CD4 T cells are rapidly depleted from tuberculosis granulomas following acute SIV co-infection

The HIV-mediated decline in circulating CD4 T cells correlates with increased the risk of active tuberculosis (TB). However, HIV/Mycobacterium tuberculosis (Mtb) co-infected individuals also have an increased incidence of TB prior to loss of CD4 T cells in blood, raising the possibility that HIV co-infection leads to disruption of CD4 T cell responses at the site of lung infection before they are observed systemically. Here we used a rhesus macaque model of SIV/Mtb co-infection to study the early effects of acute SIV infection on CD4 T cells in pulmonary Mtb granulomas. Two weeks after SIV co-infection CD4 T cells were dramatically depleted from granulomas, before significant bacterial outgrowth, disease reactivation as measured by PET-CT imaging, or CD4 T cell loss in blood, airways, and lymph nodes. Mtb-specific CD4 T cells, CCR5-expressing, in granulomas were preferentially depleted by SIV infection. Moreover, CD4 T cells were preferentially depleted from the granuloma core and lymphocyte cuff relative to B cell-rich regions, and live imaging of granuloma explants showed that SIV co-infection reduced T cell motility. Thus, Mtb-specific CD4 T cells in pulmonary granulomas may be decimated before many patients even experience the first symptoms of acute HIV infection.

Head-Down Tilt Bed Rest Improves Executive Function Amongst Younger Adults: A Pilot Project

Purpose Microgravity has been shown to be a significant stressor on the cardiovascular system and the brain due to the redistribution of fluids that occurs in the absence of gravitational force, but there is scarce literature surrounding the effects of microgravity on cerebral hemodynamics and cognition. Understanding the early effects that simulated gravity has on cognitive function is essential for developing proper physical and cognitive countermeasures to assure safe and effective cognitive/decisions making while astronauts prepare for the initial launch or when they arrive in a microgravity environment. Therefore, this study aims to determine how an acute simulation of microgravity would alter cerebral oxygenation and executive functions. Methods Sixty-five young healthy participants (22±6 years, 21 females) completed a thirty (30) minute horizontal (00 tilt) followed by a 90-min -6° head-down-tilt (HDT) protocol. Cerebral oxygenation in the prefrontal cortex was monitored throughout the testing session using near-infrared spectroscopy. Cognition was also measured using a computerized Stroop Task. Results Our results demonstrate that cerebral oxygenation was higher during HDT compared to the horizontal supine position (9.11±1.3 vs 7.51±1.8, p=0.02). For the cognitive results, the non-executive performance of the Stroop task remained stable during HDT (652.46± 19.3 vs. 632.49±14.5, p=0.09). However, reaction time during the executive task performance was improved after the HDT (1058±195 msec to 950±158 msec, p<0.01). Conclusion Our results suggest that an acute bout of simulated microgravity can enhance executive functioning.

SR Ca2+ handling in unbranched, immediately post-necrotic fast-twitch mdx fibres is similar to wt littermates

There is a lack of consensus in the literature regarding the effects of dystrophin deficiency on the Ca2+ handling properties of the sarcoplasmic reticulum (SR) in mdx mice, an animal model of Duchenne muscular dystrophy. One possible reason for this is that only a few studies control for the presence of branched fibres. Fibre branching, a consequence of degenerative-regenerative processes such as muscular dystrophy, has in itself a significant influence on the function of the SR. In our present study we attempt to detect early effects of dystrophin deficiency on SR Ca2+ handling by using unbranched fibres from the immediate post-necrotic stage in mdx mice (just regenerated following massive necrosis). Using kinetically-corrected Fura-2 fluorescence signals measured during twitch and tetanus, we analysed the amplitude, rise time and decay time of Δ[Ca2+]i in unfatigued and fatigued fibres. Decay was also resolved into SR pump and SR leak components. Fibres from mdx mice were similar in all respects to fibres from wt littermates apart from: (i) a longer rise time and slower rate of rise of [Ca2+]i during a tetanus; and (ii) a mitigation of the fall in Δ[Ca2+]i amplitude during the course of fatigue. Our findings suggest that the early effects of a loss of dystrophin on SR Ca2+ handling are only slight, and differ from the widely held view that there is significant Ca2+ pathology in mdx mice. It may be that Ca2+pathology is magnified by progressive branching and degeneration.

From eye to arrow: Attention capture by direct gaze requires more than just the eyes

Human attention is strongly attracted by direct gaze and sudden onset motion. The sudden direct-gaze effect refers to the processing advantage for targets appearing on peripheral faces that suddenly establish eye contact. Here, we investigate the necessity of social information for attention capture by (sudden onset) ostensive cues. Six experiments involving 204 participants applied (1) naturalistic faces, (2) arrows, (3) schematic eyes, (4) naturalistic eyes, or schematic facial configurations (5) without or (6) with head turn to an attention-capture paradigm. Trials started with two stimuli oriented towards the observer and two stimuli pointing into the periphery. Simultaneous to target presentation, one direct stimulus changed to averted and one averted stimulus changed to direct, yielding a 2 × 2 factorial design with direction and motion cues being absent or present. We replicated the (sudden) direct-gaze effect for photographic faces, but found no corresponding effects in Experiments 2–6. Hence, a holistic and socially meaningful facial context seems vital for attention capture by direct gaze. Statement of significance The present study highlights the significance of context information for social attention. Our findings demonstrate that the direct-gaze effect, that is, the prioritization of direct gaze over averted gaze, critically relies on the presentation of a meaningful holistic and naturalistic facial context. This pattern of results is evidence in favor of early effects of surrounding social information on attention capture by direct gaze.

Cell-based treatment of cerebral palsy: still a long way ahead

Background: Cerebral palsy (CP) is a permanent neurodevelopmental disorder with considerable global disability. Various rehabilitation strategies are currently available. However, none represents a convincing curative result. Cellular therapy recently holds much promise as an alternative strategy to repair neurologic defects. Method: In this narrative review, a comprehensive search of the MEDLINE and ClinicalTrials.gov was made, using the terms: "cell therapy" and "cerebral palsy", including published and registered clinical studies, respectively. Results: The early effects of these studies demonstrated that using cell therapy in CP patients is safe and improves the deficits for a variable duration. Despite such hopeful early bird results, the long-term outcomes are not conclusive. Conclusions: Due to the heterogeneous nature of CP, personal factors seem essential to consider. Cell dosage, routes of administration, and repeated dosing are pivotal to establish optimal personalized treatments. Future clinical trials should consider employing other cell types, specific cell modifications before administration, and cell-free platforms. Method: In this narrative review, a comprehensive search of the MEDLINE and ClinicalTrials.gov was made, using the terms: "cell therapy" and "cerebral palsy", including published and registered clinical studies, respectively. Results: The early effects of these studies demonstrated that using cell therapy in CP patients is safe and improves the deficits for a variable duration. Despite such hopeful early bird results, the long-term outcomes are not conclusive. Conclusions: Due to the heterogeneous nature of CP, personal factors seem essential to consider. Cell dosage, routes of administration, and repeated dosing are pivotal to establish optimal personalized treatments. Future clinical trials should consider employing other cell types, specific cell modifications before administration, and cell-free platforms.

Early Effects of Low Molecular Weight Heparin Therapy with Soft-Mist Inhaler for COVID-19-Induced Hypoxemia: A Phase IIb Trial

In COVID-19-induced acute respiratory distress syndrome, the lungs are incapable of filling with sufficient air, leading to hypoxemia that results in high mortality among hospitalized patients. In clinical trials, low-molecular-weight heparin was administered via a specially designed soft-mist inhaler device in an investigator initiated, single-center, open-label, phase-IIb clinical trial. Patients with evidently worse clinical presentations were classed as the “Device Group”; 40 patients were given low-molecular-weight heparin via a soft mist inhaler at a dose of 4000 IU per administration, twice a day. The Control Group, also made up of 40 patients, received the standard therapy. The predetermined severity of hypoxemia and the peripheral oxygen saturation of patients were measured on the 1st and 10th days of treatment. The improvement was particularly striking in cases of severe hypoxemia. In the 10-day treatment, low-molecular-weight heparin was shown to significantly improve breathing capability when delivered via a soft-mist inhaler.

No aggregate deforestation reductions from rollout of community land titles in Indonesia yet

In Indonesia, 60 million people live within 1 km of state forest. The government of Indonesia plans to grant community titles for 12.7 million hectares of land to communities living in and around forests. These titles allow for using nontimber forest products, practicing agroforestry, operating tourism businesses, and selective logging in designated production zones. Here, we estimate the early effects of the program’s rollout. We use data on the delineation and introduction date of community forest titles on 2.4 million hectares of land across the country. We find that, contrary to the objective of the program, community titles aimed at conservation did not decrease deforestation; if anything, they tended to increase forest loss. In contrast, community titles in zones aimed at timber production decreased deforestation, albeit from higher baseline forest loss rates.

Consumer Neuroscience: Attentional Preferences for Wine Labeling Reflected in the Posterior Contralateral Negativity

During the decision-making process, consumers notice, inspect, and visually scan different products. External characteristics of a product, such as design, packaging, label, and logo, have been shown to strongly influence how customers perceive, assess, and select a product. Marketers have put a lot of effort into determining the factors that trigger consumers’ visual attention toward products, using traditional research methods, self-reports, or observations. The use of neuroscientific tools to study consumer behavior may improve our understanding of how external characteristics influence consumers’ visual attention. Consumer neuroscience research shows that preferences for a product may already be reflected in brain activity before customers make a final decision. Using electroencephalography (EEG), we investigated whether the design of different wine labeling influences individual preferences, reflected in the neural activity related to visual attention. More specifically, we examined whether the posterior contralateral negativity (PCN) can be used to assess and predict consumers’ preferences for a specific product based on its external characteristics. The PCN is commonly used to estimate attentional selection by focusing on stimulus-side dependent EEG lateralization above parieto-occipital areas. We computed the PCN to assess whether a certain wine label caught participants’ visual attention and additionally by comparing the PCN with behavioral data (wine preferences and reaction times) to determine whether early effects of visual attention could predict participants’ final preferences for a specific label. Our findings indicate that the PCN provides relevant information on visual attention mechanisms for external characteristics, as the view of the four labels modulated PCN amplitude. We hope this study can help researchers and practitioners in examining the effects of external product characteristics on consumer choice by estimating the changes in the EEG that are related to visual attention.

Accuracy in recognising happy facial expressions is associated with antidepressant response to a NOP receptor antagonist but not placebo treatment

Background: Clinical trials with putative antidepressants can be difficult to execute as it can take up to 8 weeks before differences emerge between drug and placebo, and long expensive trials often fail. Implementation of early response biomarkers could aid this process significantly with potential to identify new treatments. Aims: In a secondary analysis, we examined the association of early effects on emotional processing with later clinical outcome following treatment with the novel NOP antagonist LY2940094 versus placebo. We hypothesised that early induction of positive bias would be associated with reduced severity of depression after 8 weeks of treatment. Methods: This was a multicentre, randomised, double-blind, parallel-group, fixed-dose, placebo-controlled, 8 week study to assess sensitivity of the facial emotional recognition task (FERT) to early changes in emotional bias induced by LY2940094. Patients who met diagnostic criteria for major depression were randomised to receive LY2940094 ( N = 70) or placebo ( N = 66). At week 1 and 6, the FERT was completed by 33 patients in the LY2940094 group and 34 in the placebo group. Results: Patients identified happy faces with higher accuracy (Wald χ2(1,33) = 14.25, p < 0.001) after 1 week treatment with LY290094 compared to placebo (Wald χ2(1,32) = 0.83, p = 0.36) and this correlated with eventual treatment response measured by the Hamilton Depression Rating Scale 7 weeks later. Conclusion: These data suggest that emotional processing biomarkers may be sensitive to early effects of antidepressant treatment indicative of later clinical response. Further studies in this area may be useful in developing new treatments and clinical trial designs for predicting antidepressant response.