The adulterated XANAX pill: a fatal intoxication with etizolam and caffeine.

A 49-year old man was found dead at home next to a glass containing a dried, white, crystalline substance and near a bag containing pills with the imprint XANAX, the trade name of alprazolam. A comprehensive screening of material collected during the autopsy revealed the presence of etizolam and caffeine in lethal concentrations (0.77 µg/mL and 190 µg/mL) but no trace of alprazolam. Benzodiazepine analogue etizolam is rarely prescribed in Germany, and as a result there are not many reports about fatal cases. It has anxiolytic, hypnotic, sedative and muscle-relaxant properties and is used for the short-term treatment of anxiety and panic attacks. The purine alkaloid caffeine, conversely, is the most widely used central nervous system stimulant. The following report outlines potentially the first reported case of a lethal combination of the downer etizolam and the upper caffeine in medical literature.

Stage-specific expression of the proline-alanine transporter in the human pathogen Leishmania.

Leishmania are obligatory intracellular parasites that cycle between the sand fly midgut (extracellular promastigotes) and mammalian macrophage phagolysosomes (intracellular amastigotes). They have developed mechanisms of adaptation to the distinct environments of host and vector that favor utilization of both proline and alanine. LdAAP24 is the L. donovani proline-alanine transporter. It is a member of Leishmania system A that translocates neutral amino acids. Since system A is promastigote-specific, we aimed to assess whether LdAAP24 is also expressed exclusively in promastigotes. Herein, we established that upon exposing L. donovani promastigotes to amastigote differentiation signal (pH 5.5 and 37 °C), parasites rapidly and completely degrade LdAAP24 protein in both axenic and in spleen-derived amastigotes. In contrast, LdAAP24 mRNA remained unchanged throughout differentiation. Addition of either MG132 or Bafilomycin A1 partially inhibited LdAAP24 protein degradation, indicating a role for both lysosome- and proteasome-mediated degradation. This work provides the first evidence for post-translational regulation of stage-specific expression of LdAAP24.

Synthesis, stability and Li-ion mobility of nanoconfined Li2B12H12.

This communication presents the first synthesis of nanoconfined Lithium closo-borate, Li2B12H12, using nanoporous SiO2 as scaffold. The yield of Li2B12H12 is up to 94 mol%. The as-synthesized nanoconfined Li2B12H12 exhibits a structural transition around 380 °C and conversion to H-deficiency Li2B12H12-x at 580 °C.

Controllable decomposition of Ca(BH4)2 for reversible hydrogen storage.

Ca(BH4)2 could reversibly store 9.6 wt% hydrogen based on the overall reaction of Ca(BH4)2 → 1/3CaB6 + 2/3CaH2 + 10/3H2. Formation of CaB6 instead of elemental boron and/or high boranes (e.g. CaB12H12) in the dehydrogenation process is crucial for rehydrogenation. Here, we reported two experimental protocols regarding how to form CaB6 from the decomposition of Ca(BH4)2: (1) decomposition below the melting point, e.g. 350 °C via CaB2H6 to CaB6 and (2) decomposition above the melting point, e.g. 400 °C via elemental boron to CaB6.

A highly stable sodium solid-state electrolyte based on a dodeca/deca-borate equimolar mixture.

Na2(B12H12)0.5(B10H10)0.5, a new solid-state sodium electrolyte is shown to offer high Na+ conductivity of 0.9 mS cm-1 at 20 °C, excellent thermal stability up to 300 °C, and a large electrochemical stability window of 3 V including stability towards sodium metal anodes, all essential prerequisites for a stable room-temperature 3 V all-solid-state sodium-ion battery.

[Unexpected Complications in the Withdrawal Treatment of the Research Chemical AH-7921]. / Unerwartete Komplikationen während des Entzugs vom Research Chemical AH-7921.

We describe the case of a young male patient who had consumed the morphine-like substance AH-7921 which is available via the internet. He was initially admitted to hospital because of obstipation and presented within a day of inpatient treatment for the first time with a generalized tonic-clonic epileptic seizure with subsequent urinary retention. Within a few hours, the patient then also developed bradycardia, while at the same time describing symptoms of physical opioid withdrawal which gradually deteriorated within the following hours. We initiated a treatment with buprenorphine which resulted in a considerable reduction of withdrawal symptoms, so the patient could be discharged from hospital.

[Interdisciplinary treatment of chronic low back pain: psychological aspects and personality traits]. / Traitement interdisciplinaire des lombalgies chroniques: aspects psychologiques et de personnalité.

Evidence on chronic low back pain treatments stresses the need for a multidimensional approach that aims a biopsychosocial rehabilitation. The caregiver team of the rheumatology division of the University Hospitals of Geneva has successfully applied this approach over the last years and this article emphasizes the value of a close collaboration with the division of liaison psychiatry. The use of cognitive-behavioral and psycho-educational techniques guaranties the definition of patient-centred and measurable treatment objectives. The inclusion of a psychotherapy group promotes free expression and sharing of psychological distress. Assessment of personality traits allows for considering the global nature of the patients rather than merely aiming the normalization of their deviant aspects.

[Chronic pain in elderly people: psychosocial dimension]. / Douleurs chroniques chez les personnes âgées: dimensions psychologiques.

Chronic pain in elderly people requires to take into account somatic co-morbidities as well as its psychosocial dimensions. Chronic pain often represents a distress signal addressed to the environment and the care providers. Psychological suffering or mood disorders can be presented in the form of somatic complaints often associated with functional impairments, sometimes severe. Therapeutic care has to address functionality through an image-enhancing approach aiming to summon the patients' resources. The treatment of a concomitant depressive state necessitates a true commitment from the therapist. Its benefits are documented in elderly patients. Analgesic treatment as a whole will seek in particular to restore feelings of self-esteem and help the patient recover a good quality of life.

[Hypnosis and anxiety problems]. / L'hypnose et les troubles anxieux.

This article describes how hypnosis can be used as an efficient technique in treating patients with anxious disorders. Hypnosis can be used to achieve a better control of the anxious symptoms through relaxation. It allows the patient to anticipate the anxiety triggering events. This technique also allows the patient to mentalise and integrate traumatic events, therefore helping him to prevent the post-traumatic anxious symptoms.

[Chronic pain and depression]. / Douleurs chroniques et dépression: un aller-retour?

Chronic pain and depression are frequently associated. Links between them are numerous and well documented. It is known for example that depression is associated with a greater number and higher intensity of pain symptoms. Similarly the presence of pain complicates the diagnostic evaluation and aggravates the prognosis of depression. The question of the causality link has no clear answer. Taking care of these patients implies to acknowledge the different aspects of their suffering in a holistic bio-psycho-social model. Treatment or medication, for instance antidepressants, should be a post-scriptum to the construction of a therapeutic relationship.

Psychiatric comorbidity in patients evaluated for chronic epilepsy: a differential role of the right hemisphere?

INTRODUCTION: Psychiatric disorders are known to occur frequently in chronic epilepsy. The aim of this study is to investigate the prevalence of psychiatric comorbidity and its relationship to regional cerebral dysfunction in patients admitted to a tertiary epilepsy center for epilepsy surgery. METHODS: 217 patients were investigated. A presurgical workup was performed and allowed precise localization of the epileptogenic focus in 156 patients. Sixty-one patients had multifocal or generalized discharges. After 1-3 psychiatric interviews, a psychiatric diagnosis was made (DSM-IV classification). RESULTS: Psychiatric comorbidity was found in 85 patients (39%), more often in those with right or bilateral hemispheric dysfunction (74%, p = 0.04) with no difference between temporal or extratemporal foci location frequency. Additionally, patients with psychiatric disorders were less likely to undergo epilepsy surgery compared to 'epilepsy-only' patients (p = 0.003), despite similar good outcome in patients with and without psychiatric comorbidity. CONCLUSIONS: Right-sided or bilateral foci seem to represent a risk factor for psychiatric comorbidity in epilepsy, although we did not find any particular association between a psychiatric syndrome and focus localization. Recognition and treatment of psychiatric comorbidity is of major importance since its presence may interfere with patient's decision making for epilepsy surgery treatment.

Difficulties of residents in training in end-of-life care. A qualitative study.

Residents in training are first-line physicians in hospital settings and they are in the process of developing knowledge and mastering clinical skills. They have to confront complex tasks calling upon their personal background, professional identity and relationships with the patients. We conducted a qualitative study investigating the difficulties they perceive in end-of-life care. In all, 24 consecutive residents were presented with a written query asking them to indicate the difficulties they identify in the management of patients hospitalised for end-of-life care. Their responses were submitted to content analysis. Physicians' mean age was 28 +/- 2.2 years, 37% were women, average postgraduate training duration was 2.5 +/- 1.3 years. Content analysis elicited eight categories of difficulties: ability to provide adequate explanations, understand the patients' needs, have sufficient theoretical knowledge, avoid flight, avoid false reassurance, manage provision of time, face one's limits as a physician and be able to help despite everything. Residents' responses showed that they identify the complexity of care in terminally-ill patients early in their training. Their responses pointed to the 'right distance' in-between getting involved and preserving oneself as a dimension of major importance.

[Quick detection of depression: a significant clinical issue]. / Détection rapide de la dépression: un problème important.

Detection of depression is a major issue for public health. In a study performed in the HUG, we tested the concordance of the self-report Patient Health Questionnaire (PHQ-9) with the Hamilton depression scale (HDRS) administered by a psychiatrist, as measures of the severity of depression. The comparison shows that the PHQ-9 distinguishes subjects with and without depressive disorders and is a good screener for severe disorders but has a poor capacity of discrimination when disorders are mild. This instrument is insufficient if the aim is to detect mild or moderate depressive disorders, wich is the most frequent occurrence in patients consulting primary care physicians.

[Length of hospital stay, discharge planning, and policy regarding the shortening of hospital stays: patients'and hospital care providers'point of view]. / Durée d'hospitalisation, programmation de la sortie et politique de raccourcissement des séjours: avis des patients et des soignants.

BACKGROUND: In the context of health care cost containment, we interviewed hospitalized patients and their health care teams concerning the length of stay they considered necessary and hospital discharge. Patients were also interviewed on the present tendency to shorten hospital stays. METHODS: Prospective study conducted in a subacute internal medicine ward with 254 consecutive patients and their health care teams. RESULTS: The mean evaluation of the length of stay considered as necessary was not significantly different between patients (9.7 days, SD=9.5) and their health care teams (9.6, SD=8.5). However, agreement between the two parties was moderate (r=0.64). Hospital discharge was considered as planned in similar proportions (18% vs 22% respectively), but was reported as more 'assured' by health care teams than by patients (p<0.001). Health care teams and patients approved discharge planning in 200 cases (63.3%), but agreement was only moderate (Kappa 0.43, IC 95%=0.34-0.51). Regarding the tendency to shorten hospital stays, patients'responses were favorable in only 9%, clearly unfavorable in 17% and disclosed explicit fears in 54% of the cases. CONCLUSIONS: These results show that what patients and health care teams consider the necessary length of stay and the right time for hospital discharge can diverge notably. They highlight the difficulties of medical decisions in the context of cost containment, and the fundamentally asymmetrical character of the relationship between patients and health care teams.

Senescence-related gene expression profiles of rosette leaves of Arabidopsis thaliana: leaf age versus plant age.

Senescence is a form of programmed cell death (PCD) which leads to the death of whole organs, e.g., leaves or flowers, and eventually to the death of entire plants. Like all forms of PCD, senescence is a highly regulated and energy consuming process. Senescence parameters, like protein content, chlorophyll content, expression of photosynthesis-associated genes or senescence-associated genes (SAGs), reveal that senescence occurs in old leaves derived from young plants (6 week old) as well as in young leaves derived from older plants (8 week old), indicating that it is governed by the actual age of the leaves. In order to analyse the differential gene expression profiles during leaf senescence, hybridizations of high-density genome arrays were performed with: i) individual leaves within the rosette of a 6-week-old plant and ii) leaves of the same position within the rosette but harvested from plants of different ages, ranging from 5 to 8 weeks. Cluster and genetree analyses, according to the expression pattern revealed that genes which are up-regulated with respect to the age of the entire plant, showed completely different expression profiles with respect to the age of the individual leaves within one rosette. This was observed even though the actual difference in leaf age was approximately the same. This indicates that gene expression appears to be governed by different parameters: i) the age of the individual leaf and ii) the age and developmental stage of the entire plant.

Rhesus factors and ammonium: a function in efflux?

Completion of fungal, plant and human genomes paved the way to the identification of erythrocytic rhesus proteins and their kidney homologs as ammonium transporters.

Quantitative Determination of Resin Loading in Solid-Phase Organic Synthesis Using (13)C MAS NMR.

The use of quantitative carbon nuclear magnetic resonance spectroscopy ((13)C NMR) for the determination of resin loadings has been investigated. Magic angle spinning (MAS) NMR spectra have been obtained for solvent-swollen resins on a conventional 7 mm CP/MAS probe using the two pulse phase modulation (TPPM) proton decoupling sequence. Loadings of resin-bound organic compounds were evaluated via addition of tetrakis(trimethylsilyl)silane as reference or using the carbon resonances of the polymeric resin material as an internal standard. Results for several functionalized Wang and trityl resins are consistent with those obtained using well-established analytical methods. The (13)C NMR method has interesting applications in the field of solid-phase organic synthesis (SPOS), since no functional group acting as a support for the attachment of a quantifiable chromophore must be available in the material of interest.

Hypersensitivity of an Arabidopsis sugar signaling mutant toward exogenous proline application.

In transgenic Arabidopsis a patatin class I promoter from potato is regulated by sugars and proline (Pro), thus integrating signals derived from carbon and nitrogen metabolism. In both cases a signaling cascade involving protein phosphatases is involved in induction. Other endogenous genes are also regulated by both Pro and carbohydrates. Chalcone synthase (CHS) gene expression is induced by both, whereas the Pro biosynthetic Delta(1)-pyrroline-5-carboxylate synthetase (P5CS) is induced by high Suc concentrations but repressed by Pro, and Pro dehydrogenase (ProDH) is inversely regulated. The mutant rsr1-1, impaired in sugar dependent induction of the patatin promoter, is hypersensitive to low levels of external Pro and develops autofluorescence and necroses. Toxicity of Pro can be ameliorated by salt stress and exogenously supplied metabolizable carbohydrates. The rsr1-1 mutant shows a reduced response regarding sugar induction of CHS and P5CS expression. ProDH expression is de-repressed in the mutant but still down-regulated by sugar. Pro toxicity seems to be mediated by the degradation intermediate Delta(1)-pyrroline-5-carboxylate. Induction of the patatin promoter by carbohydrates and Pro, together with the Pro hypersensitivity of the mutant rsr1-1, demonstrate a new link between carbon/nitrogen and stress responses.