The distinction between normality and psychopathology has long been subject to debate. DSM-III and DSM-IV provided a definition of mental disorder to help clinicians address this distinction. As part ...of the process of developing DSM-V, researchers have reviewed the concept of mental disorder and emphasized the need for additional work in this area. Here we review the DSM-IV definition of mental disorder and propose some changes. The approach taken here arguably takes a middle course through some of the relevant conceptual debates. We agree with the view that no definition perfectly specifies precise boundaries for the concept of mental/psychiatric disorder, but in line with a view that the nomenclature can improve over time, we aim here for a more scientifically valid and more clinically useful definition.
The C–H borylation of indolizines has not previously been reported. In this communication, we describe our preliminary efforts to apply this chemistry to this scaffold and contrast this approach to ...directed metalation. Through these methodologies, it was possible obtain a library of substituted indolizines functionalized on both the pyridinic and pyrrole rings.
Indolizines represent a privileged class of heterocycles with several applications in Organic Synthesis and Medicinal Chemistry. In this work, the C–H borylation of aryl indolizines is described for the first time and contrasted to directed metalation. These complementary approaches allowed us to obtain a variety of substituted indolizines functionalized on both the pyridinic and pyrrole rings.
The application of carbon nanotubes in biology is promising owing to their many unique and favorable properties, from high tensile strength and high electrical conductivity to the ability to be wet ...by water. The use of nanotubes for the immobilization and visualization of DNA and proteins is illustrated. For example, good transmission electron microscopy images of DNA strands on the surface of carbon nanotubes can be obtained upon heavy‐atom labeling. The potential biological applications of carbon nanotubes are also detailed, including their use as delivery vessels and in biomimetic systems.
The new anticancer complex cis‐PtCl2(15NH3)(2‐picoline) (1) and its 3‐picoline analogue differ from cisplatin in reactivity. The hydrolysis rates for each chloride ligand of the two complexes and the ...pKa values of their aqua and diaqua adducts have been determined by 1H, 15N 2 D NMR spectroscopy. These data, together with X‐ray crystal structures, provide an explanation for the difference.
To review the background of current ethical standards for the conduct of perinatal mental health research and describe the ethical challenges in this research domain.
Current literature reflects a ...growing sentiment in the scientific community that having no information regarding the impact of psychiatric treatment on the mother and developing fetus/infant poses dangers that may exceed the risks involved in research. However, without sufficient consensus across the scientific community, both regulatory bodies and perinatal researchers find themselves without a framework for decision making that satisfactorily limits the risks and facilitates the benefits of participation of pregnant and lactating women in clinical research.
Psychiatric research in perinatal mental health is critically important as it enables clinicians and patients to participate in informed decision-making concerning treatment for psychiatric disorders. Specific areas of concern include fetal safety, maternal risk, the therapeutic misconception, commercial interests, forensic/legal issues, the informed consent process, and study design. Developing guidelines that address ethical challenges and include the views and concerns of multiple stakeholders could improve the access of perinatal women to the benefits of participation in mental health research in addition to providing evidence-based mental healthcare for this subpopulation.
The authors consider arguments for and against the formal inclusion of mentally ill patients and their families in the deliberative processes leading to DSM-V. These discussions involve six key ...issues: the scientific status of psychiatric classifications; public policy and political considerations; the practical implications of widening the review process; the capacities of lay members of the workgroups; freedom of expression and the openness of the review process; and the uniqueness of consumer perspectives. The authors conclude that involving patients and families in the DSM review process is supportable on both scientific and public policy grounds.
Abstract Reactions between the anticancer drug titanocene dichloride (Cp2TiCl2) and various nucleotides and their constituents in aqueous solution or N,N-dimethylformamide (DMF) have been ...investigated by 1H and 31P NMR spectroscopy and in the solid state by IR spectroscopy. In aqueous solution over the pH* (pH meter reading in D2O) range 2.3-6.5, CMP forms one new species with Ti(IV) bound only to the phosphate group. In acidic media at pH*<4.6, three species containing titanocene bound to the phosphate group of dGMP, AMP, dTMP and UMP are formed rapidly. The bases also appear to influence titanocene binding. Only one of these Ti(IV)-bound species can be detected in the pH* range of 4.6-6.5 in each case. The order of reactivity towards Cp2TiCl2(aq) at pH* ca. 3 is GMP>TMP approximately AMP > CMP. At pH* > 7.0, hydrolysis of Cp2TiCl2 predominated and little reaction with the nucleotides was observed. Binding of deoxyribose 5'-phosphate and 4-nitrophenyl phosphate to Cp2TiCl2(aq) via their phosphate groups was detected by 31P NMR spectroscopy, but no reaction between Cp2TiCl2(aq) and deoxyguanosine, 9-ethylguanine or deoxy-D-ribose was observed in aqueous solution. The nucleoside phosphodiesters 3',5'-cyclic GMP and 2',3'-cyclic CMP did not react with Cp2TiCl2(aq) in aqueous solution; however, in the less polar solvent DMF, 3',5'-cyclic GMP coordination to Cp2Ti2+ via its phosphodiester group was readily observed. Binding of titanocene to the phosphodiester group of the dinucleotide GpC was also observed in DMF by 31P NMR. The nucleoside triphosphates ATP and GTP reacted more extensively with Cp2TiCl2(aq) than their monophosphates; complexes with bound phosphate groups were formed in acidic media and to a lesser extent at neutral pH. Cleavage of phosphate bonds in ATP (and GTP) by Cp2TiCl2(aq) to form inorganic phosphate, AMP (or GMP) and ADP (or GDP) was observed in aqueous solutions. In addition, titanocene binding to ATP was not inhibited by Mg(II), but the ternary complex titanocene-ATP-Mg appeared to form. These reactions contrast markedly with those of the drug cisplatin, which binds predominantly to the base nitrogen atoms of nucleotides and only weakly to the phosphate groups. The high affinity of Ti(IV) for phosphate groups may be important for its biological activity.
Using the methods of philosophical analysis, we provide a rejoinder to R. L. Spitzer's (2001) response to our own consideration of the DSMs first published in 1994. Then as now, our major contention ...has been that the DSM contents and process have been insufficiently explicit in their various value commitments, choices, and decisions. Spitzer raises four major points in his commentary, concerning our claims about the "value naivete" of past DSMs, his contention that the goals of DSM-III and III-R were not "inherently" in conflict, about our allegations of the DSM architects preferring reliability over validity, and various DSM critics' failure to offer a viable alternative to the DSMs. We address each of Spitzer's main points in turn, appealing to Spitzer's own work while acknowledging his leadership role in addressing value issues in mental disorder classification.
Engel's biopsychosocial model, while unifying the sciences relevant to medicine under general systems theory, is of limited utility in organizing bedside clinical problem solving. The authors ...consider this issue in light of the structure and goals of the clinical encounter. The biopsychosocial model is a model for organizing the sciences relevant to medicine; however, medical/psychiatric practice poses problems both within and outside the scientific realm. Since the biopsychosocial model cannot account for clinical problems to which the methods of science do not apply, the authors seek to facilitate biopsychosocial problem solving by proposing a clinical decision-making model that complements the biopsychosocial model. Their model directs the clinician's attention to three core aspects of the clinical encounter: problems of knowledge, ethics, and pragmatics. The authors reconsider Engel's case of Mr. Glover to demonstrate the anticipatory emphasis of the model. Other clinical examples are used to demonstrate the difficulties arising from mistaking one kind of aspect of medicine for another. When these three aspects of medicine are respected equally, a biopsychosocial practice is unavoidable.
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