Breaking the silence of the 500-year-old smiling garden of everlasting flowers: The En Tibi book herbarium

We reveal the enigmatic origin of one of the earliest surviving botanical collections. The 16th-century Italian En Tibi herbarium is a large, luxurious book with c. 500 dried plants, made in the Renaissance scholarly circles that developed botany as a distinct discipline. Its Latin inscription, translated as “Here for you a smiling garden of everlasting flowers”, suggests that this herbarium was a gift for a patron of the emerging botanical science. We follow an integrative approach that includes a botanical similarity estimation of the En Tibi with contemporary herbaria (Aldrovandi, Cesalpino, “Cibo”, Merini, Estense) and analysis of the book’s watermark, paper, binding, handwriting, Latin inscription and the morphology and DNA of hairs mounted under specimens. Rejecting the previous origin hypothesis (Ferrara, 1542–1544), we show that the En Tibi was made in Bologna around 1558. We attribute the En Tibi herbarium to Francesco Petrollini, a neglected 16th-century botanist, to whom also belongs, as clarified herein, the controversial “Erbario Cibo” kept in Rome. The En Tibi was probably a work on commission for Petrollini, who provided the plant material for the book. Other people were apparently involved in the compilation and offering of this precious gift to a yet unknown person, possibly the Habsburg Emperor Ferdinand I. The En Tibi herbarium is a Renaissance masterpiece of art and science, representing the quest for truth in herbal medicine and botany. Our multidisciplinary approach can serve as a guideline for deciphering other anonymous herbaria, kept safely “hidden” in treasure rooms of universities, libraries and museums

Health related quality of life in patients with anogenital warts

<p>Abstract</p> <p>Introduction</p> <p>The health-related quality-of-life (HRQoL) instruments are an important tool for the evaluation of medical outcomes. Sexually transmitted diseases (STDs) influence the patients' life. We aimed to evaluate the HRQoL in patients with anogenital warts at the time of and 1 month after the diagnosis.</p> <p>Materials and methods</p> <p>We used the short-form (SF)-36 questionnaire to compare the HRQoL of 91 patients with anogenital warts to 53 control subjects with the same socioeconomic characteristics.</p> <p>Results</p> <p>There was no statistical difference in the overall HRQoL measurement between the anogenital wart patients and controls. However, there was an improvement in the scales of vitality (65.22 ± 15.70 vs. 69.04 ± 14.11, respectively; p < 0.05) and mental health (65.00 ± 20.09 vs. 69.43 ± 18.08, respectively; p < 0.05) in anogenital warts patients between the time of diagnosis and 1 month later. Furthermore, there was a significant deterioration in the scale of social functioning (73.47 ± 22.18 vs. 72.89 ± 19.28, respectively; p < 0.05). The small sample size is a limitation of our study.</p> <p>Conclusions</p> <p>HRQoL does not appear to be influenced in anogenital wart patients, as measured by the generic instrument SF-36. It is therefore important to develop specific instruments for the measurement of HRQoL in this group of patients.</p

Measuring the burden of herpes zoster and post herpetic neuralgia within primary care in rural Crete, Greece

<p>Abstract</p> <p>Background</p> <p>Research has indicated that general practitioners (GPs) have good clinical judgment in regards to diagnosing and managing herpes zoster (HZ) within clinical practice in a country with limited resources for primary care and general practice. The objective of the current study was to assess the burden of HZ and post herpetic neuralgia (PHN) within rural general practices in Crete, Greece.</p> <p>Methods</p> <p>The current study took place within a rural setting in Crete, Greece during the period of November 2007 to November 2009 within the catchment area in which the Cretan Rural Practice-based Research Network is operating. In total 19 GP's from 14 health care units in rural Crete were invited to participate, covering a total turnover patient population of approximately 25, 000 subjects. For the purpose of this study an electronic record database was constructed and used as the main tool for monitoring HZ and PHN incidence. Stress related data was also collected with the use of the Short Anxiety Screening Test (SAST).</p> <p>Results</p> <p>The crude incidence rate of HZ was 1.4/1000 patients/year throughout the entire network of health centers and satellite practices, while among satellite practices alone it was calculated at 1.3/1000 patients/year. Additionally, the standardised incidence density within satellite practices was calculated at 1.6/1000 patients/year. In regards to the stress associated with HZ and PHN, the latter were found to have lower levels of anxiety, as assessed through the SAST score (17.4 ± 3.9 vs. 21.1 ± 5.7; <it>p </it>= 0.029).</p> <p>Conclusions</p> <p>The implementation of an electronic surveillance system was feasible so as to measure the burden of HZ and PHN within the rural general practice setting in Crete.</p

Recurrent, low-frequency coding variants contributing to colorectal cancer in the Swedish population

<div><p>Genome-wide association studies (GWAS) have identified dozens of common genetic variants associated with risk of colorectal cancer (CRC). However, the majority of CRC heritability remains unclear. In order to discover low-frequency, high-risk CRC susceptibility variants in Swedish population, we genotyped 1 515 CRC patients enriched for familial cases, and 12 108 controls. Case/control association analysis suggested eight novel variants associated with CRC risk (OR 2.0–17.6, p-value < 2.0E-07), comprised of seven coding variants in genes <i>RAB11FIP5</i>, <i>POTEA</i>, <i>COL27A1</i>, <i>MUC5B</i>, <i>PSMA8</i>, <i>MYH7B</i>, and <i>PABPC1L</i> as well as one variant downstream of <i>NEU1</i> gene. We also confirmed 27 out of 30 risk variants previously reported from GWAS in CRC with a mixed European population background. This study identified rare, coding sequence variants associated with CRC risk through analysis in a relatively homogeneous population. The segregation data suggest a complex mode of inheritance in seemingly dominant pedigrees.</p></div

Melanocortin-1 Receptor, Skin Cancer and Phenotypic Characteristics (M-SKIP) Project: Study Design and Methods for Pooling Results of Genetic Epidemiological Studies

Background: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods: Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling. Discussion: Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Αδέρφια ατόμων με ψύχωση και αδερφικός δεσμός

Η παρούσα ερευνητική προσπάθεια για τα αδέρφια ατόμων με ψύχωση είχε ως σκοπό να μελετήσει τον τρόπο με τον οποίο τα υποκείμενα βίωσαν την ασθένεια του αδερφού τους και τις επιπτώσεις της ασθένειας στη ζωή τους. Το υλικό που προέκυψε από 12 ημιδομημένες συνεντεύξεις αναλύθηκε συστηματικά με βάση τις αρχές της Θεματικής Ανάλυσης. Οι ερωτήσεις κάλυπτα θέματα που αφορούσαν την περίοδο της ασθένειας, τις επιπτώσεις της ασθένειας στα υποκείμενα, την τωρινή σχέση με τον αδερφό, τη σχέση με τον αδερφό στην παιδική ηλικία, σκέψεις που έχουν κάνει τα υποκείμενα για την ασθένεια και τέλος τις επιπτώσεις της ασθένειας στους γονείς και στις σχέσεις των υποκειμένων με τους γονείς. Επιπλέον, στα υποκείμενα δόθηκαν 10 κάρτες του προβολικού τεστ Thematic Apperception Test (T.A.T.). Στην έρευνα φάνηκε ότι τα περισσότερα υποκείμενα συνέπασχαν με το πρόβλημα του αδερφού. Σε κάποιες περιπτώσεις υπήρχε στενοχώρια και αγωνία για την κατάσταση του αδερφού και σε άλλες αρκετά μεγάλη ταύτιση με το πρόβλημα ή και ανησυχία ότι μπορεί να ασθενήσουν και τα ίδια. Οι επιπτώσεις στα υποκείμενα ήταν σημαντικές τόσο σε συναισθηματικό επίπεδο όσο και σε επίπεδο αποφάσεων ζωής. Πολλά υποκείμενα δεν έχουν κάνει οικογένεια, λόγω του φόβου της κληρονομικότητας. Η στάση των γονιών προς τον αδερφό με ψύχωση αλλά και προς τα υποκείμενα, όπως την αντιλαμβάνονταν τα υποκείμενα, φάνηκε να έχει μεγάλη σημασία. Επιπλέον, η παιδική σχέση με τον αδερφό φάνηκε ότι έχει επίπτωση στον τρόπο με τον οποίο τα αδέρφια βιώνουν την ασθένεια του αδερφού. Σε κάποιες περιπτώσεις τα υποκείμενα ένιωθαν τύψεις, λόγω της παιδικής αντιζηλίας, ή ένα χρέος απέναντι στον αδερφό, ο οποίος μπορεί να ήταν για το υποκείμενο ένα βοηθητικό πρόσωπο στην ιστορία του ή απλά κάποιος που είχε μοιραστεί τις ίδιες δυσκολίες.The present study on siblings of people with psychosis aimed at exploring the way the subjects experienced the illness of their siblings and the impact of the illness on their lives. Data that came from 12 semi-structured interviews were analysed systematically according to the principles of Thematic Analysis. The questions covered themes concerning the period of the illness, the present relationship with the sibling, the infantile relationship with the sibling, the thoughts of the subjects on the illness, and finally the impact of the illness on the parents and on the relationship between the subjects and their parents. Moreover, 10 cards of the projective test, Thematic Apperception Test (T.A.T.), were given to the subjects. The study revealed that most of the subjects took compassion on their ill siblings. In some cases there was sadness and anxiety due to the situation of the sibling and in others a quite high identification with the problem of the sibling, often combined with fears of themselves becoming also mentally ill. The impact on the subjects was important both on an emotional level as well as on the level of life decisions. Many subjects have not created a family for fear of heredity. The attitude of the parents towards the sibling with psychosis, and also towards the subjects was found to be of great importance. Moreover, the infantile relationship with the sibling was found to effect the way in which the subjects experience the illness of the sibling. In some cases the subjects felt remorse because of the infantile rivalry or felt indebted to the sibling, that could be a helpful person in the subject&apos;s history or just someone, who has shared the same difficulties

Glass Giants: Mass-optimized massive cast glass slab

The current thesis aims to explore the potential of producing large-scale structural cast glass elements with the help of 3d printed sand moulds. Until now, mostly small blocks from structural cast glass have been generated in the building industry, revealing a research gap regarding massive components. Apart from the size, the unlimited shape potentials of cast glass have hardly been explored so far. This is because glass casting can be a very challenging process when it comes to the solidification of the material which needs to be completed under specific program settings. Except from the brittleness of the body during the annealing process, it can take months, even years for a large-scale element to be completed, because of the full controllable conditions under which the annealing process takes place. In addition, the mould types that are currently used for cast glass components present several restrictions such as the manufacturing costs, the accuracy or the sizing. An existing glass slab in the Acropolis museum, in Athens, was chosen to embody the research goals. The slab is located on top of archeological discoveries making the need for transparency necessary. The current slab consists of float glass panes with a concrete substructure which severally restrains the viewing. The thesis aim is to develop a free-form monolithic slab exclusively from cast glass without the need of external substructure. In order to address the above demands, the topology optimization method was introduced. Several algorithms of topology optimization have been developed. A compliance-based optimization was demonstrated as the most appropriate for the specific project. Obtained from the literature framework, the main principles that the design follows gravitate towards the structural, cast glass and manufacturing requirements. The external applied load, in addition to the allowable structural values were calculated. The importance for a flat upper surface, where a safety float glass layer of a permitted deformation should be laminated, was established. Regarding the cast glass demands, it is necessary to acquire a design with smooth surfaces, round edges and uniform distributed material throughout the entire model. For the current project, the optimized slab is decided to mainly consist of borosilicate glass.. A slab separation is crucial for transportation reasons. After the definition of the main design principles that the final product should respect, the design development was conducted with the combination of three methods: topology optimization, manual design and structural validation. The final result of the optimized slab successfully fulfills the preset design criteria, as the obtained structure presents 55.2% less mass than the solid version that was initially designed to replace the existing slab in the museum. In addition, a more efficient material distribution in the optimized model renders the slab more compatible for the cast glass annealing process. The result of the topology optimization technique was a quite complex geometry which is not that effective to be produced in the conventional moulds that are currently available for cast glass applications. Therefore, a new technique needed to be explored, which follows the 3d printing evolution in the building industry. The main restriction of the printed moulds is the limited available sizing that the commercial printers provide. As a solution to this problem, the separation of the large-scale mould into smaller segments was studied, as well as the development of the connecting system of these parts. The entire fabrication technique, from the moulds printing method, to the assembly components and glass melting was investigated. Finally, the transportation and integration of the slab into the building was explored, concluding with structural solutions that respect the museum and the assembly order that the slab can be attached on it.Architecture, Urbanism and Building Sciences | Building Technology | Sustainable Desig

lmmunohistochemical expression of the p53, mdm2, p21/Waf-1, Rb, p16, Ki67, Cyclin DI, Cyclin A and Cyclin B1 proteins and apoptotic index in T-cell lymphomas

Fifty-seven cases of T-cell lymphomas (TCL) including 5 lymphoblastic (T-LBL) and 52 peripheral TCL (PTCL) were analyzed by immunohistochemistry for the expression of p53, mdm2, p21, Rb, cyclin DI, cyclin A, cyclin B1, and Ki67IMIB1 proteins and 39/52 PTCL were also analyzed for the expression of p16 protein and for the presence of apoptotic cells by the TUNEL method. The aim was to search for abnormal immunoprofiles of p53 and Rb growth control pathways and to determine the proliferative activity and the apoptotic index of TCL. Abnormal overexpression of p53, p21 and mdm2, in comparison to normal lymph nodes, was found in 12/57,10/57 and 2/57 cases of TCL, respectively. Abnormal loss of Rb and p16 expression was found in 1/57 and 2/39 cases, respectively, whereas abnormal overexpression of cyclin D1 was not detected in any of the 57 cases. Our data revealed entity-related p53/p21/mdm2 phenotypes. Indeed, most nodal and cutaneous CD30+ anaplastic large cell lymphomas (ALCL) showed concomitant overexpression of p53 and p21 proteins (718 cases), and mdm2 was overexpressed in 2 p53-positive nodal ALCL. In contrast, overexpression of p53 was found in 3/17 cases of nodal peripheral TCL unspecified (PTCL-UC) and 217 non- ALCL cutaneous pleomorphic TCL. Overexpression of p21 protein was detected in 213 p53-positive PTCLUC and in 112 p53-positive non-ALCL cutaneous pleomorphic TCL. Finally, al1 the remaining 25 cases of TCL did not show p53 and p21 overexpression. Overali, the p53+/p21+ phenotype in 10157 TCL suggests wildtype p53 capable of inducing p21 expression. The highest apoptotic index (Al) was found in ALCL and a positive correlation between apoptotic index and Ki67 index (p&lt;0.001) was detected. Ki67, cyclin A and cyclin B1 expression was found in al1 57 TCL and on the basis of the combined use of these 3 variables, 3 groups of proliferative activity,.could be determined: a) high in ALCL and T-LBL, b) low in mycosis fungoides (MF) and γδ hepatosplenic TCL, and c) intermediate in the remaining TCL entities. The proliferative activity in the 12 p53 overexpressing cases was higher in comparison to the 45 p53-negative cases. Ki67 expresion in more than 25% of tumour cells showed significant correlation with p53 overexpression (p&lt;0.001). Rb expression tended to be parallel to Ki67, cyclin A and cyclin B1 expression in al1 but one case of nodal PTCL-UC which displayed loss of RB expression. Interestingly, this case was p53-negative, whereas the p53-positive cases were Rb-positive. These findings suggest that different pathogenetic routes may function in some TCL, involving either the p53 or, less frequently, the Rb pathways