Drug users' willingness to encourage social, sexual, and drug network members to receive an HIV vaccine: a social network analysis.

This study examined feasibility of peer-based promotion of HIV vaccination and dyadic correlates to vaccine encouragement in risk- and non-risk networks of drug users (n = 433) in the US. Data were collected on HIV vaccine attitudes, risk compensation intentions, likelihood of encouraging vaccination, and recent (past 6 months) risk (i.e. involving sex and/or injecting drugs) and non-risk (i.e. involving co-usage of noninjected drugs and/or social support) relationships. Willingness to encourage HIV vaccination was reported in 521 and 555 risk- and non-risk relationships, respectively. However, 37 % expressed hesitancy, typically due to fear of side effects or social concerns. Encouragement was often motivated by perceived HIV risk, though 9 % were motivated by risk compensation intentions. In non-risk partnerships, encouragement was associated with drug co-usage, and in risk relationships, with perceived vaccine acceptability and encouragement by the partner. Network-based HIV vaccine promotion may be a successful strategy, but risk compensation intentions should be explored.

Barriers to opioid use disorder treatment among people who use drugs in the rural United States: A qualitative, multi-site study.

BACKGROUND: In 2020, 2.8 million people required substance use disorder (SUD) treatment in nonmetropolitan or 'rural' areas in the U.S. Among this population, only 10% received SUD treatment from a specialty facility, and 1 in 500 received medication for opioid use disorder (MOUD). We explored the context surrounding barriers to SUD treatment in the rural United States. METHODS: We conducted semi-structured, in-depth interviews from 2018 to 2019 to assess barriers to SUD treatment among people who use drugs (PWUD) across seven rural U.S. study sites. Using the social-ecological model (SEM), we examined individual, interpersonal, organizational, community, and policy factors contributing to perceived barriers to SUD treatment. We employed deductive and inductive coding and analytical approaches to identify themes. We also calculated descriptive statistics for participant characteristics and salient themes. RESULTS: Among 304 participants (55% male, mean age 36 years), we identified barriers to SUD treatment in rural areas across SEM levels. At the individual/interpersonal level, relevant themes included: fear of withdrawal, the need to "get things in order" before entering treatment, close-knit communities and limited confidentiality, networks and settings that perpetuated drug use, and stigma. Organizational-level barriers included: strict facility rules, treatment programs managed like corrections facilities, lack of gender-specific treatment programs, and concerns about jeopardizing employment. Community-level barriers included: limited availability of treatment in local rural communities, long distances and limited transportation, waitlists, and a lack of information about treatment options. Policy-level themes included insurance challenges and system-imposed barriers such as arrest and incarceration. CONCLUSION: Our findings highlight multi-level barriers to SUD treatment in rural U.S. communities. Salient barriers included the need to travel long distances to treatment, challenges to confidentiality due to small, close-knit communities where people are highly familiar with one another, and high-threshold treatment program practices. Our findings point to the need to facilitate the elimination of treatment barriers at each level of the SEM in rural America.

Network structure and the risk for HIV transmission among rural drug users.

Research suggests that structural properties of drug users' social networks can have substantial effects on HIV risk. The purpose of this study was to investigate if the structural properties of Appalachian drug users' risk networks could lend insight into the potential for HIV transmission in this population. Data from 503 drug users recruited through respondent-driven sampling were used to construct a sociometric risk network. Network ties represented relationships in which partners had engaged in unprotected sex and/or shared injection equipment. Compared to 1,000 randomly generated networks, the observed network was found to have a larger main component and exhibit more cohesiveness and centralization than would be expected at random. Thus, the risk network structure in this sample has many structural characteristics shown to be facilitative of HIV transmission. This underscores the importance of primary prevention in this population and prompts further investigation into the epidemiology of HIV in the region.

Social networks and HCV viraemia in anti-HCV-positive rural drug users.

Although social networks are known to play an important role in drug-using behaviours associated with hepatitis C virus (HCV) infection, literature on social networks and HCV is inconsistent. This exploratory study examined HCV RNA distribution within a social network of anti-HCV-positive non-medical prescription opioid users (NMPOUs) in rural Appalachia. Participants were tested serologically for HCV RNA, and behavioural, demographic, and network data were collected using interview-administered questionnaires. Multivariate analyses were performed using logistic regression. Behavioural and demographic characteristics did not differ by RNA status. In the multivariate model, recent injecting drug users (IDUs) were more likely to be RNA positive [odds ratio (OR) 4·06, 95% confidence interval (CI) 1·04-15·83], and turnover into an IDU's drug network was significantly protective (OR 0·15, 95% CI 0·03-0·75). This is the first study to date to examine HCV distribution in rural NMPOUs from a network perspective and demonstrates that network characteristics significantly contribute to the epidemiology of HCV in this understudied, high-risk population.

A qualitative analysis of rural syringe service program fidelity in Appalachian Kentucky: Staff and participant perspectives.

PURPOSE: As drug-related epidemics have expanded from cities to rural areas, syringe service programs (SSPs) and other harm reduction programs have been slow to follow. The recent implementation of SSPs in rural areas demands attention to program fidelity based on core components of SSP success. METHODS: Semistructured interviews conducted with clients and staff at 5 SSPs in 5 counties within 2 Central Appalachian health districts. Interviews covered fidelity of SSP implementation to 6 core components: (1) meet needs for harm reduction supplies; (2) education and counseling for sexual, injection, and overdose risks; (3) cooperation between SSPs and local law enforcement; (4) provide other health and social services; (5) ensure low threshold access to services; and (6) promote dignity, the impact of poor fidelity on vulnerability to drug-related harms, and the risk environment's influence on program fidelity. We applied thematic methods to analyze the data. FINDINGS: Rural SSPs were mostly faithful to the 6 core components. Deviations from core components can be attributed to certain characteristics of the local rural risk environment outlined in the risk environment model, including geographic remoteness, lack of resources and underdeveloped infrastructure, and stigma against people who inject drugs (PWID) CONCLUSIONS: As drug-related epidemics continue to expand outside cities, scaling up SSPs to serve rural PWID is essential. Future research should explore whether the risk environment features identified also influence SSP fidelity in other rural areas and develop and test strategies to strengthen core components in these vulnerable areas.

Audio-induced psychogenic non-epileptic seizures.

A 45-year-old woman presented with vague attacks, which consisted of headaches, confusion and sleepiness. An electroencephalograph was normal, but subsequent scans revealed the presence of a right-sided convexity meningioma. This was excised and complications led to the removal of an infected bone flap in a separate procedure the following year. Various types of 'seizures' resulted from the operation. These were described to involve both tonic-clonic and absence seizures. This continued for 18 years, unaffected by medication, until a specialist diagnosed pseudo-epilepsy, by fortune of a hospital fire alarm. The patient began a psychological intervention programme including cognitive-behavioural therapy, which has significantly reduced episodes. In conclusion, psychogenic non-epileptic seizures may develop after intracranial neurosurgery undertaken for indications other than the control of refractory epileptic seizures. A diagnosis of psychogenic non-epileptic seizures should be considered in patients who develop refractory seizures after neurosurgery and managed appropriately.

Electrical performances and structural designs of copper bonding in wafer-level three-dimensional integration.

The integrity of bonded Cu interconnects in wafer-level three-dimensional integration has been investigated as the function of pattern size and density, as well as bonding process parameter. The desired pattern density coupled with the application of bonding process profile we developed gives optimal yield and alignment accuracy, and provides excellent electrical connectivity and contact resistance through the entire wafer. This result is a key milestone in establishing the manufacturability of Cu-based interconnections for 3D integration technology.

The effect of NaOCl and heat treatment on static and dynamic mechanical properties and chemical changes of dentine.

OBJECTIVES: To determine the effect of heat on flexural strength (FS), maximum strain (MS), storage modulus (SM), tan delta (TD) and chemical changes through micro-Raman spectroscopy of dentine exposed to 2.5% NaOCl or saline. METHOD: ology: Dentine bars were randomly allocated to 8 test groups. Half (groups 2,4,6,8) were treated with NaOCl for 20 min; the rest (groups 1,3,5,7) remained in saline. FS/MS were measured in groups 1-4 (n = 15) (3/4 were also heated to 200 °C & re-hydrated in saline). Micro-Raman spectroscopy was performed on bars from groups 1-4. SM/TD were measured in 5-8: in 5/6 (n = 10), repeated after heating (200 °C), then following re-hydration; in 7/8 (n = 3) after heating to 25-185 °C. RESULTS: Increase in MS on heat and FS/MS on heat + NaOCl was not significant (P > 0.05). SM increased (P = 0.06) after heat treatment but reduced to initial state after rehydration (P = 0.03). TD did not change (P = 0.4) after heat (200 °C) treatment but rehydration increased it compared with pre-treatment state (P = 0.001). For dentine bars pre-treated with NaOCl, SM did not change (P = 0.6) after heat (200 °C) treatment or rehydration but TD significantly increased (P = 0.02) upon re-hydration compared with pre- (P=0.007), or post- (P = 0.03) heat-treatment states. SM and TD varied between 25-185 °C with no consistent trend amongst the NaOCl pre-treated bars. Micro-Raman only detected chemical changes following NaOCl treatment in the mineral phase. CONCLUSIONS: Exposure of dentine bars to heat and NaOCl produced only moderate changes to quasi-static but marked changes to viscoelastic properties, which may be explained by chemical alterations.

Dense collagen matrix accelerates osteogenic differentiation and rescues the apoptotic response to MMP inhibition.

Bone is distinguished from other tissues by its mechanical properties, in particular stiffness. However, we know little of how osteoblasts react to the stiffness of their microenvironment; in this study we describe their response to a dense (>10 wt.%) collagenous 3D environment. Primary pre-osteoblasts were seeded within a novel form of native collagen, dense collagen, and cultured for up to 14 days in the presence and absence of osteogenic supplements: analysis was via Q-PCR, histology, fluorescent in situ zymography, MMP loss-of-function and tensile testing. Differentiation as measured through the up-regulation of Bsp (247-fold), Alp (14.2-fold), Col1A1 (4.5-fold), Mmp-13 (8.0-fold) and Runx2 (1.2-fold) transcripts was greatly accelerated compared to 2D plastic at 7 and 14 days in the same medium. The scale of this enhancement was confirmed through the use of growth factor stimulation on 2D via the addition of BMP-6 and the Hedgehog agonist purmorphamine. In concert, these molecules were capable of the same level of osteo-induction (measured by Bsp and Alp expression) as the dense collagen alone. Mineralisation was initially localised to remodelled pericellular regions, but by 14 days embedded cells were discernible within regions of apatite (confirmed by MicroRaman). Tensile testing of the matrices showed that this had resulted in a significant increase in Young's modulus at low strain values, consistent with a stiffening of the matrix. To determine the need for matrix remodelling in the mineralisation event the broad spectrum MMP Inhibitor Ilomastat was used. It was found that in its presence mineralisation could still occur (though serum-specific) and the apoptosis associated with MMP inhibition in hydrated collagen gels was abrogated. Analysis of gene expression indicated that this was due to the up-regulation of Mmp-13 in the presence of Ilomastat in dense collagen (400-fold), demonstrating a powerful feedback loop and a potential mechanism for the rescue from apoptosis. Osteoid-like matrix (dense collagen) is therefore a potent stimulant of osteoblast differentiation in vitro and provides an environment that enables survival and differentiation in the presence of MMP inhibition.

Application of mobile phone technology for managing chemotherapy-associated side-effects.

BACKGROUND: Novel mobile phone technology linked to a server that communicates patients' symptoms to healthcare professionals has been adapted to register the side- effects of chemotherapy and provide advice on management of toxicity. We report a feasibility study to examine the utility of home monitoring of patients' symptoms via a mobile phone. METHODS: Six colon cancer patients receiving adjuvant chemotherapy, entered symptom data onto user friendly screens on a mobile phone twice daily. This 'real time' self assessment of nausea, vomiting, mucositis, diarrhoea and hand-foot syndrome and measurement of temperature was sent via a secured connection to a remote computer. In the event of moderate or severe symptoms (generating amber and red alerts respectively), the nurse was immediately alerted by the computer, via a pager. The nurse then contacted the patient to reinforce the automatic advice sent to the patient on their phone and to assess the patient using clinical algorithms. RESULTS: The patient used the mobile phones during the first two cycles of chemotherapy. The data were successfully analysed by the server software and alerts were generated alerting the study nurses to patients' symptoms at the appropriate time. There were 91 alerts-54 red and 37 amber; 54% (29/54) of the red alerts were data delay and transmission problems which were swiftly rectified. The remaining red alerts were managed appropriately by the study nurses. Both patients and staff felt confident in this approach to symptom management. CONCLUSIONS: This study demonstrates that the technology for monitoring patients' symptoms worked well. The patients felt secure in the knowledge that their symptoms were being closely monitored and that they were participating effectively in their own care management.

Prognostic value of peripheral leukocyte counts and plasma glucose in intracerebral haemorrhage.

INTRODUCTION: The value of routine blood markers as prognostic indicators is increasingly established in acute ischaemic stroke. The relationship is less well defined in haemorrhagic stroke. In this study, we examined routine admission blood markers and applied a logistic regression model to predict outcome in haemorrhagic stroke. METHOD: A retrospective study was performed between September 2009-2011 in a general admission stroke unit in the UK. 1400 patients were admitted with stroke during this period, of which 117 were haemorrhagic. Admission systolic and diastolic blood pressure, venous blood samples and pre- and post-morbid (i.e. at discharge or death) modified Rankin scores were also recorded. Patients were controlled for age, sex, smoking status, hypertension status and co-morbidities (using Charleson Comorbidity Index scores). Logistic regression models were generated using SPSS. RESULTS: 113 patients were analysed (58 male/55 female). Lower admission blood glucose (p=0.009), lower total leukocyte count (p=0.001) and lower neutrophil count (p=0.021) were found to be significantly associated with survival vs. death. 90 patients with complete glucose, leukocyte count, sex (forced) and pre-morbid Rankin score (forced) data were entered into a logistic regression model. This predicted correct group membership (survived/deceased) in 72.2% of cases (83.9% survivors/52.9% deceased correctly predicted). In females with normal leukocyte count and glucose, survival was predicted with 68% accuracy. CONCLUSION: These results suggest that a logistic regression model using low admission glucose and low total leukocyte count may be markers of better prognosis in acute haemorrhagic stroke with a differential effect between sexes.

Immune reconstitution inflammatory syndrome associated with Kaposi's sarcoma.

PURPOSE: A proportion of patients with HIV infection who subsequently receive highly active antiretroviral therapy (HAART) exhibit a deterioration in their clinical status, despite control of virologic and immunologic parameters. This clinical response, known as the immune reconstitution inflammatory syndrome (IRIS), occurs secondary to an immune response against previously diagnosed pathogens. PATIENTS AND METHODS: From our cohort of 5,832 patients treated in the HAART era, we identified 150 therapy-naive patients with a first presentation of Kaposi's sarcoma (KS). Their clinicopathologic features and progress were recorded prospectively. RESULTS: After commencing HAART, ten patients (6.6%) developed progressive KS, which we identify as IRIS-associated KS. In a comparison of these individuals with those whose KS did not progress, we found that IRIS-KS occurred in patients with higher CD4 counts (P = .03), KS-associated edema (P = .01), and therapy with both protease inhibitors and non-nucleosides together (P = .03). Time to treatment failure was similar for both groups, although the CD4 count declined more rapidly at first, in those patients with IRIS-associated KS. Despite this initial decline, in our clinical experience HAART could be successfully continued in those with IRIS-associated KS. CONCLUSION: We have identified IRIS-KS in a cohort of HIV patients with KS who start HAART.

Dopamine antagonist modulation of amphetamine response as detected using pharmacological MRI.

Functional magnetic resonance imaging (fMRI), employing BOLD-contrast, was used to measure changes in regional brain activation following amphetamine administration, either alone or after pre-treatment with the dopamine D1 receptor antagonist SCH23390, or the dopamine D2 receptor antagonist, sulpiride, in anaesthetised rat. After obtaining baseline data, rats (n=8) were given amphetamine (3 g/kg i.v) and volume data sets collected for 90 mins. Acute amphetamine challenge caused widespread increases in BOLD signal intensity in many subcortical structures with rich dopaminergic innervation, with decreases in BOLD contrast observed in the superficial layers of the cortex. Pretreatment with SCH23390 (n=8, 0.5 mg/kg, i.v) substantially attenuated the increases in BOLD activity in response to amphetamine, with lesser effects on the amphetamine-evoked decreases in BOLD signal. In contrast, sulpiride (n=8, 50 mg/kg, i.v) predominantly blocked the decrease in BOLD signal, having a smaller effect on the increases in BOLD signal. In summary, these data are supportive of the notion that different dopamine receptor types are responsible for separate components of the full amphetamine response. Furthermore the utility of BOLD contrast fMRI as a means of characterising the mechanisms of drug action in the whole brain has been demonstrated. Such studies may be of particular use for investigation of localised action and interaction of different dopaminergic agents.

Disruption of medial prefrontal synchrony in the subchronic phencyclidine model of schizophrenia in rats.

Subchronic treatment with the N-methyl-D-aspartate (NMDA) antagonist phencyclidine (PCP) produces behavioral abnormalities in rodents which are considered a reliable pharmacological model of neurocognitive deficits in schizophrenia. Alterations in prefrontal neuronal firing after acute PCP administration have been observed, however enduring changes in prefrontal activity after subchronic PCP treatment have not been studied. To address this we have recorded cortical oscillations and unit responses in putative cortical pyramidal cells in subchronic PCP-treated rats (2mg/kg twice daily for 7 days) under urethane anesthesia. We found that this regimen reduced theta oscillations in the medial prefrontal cortex. It further produced abnormal cortical synchronization in putative cortical pyramidal cells. These alterations in prefrontal cortex functioning may contribute to cognitive deficits seen in subchronic NMDA antagonist pre-treated animals in prefrontal-dependent tasks.

From Hospital to Home: Limited Nutritional and Functional Recovery for Older Adults.

BACKGROUND: The post-hospital period may be a vulnerable time for elders recovering from acute illness. Few studies have examined nutrition outcomes of older people at nutrition risk after acute hospitalisation. OBJECTIVES: This study aims to describe a) standard nutrition care received by recently discharged older medical patients, b) change in nutritional and functional status at six weeks post-discharge and c) clinical outcomes at twelve weeks post discharge. DESIGN: Prospective cohort study. SETTING: Two metropolitan teaching hospitals in Brisbane, Australia. PARTICIPANTS: Medical patients aged ≥65 years at risk of malnutrition (Malnutrition Screening Score ≥2) and discharged to independent living in the community. MEASUREMENT: Nutritional status (Mini Nutritional Assessment (MNA), weight, lean body mass), functional status (grip strength, walk speed, activities of daily living) and health-related quality of life assessed on discharge and six weeks post-discharge. Inpatient and post-discharge nutrition intervention was recorded. Death and unplanned admissions were measured at 12 weeks. RESULTS: Of the 42 consented participants, only 14% (n=6) received post-discharge dietitian review and 19% (n=8) received practical nutrition supports at home (meal delivery, shopping assistance) as part of standard care. While there was a small improvement in MNA (18.4±4.0 to 20.1±4.2, p=0.004) and walk speed (0.7±0.3 m/s to 0.9±0.3, p=0.004) at six weeks, there was no difference in mean weight, lean body mass, grip strength or activities of daily living. Five (15%) participants lost ≥5% body weight. By twelve weeks, 17 participants (46%) had at least one unplanned hospital admission and four (10%) had died. CONCLUSIONS: Few patients at nutrition risk received nutrition-focussed care in the post-hospital period, and most did not improve nutritional or functional status at 6 weeks.

Conversion, shrinkage, water sorption, flexural strength and modulus of re-mineralizing dental composites.

OBJECTIVES: Cure, volumetric changes and mechanical properties were assessed for new dental composites containing chlorhexidine (CHX) and reactive calcium phosphate-containing (CaP) to reduce recurrent caries. METHODS: 20wt.% of light curable urethane dimethacrylate based liquid was mixed with 80wt.% glass filler containing 10wt.% CHX and 0-40wt.% CaP. Conversion versus depth with 20 or 40s light exposure was assessed by FTIR. Solidification depth and polymerization shrinkage were determined using ISO 4049 and 17304, respectively. Subsequent volume expansion and biaxial flexural strength and modulus change upon water immersion were determined over 4 weeks. Hydroxyapatite precipitation in simulated body fluid was assessed at 1 week. RESULTS: Conversion decreased linearly with both depth and CaP content. Average solidification depths were 4.5, 3.9, 3.3, 2.9 and 5.0 with 0, 10, 20, and 40% CaP and a commercial composite, Z250, respectively. Conversions at these depths were 53±2% for experimental materials but with Z250 only 32%. With Z250 more than 50% conversion was achieved only below 1.1mm. Shrinkage was 3% and 2.5% for experimental materials and Z250, respectively. Early water sorption increased linearly, whilst strength and modulus decreased exponentially to final values when plotted versus square root of time. Maximum volumetric expansion increased linearly with CaP rise and balanced shrinkage at 10-20wt.% CaP. Strength and modulus for Z250 decreased from 191 to 158MPa and 3.2 to 2.5GPa. Experimental composites initial strength and modulus decreased linearly from 169 to 139MPa and 5.8 to 3.8GPa with increasing CaP. Extrapolated final values decreased from 156 to 84MPa and 4.1 to 1.7GPa. All materials containing CaP promoted hydroxyapatite precipitation. SIGNIFICANCE: The lower surface of composite restorations should both be solid and have greater than 50% conversion. The results, therefore, suggest the experimental composite may be placed in much thicker layers than Z250 and have reduced unbounded cytotoxic monomer. Experimental materials with 10-20wt.% additionally have volumetric expansion to compensate shrinkage, antibacterial and re-mineralizing components and competitive mechanical properties.

Intracerebral microdialysis in the study of physiology and behaviour.

In the past, studies relating neurotransmitter function to behaviour have involved looking at the behavioural effects of specific drugs or lesions, or using post-mortem biochemistry in animals killed after undertaking the behaviour. Whilst these methods still play an important part in behavioural pharmacology research, recent advances in the technology of in vivo methods have enabled direct measurements of neurotransmitter function to be made in conscious and unrestrained animals. Among the more important of these methods are voltammetry and brain wash methods (e.g. push-pull perfusion, cortical cup) /116/. However, perhaps the greatest impact on this field of research has been made by microdialysis. This article reviews the contribution made by microdialysis to the understanding of neurotransmitter systems underlying normal physiological function and behaviour, and points to possible future directions for this work.

Antagonism of the effect of delta sleep-inducing peptide by naloxone in the rat.

The somnogenic properties of delta sleep-inducing peptide (DSIP) were investigated using electroencephalographic criteria. The peptide caused a significant increase in both REM and non-REM sleep at the expense of waking when injected into the lateral ventricle of the rat brain in four doses of 5 micrograms during the dark (waking) phase of the light/dark cycle. Furthermore this sleep promoting effect was blocked by pre-treatment with the opiate antagonist naloxone at a dose level (0.1 mg/Kg s.c.) considered selective for mu-receptors.

Latent inhibition of conditioned dopamine release in rat nucleus accumbens.

Classical conditioning both to rewarding and to aversive stimuli is sensitive to drugs which act on the dopaminergic system: amphetamine enhances conditioning and neuroleptics attenuate it. Many lines of evidence point to the nucleus accumbens as being part of an anatomical substrate for reward. We have examined the release of dopamine in the nucleus accumbens during classical aversive conditioning using microdialysis in the unrestrained rat. Two mild footshocks caused a release of dopamine, which was potentiated when each footshock was immediately preceded by a novel tone or light stimulus. Presentation of either of these stimuli after conditioning elicited an increase in dopamine, only to that stimulus which had been conditioned; presentation of either stimulus after footshock alone without conditioning produced no dopamine response. Latent inhibition is a process whereby pre-exposure to a stimulus without consequence impairs learning about that stimulus at subsequent conditioning. This process too is believed to be under the control of dopaminergic systems, particularly in nucleus accumbens. Pre-exposure to the tone stimulus both markedly attenuated the potentiation of dopamine release at conditioning and abolished the conditioned release of dopamine at subsequent tone presentation. This is the first report of direct measurement of potentiated dopamine release during conditioning, and may provide a neurochemical basis for the effects of dopaminergic drugs on conditioning and latent inhibition. The results also support the hypothesis that disrupted latent inhibition in schizophrenia reflects increased mesolimbic dopamine function.