Impact of the COVID-19 pandemic on individuals with nystagmus and an exploration of public assumptions about the condition: an electronic questionnaire study

Purpose Nystagmus is a disorder characterized by uncontrolled, rhythmic oscillations of the eyes. It often causes reduced visual function beyond reduced visual acuity alone. There is a paucity of literature regarding the public understanding of nystagmus, and there are no published data on the impact of the COVID-19 pandemic on people living with the condition. This study explores the self-reported impact of the COVID-19 pandemic on those with nystagmus, and examines both public understanding of how nystagmus affects people who have it and the perceptions of public understanding by those with the condition and their carers. Methods A qualitative questionnaire was designed following a stakeholder engagement process. This questionnaire was advertised via social media platforms and charity websites to achieve widespread recruitment. Data were collected between November and December 2020. Participants were divided into two groups based on their response to the question: “Do you, or anyone you know well, have nystagmus?”. Questions were posed to participants in a purpose-built, branching survey. The resulting data were analyzed using descriptive and inferential statistical methods. Results One thousand six hundred forty-five respondents were recruited, of which 849 (51.6%) answered “Yes” to the initial filtering question. Analysis showed that, broadly, public understanding of nystagmus differs from the perception of it by those with nystagmus and their carers, that the COVID-19 pandemic has had a significant impact on those with nystagmus, and that respondents who have met someone with nystagmus, even briefly, tend to have a greater understanding of the impact of the condition. Conclusion This study highlights the lack of public awareness regarding nystagmus and suggests opportunities to increase the awareness of nystagmus without the need for extensive knowledge of the condition. The COVID-19 pandemic has posed additional difficulties for those living with nystagmus, which is likely to be comparable among those with similar ocular disorders. Peer Review report

Identification and characterisation of a rare MTTP variant underlying hereditary non-alcoholic fatty liver disease

Background and aimsNon-alcoholic fatty liver disease (NAFLD) is a complex trait with an estimated prevalence of 25% globally. We aimed to identify the genetic variant underlying a four-generation family with progressive NAFLD leading to cirrhosis, decompensation and development of hepatocellular carcinoma in the absence of common risk factors such as obesity and type 2 diabetes.MethodsExome sequencing and genome comparisons were used to identify the likely causal variant. We extensively characterised the clinical phenotype and post-prandial metabolic responses of family members with the identified novel variant in comparison to healthy non-carriers and wild-type patients with NAFLD. Variant-expressing hepatocyte-like cells (HLCs) were derived from human induced pluripotent stem cells generated from homozygous donor skin fibroblasts and restored to wild-type using CRISPR-Cas9. The phenotype was assessed using imaging, targeted RNA analysis and molecular expression arrays.ResultsWe identified a rare causal variant c.1691T>C p.I564T (rs745447480) in MTTP, encoding microsomal triglyceride transfer protein (MTP), associated with progressive NAFLD, unrelated to metabolic syndrome and without characteristic features of abetalipoproteinemia. HLCs derived from a homozygote donor had significantly lower MTP activity and lower lipoprotein ApoB secretion compared to wild-type cells, while having similar levels of MTP mRNA and protein. Cytoplasmic triglyceride accumulation in HLCs triggered endoplasmic reticulum stress, secretion of pro-inflammatory mediators and production of reactive oxygen species.ConclusionWe have identified and characterized a rare causal variant in MTTP and homozygosity for MTTP p.I564T is associated with progressive NAFLD without any other manifestations of abetalipoproteinemia. Our findings provide insights into mechanisms driving progressive NAFLD

SLC38A8 mutations result in arrested retinal development with loss of cone photoreceptor specialization

Foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis is an autosomal recessive disorder arising from SLC38A8 mutations. SLC38A8 is a putative glutamine transporter with strong expression within the photoreceptor layer in the retina. Previous studies have been limited due to lack of quantitative data on retinal development and nystagmus characteristics. In this multi-centre study, a custom-targeted next generation sequencing (NGS) gene panel was used to identify SLC38A8 mutations from a cohort of 511 nystagmus patients. We report 16 novel SLC38A8 mutations. The sixth transmembrane domain is most frequently disrupted by missense SLC38A8 mutations. Ninety percent of our cases were initially misdiagnosed as PAX6-related phenotype or ocular albinism prior to NGS. We characterized the retinal development in vivo in patients with SLC38A8 mutations using high-resolution optical coherence tomography. All patients had severe grades of arrested retinal development with lack of a foveal pit and no cone photoreceptor outer segment lengthening. Loss of foveal specialization features such as outer segment lengthening implies reduced foveal cone density, which contributes to reduced visual acuity. Unlike other disorders (such as albinism or PAX6 mutations) which exhibit a spectrum of foveal hypoplasia, SLC38A8 mutations have arrest of retinal development at an earlier stage resulting in a more under-developed retina and severe phenotype

Effect of Cirsium arvense L. on soil physical properties and crop growth

The re-cultivation of abandoned areas creates weed control problems. The main problems in these areas are perennial weeds, such as Cirsium arvense L. but this perennial deep-rooted plant may have a beneficial effect on the physical properties of compacted soil. In order to study the effect of C. arvenses root system on soil properties, the field experiment and a survey of arable fields were conducted in Estonia. The soil bulk density and penetration resistance were measured from soils covered by C. arvense or spring barley (Hordeum vulgare L.) on compacted and un-compacted soil. The results showed significantly lower penetration resistance and bulk density underneath C. arvense than under barley in both the field experiment and a field survey on arable soils. The shoot mass of C. arvense was less affected than the shoot mass of barley by soil compaction and was caused by C. arvenses better ability to develop its root system in compacted soil. Wheat yield, on soils affected by C. arvense, was increased by 28% on loose soil and 37% on compacted soil. It may be concluded that in areas affected by deep-rooted weed species, such C. arvense, the soils physical properties will improve at least in the first two years.

Body temperature and its regulation

Humans are homeotherms, i.e. they fix their temperature regardless of their environment. This is vital for normal cellular function and for metabolism to be independent of external temperature. The body has a warm 'core' and a cooler peripheral 'shell' whose role is to regulate heat transfer in and out of the core. Body temperature is controlled by a feedback system with both peripheral and central sensors, and an integrator located in the hypothalamus. Anaesthesia exposes patients to thermoregulatory challenges due to enhanced heat loss from the core to the shell to the environment, and interference with the hypothalamic temperature 'set-point'. In extreme circumstances, deliberate hypothermia may provide benefits that outweigh the risks. © 2014 Published by Elsevier Ltd

Ekologiczne konsekwencje degradacji gleby w warunkach estońskich

The extreme soil compaction and standard indices for Estonian soils sted to sustainable crop production are worked out which could be a basis for chracterizing the agro-ecological conditions for some particular soils. Comparison of measurements showed, that increase of subsoil hardness by compaction is mostly visible in soils with relatively weak agro-technical capability (90 and 120 kPa). The penetration resistance of arable soils is quite different depending on Estonian area. We are briefly introducing our results concerning the influence of soil compaction on penetration resistance of different soils in Estonia, on uptake of nutrients and new viewpoints concerning the changes in cellualar fluid pH of barley as depended on the soil compaction. Concerning degree of intracellular fluid pH we could conclude that this method is rather sensitive and allows us to find out plausible relations between the CpH compaction of soil and the level of the nitrogen fertilizer. Our contribution to this work justified itself and allowed us to analyse from a new point of view the positive as well as negative aspects of the effect of soil compaction and level of nitrogen fertilizer. Without nitrogen fertilizer the influence of soil compaction is rather negative. The effect of soil bulk density on cellular fluid pH of barley leaves generally depends on the number of passes. The experiment showed also that stronger decrease of nutrient content started at the same soil bulk densityvalue, at which the cellular fluid pH quickly increased. If the soil bulk density- increased up to level of 1.52-1.54 Mg·m⁻³, the cellular fluid pH increased very quickly.Opracowano wskaźniki i standardy odnoszące się do maksymalnego, z punktu widzenia zrównoważonej produkcji rolniczej, ugniecenia gleb estońskich. Mogą one stanowić podstawę charakteryzowania warunków agro-ekologicznych dla niektórych gleb. Porównanie wyników badań wykonanych w różnych miejscach wskazuje, że wzrost zwięzłości podglebia w wyniku ugniecenia jest najbardziej widoczny na glebach o stosunkowo słabej nośności agro-technicznej (90 i 120 kPa). Opory penetracji gleb uprawnych różnią się znacznie w zależności od rejonu Estonii. Przedstawiliśmy w skrócie nasze wyniki, dotyczące wpływu ugniecenia gleb na opory penetracji dla rolniczych gleb Estonii i na pobieranie składników nawozowych, a także przedstawiliśmy nasz pogląd dotyczący zmian odczynu pH płynu komórkowego jęczmienia w zależności od ugniecenia gleby. Co się tyczy poziomu odczynu pH płynu komórkowego stwierdziliśmy, że ta metoda jest dostatecznie czuła i pozwala ustalić wiarygodne relacje między CpH, ugnieceniem gleby i poziomem nawożenia azotowego. Nasz wkład w tę pracę był uzasadniony i pozwolił analizować z nowego punktu widzenia zarówno pozytywne jak i negatywne aspekty ugniecenia gleby i nawożenia azotowego. Bez nawożenia azotowego skutki ugniecenia są raczej negatywne. Wpływ gęstości gleby na pH płynu komórkowego liści jęczmienia zależy głównie od liczby przejazdów. Eksperyment wykazał również, że spadek ilości pobranego nawozu rozpoczyna się przy tej samej wartości gęstości gleby, przy której występuje gwałtowny wzrost pH płynu komórkowego. Przy wzroście gęstości gleby do poziomu 1,52-1,54 Mg·m⁻³, pH płynu komórkowego bardzo szybko wzrasta