[DOES A PRISONER HAVE THE RIGHT TO AUTONOMY? A CASE REPORT].

INTRODUCTION: The case presented discusses a prisoner, Y, in his mid-sixties with longstanding medical conditions, who was sentenced to prolonged incarceration. Y refused conventional medicine because he believed that his medical condition was exacerbated by this treatment and only complementary alternative medicine (CAM) would be helpful. He therefore demanded to be treated only by CAM. He was ready to pay for the treatment out of his own pocket. In the prison where Y was previously incarcerated over the course of 12 years, he had access to CAM remedies which were purchased by his family. After being transferred to the current facility, Y was denied access to these remedies by the prison physicians. He appealed in court against this decision and was supported by a CAM specialist, who ascertained that the remedies under consideration were not hazardous to Y's health. This case report discusses the ethical aspects of a prisoner's autonomy to choose medical treatment even when his/her autonomy has been severely curtailed by virtue of the incarceration.

Reticulating 1D Ribbons into 2D Covalent Organic Frameworks by Imine and Imide Linkages.

The design and synthesis of 2D and 3D crystalline covalent organic frameworks (COFs) from macromolecular and even infinite building units is largely undeveloped. Here, we report a strategy to link molecules and 1D ribbons into 2D cystalline frameworks. Triangular, tris(4-aminophenyl)amine (TAA), and square, 1,3,6,8-tetrakis(p-formylphenyl)pyrene (TFPPy), organic building units are joined substoichiometrically by imine linkages to produce 1D ribbons, termed COF-76, bearing free amines, which are then used to link the ribbons into 2D frameworks COF-77 and COF-78. In addition to this stepwise approach, we also demonstrate an in situ synthesis of these COFs. We believe our ability to link infinite building blocks, such as the ribbons of COF-76, into higher dimensionality COFs, paves the way to covalent frameworks composed of hierachical chemical structures.

3D Covalent Organic Frameworks Selectively Crystallized through Conformational Design.

We present a strategy whereby selective formation of imine covalent organic frameworks (COFs) based on linking of triangles and squares into the fjh topology was achieved by the conformational design of the building units. 1,3,5-Trimethyl-2,4,6-tris(4-formylphenyl)benzene (TTFB, triangle) and 1,1,2,2-tetrakis(4-aminophenyl)ethene (ETTA, square) were reticulated into [(TTFB)4(ETTA)3]imine, termed COF-790, which was fully characterized by spectroscopic, microscopic, and X-ray diffraction techniques. COF-790 exhibits permanent porosity and a Brunauer-Emmett-Teller (BET) surface area of 2650 m2 g-1. Key to the formation of this COF in crystalline form is the pre-designed conformation of the triangle and the square units to give dihedral angles in the range of 75-90°, without which the reaction results in the formation of amorphous product. We demonstrate the versatility of our strategy by also reporting the synthesis and characterization of two isoreticular forms of COF-790, COF-791 and COF-792, based on other square building units.

Molecular Recognition and Cocrystallization of Methylated and Halogenated Fragments of Danicalipin A by Enantiopure Alleno-Acetylenic Cage Receptors.

Enantiopure (P)4- and (M)4-configured alleno-acetylenic cage (AAC) receptors offer a highly defined interior for the complexation and structure elucidation of small molecule fragments of the stereochemically complex chlorosulfolipid danicalipin A. Solution (NMR), solid state (X-ray), and theoretical investigations of the formed host-guest complexes provide insight into the conformational preferences of 14 achiral and chiral derivatives of the danicalipin A chlorohydrin core in a confined, mostly hydrophobic environment, extending previously reported studies in polar solvents. The conserved binding mode of the guests permits deciphering the effect of functional group replacements on Gibbs binding energies ΔG. A strong contribution of conformational energies toward the binding affinities is revealed, which explains why the denser packing of larger apolar domains of the guests does not necessarily lead to higher association. Enantioselective binding of chiral guests, with energetic differences ΔΔG293 K up to 0.7 kcal mol-1 between diastereoisomeric complexes, is explained by hydrogen- and halogen-bonding, as well as dispersion interactions. Calorimetric studies (ITC) show that the stronger binding of one enantiomer is accompanied by an increased gain in enthalpy ΔH but at the cost of a larger entropic penalty TΔS stemming from tighter binding.

Case-Control Retrospective Study of Child Sexual Abuse History among Psychiatric Consultations in a General Hospital Emergency Room.

BACKGROUND: A history of childhood sexual abuse (CSA) has been linked to a variety of physical and psychiatric illnesses, including ischemic heart disease and post-traumatic stress disorder (PTSD). OBJECTIVES: To determine the prevalence of past CSA and re-traumatization among hospital psychiatric consultations and to determine whether a CSA group in a hospital setting shared characteristics with community samples described in the literature. METHODS: We divided 228 consecutive psychiatric consultations into two groups. One group comprised patients with a past history of CSA while the other group had no such history. Both groups were further divided into a subgroup that presented with features of re-traumatization. RESULTS: In the cohort, 38% described a history of CSA. Twenty patients were identified as presenting with features of re-traumatization. There were significant differences between the two groups. The patients with a history of CSA were more likely to have arrived at the emergency department (ED) during the preceding 12 months with a diagnosis of PTSD, personality disorder, and substance use disorder. There was a greater proportion of patients in the CSA group who had grown up in an ultra-Orthodox Jewish household and who currently identified as being secular. CONCLUSIONS: The characteristics of the patients with past CSA in this study are similar to community-based samples, except for a significant gender difference. To the best of our knowledge, this study is the first to investigate CSA history during hospital ED psychiatric consultations. A history of CSA should be considered during psychiatric consultations in a general hospital ED admission.

Molecular Recognition with Resorcin[4]arene Cavitands: Switching, Halogen-Bonded Capsules, and Enantioselective Complexation.

The development of synthetic host-guest chemistry to investigate and quantify weak, non-covalent interactions has been key to unraveling the complexity of molecular recognition in chemical and biological systems. Macrocycles have shown great utility in the design of receptors, enabling the development of highly preorganized structures. Among macrocycles, resorcin[4]arene-based cavitands have become privileged scaffolds due to their synthetic tunability, which allows access to structures with precisely defined geometries, as well as receptors that display conformational switching between two distinct states with a large difference in guest-binding properties. Here, we highlight three case studies demonstrating redox- and photoredox-controlled switching of molecular recognition properties, the formation of guest-binding supramolecular capsules based solely on halogen-bonding interactions, and enantioselective encapsulation of chiral, substituted cyclohexanes by enantiopure cage compounds as a result of perfect shape complementarity, dispersion interactions, and halogen bonding. The high geometrical and conformational control that can be achieved with resorcin[4]arene-derived host systems will continue to be a powerful resource in future molecular recognition studies.

Psychopathology of Israeli Soldiers Presenting to a General Hospital Emergency Department: Lessons for the Attending Physician and Psychiatrist.

BACKGROUND: There is scant research on the psychopathology of Israeli soldiers who present to a general hospital emergency department (ED). OBJECTIVES: To assess the psychopathology among a cohort of Israeli soldiers who presented to a general hospital ED for mental health assessment. METHODS: The demographic and clinical characteristics of 124 consecutive soldiers who presented to the ED for psychiatric assessment between January 2008 and September 2012 were reviewed. Twenty-seven soldiers from the cohort were contacted for follow-up by telephone on average 52 months later. RESULTS: The reasons for presentation to the ED, usually during the early stages of military service, included self-harming behavior, suicidal ideation, somatoform complaints, and dissatisfaction with their military service. Psychiatric diagnoses included adjustment disorder and personality disorder. Self-harming behavior/suicidal ideation was significantly correlated with unspecified adjustment disorder (P = 0.02) and personality disorder (P = 0.001). At follow-up, there was a lack of substantial psychopathology: none of the subjects engaged in self-harming behavior/suicidal ideation and a consistent trend was observed toward clinical improvement. CONCLUSIONS: Psychiatric intervention of soldiers who present to a general hospital ED because of emotional difficulties may provide the opportunity for crisis intervention and validation of the soldier's distress. To the best of our knowledge this is the first Israeli study of psychopathology among soldiers who presented to an ED.

Complexation and Structure Elucidation of the Axial Conformers of Mono- and (±)-trans-1,2-Disubstituted Cyclohexanes by Enantiopure Alleno-Acetylenic Cage Receptors.

Single crystal X-ray diffraction is a powerful method to unambiguously characterize the structure of molecules with atomic resolution. Herein, we review the molecular recognition of the (di)axial conformers of Mono- and (±)-trans-1,2-disubstituted cyclohexanes by enantiopure alleno-acetylenic cage receptors in solution and in the solid state. Single crystals of the host-guest complexes suitable for X-ray diffraction allow for the first time to study the dihedral angles of a series of Mono- and (±)-trans-1,2-disubstituted cyclohexanes in their (di)axial chair conformation. Theoretical studies indicate negligible influence of the host structure on the guest conformation, suggesting that the structural information obtained from the host-guest complexes give insight into the innate structures of Mono- and (±)-trans-1,2-disubstituted cyclohexanes. Strong deviation of the dihedral angles a,a(X-C(1)-C(2)-X) from the idealized 180° are observed, accompanied by substantial flattening of the ring dihedral angles ρ(X-C(1)-C(2)-C(3)).

Hydrogen-Bonded Networks: Molecular Recognition of Cyclic Alcohols in Enantiopure Alleno-Acetylenic Cage Receptors.

Enantiopure (P)4 - and (M)4 -alleno-acetylenic cage (AAC) receptors form circular fourfold hydrogen-bonding networks in their closed cage conformation. Theoretical studies reveal a preferential clockwise (cw) orientation of the H-bonding array for (P)4 -configured and counterclockwise (ccw) for (M)4 -configured receptors (ΔEcw-ccw =-2.6 to -3.1 kcal mol-1 ). Solution and solid-state studies show how the H-bonding network of the receptor is expanded upon encapsulation of alcohol-containing guests. Topologies reminiscent of those found in isolated water clusters are observed: circular fourfold & docking, pentagonal, linear fivefold, and hexagonal boat-shaped. Expansion of the H-bonding network together with optimal space occupancy yields very high ligand affinities (ΔG293 K =-9.0 kcal mol-1 for endo-tropine). The H-bonding network in the complexes also contributes substantially to the enantioselective complexation of chiral diols, such as (R,R)- and (S,S)-trans-cyclohexane-1,2-diol.

Dispersion and Halogen-Bonding Interactions: Binding of the Axial Conformers of Monohalo- and (±)-trans-1,2-Dihalocyclohexanes in Enantiopure Alleno-Acetylenic Cages.

Enantiopure alleno-acetylenic cage (AAC) receptors with a resorcin[4]arene scaffold, from which four homochiral alleno-acetylenes converge to shape a cavity closed by a four-fold OH-hydrogen-bonding array, form a highly ordered porous network in the solid state. They enable the complexation and co-crystallization of otherwise non-crystalline small molecules. This paper analyzes the axial conformers of monohalo- and (±)-trans-1,2-dihalocyclohexanes, bound in the interior cavity of the AACs, on the atomic level in the solid state and in solution, accompanied by accurate calculations. The dihedral angles ϑa,a (X-C(1)-C(2)-X/H) of the axial/diaxial conformers deviate substantially from 180°, down to 144°, accompanied by strong flattening of the ring dihedral angles. Structure optimization of the isolated guest molecules demonstrates that the non-covalent interactions with the host hardly affect the dihedral angles, validating that the host is an ideal means to study the elusive axial/diaxial conformers. X-ray co-crystal structures of AACs further allowed for a detailed investigation, both experimentally and theoretically, on the interplay between space occupancy, guest conformation, and chiral recognition based purely on dispersion forces and weak C-X···π (X = Cl, Br, I) and C-X···||| (acetylene) contacts (X = Cl, Br). The theoretical analysis of the non-covalent interactions between host and guest confirmed the high shape complementarity with fully enveloping dispersive interactions between the binding partners, rationalizing the high degree of enantioselectivity in the previously communicated complexation of (±)-trans-1,2-dimethylcyclohexane. This study also showed that (±)-trans-1,2-dihalocyclohexanes (X = Cl, Br) engage in significant halogen bonding (XB) interactions C-X···||| with the hosts. Slow host-guest exchange on the NMR time scale enabled the characterization of the encapsulated guests in solution, demonstrating that the complexes have identical geometries to those seen in the solid state, with the guests bound in axial/diaxial conformations.

Alleno-Acetylenic Cage (AAC) Receptors: Chiroptical Switching and Enantioselective Complexation of trans-1,2-Dimethylcyclohexane in a Diaxial Conformation.

Four enantiopure 1,3-diethynylallenes (DEAs) with OH termini were attached to the rim of a resorcin[4]arene cavitand. The system undergoes conformational switching between a cage form, closed by a circular H-bonding array, and an open form, with the tertiary alcohol groups reaching outwards. The cage form is predominant in apolar solvents, and the open conformation in small, polar solvents. Both states were confirmed in solution and in X-ray co-crystal structures. ECD spectra of the alleno-acetylenic cages (AACs) are highly conformation sensitive, the longest wavelength Cotton effect at 304 nm switches from Δϵ=+191 m-1 cm-1 for open (P)4 -AAC⊂acetonitrile to Δϵ=-691 m-1 cm-1 (ΔΔϵ=882 m-1 cm-1 ) for closed (P)4 -AAC⊂cyclohexane. Complete chiral resolution of (±)-trans-1,2-dimethylcyclohexane was found in the X-ray structures, with (P)4 -AAC exclusively bound to the (R,R)- and (M)4 -AAC to the (S,S)-guest. Guest inclusion occurs in a higher energy diaxial conformation.

Update on hormesis and its relation to homeopathy.

INTRODUCTION: Hormesis is a dose-response relationship characterized by a biphasic dose response to stressors with a low dose stimulation and a high dose inhibition. The first systematic description of hormesis appeared toward the close of the 18th century by the German pharmacology professor Hugo Schulz. The stressor agent can be any agent or factor capable of causing a deleterious effect. The biological systems can be diverse: bacteria, fungi, algae, yeasts, animals, humans, protozoa and plants. The range of endpoints covers longevity, reproduction, cancer, survival, growth, metabolic effects and others. Hormesis is a nonspecific phenomenon, which can occur in any biological system and can be caused by any stressor. It is quantifiable and reproducible. The apparent similarity between the basic principle of hormesis and homeopathy's Similia Principle, together with the homeopathic claim that hormesis validates homeopathy caused its marginalization, and its rejection during the past century by central figures in pharmacology. Recent years have seen a slight renaissance in the conventional scientific attitude towards hormesis. METHOD: We compared hormesis and homeopathy. RESULT: There is no convincing evidence of similarity between these two systems. Moreover, there are several crucial differences between them, which seem to refute any idea that they stem from the same root. This paper discusses these differences. The rejection of hormesis on grounds of its similarity to homeopathy is unjustified. CONCLUSION: The authors suggest exploring the differences between both systems. Such exploration may answer the key question of whether they do indeed share a root or embrace the same principles. Such exploration may also spur research within both systems to answer further open questions.

Unequal brothers : are homeopathy and hormesis linked?

The debate between those who believe homeopathy and hormesis derive from the same root and those who believe the two are different phenomena is as old as hormesis. It is an emotionally loaded discussion, with both sides fielding arguments which are far from scientific. Careful analysis of the basic paradigms of the two systems questions the claim of the homeopaths, who find similarities between them. The authors discuss these paradigms, indicating the differences between the claims of homeopathy and hormesis. It is time for thorough and serious research to lay this question to rest. One possible approach is to compare the activity of a hormetic agent, prepared in the usual way, with that of the same agent in the same concentration prepared homeopathically by serial dilution and succussion.

Prevalence and characteristics of cluster B personality disorder in a consultation-liaison psychiatry practice.

OBJECTIVE: Quantitative studies on cluster B-personality disorder (PD) in the general hospital are scarce. The aim of this study is to examine the prevalence and characteristics of cluster B-PD patients in a consultation-liaison practice. METHODS: Files of 258 consecutive patients referred for psychiatric consultation were examined. Cluster B patients were compared with the remaining patients. RESULTS: Eleven point six percent of these patients were diagnosed with a cluster B-PD. On univariate analysis, cluster B patients were more likely to be younger (P < 0.001), unmarried (P = 0.005), and without organic medical illness (P < 0.001).These patients had a shorter admission (P < 0.0001), and were more frequently treated in the emergency room (66.6% versus 37.5%, P = 0.02).There was a trend toward comorbid substance use disorder (P = 0.09). On multivariate analysis, cluster B patients presented significantly with self-harming behavior/ideation (80% versus 18%, OR = 12.07; 95% CI = 4.37-33.31; P < 0.0001). CONCLUSIONS: In view of the high prevalence of cluster B-PD in our preliminary study, general hospital staff requires practical skills for managing these high-maintenance patients. We believe that this study and further research will promote evidence-based recommendations for consultation-liaison psychiatrists.

[Martin Heidegger, beneficence, health, and evidence based medicine--contemplations regarding ethics and complementary and alternative medicine].

Beneficence is considered a core principle of medical ethics. Evidence Based Medicine (EBM) is used almost synonymously with beneficence and has become the gold standard of efficiency of conventional medicine. Conventional modern medicine and EBM in particular are based on what Heidegger called calculative thinking, whereas complementary medicine (CM) is often based on contemplative thinking according to Heidegger's distinction of different thinking processes. A central issue of beneficence is the striving for health and wellbeing. EBM is little concerned directly with wellbeing, though it does claim to aim at improving quality of life by correcting pathological processes and conditions like infectious diseases, ischemic heart disease but also hypertension and hyperlipidemia. On the other hand, wellbeing is central to therapeutic efforts of CM. Scientific methods to gauge results of EBM are quantitative and based on calculative thinking, while results of treatments with CM are expressed in a qualitative way and based on meditative thinking. In order to maximize beneficence it seems important and feasible to use both approaches, by combining EBM and CM in the best interest of the individual patient.

Evaluation of hydrogen-bond acceptors for redox-switchable resorcin[4]arene cavitands.

Various H-bond acceptor groups were evaluated for their propensity to induce conformational switching between the kite and vase forms of diquinone-diquinoxaline resorcin[4]arene cavitands upon redox interconversion. The H-bond acceptors were placed on the quinoxaline walls with the purpose of stabilizing the vase form only in the reduced hydroquinone state of the cavitand by forming H-bonds with the hydroquinone OH groups. Design guidelines for successful acceptors were derived. The carboxamide acceptor was shown to be the best candidate. Based on this moiety, a redox-switchable triptycene-based basket that can completely sterically encapsulate a guest in its closed vase conformation was prepared. The basket binds small molecule guests with association constants of up to 10(4) M(-1) in mesitylene-d12 and exhibits slow guest exchange kinetics with a half-life for guest release in the order of 10(4) s.

A validated questionnaire to assess the knowledge of psychiatric aspects of alcohol use disorder.

BACKGROUND: To the best of our knowledge, there is no validated instrument for measuring knowledge of psychiatric aspects of alcohol use disorder (AUD) amongst medical students. Our aim was to develop an instrument for this purpose and to describe the instrument's psychometric properties. We also investigated whether the instrument could demonstrate a significant change in scores following an educational intervention consisting of a 60-minute PowerPoint lecture on AUD, associated handouts, and role-plays. METHODS: The Knowledge of Psychiatric Aspects of Alcohol Questionnaire (KPAAQ) was developed from the Kaplan and Saddock textbook synopsis chapter on alcohol related disorders. The questionnaire included 6 categories of clinically relevant material: metabolism of alcohol, short-term effects of alcohol, long-term effects of alcohol, AUD, alcohol withdrawal, and alcohol use in pregnancy. The KPAAQ was administered to 75 medical students in Years 4 and 5 from the Hebrew University in Jerusalem, Israel, during a relevant clinical rotation. Following the initial administration of the KPAAQ, the students attended a 60-minute lecture (in Hebrew) based on material from the University of Sydney's learning module on alcohol. The KPAAQ was readministered to the students immediately following the lecture. RESULTS: The KPAAQ demonstrated good reliability (Cronbach α =.92 for all questions) and validity r(209) =.674, P <.001. Knowledge of alcohol and alcoholism significantly increased after the educational intervention (F(2, 154) = 151.60, P <.001). Post hoc comparisons using the Scheffe test revealed a significant positive change in knowledge after students received the intervention (mean difference = 33, P <.001). CONCLUSIONS: These initial findings suggest that the KPAAQ is a reliable and valid instrument for assessing medical student knowledge of psychiatric aspects of AUD over 6 clinical categories.