Surgical treatment of post-traumatic changes of eyelids, orbit and periorbital region

ЦелДа представим нашия опит в хирургичното лечение на пациенти с посттравматични промени в нормалната структура и функция на клепачите, орбитата и периорбиталната зона. Да опишем разнообразни реконструктивни техники и подходи, използвани при пациентите с този тип увреди.МетодиПредставяме 17 пациенти на средна възраст 36 години (от 9 до 64 години); 5 жени и 12 мъже, претърпели хирургично лечение по повод посттравматични промени в областта на клепачите, орбитата и периорбиталната зона, за периода от март 2015 до април 2018.При петнадесет от представените пациенти наблюдаваните промени са посттравматични (давност на травмата от 15 години до 4 дни), като пациентите са били подложени на първична обработка и лечение в други звена, a проведените предходни оперативни интервенции често са били повече от една. Само при двама от представените 17 пациенти, осъществената от нас хирургична обработка е била първична.В един от описаните случаи, травмата на клепачите, орбитата и периорбиталната зона е била съчетана с увреждане на булба. В останалите - увредите ангажират само меките тъкани.В зависимост от наблюдаваните увреждания и зоните, които те ангажират, пациентите са разделени на четири основни групи: травматични промени в орбитата - 2 пациенти; посттравматични цикатрициални промени на клепачите- 12 пациенти (5 с цикатрициален ектропион и 7 с цикатрициален ентропион и трихиаза); посттравматична птоза - 1 пациент, и разкъсно-контузни рани на клепача с ангажиране на слъзните каналикули - 2 пациенти.Всички пациенти бяха подложени на хирургично лечение с използване на разнообразни реконструктивни техники. В три от случаите се наложи провеждане на операция на втори етап.РезултатиПри всички пациенти постигнахме задоволителни естетични резултати. Постоперативно се възстанови нормалното положение на клепачите и тъканите от периорбиталната зона, което осигури протекция на очната повърхност и намаляване на оплакванията на пациентите.ЗаключениеКорекцията на посттравматичните промени често е предизвикателство за окулопластичните хирурзи. То изисква използването на разнообразни реконструктивни техники и методи, демонстрирани в нашето проучване. Постигането на добър резултат обаче е от важно значение за функционалната и социална рехабилитация на пациенти с подобни проблеми.Aim            The aim of the article is to show our experience in the surgical treatment of patients with post-traumatic changes in the normal structure and function of the eyelids, orbit and periorbital region. In addition, it aims to demonstrate a variety of reconstructive techniques and approaches used in patients with these types of injuries.  Materials and MethodsWe present 17 patients at an average age of 36 (from 9 to 64 years); 5 females and 12 males who underwent surgical treatment of post-traumatic changes in the eyelids, orbit and periorbital region from March, 2015 to April, 2018.In fifteen of the presented patients, the changes were post-traumatic (trauma dating back to 15 to 4 days ago). These patients had experienced primary treatment in other hospitals and underwent previous surgical interventions, often more than one. In only two of the 17 patients, the surgical treatment we performed was primary.In only one of the described cases, the trauma of the eyelids, orbit and periorbital region was associated with bulb damage. In other cases, the injuries involved only the soft tissues.Depending on the traumatic changes and the area they involve, the patients were divided into four main groups: traumas of the orbit - 2 patients; post-traumatic cicatricial changes of the eyelids - 12 patients (5 with ectropion and 7 with entropion and trichiasis); post-traumatic ptosis -1 patient, and eyelid lacerations with the involvement of lacrimal punctum and canaliculus - 2 patients.All patients have undergone surgical treatment using a variety of reconstructive techniques and methods. In five of the cases, a second stage surgery was performed: with additional skin graft - 3 patients, reconstruction for eyelid splitting due to the use of Hughes procedure - 1 patient, and postoperative application of hyaluronic acid in a scar - 1 patient.All patients underwent surgical treatment using a variety of reconstructive techniques. In three cases, a second stage operation was required.ResultsWe achieved satisfactory esthetic results in all patients. Postoperatively, the normal position of the eyelids and tissues from the periorbital zone was restored, providing ocular surface protection and reduction of patients' complaints.ConclusionCorrection of post-traumatic changes is often a challenge for oculoplastic surgeons. It requires the use of various reconstructive techniques demonstrated in our study. Achieving good results, however, is important for the functional and social rehabilitation of patients with such problems

Spark plasma sintering synthesis of Ni1−xZnxFe2O4 ferrites: Mössbauer and catalytic study

Nickel-zinc ferrite nanoparticles, Ni1-xZnxFe2O4 (x ¼ 0, 0.2, 0.5, 0.8, 1.0) were prepared by combination of chemical precipitation and spark plasma sintering (SPS) techniques and conventional thermal treatment of the obtained precursors. The phase composition and structural properties of the obtained materials were investigated by X-ray diffraction and Mössbauer spectroscopy and their catalytic activity in methanol decomposition was tested. A strong effect of reaction medium leading to the transformation of ferrites to a complex mixture of different iron containing phases was detected. A tendency of formation of Fe-carbide was found for the samples synthesized by SPS, while predominantly iron-nickel alloys ware registered in TS obtained samples. The catalytic activity and selectivity in methanol decomposition to CO and methane depended on the current phase composition of the obtained ferrites, which was formed by the influence of the reaction medium

Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinsons disease study.

Estimates of the spectrum and frequency of pathogenic variants in Parkinsons disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinsons disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10-34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10-35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10-4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10-14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Pathophysiological Role of Adiponectin, Leptin and Asymmetric Dimethylarginine in the Process of Atherosclerosis

Adipose tissue is recognized as a rich source of proinflammatory mediators that may directly contribute to vascular injury, insulin resistance, and atherogenesis. Many studies have shown that adiponectin has antiatherogenic and anti-inflammatory properties. Adiponectin acts not only as a factor increasing insulin sensitivity, and the protective effect may result from its ability to suppress production of proinflammatory cytokines. It negatively regulates the expression of TNF-alpha and C-reactive protein (CRP) in adipose tissue; reduces expression of vascular and intracellular adhesion molecules (VCAM-1, ICAM-1), E-selectin, interleukin-8 (IL-8). Hyperleptinemia has been linked with the development of hypertension and endothelial dysfunction/atherosclerosis, two main pathophysiological conditions associated with cardiovascular disease development. Leptin-mediated increases in sympathetic nervous system activity may be among the principal mechanisms evoking obesity related hypertension. Leptin stimulates the secretion of proinflammatory cytokines, and increases the release of endothelin-1 (ET-1), which may promote hypertension. Increased serum levels of asymmetric dimethylarginine (ADMA), a physiological regulator of the biosynthesis of nitric oxide (NO), promote the process of atherosclerosis, leading to the occurrence of endothelial dysfunction and cardiovascular disease

Phytochemical and biological investigations on Centranthus kellereri (Stoj., Stef. & T. Georgiev) Stoj. & Stef. and C. ruber (L.) DC. and their potential as new medicinal and ornamental plants.

IntroductionCentranthus kellereri is a Bulgarian endemic plant species, found only in two locations in the world: The Balkans Mountains (Stara Planina), above the town of Vratsa, and The Pirin Mountains, above the town of Bansko, Bulgaria. Being endemic and endangered species precluded any significant research on it. The hypothesis of this study was that the populations of C. kellereri may represent genetically, phytochemically, and morphologically distinct forms and these will differentiate from C. ruber. Furthermore, C. kellereri possibly imperfect embryology may preclude its more widespread distribution under natural conditions.ResultsThis study revealed the phytochemical profile, antioxidant activity, embryology, surface microstructural morphological traits, and genetic differences between the C. kellereri plants from the only two natural populations and compares them to the ones of the related and better-known plant C. ruber. The essential oil (EO) content in aboveground plant parts and in roots was generally low and the EO composition varied significantly as a function of plant part, year of sampling, location, and species. Methylvaleric acid was a major EO constituent in the C. kellereri EO, ranging between 60.2% and 71.7% of the total EO. The EO included monoterpenes, sequiterpenes, long-chain alkanes and fatty acids. Phytochemical analyses of plant tissue revealed the occurrence of 32 compounds that were tentatively identified as 6 simple phenolics, 18 flavonoids, 1 quinone, 1 lipid, 1 alkaloid, 2 diterpenes, and 3 triterpenes. There were differences in detected compounds between the C. kellereri plants at the two locations and between the roots and shoots in both species. The total phenols and flavonoids varied between the two species but were also dissimilar between the plants from the two populations of C. kelleri. Free radical scavenging activity, measured with ABTS and DPPH in aqueous and methanol extracts, had similar values; however, overall, C. kellereri from Vratsa showed the highest antioxidant activity while C. ruber had the lowest activity. Genetic analyses showed a clear differentiation between C. kellereri and C. ruber, and between the two populations of C. kellereri. Embryological studies revealed the peculiarities of the male and female generative spheres of the two species that were defined as being sexually reproducing. The pollen had high viability; however, the low viability of seeds demonstrated possible high sensitivity of C. kellereri to the environmental conditions, perhaps the main factor modifying and restricting the population sizes. The SEM analyses exposed differences in surface microstructural traits between the species (C. kellereri and C. ruber) but also between the two populations of C. kellereri. The observed dissimilarities in genetic makeup, micromorphological characteristics, and phytochemical composition strongly indicate that the two populations can be classified as distinct subspecies or varieties of C. kellereri; var. pirinensis and var. balkanensis. Further research is needed to introduce C. kellereri into culture and develop it as a high-value specialty crop or ornamental in order to conserve C. kellereri natural populations. C. kellereri may be utilized as a source for phytochemicals of interest and as an ornamental plant like C. ruber; however, it may have a greater environmental plasticity and adaptation as evidenced by its current locations