From Substance Use Disorders in Life to Autopsy Findings: A Combined Case-Record and Medico-Legal Study.

Objectives: Several studies have shown mortality and suicide risk in substance use disorders, and autopsy findings with respect to the used substances. However, there seems to be a gap in the knowledge about substances misused in life and at death at the within-person level. Methods: All consecutive, autopsied patients during 1993 to 1997, who had been in contact with the Addiction Centre in Malmö from 1968, were investigated (365 subjects). Drug misuse in the long-term course noted in case records was related to autopsy findings. Self-inflicted death (suicide/undetermined suicide/accidental overdose) was compared with natural death. Results: Benzodiazepine misuse was associated with a high risk of autopsy findings of the substance in suicide and death of undetermined intent. It was also associated among non-misusers, but less so. An alcohol level above 1‰ was found more often in self-inflicted death. Prescription opioids at autopsy were mainly found in self-inflicted death among non-misusers. Heroin misuse was related to overdose. Central nervous system stimulants (CNS-S) and cannabis were rarely found in self-inflicted death among previous misusers. The overlap between depression in life and antidepressants at death was low. Conclusions: Benzodiazepines and alcohol seem to disinhibit suicidal tendencies. Suicide risk among users of cannabis and CNS-S may be related to other risk factors than acute use. Implications for suicide prevention are discussed.

Antibiotic-Free Cationic Dendritic Hydrogels as Surgical-Site-Infection-Inhibiting Coatings.

A non-toxic hydrolytically fast-degradable antibacterial hydrogel is herein presented to preemptively treat surgical site infections during the first crucial 24 h period without relying on conventional antibiotics. The approach capitalizes on a two-component system that form antibacterial hydrogels within 1 min and consist of i) an amine functional linear-dendritic hybrid based on linear poly(ethylene glycol) and dendritic 2,2-bis(hydroxymethyl)propionic acid, and ii) a di-N-hydroxysuccinimide functional poly(ethylene glycol) cross-linker. Broad spectrum antibacterial effect is achieved by multivalent representation of catatonically charged ß-alanine on the dendritic periphery of the linear dendritic component. The hydrogels can be applied readily in an in vivo setting using a two-component syringe delivery system and the mechanical properties can accurately be tuned in the range equivalent to fat tissue and cartilage (G' = 0.5-8 kPa). The antibacterial effect is demonstrated both in vitro toward a range of relevant bacterial strains and in an in vivo mouse model of surgical site infection.

Clinical Prediction of Suicide and Undetermined Death: A Pseudo-Prospective Clinical and Medico-Legal Study of Substance Abusers.

This study examines aspects of prediction of suicide and death of undetermined intent. We investigated all consecutive, autopsied patients between 1993 and 1997 who had been in contact with the Addiction Centre in Malmö from 1968 onwards. The staff was asked, shortly after autopsy but before they knew of the manner of death, if they thought the patient had committed suicide. The case records were blindly evaluated, and toxicological autopsy findings for alcohol in blood samples investigated. The specificity of prediction was 83% and significantly more often correct than the sensitivity, which was only 45% for suicide and for suicide/death of undetermined intent (93% versus 39%). Suicidal communication was more often considered non-serious before death of undetermined intent than before suicide. The former could be predicted by ideation but not by suicide attempt reported in case records, unlike suicide, which was predicted by both. The undetermined group also showed higher levels of alcohol in the blood at autopsy. We concluded that more serious clinical investigation of suicidal feelings, which may be hidden and not taken seriously, and treatment of alcohol use disorders with active follow-up appear urgent in the efforts to prevent suicide.

Dual-purpose PEG scaffolds for the preparation of soft and biofunctional hydrogels: the convergence between CuAAC and thiol-ene reactions.

Orthogonally functionalized PEGs displaying alkenes and azides have been prepared and their dual-purpose scaffolding potential was exploited via click chemistry for controlled insertion of biorelevant moieties as well as facile fabrication of soft, non-toxic and degradable hydrogels.

Templating gold surfaces with function: a self-assembled dendritic monolayer methodology based on monodisperse polyester scaffolds.

The antibiotic resistance developed among several pathogenic bacterial strains has spurred interest in understanding bacterial adhesion down to a molecular level. Consequently, analytical methods that rely on bioactive and multivalent sensor surfaces are sought to detect and suppress infections. To deliver functional sensor surfaces with an optimized degree of molecular packaging, we explore a library of compact and monodisperse dendritic scaffolds based on the nontoxic 2,2-bis(methylol)propionic acid (bis-MPA). A self-assembled dendritic monolayer (SADM) methodology to gold surfaces capitalizes on the design of aqueous soluble dendritic structures that bear sulfur-containing core functionalities. The nature of sulfur (either disulfide or thiol), the size of the dendritic framework (generation 1-3), the distance between the sulfur and the dendritic wedge (4 or 14 Å), and the type of functional end group (hydroxyl or mannose) were key structural elements that were identified to affect the packaging densities assembled on the surfaces. Both surface plasmon resonance (SPR) and resonance-enhanced surface impedance (RESI) experiments revealed rapid formation of homogenously covered SADMs on gold surfaces. The array of dendritic structures enabled the fabrication of functional gold surfaces displaying molecular covering densities of 0.33-2.2 molecules·nm(-2) and functional availability of 0.95-5.5 groups·nm(-2). The cell scavenging ability of these sensor surfaces for Escherichia coli MS7fim+ bacteria revealed 2.5 times enhanced recognition for G3-mannosylated surfaces when compared to G3-hydroxylated SADM surfaces. This promising methodology delivers functional gold sensor surfaces and represents a facile route for probing surface interactions between multivalently presented motifs and cells in a controlled surface setting.

Increased water transport in PDMS silicone films by addition of excipients.

The development of new adhesive wound care products intended for an application over a prolonged time requires good water transporting properties of the adhesive for the maintenance of a suitable environment around the wound. The ability of polydimethylsiloxane (PDMS)-based silicone films to transport water has led to its use in skin pressure-sensitive adhesives and it would be advantageous to find ways for controlling or increasing water transport across PDMS films in order to be able to develop improved skin adhesives. In this study we present a way to increase water transport in such films by the addition of hydrophilic excipients. Three hydrophilic additives, highly water-soluble sucrose and the two superabsorbent polymers (SAP) Carbopol® and Pemulen™, were investigated. The effect of the excipients was characterized by water transport studies, swelling tests, scanning electron microscopy imaging and confocal microscopy. The cross-linked polymers, primarily Pemulen™, were efficient water transport enhancers, whereas sucrose did not show any effect. The effect of the additives seemed to correlate with their water binding capacity. For SAPs the formation of a percolating structure by swollen polymer was also suggested, which enhances water penetration by the higher volume fraction of areas with a higher diffusion constant (swollen SAP), leading to a faster transport through the entire film.

Number of addictive substances used related to increased risk of unnatural death: a combined medico-legal and case-record study.

BACKGROUND: Substance use disorders have repeatedly been found to lead to premature death, i.e. drug-related death by disease, fatal intoxications, or trauma (accidents, suicide, undetermined suicide, and homicide). The present study examined the relationship between multi-drug substance use and natural and unnatural death. METHODS: All consecutive, autopsied patients who had been in contact with the Addiction Centre in Malmö University Hospital from 1993 to 1997 inclusive were investigated. Drug abuse was investigated blindly in the case records and related to the cause of death in 387 subjects. RESULTS: Every substance apart from alcohol used previously in life added to the risk of unnatural death in a linear way. There were independent increased risks of fatal heroin overdoses or undetermined suicide. Death by suicide and violent death were unrelated to additional abuse. CONCLUSION: The number of drugs used was related to an increased risk of unnatural death by undetermined suicide (mainly fatal intoxications) and heroin overdose.

Matrix-assisted and polymer-assisted laser desorption/ionization time-of-flight mass spectrometric analysis of low molecular weight polystyrenes and polyethylene glycols.

Recently, matrices based on oligomers of dioxin and thiophene (polymer-assisted laser desorption/ionization (PALDI)) have been described for mass spectrometric (MS) analysis of low molecular weight compounds (Woldegiorgis A, von Kieseritzky F, Dahlstedt E, Hellberg J, Brinck T, Roeraade J. Rapid Commun. Mass Spectrom. 2004; 18: 841-852). In this paper, we report the use of PALDI matrices for low molecular weight polymers. An evaluation with polystyrene and polyethylene glycol showed that no charge transfer ionization occurs. Ionization is mediated through metal ion adduction. Comparison of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) data for two very low molecular weight polymers with data obtained from size-exclusion chromatography (SEC) revealed a systematic difference regarding mean molecular weight and dispersity. Further, the mass spectra obtained with PALDI matrices had a higher signal-to-noise ratio than the spectra obtained with conventional matrices. For polymers with higher molecular weights (>1500 Da), the conventional matrices gave better performance. For evaluation of the MALDI spectra, three non-linear mathematical models were evaluated to model the cumulative distributions of the different oligomers and their maximal values of Mw, Mn and PDI. Models based on sigmoidal or Boltzmann equations proved to be most suitable. Objective modeling tools are necessary to compare different sample and instrumental conditions during method optimization of MALDI analysis of polymers, since the bias between MALDI and SEC data can be misleading.