Venous access and care: harnessing pragmatics in harm reduction for people who inject drugs

Aim To explore the facilitators of long‐term hepatitis C avoidance among people who inject drugs. Design We employed a qualitative life history design. Setting Recruitment took place through low‐threshold drug services and drug user networks in South East and North London. Participants were interviewed at the recruitment services or in their homes. Participants The sample comprised 35 people who inject drugs, 20 of whom were hepatitis C antibody‐negative. Participants' average injecting trajectory was 19 years (6–33), with 66% primarily injecting heroin, and 34% a crack and heroin mix. Nine (26%) of the sample were female and the average age was 39 years (23–53). Measurements Two interviews were conducted with each participant, with the second interview incorporating reference to a computer‐constructed life history time‐line. Interview accounts were audiorecorded, transcribed verbatim and analysed thematically. Findings Hepatitis C risk awareness was recent and deprioritized by the majority of participants. The facilitation of venous access and care was an initial and enduring rationale for safe injecting practices. Difficult venous access resulted in increased contamination of injecting environments and transitions to femoral injecting. Participants expressed an unmet desire for non‐judgemental venous access information and advice. Conclusions Harm reduction interventions which attend to the immediate priorities of people who inject drugs, such as venous access and care, have the potential to re‐engage individuals who are jaded or confused by hepatitis C prevention messages.     

Attachment of hybridizable oligonucleotides to a silica support and its application for selective extraction of unmodified and antisense oligonucleotides from serum samples

The main aim of the present study was the synthesis of an oligonucleotide-based material with high chemical stability, repeatability and specificity to complementary oligonucleotides. The oligonucleotides were attached to a silica gel surface modified with amino acids during one-step synthesis. The amount of the oligonucleotides immobilized on the support surface had an impact on adsorption effectiveness, due to steric interference. The adsorption capacity corresponds to 4.7 μg of complementary oligonucleotide per 1 mg of material, which reflects 50% of immobilized oligonucleotides. The presented results contain comprehensive studies on hybridization and release of fully complementary, partially complementary, non-complementary and antisense oligonucleotides from the newly synthesized adsorbent. The salt concentration and time period were the most influential parameters in the case of adsorption, while high temperature and low salt content were indispensable for effective desorption. Selectivity studies revealed that the adsorption percentage increases with the decreasing number of base mismatches. Consequently, the desorption of low complementarity oligonucleotides was always greater in comparison with the fully complementary sequence. Furthermore, it was shown that oligonucleotide-based materials may be successfully used for the extraction of antisense oligonucleotides and their metabolites from serum samples with recoveries ranging between 65 and 73%.

The main aim of the present study was the synthesis of an oligonucleotide-based material with high chemical stability, repeatability and specificity to complementary oligonucleotides.     

Immediate and Longer‐Term Stressors and the Mental Health of Hurricane Ike Survivors

Previous research has documented that individuals exposed to more stressors during disasters and their immediate aftermath (immediate stressors) are at risk of experiencing longer‐term postdisaster stressors. Longer‐term stressors, in turn, have been found to play a key role in shaping postdisaster psychological functioning. Few studies have simultaneously explored the links from immediate to longer‐term stressors, and from longer‐term stressors to psychological functioning, however. Additionally, studies have inadequately explored whether postdisaster psychological symptoms influence longer‐term stressors. In the current study, we aimed to fill these gaps. Participants (N = 448) were from population‐based study of Hurricane Ike survivors and completed assessments 2–5 months (Wave 1), 5–9 months (Wave 2) and 14–18 months (Wave 3) postdisaster. Through path analysis, we found that immediate stressors, assessed at Wave 1, were positively associated with Wave 2 and Wave 3 stressors, which in turn were positively associated with Wave 2 and Wave 3 posttraumatic stress and depressive symptoms. Wave 2 posttraumatic stress symptoms were positively associated with Wave 3 stressors, and Wave 1 depressive symptoms were positively associated with Wave 2 stressors. The findings suggest that policies and interventions can reduce the impact of disasters on mental health by preventing and alleviating both immediate and longer‐term postdisaster stressors.     

Functional neuroimaging of the interference between working memory and the control of periodic ankle movement timing

Background

Limited information processing capacity in the brain necessitates task prioritisation and subsequent adaptive behavioural strategies for the dual-task coordination of locomotion with severe concurrent cognitive loading. Commonly observed strategies include prioritisation of gait at the cost of reduced performance in the cognitive task. Alternatively alterations of gait parameters such as gait velocity have been reported presumably to free processing capacity for the benefit of performance in the cognitive task. The aim of this study was to describe the neuroanatomical correlates of adaptive behavioural strategies in cognitive-motor dual-tasking when the competition for information processing capacity is severe and may exceed individuals’ capacity limitations.

Methods

During an fMRI experiment, 12 young adults performed slow continuous, auditorily paced bilateral anti-phase ankle dorsi-plantarflexion movements as an element of normal gait at .5 Hz in single and dual task modes. The secondary task involved a visual, alphabetic N-back task with presentation rate jittered around .7 Hz. The N-back task, which randomly occurred in 0-back or 2-back form, was modified into a silent counting task to avoid confounding motor responses at the cost of slightly increasing the task′s general coordinative complexity. Participants’ ankle movements were recorded using an optoelectronic motion capture system to derive kinematic parameters representing the stability of the movement timing and synchronization. Participants were instructed to perform both tasks as accurately as possible.

Results

Increased processing complexity in the dual-task 2-back condition led to significant changes in movement parameters such as the average inter-response interval, the coefficient of variation of absolute asynchrony and the standard deviation of peak angular velocity. A regions-of-interest analysis indicated correlations between these parameters and local activations within the left inferior frontal gyrus (IFG) such that lower IFG activations coincided with performance decrements.

Conclusions

Dual-task interference effects show that the production of periodically timed ankle movements, taken as modelling elements of the normal gait cycle, draws on higher-level cognitive resources involved in working memory. The interference effect predominantly concerns the timing accuracy of the ankle movements. Reduced activations within regions of the left IFG, and in some respect also within the superior parietal lobule, were identified as one factor affecting the timing of periodic ankle movements resulting in involuntary ‘hastening’ during severe dual-task working memory load. This ‘hastening’ phenomenon may be an expression of re-automated locomotor control when higher-order cognitive processing capacity can no longer be allocated to the movements due to the demands of the cognitive task. The results of our study also propose the left IFG as a target region to improve performance during dual-task walking by techniques for non-invasive brain stimulation.     

Tremor associated with focal and segmental dystonia

Background and purposeTremor occurs in 10–85% of patients with focal dystonia as so-called dystonic tremor or tremor associated with dystonia. The aim of this study was to assess the incidence and to characterize parameters of tremor accompanying focal and segmental dystonia.Material and methodsOne hundred and twenty-three patients with diagnosis of focal and segmental dystonia together with 51 healthy controls were included in the study. For each participant, clinical examination and objective assessment (accelerometer, electromyography, graphic tablet) of hand tremor was performed. Frequency and severity of tremor were assessed in three positions: at rest (rest tremor); with hands extended (postural tremor); during ‘finger-to-nose’ test and during Archimedes spiral drawing (kinetic tremor). Based on the mass load test, type of tremor was determined as essential tremor type or enhanced physiological type.ResultsThe incidence of tremor was significantly higher in dystonic patients as compared to controls (p = 0.0001). In clinical examination, tremor was found in 50% of dystonic patients, and in instrumental assessment in an additional 10–20%. The most frequent type of tremor was postural and kinetic tremor with 7 Hz frequency and featured essential tremor type. In the control group, tremor was detected in about 10% of subjects as 9-Hz postural tremor of enhanced physiological tremor type. No differences were found between patients with different types of dystonia with respect to the tremor incidence, type and parameters (frequency and severity). No correlations between tremor severity and dystonia severity were found either.     

Embryonal tumor with abundant neuropil and true rosettes: an autopsy case-based update and review of the literature

Introduction

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a rare subtype of primitive neuroectodermal tumors first reported in 2000. It is rare among the group of embryonal central nervous system tumors with approximately 50 reported cases. ETANTR has been suggested to be a separate entity among this group of tumors.

Case report

Herein, we present only the second autopsy case of ETANTR, which occurred in a 17-month-old boy, and was located in the brainstem. The tumor was inoperable, and despite chemotherapy, the child died 3 months after initial hospitalization. A brain only autopsy was performed.

Discussion

Neuropathological and neuroimaging examinations suggest ETANTR grew by expansion rather than invasion distorting anatomical structures of the posterior fossa. We suggest that the characteristic histopathological picture of the tumor is the result of multifocal and dispersed germinative activity surrounded by mature neuropil-like areas.

Conclusion

ETANTR is a pediatric tumor occurring in children under 4 with a significantly poor prognosis with more cases and research required to characterize this rare embryonal tumor.     

Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study

Invasive vagus nerve stimulation has been demonstrated to be an effective treatment in major depressive episodes. Recently, a novel non-invasive method of stimulating the vagus nerve on the outer canal of the ear has been proposed. In healthy subjects, a prominent fMRI BOLD signal deactivation in the limbic system was found. The present pilot study investigates the effects of this novel technique of auricular transcutaneous electric nerve stimulation in depressed patients for the first time. A total of 37 patients suffering from major depression were included in two randomized sham controlled add-on studies. Patients were stimulated five times a week on a daily basis for the duration of 2 weeks. On days 0 and 14, the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) were assessed. In contrast to sham-treated patients, electrically stimulated persons showed a significantly better outcome in the BDI. Mean decrease in the active treatment group was 12.6 (SD 6.0) points compared to 4.4 (SD 9.9) points in the sham group. HAMD score did not change significantly in the two groups. An antidepressant effect of a new transcutaneous auricular nerve stimulation technique has been shown for the first time in this controlled pilot study. Regarding the limitations of psychometric testing, the risk of unblinding for technical reasons, and the small sample size, further studies are necessary to confirm the present results and verify the practicability of tVNS in clinical fields.     

Effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline on the protective action of various antiepileptic drugs in the maximal electroshock-induced seizure model: a type II isobolographic analysis

The aim of this study was to characterize the interaction between 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTHIQ—an endogenous parkinsonism-preventing substance) and various antiepileptic drugs [AEDs: clonazepam (CZP), ethosuximide (ETS), gabapentin (GBP), levetiracetam (LEV), tiagabine (TGB) and vigabatrin (VGB)] in the mouse maximal electroshock (MES)-induced seizure model. Results indicate that 1-MeTHIQ in combination with CZP (at the fixed ratios of 50:1 and 25:1), ETS (1:10) and GBP (1:1, 1:2, 1:5 and 1:10) exerted supra-additive (synergistic) interactions in the mouse MES model. In contrast, 1-MeTHIQ in combination with CZP (200:1 and 100:1), ETS (1:1, 1:2 and 1:5), LEV and VGB (1:1, 1:2, 1:5 and 1:10), and TGB (200:1, 100:1, 50:1 and 25:1) produced additive interaction in the mouse MES model. Total brain AED concentrations were unaffected by 1-MeTHIQ, and inversely, CZP, ETS and GBP had no impact on total brain concentrations of 1-MeTHIQ, indicating pharmacodynamic nature of synergistic interactions between 1-MeTHIQ and the tested AEDs in the mouse MES model. In conclusion, the supra-additive interactions of 1-MeTHIQ with CZP (at the fixed ratios of 50:1 and 25:1), ETS (1:10) and GBP (1:1, 1:2, 1:5 and 1:10) in the mouse MES model appear to be particularly favorable combinations from a clinical viewpoint. The additive combinations of 1-MeTHIQ with CZP (100:1, 50:1), ETS (1:1, 1:2 and 1:5), LEV and VGB (1:1, 1:2, 1:5, and 1:10), and TGB (200:1, 100:1, 50:1 and 25:1) seem to be neutral and worthy of consideration in further clinical practice.