Subthalamic Nucleus Deep Brain Stimulation Does Not Improve Visuo-Motor Impairment in Parkinson’s Disease

Objective

To evaluate how bilateral subthalamic nucleus deep brain stimulation (STN-DBS) affects visuo-motor coordination (VMC) in patients with Parkinson’s disease (PD).

Background

VMC involves multi-sensory integration, motor planning, executive function and attention. VMC deficits are well-described in PD. STN-DBS conveys marked motor benefit in PD, but pyscho-cognitive complications are recognized and the effect on VMC is not known.

Methods

Thirteen PD patients with bilateral STN-DBS underwent neurological, cognitive, and mood assessment before VMC testing with optimal DBS stimulation parameters (‘on-stimulation’) and then, on the same day without any medication changes, after DBS silencing and establishing motor function deterioration (‘off-stimulation’). Twelve age-matched healthy controls performed 2 successive VMC testing sessions, with a break of similar duration to that of the PD group. The computer cursor was controlled with a dome-shaped ‘mouse’ hidden from view that minimized tremor effects. Movement duration, hand velocity, tracking continuity, directional control variables, and feedback utilization variables were measured. MANOVA was performed on (1) clinically measured motor function, (2) VMC performance and (3) mood and attention, looking for main and interaction effects of: (1) group (controls/PD), (2) test-order (controls: first/second, PD: on-stimulation/off-stimulation), (3) path (sine/square/circle) and (4) hand (dominant/non-dominant).

Results

Unified PD Rating Scale (UPDRS) Part III worsened off-stimulation versus on-stimulation (mean: 42.3 versus 21.6, p = 0.02), as did finger tapping (p = 0.02), posture-gait (p = 0.01), upper limb function (p<0.001) and backwards digit span (p = 0.02). Stimulation state did not affect mood. PD patients performed worse in non-velocity related VMC variables than controls (F_(5,18) = 8.5, p<0.001). In the control group there were significant main effects of hand (dominant/non-dominant), path (sine/square/circle) and test-order (Test_1/Test_2). In the PD group, hand and path effects, but no test-order (on-stimulation/off-stimulation), were found.

Conclusions

‘Low-level’ clinically-measured motor function responds to STN-DBS but ‘high-level’ motor and cognitive functions relating to VMC may be unresponsive to STN-DBS.     

Costs of Inaction on Maternal Mortality: Qualitative Evidence of the Impacts of Maternal Deaths on Living Children in Tanzania

Background

Little is known about the interconnectedness of maternal deaths and impacts on children, beyond infants, or the mechanisms through which this interconnectedness is established. A study was conducted in rural Tanzania to provide qualitative insight regarding how maternal mortality affects index as well as other living children and to identify shared structural and social factors that foster high levels of maternal mortality and child vulnerabilities.

Methods and Findings

Adult family members of women who died due to maternal causes (N = 45) and key stakeholders (N = 35) participated in in-depth interviews. Twelve focus group discussions were also conducted (N = 83) among community leaders in three rural regions of Tanzania. Findings highlight the widespread impact of a woman’s death on her children’s health, education, and economic status, and, by inference, the roles that women play within their families in rural Tanzanian communities.

Conclusions

The full costs of failing to address preventable maternal mortality include intergenerational impacts on the nutritional status, health, and education of children, as well as the economic capacity of families. When setting priorities in a resource-poor, high maternal mortality country, such as Tanzania, the far-reaching effects that reducing maternal deaths can have on families and communities, as well as women’s own lives, should be considered.     

Shared Decision Making Does Not Influence Physicians against Clinical Practice Guidelines

Background

While shared decision making (SDM) and adherence to clinical practice guidelines (CPGs) are important, some believe they are incompatible. This study explored the mutual influence between physicians’ intention to engage in SDM and their intention to follow CPGs.

Methods

Embedded within a clustered randomized trial to assess the impact of training physicians in SDM about using antibiotics to treat acute respiratory tract infections, this study evaluated physicians’ intentions to both engage in SDM and follow CPGs. A self-administered questionnaire based on the theory of planned behavior evaluated both behavioral intentions and their respective determinants (attitude, subjective norm and perceived behavioral control) at study entry and exit. We used path analysis to explore the relationships between the intentions. We conducted statistical analyses using the maximum likelihood method and the variance-covariance matrix. Goodness of fit indices encompassed the chi-square statistic, the comparative fit index and the root mean square error of approximation.

Results

We analyzed 244 responses at entry and 236 at exit. In the control group, at entry we observed that physicians’ intention to engage in SDM (r = 0, t = 0.03) did not affect their intention to follow CPGs; however, their intention to follow CPGs (r = −0.31 t = −2.82) did negatively influence their intention to engage in SDM. At exit, neither behavioral intention influenced the other. In the experimental group, at entry neither behavioral intention influenced the other; at exit, the intention to engage in SDM still did not influence the intention to use CPGs, although the intention to follow CPGs (r = −0.15 t = −2.02) slightly negatively influenced the intention to engage in SDM, but this was not clinically significant.

Conclusion

Physicians’ intention to engage in SDM does not affect their intention to adopt CPGs even after SDM training. Physicians’ intention to adopt CPGs had no clinically significant influence on intention to engage in SDM.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01116076","term_id":"NCT01116076"}}NCT01116076     

Computed Tomography of Aortic Wall Calcifications in Aortic Dissection Patients

Objectives

To investigate the frequency of aortic calcifications at the outer edge of the false lumen and the frequency of fully circular aortic calcifications in a consecutive series of patients with aortic dissection who underwent contrast-enhanced CT.

Methods

The study population compromised of 69 consecutive subjects aged 60 years and older with a contrast-enhanced CT scan demonstrating an aortic dissection. All CT scans were evaluated for the frequency of aortic calcifications at the outer edge of the false lumen and the frequency of fully circular aortic calcifications by two experienced observers. Between observer reliability was evaluated by using Cohen’s Kappa. Differences between groups were tested using unpaired T test and Chi-square test.

Results

Presumed media calcifications were observed in 22 (32%) patients of 60 years and older and were found more frequently in chronic aortic dissection (N = 12/23, 52%) than in acute aortic dissection (N = 10/46, 22%).

Conclusion

As the intima has been torn away by the aortic dissection it is highly likely that CT scans can visualize the calcifications in the tunica media of the aorta.     

Time-Wise Change in Neck Pain in Response to Rehabilitation with Specific Resistance Training: Implications for Exercise Prescription

Purpose

To determine the time-wise effect of specific resistance training on neck pain among industrial technicians with frequent neck pain symptoms.

Methods

Secondary analysis of a parallel-group cluster randomized controlled trial of 20 weeks performed at two large industrial production units in Copenhagen, Denmark. Women with neck pain >30 mm VAS (N = 131) were included in the present analysis. The training group (N = 77) performed specific resistance training for the neck/shoulder muscles three times a week, and the control group (N = 54) received advice to stay active. Participants of both groups registered neck pain intensity (0–100 mm VAS) once a week.

Results

Neck pain intensity was 55 mm (SD 23) at baseline. There was a significant group by time interaction for neck pain (F-value 2.61, P<0.001, DF = 19). Between-group differences in neck pain reached significance after 4 weeks (11 mm, 95% CI 2 to 20). The time-wise change in pain showed three phases; a rapid decrease in the training group compared with the control group during the initial 7 weeks, a slower decrease in pain during the following weeks (week 8–15), and a plateau during the last weeks (week 16–20). Adherence to training followed a two-phase pattern, i.e. weekly participation rate was between 70–86% during the initial 7 weeks, dropping towards 55–63% during the latter half of the training period.

Conclusion

Four weeks of specific resistance training reduced neck pain significantly, but 15 weeks is required to achieve maximal pain reduction. The time-wise change in pain followed a three-phase pattern with a rapid effect during the initial 7 weeks followed by a slower but still positive effect, and finally a plateau from week 15 and onwards. Decreased participation rate may explain the decreased efficacy during the latter phase of the intervention.     

Dentists’ Dietary Perception and Practice Patterns in a Dental Practice-Based Research Network

Background

Dental caries are largely preventable, and epidemiological evidence for a relationship between diet and oral health is abundant. To date, however, dentists’ perceptions about the role of diet and dentists’ practice patterns regarding diet counseling have not been clarified.

Objective

The purposes of this study were to: (1) examine discordance between dentists’ perception of the importance of diet in caries treatment planning and their actual provision of diet counseling to patients, and (2) identify dentists’ characteristics associated with their provision of diet counseling.

Design

The study used a cross-sectional study design consisting of a questionnaire survey in Japan.

Participants

The study queried dentists working in outpatient dental practices who were affiliated with the Dental Practice-Based Research Network Japan (JDPBRN), which aims to allow dentists to investigate research questions and share experiences and expertise (n = 282).

Measurement

Dentists were asked about their perceptions on the importance of diet and their practice patterns regarding diet counseling, as well as patient, practice, and dentist background data.

Results

The majority of participants (n = 116, 63%) recognized that diet is “more important” to oral health. However, among participants who think diet is “more important” (n = 116), only 48% (n = 56) provide diet counseling to more than 20% of their patients. Multiple logistic regression analysis suggested that several variables were associated with providing diet counseling; dentist gender, practice busyness, percentage of patients interested in caries prevention, caries risk assessment, and percentage of patients who receive blood pressure screening.

Conclusions

Some discordance exists between dentists’ perception of the importance of diet in caries treatment planning and their actual practice pattern regarding diet counseling to patients. Reducing this discordance may require additional dentist education, including nutritional and systemic disease concepts; patient education to increase perception of the importance of caries prevention; or removing barriers to practices’ implementation of counseling.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01680848","term_id":"NCT01680848"}}NCT01680848     

Effects of Caller Characteristics on Auditory Laterality in an Early Primate (Microcebus murinus)

Background

Auditory laterality is suggested to be characterized by a left hemisphere dominance for the processing of conspecific communication. Nevertheless, there are indications that auditory laterality can also be affected by communicative significance, emotional valence and social recognition.

Methodology/Principal Findings

In order to gain insight into the effects of caller characteristics on auditory laterality in the early primate brain, 17 gray mouse lemurs were tested in a head turn paradigm. The head turn paradigm was established to examine potential functional hemispheric asymmetries on the behavioral level. Subjects were presented with playbacks of two conspecific call types (tsak calls and trill calls) from senders differing in familiarity (unfamiliar vs. familiar) and sex (same sex vs. other sex). Based on the head turn direction towards these calls, evidence was found for a right ear/left hemisphere dominance for the processing of calls of the other sex (Binomial test: p = 0.021, N = 10). Familiarity had no effect on the orientation biases.

Conclusions/Significance

The findings in this study support the growing consensus that auditory laterality is not only determined by the acoustic processing of conspecific communication, but also by other factors like the sex of the sender.     

Tinnitus Intensity Dependent Gamma Oscillations of the Contralateral Auditory Cortex

Background

Non-pulsatile tinnitus is considered a subjective auditory phantom phenomenon present in 10 to 15% of the population. Tinnitus as a phantom phenomenon is related to hyperactivity and reorganization of the auditory cortex. Magnetoencephalography studies demonstrate a correlation between gamma band activity in the contralateral auditory cortex and the presence of tinnitus. The present study aims to investigate the relation between objective gamma-band activity in the contralateral auditory cortex and subjective tinnitus loudness scores.

Methods and Findings

In unilateral tinnitus patients (N = 15; 10 right, 5 left) source analysis of resting state electroencephalographic gamma band oscillations shows a strong positive correlation with Visual Analogue Scale loudness scores in the contralateral auditory cortex (max r = 0.73, p<0.05).

Conclusion

Auditory phantom percepts thus show similar sound level dependent activation of the contralateral auditory cortex as observed in normal audition. In view of recent consciousness models and tinnitus network models these results suggest tinnitus loudness is coded by gamma band activity in the contralateral auditory cortex but might not, by itself, be responsible for tinnitus perception.     

Preliminary Development and Validation of a New End-of-Life Patient-Reported Outcome Measure Assessing the Ability of Patients to Finalise Their Affairs at the End of Life

Introduction

The ability of patients to finalise their affairs at the end of life is an often neglected aspect of quality of life (QOL) measurement in palliative care effectiveness research despite compelling evidence of the high value patients place on this domain.

Objective

This paper describes the preliminary development and evaluation of a new, single-item, end-of-life patient-reported outcome measure (EOLPRO) designed to capture changes in the ability of patients to finalise their affairs at the end of life.

Methods

Cognitive interviews with purposively sampled Australian palliative care patients (N = 9) were analysed thematically to explore content validity. Simultaneously, secondary analysis of data from a randomised controlled trial comparing ketamine and placebo for the management of cancer pain (N = 185) evaluated: construct validity; test-retest reliability; and responsiveness.

Results

Preliminary findings suggest patients interpret the new measure consistently. The EOLPRO captures the ability to complete physical tasks and finalise practical matters although it is unclear whether emotional tasks or resolution of relationship issues are considered. Personal and financial affairs should be separated to allow for differences in ability for these two types of affairs. The significant correlation between performance status and EOLPRO scores (r = 0.41, p<0.01, n = 137) and expected relationships between EOLPRO and proximity to death and constipation demonstrated construct validity. Pre- and post-treatment EOLPRO scores moderately agreed (n = 14, κ = 0.52 [95% CI 0.19, 0.84]) supporting reliability. The measure’s apparent lack of sensitivity to discriminate between treatment responders and non-responders may be confounded.

Conclusion

Based on the preliminary findings, the EOLPRO should be separated into ‘personal’ and ‘financial’ affairs with further testing suggested, particularly to verify coverage and responsiveness. Initial evaluation suggests that the single-item EOLPRO is a useful addition to QOL outcome measurement in palliative care effectiveness research because common palliative care specific QOL questionnaires do not include or explicitly capture this domain.     

Influence of a Polyphenol-Enriched Protein Powder on Exercise-Induced Inflammation and Oxidative Stress in Athletes: A Randomized Trial Using a Metabolomics Approach

Objectives

Polyphenol supplementation was tested as a countermeasure to inflammation and oxidative stress induced by 3-d intensified training.

Methods

Water soluble polyphenols from blueberry and green tea extracts were captured onto a polyphenol soy protein complex (PSPC). Subjects were recruited, and included 38 long-distance runners ages 19–45 years who regularly competed in road races. Runners successfully completing orientation and baseline testing (N = 35) were randomized to 40 g/d PSPC (N = 17) (2,136 mg/d gallic acid equivalents) or placebo (N = 18) for 17 d using double-blinded methods and a parallel group design, with a 3-d running period inserted at day 14 (2.5 h/d, 70% VO_2max). Blood samples were collected pre- and post-14 d supplementation, and immediately and 14 h after the third day of running in subjects completing all aspects of the study (N = 16 PSPC, N = 15 placebo), and analyzed using a metabolomics platform with GC-MS and LC-MS.

Results

Metabolites characteristic of gut bacteria metabolism of polyphenols were increased with PSPC and 3 d running (e.g., hippurate, 4-hydroxyhippurate, 4-methylcatechol sulfate, 1.8-, 1.9-, 2.5-fold, respectively, P<0.05), an effect which persisted for 14-h post-exercise. Fatty acid oxidation and ketogenesis were induced by exercise in both groups, with more ketones at 14-h post-exercise in PSPC (3-hydroxybutyrate, 1.8-fold, P<0.05). Established biomarkers for inflammation (CRP, cytokines) and oxidative stress (protein carbonyls) did not differ between groups.

Conclusions

PSPC supplementation over a 17-d period did not alter established biomarkers for inflammation and oxidative stress but was linked to an enhanced gut-derived phenolic signature and ketogenesis in runners during recovery from 3-d heavy exertion.

Trial Registration

ClinicalTrials.gov, U.S. National Institutes of Health, identifier: {"type":"clinical-trial","attrs":{"text":"NCT01775384","term_id":"NCT01775384"}}NCT01775384     

Screening Accuracy and Clinical Application of the Brief Infant-Toddler Social and Emotional Assessment (BITSEA)

Background

The Brief Infant-Toddler Social and Emotional Assessment (BITSEA) is a promising questionnaire for the early detection of psychosocial problems in toddlers. The screening accuracy and clinical application were evaluated.

Methods

In a community sample of 2-year-olds (N = 2060), screening accuracy of the BITSEA Problem scale was examined regarding a clinical CBCL1.5-5 Total Problem score. For the total population and subgroups by child’s gender and ethnicity Receiver Operating Characteristic (ROC) curves were calculated, and across a range of BITSEA Problem scores, sensitivity, specificity, likelihood ratio’s, diagnostic odds ratio and Youden’s index. Clinical application of the BITSEA was examined by evaluating the relation between the scale scores and the clinical decision of the child health professional.

Results

The area under the ROC curve (95% confidence interval) of the Problem scale was 0.97(0.95–0.98), there were no significant differences between subgroups. The association between clinical decision and BITSEA Problem score (B = 2.5) and Competence score (B = −0.7) was significant (p<0.05).

Conclusions

The results indicate that the BITSEA Problem scale has good discriminative power to differentiate children with and without psychosocial problems. Referred children had less favourable scores compared to children that were not referred. The BITSEA may be helpful in the early detection of psychosocial problems.     

Epidemiology of Anorexia Nervosa in Men: A Nationwide Study of Finnish Twins

Background

To examine the epidemiology of anorexia nervosa in men, we screened Finnish male twins born in 1975–79.

Methods and Findings

Men (N = 2122) from FinnTwin16 birth cohorts were screened for lifetime eating disorders by a questionnaire. The screen positives (N = 18), their male co-twins (N = 10) and those with lifetime minimum BMI≤17.5 (N = 21) were administered the Structured Clinical Interview for DSM-IV anorexia nervosa. The incidence rate of anorexia nervosa for the presumed peak age of risk (10–24y) was 15.7 per 100 000 person-years; its lifetime prevalence was 0.24%. All probands had recovered from eating disorders, but suffered from substantial psychiatric comorbidity, which also manifested in their co-twins. Additionally, male co-twins displayed significant dissatisfaction with body musculature, a male-specific feature of body dysmorphic disorder.

Conclusions

Anorexia nervosa in males in the community is more common, transient and accompanied by more substantial comorbidity than previously thought.     

The Effect of Visual Cues on Auditory Stream Segregation in Musicians and Non-Musicians

Background

The ability to separate two interleaved melodies is an important factor in music appreciation. This ability is greatly reduced in people with hearing impairment, contributing to difficulties in music appreciation. The aim of this study was to assess whether visual cues, musical training or musical context could have an effect on this ability, and potentially improve music appreciation for the hearing impaired.

Methods

Musicians (N = 18) and non-musicians (N = 19) were asked to rate the difficulty of segregating a four-note repeating melody from interleaved random distracter notes. Visual cues were provided on half the blocks, and two musical contexts were tested, with the overlap between melody and distracter notes either gradually increasing or decreasing.

Conclusions

Visual cues, musical training, and musical context all affected the difficulty of extracting the melody from a background of interleaved random distracter notes. Visual cues were effective in reducing the difficulty of segregating the melody from distracter notes, even in individuals with no musical training. These results are consistent with theories that indicate an important role for central (top-down) processes in auditory streaming mechanisms, and suggest that visual cues may help the hearing-impaired enjoy music.     

Regional Brain Structural Abnormality in Meal-Related Functional Dyspepsia Patients: A Voxel-Based Morphometry Study

Background and Aims

Brain dysfunction in functional dyspepsia (FD) has been identified by multiple neuroimaging studies. This study aims to investigate the regional gray matter density (GMD) changes in meal-related FD patients and their correlations with clinical variables, and to explore the possible influence of the emotional state on FD patients’s brain structures.

Methods

Fifty meal-related FD patients and forty healthy subjects (HS) were included and underwent a structural magnetic resonance imaging scan. Voxel-based morphometry analysis was employed to identify the cerebral structure alterations in meal-related FD patients. Regional GMD changes'' correlations with the symptoms and their durations, respectively, have been analyzed.

Results

Compared to the HS, the meal-related FD patients showed a decreased GMD in the bilateral precentral gyrus, medial prefrontal cortex (MPFC), anterior cingulate cortex (ACC) and midcingulate cortex (MCC), left orbitofrontal cortex (OFC) and right insula (p<0.05, FWE Corrected, Cluster size>50). After controlling for anxiety and depression, the meal-related FD patients showed a decreased GMD in the bilateral middle frontal gyrus, left MCC, right precentral gyrus and insula (p<0.05, FWE Corrected, Cluster size>50). Before controlling psychological factors, the GMD decreases in the ACC were negatively associated with the symptom scores of the Nepean Dyspepsia Index (NDI) (r = −0.354, p = 0.048, Bonferroni correction) and the duration of FD (r = −0.398, p = 0.02, Bonferroni correction) respectively.

Conclusions

The regional GMD of meal-related FD patients, especially in the regions of the homeostatic afferent processing network significantly differed from that of the HS, and the psychological factors might be one of the essential factors significantly affecting the regional brain structure of meal-related FD patients.     

The Effects of Ecstasy (MDMA) on Brain Serotonin Transporters Are Dependent on Age-of-First Exposure in Recreational Users and Animals

Rationale and Objective

Little is known on the effects of ecstasy (MDMA, a potent 5-HT-releaser and neurotoxin) exposure on brain development in teenagers. The objective of this study was to investigate whether in humans, like previous observations made in animals, the effects of MDMA on the 5-HT system are dependent on age-of-first exposure.

Methods

5-HT transporter (SERT) densities in the frontal cortex and midbrain were assessed with [¹²³I]β-CIT single photon emission computed tomography in 33 users of ecstasy. Subjects were stratified for early-exposed users (age-at-first exposure 14–18 years; developing brain), and late-exposed users (age-at-first exposure 18–36 years; mature brain). In parallel, we investigated the effects of age experimentally with MDMA in early-exposed (adolescent) rats and late-exposed (adult) rats using the same radioligand.

Results

On average, five years after first exposure, we found a strong inverse relationship, wherein age-at-first exposure predicted 79% of the midbrain SERT variability in early (developing brain) exposed ecstasy users, whereas this was only 0.3% in late (mature brain) exposed users (p = 0.007). No such effect was observed in the frontal cortex. In rats, a significant age-BY-treatment effect (p<0.01) was observed as well, however only in the frontal cortex.

Conclusions

These age-related effects most likely reflect differences in the maturational stage of the 5-HT projection fields at age-at-first exposure and enhanced outgrowth of the 5-HT system due to 5-HT’s neurotrophic effects. Ultimately, our findings stress the need for more knowledge on the effects of pharmacotherapies that alter brain 5-HT levels in the pediatric population.     

Blood Glutathione S-Transferase-π as a Time Indicator of Stroke Onset

Background

Ability to accurately determine time of stroke onset remains challenging. We hypothesized that an early biomarker characterized by a rapid increase in blood after stroke onset may help defining better the time window during which an acute stroke patient may be candidate for intravenous thrombolysis or other intravascular procedures.

Methods

The blood level of 29 proteins was measured by immunoassays on a prospective cohort of stroke patients (N = 103) and controls (N = 132). Mann-Whitney U tests, ROC curves and diagnostic odds ratios were applied to evaluate their clinical performances.

Results

Among the 29 molecules tested, GST-π concentration was the most significantly elevated marker in the blood of stroke patients (p<0.001). More importantly, GST-π displayed the best area under the curve (AUC, 0.79) and the best diagnostic odds ratios (10.0) for discriminating early (N = 22, <3 h of stroke onset) vs. late stroke patients (N = 81, >3 h after onset). According to goal-oriented distinct cut-offs (sensitivity(Se)-oriented: 17.7 or specificity(Sp)-oriented: 65.2 ug/L), the GST-π test obtained 91%Se/50%Sp and 50%Se/91%Sp, respectively. Moreover, GST-π showed also the highest AUC (0.83) and performances for detecting patients treated with tPA (N = 12) compared to ineligible patients (N = 103).

Conclusions

This study demonstrates that GST-π can accurately predict the time of stroke onset in over 50% of early stroke patients. The GST-π test could therefore complement current guidelines for tPA administration and potentially increase the number of patients accessing thrombolysis.     

Clinical Application of Estimating Hepatitis B Virus Quasispecies Complexity by Massive Sequencing: Correlation between Natural Evolution and On-Treatment Evolution

Aim

To evaluate HBV quasispecies (QA) complexity in the preCore/Core regions in relation to HBeAg status, and explore QA changes under natural evolution and nucleoside analogue (NUC) treatment.

Methods

Ultra-deep pyrosequencing of HBV preCore/Core regions in 30 sequential samples (baseline [diagnosis], treatment-free, and treatment-nonresponse) from 10 retrospectively selected patients grouped according to HBeAg status over time: HBeAg+ (N = 4), HBeAg- (N = 2), and fluctuating HBeAg (transient seroreversion/seroconversion pattern) (N = 4). QA complexity was defined by Shannon entropy, mutation frequency, nucleotide diversity, and mutation frequency of amino acids (MfAA) in preCore and Core.

Results

The QA was less complex in HBeAg+ than in HBeAg- or fluctuating HBeAg. High complexity in preCore was associated with decreased viral replication (preCore MfAA negatively correlated with HBV-DNA, p = 0.005). QA complexity in the treatment-free period negatively correlated with values seen during treatment. Specific variants were mainly selected in the Core region in HBeAg- and fluctuating HBeAg patients, suggesting higher immune pressure than in HBeAg+.

Conclusions

The negative correlation between QA natural evolution and on-treatment evolution indicates the importance of pre-treatment QA study to predict QA changes in NUC nonresponders. Study of QA complexity could be useful for managing HBV infection.     

Is Serum Zinc Associated with Pancreatic Beta Cell Function and Insulin Sensitivity in Pre-Diabetic and Normal Individuals? Findings from the Hunter Community Study

Aim

To determine if there is a difference in serum zinc concentration between normoglycaemic, pre-diabetic and type-2 diabetic groups and if this is associated with pancreatic beta cell function and insulin sensitivity in the former 2 groups.

Method

Cross sectional study of a random sample of older community-dwelling men and women in Newcastle, New South Wales, Australia. Beta cell function, insulin sensitivity and insulin resistance were calculated for normoglycaemic and prediabetes participants using the Homeostasis Model Assessment (HOMA-2) calculator.

Result

A total of 452 participants were recruited for this study. Approximately 33% (N = 149) had diabetes, 33% (N = 151) had prediabetes and 34% (N = 152) were normoglycaemic. Homeostasis Model Assessment (HOMA) parameters were found to be significantly different between normoglycaemic and prediabetes groups (p<0.001). In adjusted linear regression, higher serum zinc concentration was associated with increased insulin sensitivity (p = 0.01) in the prediabetic group. There was also a significant association between smoking and worse insulin sensitivity.

Conclusion

Higher serum zinc concentration is associated with increased insulin sensitivity. Longitudinal studies are required to determine if low serum zinc concentration plays a role in progression from pre-diabetes to diabetes.