The programming of sequences of saccades

Saccadic eye movements move the high-resolution fovea to point at regions of interest. Saccades can only be generated serially (i.e., one at a time). However, what remains unclear is the extent to which saccades are programmed in parallel (i.e., a series of such moments can be planned together) and how far ahead such planning occurs. In the current experiment, we investigate this issue with a saccade contingent preview paradigm. Participants were asked to execute saccadic eye movements in response to seven small circles presented on a screen. The extent to which participants were given prior information about target locations was varied on a trial-by-trial basis: participants were aware of the location of the next target only, the next three, five, or all seven targets. The addition of new targets to the display was made during the saccade to the next target in the sequence. The overall time taken to complete the sequence was decreased as more targets were available up to all seven targets. This was a result of a reduction in the number of saccades being executed and a reduction in their saccade latencies. Surprisingly, these results suggest that, when faced with a demand to saccade to a large number of target locations, saccade preparation about all target locations is carried out in paralle

Reprogramming of Embryonic Human Fibroblasts into Fetal Hematopoietic Progenitors by Fusion with Human Fetal Liver CD34+ Cells

Experiments with somatic cell nuclear transfer, inter-cellular hybrid formation_ENREF_3, and ectopic expression of transcription factors have clearly demonstrated that cell fate can be dramatically altered by changing the epigenetic state of cell nuclei. Here we demonstrate, using chemical fusion, direct reprogramming of the genome of human embryonic fibroblasts (HEF) into the state of human fetal liver hFL CD34+ (hFL) hematopoietic progenitors capable of proliferating and differentiating into multiple hematopoietic lineages. We show that hybrid cells retain their ploidy and can differentiate into several hematopoietic lineages. Hybrid cells follow transcription program of differentiating hFL cells as shown by genome-wide transcription profiling. Using whole-genome single nucleotide polymorphism (SNP) profiling of both donor genomes we demonstrate reprogramming of HEF genome into the state of hFL hematopoietic progenitors. Our results prove that it is possible to convert the fetal somatic cell genome into the state of fetal hematopoietic progenitors by fusion. This suggests a possibility of direct reprogramming of human somatic cells into tissue specific progenitors/stem cells without going all the way back to the embryonic state. Direct reprogramming of terminally differentiated cells into the tissue specific progenitors will likely prove useful for the development of novel cell therapies

Treatment outcomes of fixed-dose combination versus separate tablet regimens in pulmonary tuberculosis patients with or without diabetes in Qatar

Background: Tuberculosis is considered the second most common cause of death due to infectious agent. The currently preferred regimen for treatment of pulmonary tuberculosis (PTB) is isoniazid, rifampin, pyrazinamide, and ethambutol, which has been used either as separate tablets (ST) or as fixed-dose combination (FDC). To date, no studies have compared both regimens in Qatar. We aim to evaluate the safety and effectiveness of FDC and ST regimen for treating PTB, in addition to comparing safety and efficacy of FDC and ST regimens in patients with diabetes treated for TB. Methods: A retrospective observational study was conducted in two general hospitals in Qatar. Patients diagnosed with PTB received anti-tuberculosis medications (either as FDC or ST) administered by the nurse. Sputum smears were tested weekly. We assessed the time to negative sputum smear and incidence of adverse events among FDC and ST groups. Results: The study included 148 patients. FDC was used in 90 patients (61%). Effectiveness was not different between FDC and ST regimens as shown by mean time to sputum conversion (29.9 ± 18.3 vs. 35.6 ± 23 days, p = 0.12). Similarly, there was no difference in the incidence of adverse events, except for visual one that was higher in ST group. Among the 33 diabetic patients, 19 received the FDC and had faster sputum conversion compared to those who received ST (31 ± 12 vs. 49.4 ± 30.9 days, p = 0.05). Overall, diabetic patients needed longer time for sputum conversion and had more hepatotoxic and gastric adverse events compared to non-diabetics. Conclusion: ST group had higher visual side effects compared to FDC. FDC may be more effective in diabetic patients; however, further studies are required to confirm such finding.PublishedN/

The concurrent programming of saccades

Sequences of saccades have been shown to be prepared concurrently however it remains unclear exactly what aspects of those saccades are programmed in parallel. To examine this participants were asked to make one or two target-driven saccades: a reflexive saccade; a voluntary saccade; a reflexive then a voluntary saccade; or vice versa. During the first response the position of a second target was manipulated. The new location of the second saccade target was found to impact on second saccade latencies and second saccade accuracy showing that some aspects of the second saccade program are prepared in parallel with the first. However, differences were found in the specific pattern of effects for each sequence type. These differences fit well within a general framework for saccade control in which a common priority map for saccade control is computed and the influence of saccade programs on one another depends not so much on the types of saccade being produced but rather on the rate at which their programs develop

Improvements in vascular health by a low-fat diet, but not a high-fat diet, are mediated by changes in adipocyte biology

<p>Abstract</p> <p>Background</p> <p>Low-fat (LF) and high-fat (HF) weight loss diets improve brachial artery flow-mediated dilation (FMD) in obese individuals, although results are conflicting. Moreover, the role that adipose tissue plays in mediating these diet-related effects are unknown.</p> <p>Objective</p> <p>This study examined how modulations in FMD by HF and LF diets relate to changes in adipocyte parameters.</p> <p>Design</p> <p>Obese subjects (n = 17) were randomized to a HF diet (60% kcal as fat) or a LF diet (25% kcal as fat) for 6 weeks. Both groups were restricted by 25% of energy needs.</p> <p>Results</p> <p>Body weight decreased (<it>P <</it>0.05) in both groups (HF: -6.6 ± 0.5 kg, LF: -4.7 ± 0.6 kg). Fat mass and waist circumference were reduced (<it>P <</it>0.05) in the LF group only (-4.4 ± 0.3 kg; -3.6 ± 0.8 cm, respectively). FMD improved (<it>P <</it>0.05) in the LF group (7.4 ± 0.8% to 9.8 ± 0.8; 32% increase) and was impaired in the HF group (8.5 ± 0.6% to 6.9 ± 0.7; 19% reduction). Increases in plasma adiponectin (<it>P <</it>0.05, 16 ± 5%), and decreases in resistin (<it>P <</it>0.05, -26 ± 11%), were shown by the LF diet only. Greater decreases in leptin were observed with LF (-48 ± 9%) versus HF (-28 ± 12%) (<it>P <</it>0.05, diet × time). Increased FMD by the LF diet was associated with increased adiponectin, and decreased fat mass, waist circumference, leptin, and resistin.</p> <p>Conclusion</p> <p>Beneficial modulations in vascular health by LF diets may be mediated by improvements in adipocyte parameters.</p

Negative regulation of signal transducer and activator of transcription-3 signalling cascade by lupeol inhibits growth and induces apoptosis in hepatocellular carcinoma cells

Background: Constitutive activation of signal transducer and activator of transcription signalling 3 (STAT3) has been linked with survival, proliferation and angiogenesis in a wide variety of malignancies including hepatocellular carcinoma (HCC). Methods: We evaluated the effect of lupeol on STAT3 signalling cascade and its regulated functional responses in HCC cells. Results: Lupeol suppressed constitutive activation of STAT3 phosphorylation at tyrosine 705 residue effectively in a dose- and time-dependent manner. The phosphorylation of Janus-activated kinases (JAKs) 1 and 2 and Src was also suppressed by lupeol. Pervanadate treatment reversed the downregulation of phospho-STAT3 induced by lupeol, thereby indicating the involvement of a phosphatase. Indeed, we observed that treatment with lupeol increased the protein and mRNA levels of SHP-2, and silencing of SHP-2 abolished the inhibitory effects of lupeol on STAT3 activation. Treatment with lupeol also downregulated the expression of diverse STAT3-regulated genes and decreased the binding of STAT3 to VEGF promoter. Moreover, the proliferation of various HCC cells was significantly suppressed by lupeol, being associated with substantial induction of apoptosis. Depletion of SHP-2 reversed the observed antiproliferative and pro-apoptotic effects of lupeol. Conclusions: Lupeol exhibited its potential anticancer effects in HCC through the downregulation of STAT3-induced pro-survival signalling cascade

Implementing psychological support for health and social care staff affected by the COVID-19 pandemic: a qualitative exploration of staff well-being hubs (‘Resilience Hubs’) using normalisation process theory

Objectives Evaluate the implementation of Hubs providing access to psychological support for health and social care keyworkers affected by the COVID-19 pandemic. Design Qualitative interviews informed by normalisation process theory to understand how the Hub model became embedded into normal practice, and factors that disrupted normalisation of this approach. Setting Three Resilience Hubs in the North of England. Participants Hub staff, keyworkers who accessed Hub support (Hub clients), keyworkers who had not accessed a Hub, and wider stakeholders involved in the provision of staff support within the health and care system (N=63). Results Hubs were generally seen as an effective way of supporting keyworkers, and Hub clients typically described very positive experiences. Flexibility and adaptability to local needs were strongly valued. Keyworkers accessed support when they understood the offer, valuing a confidential service that was separate from their organisation. Confusion about how Hubs differed from other support prevented some from enrolling. Beliefs about job roles, unsupportive managers, negative workplace cultures and systemic issues prevented keyworkers from valuing mental health support. Lack of support from managers discouraged keyworker engagement with Hubs. Black, Asian and minority ethnic keyworkers impacted by racism felt that the Hubs did not always meet their needs. Conclusions Hubs were seen as a valuable, responsive and distinct part of the health and care system. Findings highlight the importance of improving promotion and accessibility of Hubs, and continuation of confidential Hub support. Policy implications for the wider health and care sector include the central importance of genuine promotion of and value placed on mental health support by health and social care management, and the creation of psychologically safe work environments. Diversity and cultural competency training is needed to better reach under-represented communities. Findings are consistent with the international literature, therefore, likely to have applicability outside of the current context