Oral Insulin Delay of Stage 3 Type 1 Diabetes Revisited in HLA DR4-DQ8 Participants in the TrialNet Oral Insulin Prevention Trial (TN07).

OBJECTIVE: To explore if oral insulin could delay onset of stage 3 type 1 diabetes (T1D) among patients with stage 1/2 who carry HLA DR4-DQ8 and/or have elevated levels of IA-2 autoantibodies (IA-2As). RESEARCH AND METHODS: Next-generation targeted sequencing technology was used to genotype eight HLA class II genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, and DPB1) in 546 participants in the TrialNet oral insulin preventative trial (TN07). Baseline levels of autoantibodies against insulin (IAA), GAD65 (GADA), and IA-2A were determined prior to treatment assignment. Available clinical and demographic covariables from TN07 were used in this post hoc analysis with the Cox regression model to quantify the preventive efficacy of oral insulin. RESULTS: Oral insulin reduced the frequency of T1D onset among participants with elevated IA-2A levels (HR 0.62; P = 0.012) but had no preventive effect among those with low IA-2A levels (HR 1.03; P = 0.91). High IA-2A levels were positively associated with the HLA DR4-DQ8 haplotype (OR 1.63; P = 6.37 × 10-6) and negatively associated with the HLA DR7-containing DRB1*07:01-DRB4*01:01-DQA1*02:01-DQB1*02:02 extended haplotype (OR 0.49; P = 0.037). Among DR4-DQ8 carriers, oral insulin delayed the progression toward stage 3 T1D onset (HR 0.59; P = 0.027), especially if participants also had high IA-2A level (HR 0.50; P = 0.028). CONCLUSIONS: These results suggest the presence of a T1D endotype characterized by HLA DR4-DQ8 and/or elevated IA-2A levels; for those patients with stage 1/2 disease with such an endotype, oral insulin delays the clinical T1D onset.

Application of microphysiological systems for nonclinical evaluation of cell therapies.

Microphysiological systems (MPS) are gaining broader application in the pharmaceutical industry but have primarily been leveraged in early discovery toxicology and pharmacology studies with small molecules. The adoption of MPS offers a promising avenue to reduce animal use, improve in-vitro-to-in-vivo translation of pharmacokinetics/pharmacodynamics and toxicity correlation, and provide mechanistic understanding of model species suitability. While MPS have demonstrated utility in these areas with small molecules and biologics, cell therapeutic MPS models in drug development have not been fully explored, let alone validated. Distinguishing features of MPS, including long-term viability and physiologically relevant expression of functional enzymes, receptors, and pharmacological targets make them attractive tools for nonclinical characterization. However, there is currently limited published evidence of MPS being utilized to study the disposition, metabolism, pharmacology, and toxicity profiles of cell therapies. This review provides an industry perspective on the nonclinical application of MPS on cell therapies, first with a focus on oncology applications followed by examples in regenerative medicine.

Microphysiological systems (MPS) are advanced cell models, applied in the pharmaceutical industry to characterize novel therapies. While their application in studies of small molecule therapies has been very successful, the use of these models to study cell therapies has been limited. Cell therapies consist of cells and are living drugs, often with complex biological mechanisms of action, which can be very challenging to study. However, MPS have several features that make them attractive for studying cell therapies, including possibilities for longer-term studies and the ability to mimic physiologically relevant biological functions. MPS can mimic complex biological systems and processes, as such, the adoption of MPS offers a promising avenue to reduce the use of animals in the characterization of novel therapies. This review provides an industry perspective on current challenges and highlights opportunities for using MPS in the development of cell therapies.

HLA Class II (DR, DQ, DP) Genes Were Separately Associated With the Progression From Seroconversion to Onset of Type 1 Diabetes Among Participants in Two Diabetes Prevention Trials (DPT-1 and TN07).

OBJECTIVE: To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Next-generation targeted sequencing was used to genotype eight HLAII genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1) in 1,216 participants from the Diabetes Prevention Trial-1 and Randomized Diabetes Prevention Trial with Oral Insulin sponsored by TrialNet. By the linkage disequilibrium, DQA1 and DQB1 are haplotyped to form DQ haplotypes; DP and DR haplotypes are similarly constructed. Together with available clinical covariables, we applied the Cox regression model to assess HLAII immunogenic associations with the disease progression. RESULTS: First, the current investigation updated the previously reported genetic associations of DQA1*03:01-DQB1*03:02 (hazard ratio [HR] = 1.25, P = 3.50*10-3) and DQA1*03:03-DQB1*03:01 (HR = 0.56, P = 1.16*10-3), and also uncovered a risk association with DQA1*05:01-DQB1*02:01 (HR = 1.19, P = 0.041). Second, after adjusting for DQ, DPA1*02:01-DPB1*11:01 and DPA1*01:03-DPB1*03:01 were found to have opposite associations with progression (HR = 1.98 and 0.70, P = 0.021 and 6.16*10-3, respectively). Third, DRB1*03:01-DRB3*01:01 and DRB1*03:01-DRB3*02:02, sharing the DRB1*03:01, had opposite associations (HR = 0.73 and 1.44, P = 0.04 and 0.019, respectively), indicating a role of DRB3. Meanwhile, DRB1*12:01-DRB3*02:02 and DRB1*01:03 alone were found to associate with progression (HR = 2.6 and 2.32, P = 0.018 and 0.039, respectively). Fourth, through enumerating all heterodimers, it was found that both DQ and DP could exhibit associations with disease progression. CONCLUSIONS: These results suggest that HLAII polymorphisms influence progression from islet autoimmunity to T1D among at-risk subjects with islet autoantibodies.

Alternative Crops for the European Tobacco Industry: A Systematic Review.

Tobacco (Nicotiana tabacum L.) is a major industrial crop that has being cultivated for centuries for the manufacturing of cigarettes, cigars, and other smoking products. Due to its negative effects on both human health and the environment, the European Union has adopted strict policies that aspire to reduce the consumption of tobacco. Herbal cigarettes are alternative smoking products that are often advertised as healthier than conventional tobacco cigarettes and are especially popular in Asian markets. Even though the available literature suggests that they are equally detrimental to human health, the introduction of tobacco-alternative crops (TACs) to the European tobacco industry could smoothen the abandonment of tobacco, and eventually smoking products altogether, in the EU. The aim of the present systematic review was to compile a list of possible TACs that could be incorporated in the European smoking industry, and highlight their strengths and weaknesses. The most dominant crops in the literature (and in the existing market products) were calendula (Calendula officinalis L.), mullein (Verbascum thapsus L.), ginseng (Panax ginseng C.A.Mey.), tea (Camellia sinensis (L.) Kuntze), chamomile (Matricaria chamomilla L.), and mentha (Mentha spp.). Even though these crops are promising, further research is required for their incorporation in the European tobacco industry.

EASIER: A new model for online learning of minimally invasive surgery skills.

INTRODUCTION: Technology Enhanced Learning (TEL) can provide the tools to safely master minimally invasive surgery (MIS) skills in patient-free environments and receive immediate objective feedback without the constant presence of an instructor. However, TEL-based systems tend to work isolated from one another, focus on different skills, and fail to provide contents without a sound pedagogical background. OBJECTIVE: The objective of this descriptive study is to present in detail EASIER, an innovative TEL platform for surgical and interventional training, as well as the results of its validation. METHODS: EASIER provides a Learning Management System (LMS) for institutions and content creators that can connect and integrate TEL "external assets" (virtual reality simulators, augmented box trainers, augmented videos, etc.) addressing different skills. The platform integrates all skills under an Assessment Module that measures skills' progress in different courses. Finally, it provides content creators with a pedagogical model to scaffold contents while retaining flexibility to approach course design with different training philosophies in mind. Three courses were developed and hosted in the platform to validate it with end-users in terms of usability, performance, learning results in the courses and student self-perception on learning. RESULTS: In total 111 volunteers completed the validation. The study was limited due to the COVID-19 pandemic, which limited access to external assets (virtual reality simulators). Nevertheless, usability was rated with 73.1 in the System Usability Scale. Most positive aspects on performance were easiness to access the platform, easiness to change the configuration and not requiring additional plug-ins to use the platform. The platform was rated above average in the six scales of the User Experience Questionnaire. Overall, student results improved significantly across the three courses (p < 0.05). CONCLUSIONS: This study provides, within its limitations, evidence on the usefulness of the EASIER platform for distance learning of MIS skills. Results show the potential impact of the platform and are an encouraging boost for the future, especially in the aftermath of the COVID-19 pandemic.

Autoimmune susceptible HLA class II motifs facilitate the presentation of modified neoepitopes to potentially autoreactive T cells.

Rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes (T1D), and celiac disease (CD), are strongly associated with susceptible HLA class II haplotypes. The peptide-binding pockets of these molecules are polymorphic, thus each HLA class II protein presents a distinct set of peptides to CD4+ T cells. Peptide diversity is increased through post-translational modifications, generating non-templated sequences that enhance HLA binding and/or T cell recognition. The high-risk HLA-DR alleles that confer susceptibility to RA are notable for their ability to accommodate citrulline, promoting responses to citrullinated self-antigens. Likewise, HLA-DQ alleles associated with T1D and CD favor the binding of deamidated peptides. In this review, we discuss structural features that promote modified self-epitope presentation, provide evidence supporting the relevance of T cell recognition of such antigens in disease processes, and make a case that interrupting the pathways that generate such epitopes and reprogramming neoepitope-specific T cells are key strategies for effective therapeutic intervention.

Lessons Learned from Older Adults Fusing of an Augmented Reality, Assisted Living and Social Interaction Platform.

The aging population and the subsequent changing societal structures are foreseen to bring both opportunities and challenges for the economy, services and society at large. Digital exclusion among older people may become less of an issue in the future, as those who have used the Internet in their working and social lives continue to do so as they reach old age. However, given the rapid pace of technological advances, older adults, may still experience some degree of digital exclusion. Technological advances may offer benefits for older adults, such as maintaining their independence and connection to society. Nevertheless, adopting new technologies like augmented reality (AR) may be difficult for older adults commonly due to the decline of cognitive and physical abilities and/or their lack of familiarity, apprehension and understanding on these new technologies. In this study, the GUIDed system is presented, an AR-operated app developed in this work, aiming to support the independence and quality of life of older people. Finally, the paper discusses lessons learned from the co-creation process, including the evaluation methods, paper prototypes, focus groups and living labs, and the results on the acceptance of the AR functionality and for improving the GUIDed system.

eSticky: An Advanced Remote Reminder System for People with Early Dementia.

While the European population is ageing, the number of people with dementia is dramatically rising. With this comes an increased need for products that help affected people to be more independent and able to live in their own home for as long as possible. eSticky addresses this need by providing a sophisticated reminder system that replaces the old-fashioned sticky notes by electronic versions thereof, which can be programmed from near and far in a device-independent manner via the internet and using a standard web browser. For this purpose, a set of low-cost ePaper displays are used, accompanied by a small and unobtrusive base station situated at the user's home, and supported by a web platform for user management and the authoring and scheduling of the message reminders. The displays can be placed at several strategically useful places in a user's home, to enable users and/or care persons to place reminders that will, based on the user's daily routines, most probably be read. A sub-set of displays, named active displays, even enable the user to press a confirmation button to show that he or she has actually read the reminder. The confirmation is then made available to the authors of the particular reminder through the web platform. The system is developed using a user-centred design approach, to take all stakeholders' wishes and needs into account, in order to come up with a system that is easy to use and provides good service to many people. In this extended version of the paper, besides a detailed description of the technological advancements of the project, both in terms of software and hardware, we provide an insight of the eSticky device design methodology and results from the design user evaluation.

On the Path towards a "Greener" EU: A Mini Review on Flax (Linum usitatissimum L.) as a Case Study.

Due to the pressures imposed by climate change, the European Union (EU) has been forced to design several initiatives (the Common Agricultural Policy, the European Green Deal, Farm to Fork) to tackle the climate crisis and ensure food security. Through these initiatives, the EU aspires to mitigate the adverse effects of the climate crisis and achieve collective prosperity for humans, animals, and the environment. The adoption or promotion of crops that would facilitate the attaining of these objectives is naturally of high importance. Flax (Linum usitatissimum L.) is a multipurpose crop with many applications in the industrial, health, and agri-food sectors. This crop is mainly grown for its fibers or its seed and has recently gained increasing attention. The literature suggests that flax can be grown in several parts of the EU, and potentially has a relatively low environmental impact. The aim of the present review is to: (i) briefly present the uses, needs, and utility of this crop and, (ii) assess its potential within the EU by taking into account the sustainability goals the EU has set via its current policies.

A Simulation Study of the Effect of Naturally Occurring Point Mutations on the SRY-DNA Complex.

Molecular dynamics (MD) simulations were conducted in order to investigate the effect of the naturally occurring point mutations of the transcription factor (TF) sex-determining region Y (SRY) on the structure and dynamics of the SRY-DNA complex. The normal SRY, along with the two mutants I13T and G40R, comprising point mutations on the SRY chain, which have been clinically identified in patients with sex developmental disorders, were modeled as DNA complexes. Our modeling work aims at elucidating atomic-level structural determinants of the aberrant SRY-DNA complexation by means of µs-long MD. The results suggest that the observed disorders brought about by the G40R-DNA and I13T-DNA may arise predominantly from the destabilization of the complex being in accord with in vitro assays found elsewhere and from modifications of the DNA bending as revealed in this study. Comparative potential of mean force computations, over a sequence of short separation distances for the three complexes, verified a higher stability of the normal SRY-DNA. Examining the way the SRY mutations modulate the SRY-DNA complex dynamics at the microscopic level is important also toward elucidating molecular determinants of function for proteins capable of binding to DNA.

Molecular and clinical profile of patients referred as Noonan or Noonan-like syndrome in Greece: a cohort of 86 patients.

Noonan syndrome (NS) is an autosomal dominant disorder characterized by clinical and genetic heterogeneity. It belongs to a wider group of pathologies, known as Rasopathies, due to the implication of genes encoding components of the Ras/MAPK signalling pathway. Recording the genetic alterations across populations helps assessing specific features to specific genes which is essential for better disease's recognition, prognosis and monitoring. Herein, we report the clinical and molecular data of a Greek cohort comprising of 86 NS or NS-like patients admitted at a single tertiary Centre in Athens, Greece. The analysis was performed using Sanger and next-generation sequencing, comprising 14 different genes. The mutational rates of the confirmed NS-associated genes in the Greek NS population are as follows: PTPN11 32.5%; RIT1 5.8%; SOS1 4.7%; BRAF 1.2%; CBL 1.2%; KRAS 1.2%; MAP2K1 1.2%; RAF1 1.2%; SHOC2 1.2%, corresponding to 50% of positivity in total NS population. The genotype-phenotype analysis showed statistically significant differences in craniofacial dysmorphisms (p = 0.005) and pulmonary valve stenosis (PS) (p < 0.001) frequencies between patients harbouring a pathogenic variant and patients without pathogenic variant in any of the tested genes. Patients with at least a pathogenic variant had 6.71 times greater odds to develop PS compared to pathogenic variant-negative patients (OR = 6.71, 95%; CI = (2.61, 17.27)). PTPN11 positive patients showed higher frequency of epicanthal folds (p = 0.004), ptosis (p = 0.001) and coarseness (p = 0.001) and lower frequency of neurological findings (p = 0.006), compared to patients carrying pathogenic variants in other genes. CONCLUSION: Craniofacial dysmorphism and PS prevail among pathogenic variant positive compared to pathogenic variant negative NS and NS-like patients while neurological defects are less common in PTPN11-affected NS patients compared to patients harbouring pathogenic variants in other genes. The significant prevalence of the Ras/MAPK pathogenic variants (17.4%), other than PTPN11, in Greek NS patients, highlights the necessity of a wider spectrum of molecular diagnosis. WHAT IS KNOWN: • Noonan syndrome (NS) has been associated with pathogenic variants in molecules-components of the Ras/MAPK pathway. • Clinical and genetic description of NS patients worldwide helps establishing personalized monitoring. WHAT IS NEW: • NS and NS-like mutational rate in Greece reaches 50% with pathogenic variants identified mostly in PTPN11 (32.5%), RIT1 (6%) and SOS1 (4.7%) genes. • The risk for pulmonary stenosis increases 6.71-fold in NS patients with a pathogenic variant compared to patients without genetic alterations.

Cost-effectiveness analysis of arthroscopic injection of a bioadhesive hydrogel implant in conjunction with microfracture for the treatment of focal chondral defects of the knee - an Australian perspective.

AIM: JointRep is a bioadhesive hydrogel arthroscopically injected to facilitate cartilage regeneration. The cost-effectiveness of JointRep with microfracture surgery compared to microfracture alone was evaluated from the Australian healthcare system perspective, in patients with symptomatic focal chondral defects (Outerbridge Grade 3 or 4) of the knee who had failed conservative treatment and were indicated for surgery. MATERIALS AND METHODS: A de novo Markov model comprising two health states- 'Alive' and 'Dead' was developed. Model transition probability was based on the general population mortality rates. Clinical outcomes were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, a validated patient-reported tool measuring pain, stiffness, and physical function. The utility was derived by mapping WOMAC scores to EQ-5D scores using a published algorithm. Cost inputs were based on published Australian costs from AR-DRGs, Medicare Benefits Schedule, and Prostheses List. Model outcomes included costs, Quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Base-case analysis was conducted for a time horizon of 3 years and a cycle length of 1 year. Cost and health outcomes were discounted at 5% per annum. Sensitivity and scenario analyses were also conducted. RESULTS: Total QALYs were estimated to be higher for JointRep with microfracture surgery (2.61) compared to microfracture surgery alone (1.66), an incremental gain of 0.95 QALY. JointRep with microfracture surgery was associated with an incremental cost of $6,022 compared to microfracture surgery alone, thus leading to an ICER of $6,328. Results were substantially robust to varying parameters in the sensitivity analyses conducted, alternative model settings and assumptions in scenario analyses. LIMITATIONS: The clinical inputs used in the model were based on data from short duration, non-randomized, post-market clinical trial. CONCLUSIONS: JointRep with microfracture surgery is a cost-effective treatment option compared to microfracture alone from the Australian health care system perspective.

Economic crisis in Greece: The invisible enemy of blood donation or not?

INTRODUCTION: Volunteering presupposes having free time and refers to the provision of services without the motivation of material reward, for the benefit of society. In this study, we aimed to provide insight into the impact of economic crisis on blood donors and their motivation to donate blood during that period. STUDY DESIGN AND METHODS: We asked blood donors about their blood donation activity and motivation to donate using a standardized, anonymous questionnaire (n = 3000). Descriptive analysis was performed for the consideration of donor turnout during this economic period. The results were analyzed using the χ2 test and Spearman's correlation coefficient. RESULTS: Regarding gender, 68.2% were males, while 31.8% were females. Most blood donors donated voluntarily (75.8%) and only 24.2% were replacement or family blood donors. The economic crisis has affected the inhabitants of Athens more than the inhabitants of the province (χ2 = 9.910,p = 0.007). The influence of economic crisis on the regular blood donors' quality of life was greater than the non-regular donors (χ2 = 16.227,p < 0.001). According to our results, the economic crisis reduced the quality of life, but it did not affect the frequency of blood donations in a percentage of 87,3%. Not any significant difference was found between employment status, economic crisis and blood donation. CONCLUSION: Although the economic crisis has affected the lives of blood donors, it does not seem to affect the frequency of blood donation. We suggest that blood collection services should consider specialist campaigns that focus on the altruistic motivation of donors during an economic crisis.

Association of HLA-DQ Heterodimer Residues -18ß and ß57 With Progression From Islet Autoimmunity to Diabetes in the Diabetes Prevention Trial-Type 1.

OBJECTIVE: The purpose was to test the hypothesis that the HLA-DQαß heterodimer structure is related to the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Next-generation targeted sequencing was used to genotype HLA-DQA1-B1 class II genes in 670 subjects in the Diabetes Prevention Trial-Type 1 (DPT-1). Coding sequences were translated into DQ α- and ß-chain amino acid residues and used in hierarchically organized haplotype (HOH) association analysis to identify motifs associated with diabetes onset. RESULTS: The opposite diabetes risks were confirmed for HLA DQA1*03:01-B1*03:02 (hazard ratio [HR] 1.36; P = 2.01 ∗ 10-3) and DQA1*03:03-B1*03:01 (HR 0.62; P = 0.037). The HOH analysis uncovered residue -18ß in the signal peptide and ß57 in the ß-chain to form six motifs. DQ*VA was associated with faster (HR 1.49; P = 6.36 ∗ 10-4) and DQ*AD with slower (HR 0.64; P = 0.020) progression to diabetes onset. VA/VA, representing DQA1*03:01-B1*03:02 (DQ8/8), had a greater HR of 1.98 (P = 2.80 ∗ 10-3). The DQ*VA motif was associated with both islet cell antibodies (P = 0.023) and insulin autoantibodies (IAAs) (P = 3.34 ∗ 10-3), while the DQ*AD motif was associated with a decreased IAA frequency (P = 0.015). Subjects with DQ*VA and DQ*AD experienced, respectively, increasing and decreasing trends of HbA1c levels throughout the follow-up. CONCLUSIONS: HLA-DQ structural motifs appear to modulate progression from islet autoimmunity to diabetes among at-risk relatives with islet autoantibodies. Residue -18ß within the signal peptide may be related to levels of protein synthesis and ß57 to stability of the peptide-DQab trimolecular complex.

The Effect of Cold Periods on the Biological Cycle of Marchalina hellenica.

Climate change is considered a major factor affecting honeybees' behavior and productivity with major consequences in both honey and agricultural production. Many research studies have expressed serious concerns about the mass losses of bee colonies and the role of bees as pollinators, while others have underlined important issues for the impact of the increase in temperature on honeybee abundance and honey yields. In the present work, we draw our attention to Marchalina hellenica, which is the most important honeydew-producing insect in Greece. A statistically significant forecasting model for the effect of cold periods in February on the life cycle of the insect is constructed, with the aid of the Cumulative Logit Model and the theory of runs. The forecasting model may help beekeepers plan the timely exploitation of honeydew secretions of pine trees, which will be beneficial for beekeepers, the rural economy, and forest protection. The new suggested model also indicates that, in view of the climate change scenarios seen in the literature, the life cycle of M. hellenica is expected to be drastically shorter.

Paediatric and adult congenital cardiology education and training in Europe.

BACKGROUND: Limited data exist on training of European paediatric and adult congenital cardiologists. METHODS: A structured and approved questionnaire was circulated to national delegates of Association for European Paediatric and Congenital Cardiology in 33 European countries. RESULTS: Delegates from 30 countries (91%) responded. Paediatric cardiology was not recognised as a distinct speciality by the respective ministry of Health in seven countries (23%). Twenty countries (67%) have formally accredited paediatric cardiology training programmes, seven (23%) have substantial informal (not accredited or certified) training, and three (10%) have very limited or no programme. Twenty-two countries have a curriculum. Twelve countries have a national training director. There was one paediatric cardiology centre per 2.66 million population (range 0.87-9.64 million), one cardiac surgical centre per 4.73 million population (range 1.63-10.72 million), and one training centre per 4.29 million population (range 1.63-10.72 million population). The median number of paediatric cardiology fellows per training programme was 4 (range 1-17), and duration of training was 3 years (range 2-5 years). An exit examination in paediatric cardiology was conducted in 16 countries (53%) and certification provided by 20 countries (67%). Paediatric cardiologist number is affected by gross domestic product (R2 = 0.41). CONCLUSION: Training varies markedly across European countries. Although formal fellowship programmes exist in many countries, several countries have informal training or no training. Only a minority of countries provide both exit examination and certification. Harmonisation of training and standardisation of exit examination and certification could reduce variation in training thereby promoting high-quality care by European congenital cardiologists.

Evaluation and validation of a patient-reported quality-of-life questionnaire for Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a chronic, progressive illness with a profound impact on the health-related quality of life (HRQoL). Disease-specific patient-reported HRQoL measures, such as PDQ-39 and its short version PDQ-8, are increasingly used in clinical practice to address the consequences of PD on everyday life. Due to limitations in the content, especially in non-motor symptoms and sleep disturbances of PDQ-8, PDQoL7, a 7-item, short-term, self-reported, PD-specific HRQoL questionnaire was developed. METHODS: A representative sample of 60 adults with idiopathic PD completed the PDQoL7 questionnaire and the existing validated PDQ-8 and EQ-5D-5L questionnaires (all in Greek). RESULTS: PDQoL7 summary index strongly correlated with PDQ-8 (rs = 0.833, P < 0.001) and EQ-5D-5L (rs = - 0.852, P < 0.001). The correlation between PDQoL7 and EQ-5D-5L was statistically significantly stronger compared to PDQ-8 and EQ-5D-5L (rs = - 0.852 vs rs = - 0.789 respectively, P < 0.001). The internal consistency of PDQoL7 was not affected by item deletion (positive item to total correlations: 0.29-0.63). No redundant items (with inter-item correlation coefficients greater than 0.80) were identified. Cronbach's α for PDQoL7 was comparable to PDQ-8 (0.804 versus 0.799 respectively). As PDQoL7 had three-dimensional structure, omega coefficient analysis confirmed its reliability (omega total: 0.88; omega hierarchical: 0.58). CONCLUSIONS: PDQoL7 is an acceptable, easy to use, valid and reliable tool for the determination of HRQoL in PD patients that is potentially more comprehensive than PDQ-8 based on the available evidence. PDQoL7 could allow for a more thorough evaluation of the impact of PD and contribute to guiding healthcare decisions. This will be confirmed in subsequent analysis on larger patient cohorts.

A Localized Enantioselective Catalytic Site on Short DNA Sequences and Their Amphiphiles.

A DNA-based artificial metalloenzyme (ArM) consisting of a copper(II) complex of 4,4'-dimethyl-2,2'-bipyridine (dmbipy-Cu) bound to double-stranded DNA (dsDNA) as short as 8 base pairs with only 2 contiguous central pairs (G for guanine and C for cytosine) catalyzes the highly enantioselective Diels-Alder reaction, Michael addition, and Friedel-Crafts alkylation in water. Molecular simulations indicate that these minimal sequences provide a single site where dmbipy-Cu is groove-bound and able to function as an enantioselective catalyst. Enantioselective preference inverts when d-DNA is replaced with l-DNA. When the DNA is conjugated to a hydrophobic tail, the obtained ArMs exhibit enantioselective performance in a methanol-water mixture superior to that of non-amphiphilic dsDNA, and dsDNA-amphiphiles with more complex G•C-rich sequences.

Symptomatic pseudoaneurysms following laparoscopic cholecystectomy: Focus on an unusual and dangerous complication.

BACKGROUND: Laparoscopic cholecystectomy (LC) has been associated with an increase in the incidence of biliary and vascular injuries. Pseudoaneurysms (PAs) following LC are rare life-threatening events with limited available experience regarding diagnosis and treatment. MATERIALS AND METHODS: An extensive review of literature during a 26-year period (1994-2020) using MEDLINE® database and Google Scholar® academic search engine revealed 134 patients with at least one symptomatic PA following LC. RESULTS: Nearly.81% of patients with PAs become symptomatic during the first 8 weeks following LC. The most common symptoms were gastrointestinal bleeding (74%) and abdominal pain (61%). In 28% of cases, there was a concomitant bile duct injury or leak from the cystic duct stump, whereas in about one-third of cases, PAs presented following an uneventful LC. The most common involved arteries were the right hepatic artery (70%), the cystic artery (19%) or both of them (3%). Trans-arterial embolisation was the favoured first-line treatment with a success rate of 83%. During a median follow-up of 9 months, the mortality rate was 7%. CONCLUSION: Clinicians should be aware of the PA occurrence following LC. Prompt diagnosis and treatment are essential.