The effect of prolonged monocular occlusion on latent nystagmus in the treatment of amblyopia

We recorded eye movements in 5 patients with latent nystagmus (LN) before and after 2 days of occlusion of the better eye. The slow-phase speed of the nystagmus (SPS) was in general, before occlusion, lower when the better eye fixated but, after occlusion, lower when the worse eye fixated. However, the sum of SPS during right fixation and SPS during left fixation remained constant. Oscillopsia complaints gradually disappeared during the period of occlusion. These findings indicate that the difference between the SPS during fixation with the right eye and the SPS during fixation with the left eye in LN patients is caused by a compensatory drift that decreases LN during fixation with the better eye but increases LN during fixation with the worse eye. During occlusion, this compensatory drift changes its direction and magnitude slowly over days. Hence, occlusion of the better eye in children with amblyopia and LN should be prescribed only in days per week, not in hours per day

Local Chatter or International Buzz? Language Differences on Posts about Zika Research on Twitter and Facebook

Background When the Zika virus outbreak became a global health emergency in early 2016, the scientific community responded with an increased output of Zika-related research. This upsurge in research naturally made its way into academic journals along with editorials, news, and reports. However, it is not yet known how or whether these scholarly communications were distributed to the populations most affected by Zika. Methodology/Principal findings To understand how scientific outputs about Zika reached global and local audiences, we collected Tweets and Facebook posts that linked to Zika-related research in the first six months of 2016. Using a language detection algorithm, we found that up to 90% of Twitter and 76% of Facebook posts are in English. However, when none of the authors of the scholarly article are from English-speaking countries, posts on both social media are less likely to be in English. The effect is most pronounced on Facebook, where the likelihood of posting in English is between 11 and 16% lower when none of the authors are from English-speaking countries, as compared to when some or all are. Similarly, posts about papers written with a Brazilian author are 13% more likely to be in Portuguese on Facebook than when made on Twitter. Conclusions/Significance Our main conclusion is that scholarly communication on Twitter and Facebook of Zikarelated research is dominated by English, despite Brazil being the epicenter of the Zika epidemic. This result suggests that scholarly findings about the Zika virus are unlikely to be distributed directly to relevant populations through these popular online mediums. Nevertheless, there are differences between platforms. Compared to Twitter, scholarly communication on Facebook is more likely to be in the language of an author’s country. The Zika outbreak provides a useful case-study for understanding how scientific outputs are communicated to relevant populations. Our results suggest that Facebook is a more effective channel than Twitter, if communication is desired to be in the native language of the affected country. Further research should explore how local media—such as governmental websites, newspapers and magazines, as well as television and radio—disseminate scholarly publication

G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests

Malaria elimination will be possible only with serious attempts to address asymptomatic infection and chronic infection by both Plasmodium falciparum and Plasmodium vivax. Currently available drugs that can completely clear a human of P. vivax (known as “radical cure”), and that can reduce transmission of malaria parasites, are those in the 8-aminoquinoline drug family, such as primaquine. Unfortunately, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency risk having severe adverse reactions if exposed to these drugs at certain doses. G6PD deficiency is the most common human enzyme defect, affecting approximately 400 million people worldwide. Scaling up radical cure regimens will require testing for G6PD deficiency, at two levels: 1) the individual level to ensure safe case management, and 2) the population level to understand the risk in the local population to guide Plasmodium vivax treatment policy. Several technical and operational knowledge gaps must be addressed to expand access to G6PD deficiency testing and to ensure that a patient’s G6PD status is known before deciding to administer an 8-aminoquinoline-based drug. In this report from a stakeholder meeting held in Thailand on October 4 and 5, 2012, G6PD testing in support of radical cure is discussed in detail. The focus is on challenges to the development and evaluation of G6PD diagnostic tests, and on challenges related to the operational aspects of implementing G6PD testing in support of radical cure. The report also describes recommendations for evaluation of diagnostic tests for G6PD deficiency in support of radical cure

Prefrontal Cortex Based Sex Differences in Tinnitus Perception: Same Tinnitus Intensity, Same Tinnitus Distress, Different Mood

BACKGROUND: Tinnitus refers to auditory phantom sensation. It is estimated that for 2% of the population this auditory phantom percept severely affects the quality of life, due to tinnitus related distress. Although the overall distress levels do not differ between sexes in tinnitus, females are more influenced by distress than males. Typically, pain, sleep, and depression are perceived as significantly more severe by female tinnitus patients. Studies on gender differences in emotional regulation indicate that females with high depressive symptoms show greater attention to emotion, and use less anti-rumination emotional repair strategies than males. METHODOLOGY: The objective of this study was to verify whether the activity and connectivity of the resting brain is different for male and female tinnitus patients using resting-state EEG. CONCLUSIONS: Females had a higher mean score than male tinnitus patients on the BDI-II. Female tinnitus patients differ from male tinnitus patients in the orbitofrontal cortex (OFC) extending to the frontopolar cortex in beta1 and beta2. The OFC is important for emotional processing of sounds. Increased functional alpha connectivity is found between the OFC, insula, subgenual anterior cingulate (sgACC), parahippocampal (PHC) areas and the auditory cortex in females. Our data suggest increased functional connectivity that binds tinnitus-related auditory cortex activity to auditory emotion-related areas via the PHC-sgACC connections resulting in a more depressive state even though the tinnitus intensity and tinnitus-related distress are not different from men. Comparing male tinnitus patients to a control group of males significant differences could be found for beta3 in the posterior cingulate cortex (PCC). The PCC might be related to cognitive and memory-related aspects of the tinnitus percept. Our results propose that sex influences in tinnitus research cannot be ignored and should be taken into account in functional imaging studies related to tinnitus

Modulation of γ-Secretase Activity by Multiple Enzyme-Substrate Interactions: Implications in Pathogenesis of Alzheimer's Disease

BACKGROUND: We describe molecular processes that can facilitate pathogenesis of Alzheimer's disease (AD) by analyzing the catalytic cycle of a membrane-imbedded protease γ-secretase, from the initial interaction with its C99 substrate to the final release of toxic Aβ peptides. RESULTS: The C-terminal AICD fragment is cleaved first in a pre-steady-state burst. The lowest Aβ42/Aβ40 ratio is observed in pre-steady-state when Aβ40 is the dominant product. Aβ42 is produced after Aβ40, and therefore Aβ42 is not a precursor for Aβ40. The longer more hydrophobic Aβ products gradually accumulate with multiple catalytic turnovers as a result of interrupted catalytic cycles. Saturation of γ-secretase with its C99 substrate leads to 30% decrease in Aβ40 with concomitant increase in the longer Aβ products and Aβ42/Aβ40 ratio. To different degree the same changes in Aβ products can be observed with two mutations that lead to an early onset of AD, ΔE9 and G384A. Four different lines of evidence show that γ-secretase can bind and cleave multiple substrate molecules in one catalytic turnover. Consequently depending on its concentration, NotchΔE substrate can activate or inhibit γ-secretase activity on C99 substrate. Multiple C99 molecules bound to γ-secretase can affect processive cleavages of the nascent Aβ catalytic intermediates and facilitate their premature release as the toxic membrane-imbedded Aβ-bundles. CONCLUSIONS: Gradual saturation of γ-secretase with its substrate can be the pathogenic process in different alleged causes of AD. Thus, competitive inhibitors of γ-secretase offer the best chance for a successful therapy, while the noncompetitive inhibitors could even facilitate development of the disease by inducing enzyme saturation at otherwise sub-saturating substrate. Membrane-imbedded Aβ-bundles generated by γ-secretase could be neurotoxic and thus crucial for our understanding of the amyloid hypothesis and AD pathogenesis

Viable Tumor Tissue Adherent to Needle Applicators after Local Ablation: A Risk Factor for Local Tumor Progression

Background. Local tumor progression (LTP) is a serious complication after local ablation of malignant liver tumors, negatively influencing patient survival. LTP may be the result of incomplete ablation of the treated tumor. In this study, we determined whether viable tumor cells attached to the needle applicator after ablation was associated with LTP and disease-free survival. Methods. In this prospective study, tissue was collected of 96 consecutive patients who underwent local liver ablations for 130 liver malignancies. Cells and tissue attached to the needle applicators were analyzed for viability using glucose-6-phosphate-dehydrogenase staining and autofluorescence intensity levels of H&E stained sections. Patients were followed-up until disease progression. Results. Viable tumor cells were found on the needle applicators after local ablation in 26.7% of patients. The type of needle applicator used, an open approach, and the omission of track ablation were significantly correlated with viable tumor tissue adherent to the needle applicator. The presence of viable cells was an independent predictor of LTP. The attachment of viable cells to the needle applicators was associated with a shorter time to LTP. Conclusions. Viable tumor cells adherent to the needle applicators were found after ablation of 26.7% of patients. An independent risk factor for viable cells adherent to the needle applicators is the omission of track ablation. We recommend using only RFA devices that have track ablation functionality. Adherence of viable tumor cells to the needle applicator after local ablation was an independent risk factor for LT

Analysis of two methods of isometric muscle contractions during the anti-G straining maneuver

This study investigated the difference in Mean Arterial Pressure (MAP) and Cardiac Output (CO) between two methods of isometric muscle contractions during the Anti-G Straining Maneuver (AGSM). 12 subjects (ages 18 to 38 yrs, height 176.8 +/- 7.4 cm, body mass 78.8 +/- 15.6 kg, percent body fat 14.3 +/- 6.6%) participated in the study. The study was a one-way within-subject design with test conditions counterbalanced. Two methods of isometric muscle contractions lasting 30 seconds each were assessed; an isometric push contraction and an isometric muscle tensing contraction. The dependent parameters were MAP and CO. The average MAP during the push contraction was 123 mmHg, SD +/- 11 and for tense was 118 mmHg, SD +/- 8. CO was 7.6 L/min, SD +/- 1.6 for push and 7.9 L/min, SD +/- 2.0 for tense method. Dependent t-tests revealed t(11) = 1.517, p = 0.157 for MAP and t(11) = 0.875, p = 0.400 for CO. This study demonstrated that the two methods of isometric muscle contractions were not statistically different with regards to MAP and CO. Therefore, both forms of isometric contractions may be potentially useful when performing the muscle contraction portion of the AGSM

Improving GHB withdrawal with baclofen: study protocol for a feasibility study for a randomised controlled trial

Background: GHB (gamma-hydroxybutyrate) and its pro-drugs GBL (gamma-butyrolactone) and 1,4-butanediol (1,4-BD) are central nervous system depressants whose street names include ‘G’ and ‘liquid ecstasy’. They are used recreationally predominately for their stimulant and pro-sexual effects or for sedation to help with sleep and/or to ‘come down’ after using stimulant recreational drugs. Although overall population prevalence is low (0.1 %), in some groups such as men who have sex with men, GHB/GBL use may reach 20 %. GHB/GBL dependence may be associated with severe withdrawal with individuals presenting either acutely to emergency departments or to addiction services for support. Benzodiazepines are currently prescribed for GHB/GBL detoxification but do not prevent all complications, such as behavioural disinhibition, that may require hospitalisation or admission to a high dependency /intensive care unit. The GABAB receptor mediates most effects of GHB/GBL and the GABAB agonist, baclofen, has shown promise as an adjunct to benzodiazepines in reducing withdrawal severity when prescribed both during withdrawal and as a 2-day ‘preload’ prior to detoxification. The key aim of this feasibility study is provide information about recruitment and characteristics of the proposed outcome measure (symptom severity, complications including delirium and treatment escalation) to inform an application for a definitive randomised placebo controlled trial to determine the role of baclofen in the management of GHB/GBL withdrawal and whether starting baclofen 2 days earlier improves outcomes further. Methods/design: This is a prospective, randomised, double-blind, placebo-controlled feasibility study that will recruit participants (aged over 18 years) who are GHB/GBL- dependent and wish to undergo planned GHB/GBL detoxification or are at risk of acute withdrawal and are inpatients requiring unplanned withdrawal. We aim to recruit 88 participants: 28 unplanned inpatients and 60 planned outpatients. During detoxification we will compare baclofen 10 mg three times a day with placebo as an adjunct to the usual benzodiazepine regimen. In the planned outpatient arm, we will also compare a 2-day preload of baclofen 10 mg three times a day with placebo. Ratings of GHB/GBL withdrawal, sleep, depression, anxiety as well as GHB/GBL use will be collected. The main data analyses will be descriptive about recruitment and characterising the impact of adding baclofen to the usual benzodiazepine regimen on measures and outcomes of GHB/GBL withdrawal to provide estimates of variability and effect size. A qualitative approach will evaluate research participant and clinician acceptability and data collected to inform cost-effectiveness. Discussion: This feasibility study will inform a randomised controlled trial to establish whether adding baclofen to a benzodiazepine regimen reduces the severity and complications of GHB/GBL withdrawal