Small fiber neuropathy for assessment of disease severity in amyotrophic lateral sclerosis: corneal confocal microscopy findings

Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with progressive motor system impairment, and recent evidence has identified the extra-motor involvement. Small fiber neuropathy reflecting by sensory and autonomic disturbances in ALS has been reported to accompany the motor damage. However, non-invasive assessment of this impairment and its application in disease evaluation of ALS is scarce. We aim to evaluate the use of corneal confocal microscopy (CCM) to non-invasively quantify the corneal small fiber neuropathy in ALS and explore its clinical value in assessing disease severity of ALS. Methods Sixty-six patients with ALS and 64 healthy controls were included in this cross-sectional study. Participants underwent detailed clinical assessments and corneal imaging with in vivo CCM. Using ImageJ, the following parameters were quantified: corneal nerve length (IWL) and dendritic cell density (IWDC) in the inferior whorl region and corneal nerve fiber length (CNFL), nerve fiber density (CNFD), nerve branch density (CNBD), and dendritic cell density (CDC) in the peripheral region. Disease severity was evaluated using recognized scales. Results Corneal nerve lengths (IWL and CNFL) were lower while dendritic cell densities (IWDC and CDC) were higher in patients with ALS than controls in peripheral and inferior whorl regions (p < 0.05). Additionally, corneal nerve complexity in the peripheral region was greater in patients than controls with higher CNBD (p = 0.040) and lower CNFD (p = 0.011). IWL was significantly associated with disease severity (p < 0.001) and progression (p = 0.002) in patients with ALS. Patients with bulbar involvement showed significantly lower IWL (p = 0.014) and higher IWDC (p = 0.043) than patients without bulbar involvement. Conclusions CCM quantified significant corneal neuropathy in ALS, and alterations in the inferior whorl region were closely associated with disease severity. CCM could serve as a noninvasive, objective imaging tool to detect corneal small fiber neuropathy for clinical evaluation in ALS.

REGIONAL VARIATION IN FLUID RESERVOIR THICKNESS, OXYGEN TRANSMISSIBILITY AND CORNEAL OEDEMA DURING SCLERAL LENS WEAR

Purpose: To determine if regional variation in post lens fluid reservoir thickness (PLFT) during scleral lens wear leads to regional variation in oxygen transmissibility and corneal edema during 4 hours of non-fenestrated scleral lens wear.Methods: About 20 healthy subjects (mean age, 28.8 ± 4.2 years) were fitted with nonfenestrated rotationally symmetric scleral lenses. Anterior segment optical coherence tomography was used to measure cornea thickness before and after lens wear, PLFT 10 minutes and 4 hours after lens application, and scleral lens thickness (with the scleral lens in situ) 4 hours after scleral lens application. These measurements were limited to the central 6 mm and divided into three zones (central, mid-peripheral, and peripheral zones). In the mid-peripheral and peripheral zones, eight principal meridians were measured, generating 17 measurement points in total. Scleral lens thickness and PLFT measurements were corrected for optical distortions by a series of equations. Oxygen transmissibility was calculated by dividing the scleral lens oxygen permeability by the optically-corrected scleral lens thickness, taking into account the oxygen permeability of saline and fluid reservoir thickness.Results: A significant regional variation in PLFT (F = 12.860, P = 0. 012) was observed after 10 minutes of the lens application, PLFT was thickest and thinnest in the inferotemporal and the superonasal region of the peripheral zones( 322.6 ± 161.8 µm and 153.8 ± 96.4 µm, respectively); however, this variation was not statistically significant at 4 hours of scleral lens wear (F = 4.692; P = 0.073). Despite significant regional variation in oxygen transmissibility (F = 48.472; P = 0.001) and relatively low oxygen transmissibility through the scleral lens, induced corneal edema did not vary significantly in different regions (F = 3.346; P = 0.126). In the central corneal region, the induced corneal edema correlated moderately with PLFT (r = 0.468; P = 0.037) and oxygen transmissibility (r = -0.528; P = 0.017). This relationship was insignificant in the peripheral cornea.Conclusion: The inferotemporal peripheral region had the thickest PLFT and least oxygen transmissibility, and the superonasal region had the vice versa. Despite significant variation in PLFT and oxygen transmissibility initially, in healthy corneas, this variation does not seem to induce statistically significant regional variation in corneal edema. Increased central PLFT and decreased oxygen transmissibility moderately correlate with central corneal edema.

‘An Epic Tale of England’: Atmospheric authentication of nationalist narratives

Kynren is an outdoor spectacular pageantry performance which tells a tale of England, drawing on myth and history, to make several claims about Englishness and Britishness. It does so in the political wake, first, of constitutional crises in the UK centred around Brexit; and second, of debates around heritage, empire, race and nation which have been driven by responses to the Black Lives Matter movement. These themselves are manifestations of broader, global trends in which populist movements have attempted to reassert state-legitimacy through nationalism, heritage and culture. This paper explores, how Kynren affectively presents and discursively performs a narrative which puts place and landscape, and specifically the place and landscape of the peripheral region of County Durham in which it is located, at the heart of nation. We argue that the ways in which this narrative is authenticated performatively through the spectacular affective atmosphere of Kynren show how and which nationalist narratives resonate most readily in popular culture.

Quo Vadis? School Principals' Educational Leadership in the Technological Era of the 21st Century

This article focuses on a case study of primary schools in the northern peripheral region in Israel. Its aim is acquiring insights into the influence of principals as educational leaders of meaningful use of information and communication technologies (ICT) in teaching and learning. The data source in this study is qualitative based on personal interviews with 6 school principals and 9 teachers. The conclusion arising from these interviews was that school principals’ areas of responsibility are anchored in leading teaching, educational and learning processes, molding schools’ future image – vision and managing change, leading, and professionally developing staff, while concentrating on in individuals, managing links between schools and communities. School leaders do not need to be IT experts, but it is important they have the vision to adopt change reform in the technological era of the 21st century. Principals are role models for teachers when they provide them with support and training to encourage them to employ ICT in planning their lessons. which is likely to improve their teaching and students’ learning.

Sindh in Transition: From Mughal Rule to British Annexation, Early Eighteenth Century to 1843

<p>The eighteenth century in India saw the decline of the Mughal empire and the rise of several regional states. From the mid-1700s, however, the consolidation of regional states was checked by British expansion in the subcontinent. This thesis is a case study of one regional state, the state of Sindh in present day Pakistan. It engages in the historiographical debates about the relative importance of political and economic factors in explanations of Mughal decline during the eighteenth century. It also addresses questions about the motives that impelled British annexation, and the processes through which annexation was achieved. The study analyses Sindh’s transition from being a peripheral region in the twilight days of the Mughal empire to its annexation by the British in 1843. It is based on some Persian sources, along with British archival records and a number of eighteenth and nineteenth century travelogues. The thesis begins with a study of the process of state formation in Sindh by the Sufi Kalhora tribe. Although increasingly independent from 1701, the Sindh state continued to pay tribute to the Mughals until 1739, then to Persia until 1747, and then to the Afghan king until 1783, when the Talpur Meers replaced the Kalhoras as Sindh’s ruler. Under both the Kalhoras and the Talpurs, a significant expansion of trade helped sustain the Sindh state and resulted in the emergence of a strong mercantile class. The thesis critically examines the role of the new commercial class and its relationship with Sindh’s rulers. But the political edifice constructed by the Talpurs was weak. The thesis argues that when the rise of French and Russian imperialism in the Middle East made Sindh strategically and commercially important to the British, the political weakness of the Talpur regime facilitated British encroachment in Sindh. The final annexation of Sindh in 1843, following two battles with the Meers, was the result of a number of developments: it was the culmination of a long-drawn-out weakening of the Sindhi polity; it was connected to European rivalries in Central Asia and also to the East India Company’s new appreciation of the commercial importance of Sindhi trade along the Indus river. More broadly, the annexation in 1843 needs to be understood in the context of the interplay of British, French, Russian, Afghan, Sikh and Persian ambitions since the beginning of the nineteenth century.</p>

Sindh in Transition: From Mughal Rule to British Annexation, Early Eighteenth Century to 1843

<p>The eighteenth century in India saw the decline of the Mughal empire and the rise of several regional states. From the mid-1700s, however, the consolidation of regional states was checked by British expansion in the subcontinent. This thesis is a case study of one regional state, the state of Sindh in present day Pakistan. It engages in the historiographical debates about the relative importance of political and economic factors in explanations of Mughal decline during the eighteenth century. It also addresses questions about the motives that impelled British annexation, and the processes through which annexation was achieved. The study analyses Sindh’s transition from being a peripheral region in the twilight days of the Mughal empire to its annexation by the British in 1843. It is based on some Persian sources, along with British archival records and a number of eighteenth and nineteenth century travelogues. The thesis begins with a study of the process of state formation in Sindh by the Sufi Kalhora tribe. Although increasingly independent from 1701, the Sindh state continued to pay tribute to the Mughals until 1739, then to Persia until 1747, and then to the Afghan king until 1783, when the Talpur Meers replaced the Kalhoras as Sindh’s ruler. Under both the Kalhoras and the Talpurs, a significant expansion of trade helped sustain the Sindh state and resulted in the emergence of a strong mercantile class. The thesis critically examines the role of the new commercial class and its relationship with Sindh’s rulers. But the political edifice constructed by the Talpurs was weak. The thesis argues that when the rise of French and Russian imperialism in the Middle East made Sindh strategically and commercially important to the British, the political weakness of the Talpur regime facilitated British encroachment in Sindh. The final annexation of Sindh in 1843, following two battles with the Meers, was the result of a number of developments: it was the culmination of a long-drawn-out weakening of the Sindhi polity; it was connected to European rivalries in Central Asia and also to the East India Company’s new appreciation of the commercial importance of Sindhi trade along the Indus river. More broadly, the annexation in 1843 needs to be understood in the context of the interplay of British, French, Russian, Afghan, Sikh and Persian ambitions since the beginning of the nineteenth century.</p>

Plant root PET: visualization of photosynthate translocation to roots in rice plant

Roots are essential to plants for uptake of water and nutrients. For the improvement of crop production, it is necessary to understand the elucidation of the root development and its function under the ground. Especially, photosynthate translocation from plant leaves to roots is an important physiological function that affects the root elongation, adaptation to the soil environment and nutrients uptake. To evaluate the translocation dynamics to roots, positron emission tomography (PET) and 11C tracer have been used. However, the spatial resolution is degraded at roots that develop around the peripheral area of field of view (FOV) due to parallax errors. In this study, to overcome this problem, we developed a small OpenPET prototype applying four-layer depth-of-interaction detectors. We demonstrated the imaging capability of 11C-photosynthate translocation to rice roots that develop throughout the entire PET field. We also tried to obtain structural information of roots by high-throughput X-ray computerized tomography (CT) system using the same test plant. As a result, we succeeded in visualizing the root structure that developed around the peripheral region of FOV and imaging the accumulation of 11C-photosynthate to the roots in those areas without degrading the spatial resolution. From obtained images, we also succeeded in evaluating the translocation dynamics varied by roots. The combined use of the high-throughput CT system and the OpenPET prototype was demonstrated to be appropriate for structural and functional analysis of roots.

Synthesis and Evaluation of the Acetylcholinesterase Inhibitory Activities of Some Flavonoids Derived from Naringenin

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease that affects many older people adversely. AD has been putting a huge socioeconomic burden on the healthcare systems of many developed countries with aging populations. The need for new therapies that can halt or reverse the progression of the disease is now extremely great. A research approach in the finding new treatment for AD that has attracted much interest from scientists for a long time is the reestablishment of cholinergic transmission through inhibition of acetylcholinesterase (AChE). Naringenin is a flavonoid with the potential inhibitory activity against AChE. From naringenin, many other flavonoid derivatives, such as flavanones and chalcones, can be synthesized. In this study, by applying the Williamson method, nine flavonoid derivatives were synthesized, including four flavanones and five chalcones. The evaluation of AChE inhibitory activity by the Ellman method showed that there were four substances (2, 4, 5, and 7) with relatively good biological activities (IC50 < 100 μM), and these biological activities were better than that of naringenin. The molecular docking revealed that strong interactions with amino acid residue Ser200 of the catalytic triad and those of the peripheral region of the enzyme were crucial for strong effects against AChE. Compound 7 had the strongest AChE inhibitory activity (IC50 13.0 ± 1.9 μM). This substance could be used for further studies.

Social Responsibility: A Case Study of Women Coffee Growers in a Peripheral Region of Colombia

The objective of this article is to show the practices of social responsibility in women belonging to organizations that produce differentiated coffees in a peripheral region of Colombia. In this regard, a quantitative, descriptive, and cross-sectional investigation was carried out, for which a model of its own was designed to characterize said practices from four dimensions: environment, society, values, transparency and government and labour matters. A questionnaire-type instrument with a Likert scale was applied to 430 women. Regarding the results, it was found that more than half of the women in the associations (58.7%) perceive actions related to management in the margin of social responsibility. Dimensions such as Values, Transparency and Governance (VTG), Environment (E) and Society (S), have a rating higher than 50%; however, the Labour Things (LT) dimension obtained the lowest percentage rating (47.6%).