasty without mesh.

Why Are Vinyl Cations Sluggish Electrophiles?

The kinetics of the reactions of the vinyl cations 2 [PhC═C-(4-MeO-CH)] and 3 [MeC═C-(4-MeO-CH)] (generated by laser flash photolysis) with diverse nucleophiles (e.g., pyrroles, halide ions, and solvents containing variable amounts of water or alcohol) have been determined photometrically.

Ambident Reactivity of Acetyl- and Formyl-Stabilized Phosphonium Ylides.

The kinetics and mechanism of the reactions of formyl-stabilized ylide Ph3P═CHCHO (1) and acetyl-stabilized ylide Ph3P═CHCOMe (2) with benzhydrylium ions (Ar2CH(+), 3) were investigated by UV-vis and NMR spectroscopy. As ambident nucleophiles, ylides 1 and 2 can react at oxygen as well as at the α-carbon. For some reactions, it was possible to determine the second-order rate constant for O-attack as well as for C-attack and to derive the nucleophile-specific parameters N and sN according to the correlation lg k (20 °C) = sN(E + N) for both nucleophilic sites.

The Mechanism of Phosphonium Ylide Alcoholysis and Hydrolysis: Concerted Addition of the O-H Bond Across the P=C Bond.

The previous work on the hydrolysis and alcoholysis reactions of phosphonium ylides is summarized and reviewed in the context of their currently accepted mechanisms. Several experimental facts relating to ylide hydrolysis and to salt and ylide alcoholysis are shown to conflict with those mechanisms. In particular, we demonstrate that the pKa values of water and alcohols are too high in organic media to bring about protonation of ylide.

Oxytocin neuron activation prevents hypertension that occurs with chronic intermittent hypoxia/hypercapnia in rats.

Hypertension is a common outcome associated with obstructive sleep apnea (OSA), a prevalent yet poorly treated cardiovascular disease. Recent studies showed oxytocin (OXT), released from hypothalamic paraventricular nucleus (PVN) neurons, activates cardiac vagal neurons in the dorsal motor nucleus of the vagus (DMNX) and may blunt cardiovascular responses to stress. This study tests whether the release of OXT from PVN fibers in the DMNX is diminished with chronic intermittent hypoxia-hypercapnia (CIH/H) exposure, an animal model of OSA, and whether activation of PVN OXT neurons restores OXT release in the DMNX and prevents the hypertension resulting from CIH/H.

First ever observation of the intermediate of phosphonium salt and ylide hydrolysis: P-hydroxytetraorganophosphorane.

P-Hydroxytetraorganophosphorane, the long-postulated intermediate in phosphonium salt and ylide hydrolysis, has been observed and characterised by low temperature NMR, finally definitively establishing its involvement in these reactions. The results require modification of the previously accepted mechanism for ylide hydrolysis: P-hydroxytetraorganophosphorane is generated directly by 4-centre reaction of ylide with water.

Assessing Sexual Interest in Adolescents Who Have Sexually Offended.

Adolescents who have sexually offended have unique treatment needs. For mental health professionals to adequately address these unique needs, further research is necessary. To that end, we explored the assessment of sexual interest (which may play an integral role in understanding potential for sexual reoffending) in a sample of 103 male adolescents who have sexually offended.

Optogenetic stimulation of locus ceruleus neurons augments inhibitory transmission to parasympathetic cardiac vagal neurons via activation of brainstem α1 and β1 receptors.

Locus ceruleus (LC) noradrenergic neurons are critical in generating alertness. In addition to inducing cortical arousal, the LC also orchestrates changes in accompanying autonomic system function that compliments increased attention, such as during stress, excitation, and/or exposure to averse or novel stimuli. Although the association between arousal and increased heart rate is well accepted, the neurobiological link between the LC and parasympathetic neurons that control heart rate has not been identified.

Induction of thyroid neoplasm following plant medicine marine algae (sargassum): a rare case and review of the literature.

In this study induction of neoplasm in thyroid gland of one postoperative patient with breast cancer was conducted by marine algae (also seaweed, sargassum), which is presented here. A 41-year-old women was diagnosed as her right breast cancer complicated with lymph node metastasis in her right axilla on February, 1999. In June 19, 1999 she was given the combination chemotherapy of vincristine, cyclophosphamide, 5-Fluorouracil and cinobufacini drugs due to two lymph nodes on her right superclavicular following radical mastectomy.

The modern interpretation of the Wittig reaction mechanism.

The mechanism of the Wittig reaction has long been a contentious issue in organic chemistry. Even now, more than 50 years after its announcement, its presentation in many modern undergraduate textbooks is either overly simplified or entirely inaccurate. In this review, we gather together the huge body of evidence that has been amassed to show that the Li salt-free Wittig reactions of non-stabilised, semi-stabilised and stabilised ylides all occur under kinetic control by a common mechanism in which oxaphosphetane (OPA) is the first-formed and only intermediate.

Piezochromism in nickel salicylaldoximato complexes: tuning crystal-field splitting with high pressure.

The crystal structures of bis(3-fluoro-salicylaldoximato)nickel(II) and bis(3-methoxy-salicylaldoximato)nickel(II) have been determined at room temperature between ambient pressure and approximately 6 GPa. The principal effect of pressure is to reduce intermolecular contact distances. In the fluoro system molecules are stacked, and the Ni⋅⋅⋅Ni distance decreases from 3.