How Can We Strengthen the Global Genetic Resources' Conservation and Use System?

Genetic resources serve as the foundation of our food supply and are building blocks for the development of new crop varieties that support sustainable crop production in the face of climate change, as well as for the delivery of healthy diets to a continuously growing global population. With the encouragement of the FAO and with technical guidance and assistance from the International Board for Plant Genetic Resources (IBPGR), almost 2000 genebanks have been established worldwide for the ex situ conservation of genetic resources since the middle of the last century. The global genetic resources' conservation and use system has evolved over several decades and presents apparent weaknesses, without a clear blueprint. Therefore, a Special Issue (SI) of Plants on 'A Critical Review of the Current Approaches and Procedures of Plant Genetic Resources Conservation and Facilitating Use: Theory and Practice' was initiated. This SI comprises 13 review and research papers that shed light on the history and the political dimensions of the global system; its current strengths, weaknesses, and limitations; and how the effectiveness and efficiency of the system could be improved to satisfy the germplasm users (plant breeders, researchers) and benefit consumers and society at large. This SI provides insight into new approaches and technical developments that have revolutionised ex situ conservation and the use of germplasm and related information. It also reflects on complementary conservation approaches (in situ, on-farm, home gardens) to ex situ genebanks, as well as how-through new forms of collaboration at national, regional, and global levels and through stronger links between public genebanks-synergies between the private breeding sector and botanic garden community could be achieved to strengthen the global conservation and use system. Special attention has also been given to the governance of genetic resources and access and benefit-sharing issues that increasingly hamper the needed access to a wide range of genetic resources that is essential for plant breeders to fulfil their mission.

Fetoscopic laser coagulation for twin-to-twin transfusion syndrome: a comparison of flexible 1.0/1.2 mm fetoscopes with curved sheaths of 2.7/3.3 mm2 vs. 2 mm fetoscopic lens technique with sheaths of 6.6/11.3 mm2.

OBJECTIVES: Fetoscopic laser coagulation of placental anastomoses is usually performed for a treatment of twin-to-twin transfusion syndrome (TTTS). A common complication of fetoscopic laser coagulation for TTTS is preterm preliminary rupture of fetal membranes (PPROM) aggravating the neonatal outcome significantly. However, use of an flexible 1 mm fetoscope with an curved sheath could reduce iatrogenic damage of the amniotic membrane and improve neonatal outcomes after laser treatment. The aim of this study was to compare neonatal outcomes using this flexible fetoscope with curved sheath vs. use of a standard lens technique. METHODS: Outcomes were retrospective analyzed after use of a standard lens fetoscope of 2 mm (sheath 6.63 mm2 or 11.27 mm2 for anterior placenta) and a flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2) in two German centers of fetal surgery, performed during 2006-2019. RESULTS: Neonatal outcome of 247 TTTS patients were analyzed including the rates of double and single fetal survival. The survival of at least one fetus was 97.2 % in the group with the ultrathin technique (n=154) compared to 88.3 % (n=93) in the group with the standard lens fetoscope (p=0.008). Survival of both fetuses was not different between groups (81.0 vs. 75.3 %). The procedure to delivery interval was significantly increased using the ultrathin fetoscope (89.1±35.0 d vs. 71.4±35.4 d, p=0.001) resulting in an increased gestational age at delivery by 11 days on average (231.9±28.1 d vs. 221.1±32.7 d, p=0.012). CONCLUSIONS: Fetal survival can be significantly increased following TTTS using flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2).

Collaboration between Private and Public Genebanks in Conserving and Using Plant Genetic Resources.

Among the most important users of plant genetic resources, conserved predominantly in public genebanks around the world, are public and private plant breeders. Through their breeding efforts, they contribute significantly to global, regional, and local food and nutrition security. Plant breeders need genetic diversity to be able to develop competitive new varieties that are adapted to the changing environmental conditions and suit the needs of consumers. To ensure continued and timely access to the genetic resources that contain the required characteristics and traits, plant breeders established working collections with breeding materials and germplasm for the crops they were breeding. However, with the changing and increasingly more restrictive access conditions, triggered by new global legal instruments like the Convention on Biological Diversity/Nagoya Protocol and the International Treaty, plant breeders started to establish their own genebanks at the turn of the 21st century. This paper analyses the conditions that contributed to this situation as well as the historical ways that plant breeders used to acquire the germplasm they needed. Public genebanks played and continue to play a conducive role in providing genetic resources to users, including private-sector plant breeders. However, also the practices of the germplasm curators to collect and distribute germplasm were affected by the new legal framework that had been developed in global fora. It is against this background that the complementarity and collaboration between public and private sector genebanks have been assessed. Whenever possible, vegetable genetic resources and vegetable private breeding companies have been used to analyze and illustrate such collaboration. The authors look at reported successful examples of collaborative efforts and consider opportunities and approaches under which such collaboration can be established and strengthened to ensure the continued availability of the building blocks for food and nutrition security.

[Recurrent tinea corporis generalisata due to Terbinafine-resistant Trichophyton rubrum strain : Long-term treatment with super bioavailability itraconazole]. / Rezidivierende Tinea corporis generalisata durch einen Terbinafin-resistenten Trichophyton-rubrum-Stamm : Langzeitbehandlung mit Super-Bioavailability-Itraconazol.

For more than 30 years, an 82-year-old man has been suffering from tinea corporis generalisata in the sense of Trichophyton rubrum syndrome. The patient received long-term treatment with terbinafine. Fluconazole had no effect. There was an increase in liver enzymes with itraconazole. Super bioavailability (SUBA) itraconazole was initially not tolerated. A therapy attempt with voriconazole was successful, but was stopped due to side effects. The Trichophyton (T.) rubrum strain isolated from skin scales was tested for terbinafine resistance using the breakpoint method and found to be (still) sensitive. Sequencing of the squalene epoxidase (SQLE) gene revealed a previously unknown point mutation of the codon for isoleucine ATC→ACC with amino acid substitution I479T (isoleucine479 threonine). Long-term therapy with terbinafine 250 mg had been given every 3 days since 2018. In addition, bifonazole cream, ciclopirox solution, and occasionally terbinafine cream were used. The skin condition was stable until an exacerbation of the dermatophytosis in 2021. There were erythematosquamous, partly atrophic, centrifugal, scaly, confluent plaques on the integument and the extremities. Fingernails and toenails had white to yellow-brown discoloration, and were hyperkeratotic and totally dystrophic. T. rubrum was cultured from skin scales from the integument, from the feet, from nail shavings from the fingernails and also toenails and detected by PCR. In the breakpoint test, the T. rubrum isolates from tinea corporis and nail samples showed a minimum inhibitory concentration (MIC) of 0.5 µg ml-1 (terbinafine resistance in vitro). Sequencing of the SQLE gene of the T. rubrum isolate revealed evidence of a further point mutation that led to amino acid substitution I479V (isoleucine 479 valine). Long-term therapy was started with SUBA itraconazole: 14 days 2â€¯× 1 capsule daily, then twice weekly administration of 2â€¯× 50 mg. During breaks in therapy, the mycosis regularly flared up again. Finally, 50 mg SUBA itraconazole was given 5 days a week, which completely suppressed the dermatophytosis. Topically, ciclopirox and miconazole cream were used alternately. In conclusion, in the case of recurrent and therapy-refractory dermatophytoses caused by T. rubrum, terbinafine resistance must also be considered in individual cases. An in vitro resistance test and point mutation analysis of the squalene epoxidase gene confirms the diagnosis. Itraconazole, also in the form of SUBA itraconazole, is the drug of choice for the oral antifungal treatment of these patients.

Critical Review of the Increasing Complexity of Access and Benefit-Sharing Policies of Genetic Resources for Genebank Curators and Plant Breeders-A Public and Private Sector Perspective.

Plant breeders develop competitive, high-yielding, resistant crop varieties that can cope with the challenges of biotic stresses and tolerate abiotic stresses, resulting in nutritious food for consumers worldwide. To achieve this, plant breeders need continuous and easy access to plant genetic resources (PGR) for trait screening, to generate new diversity that can be built into newly improved varieties. International agreements such as the Convention on Biological Diversity (CBD), the International Treaty on Plant Genetic Resources for Food and Agriculture (ITPGRFA) and the Nagoya Protocol recognised the sovereign rights of countries over their genetic resources. Under the CBD/Nagoya Protocol, countries are free to establish specific national legislations regulating germplasm access and benefit-sharing to be negotiated bilaterally. Consequently, access to PGR became increasingly restricted and cumbersome, resulting in a decrease in germplasm exchange. The ITPGRFA attempted to ease this situation by establishing a globally harmonised multilateral system (MLS). Unfortunately, the MLS is (still) restricted to a limited number of food and forage crops, with very few vegetable crops. Easy and continuous access to genetic diversity combined with equitable and fair sharing of derived benefits is a prerequisite to breeding new varieties. Facilitated access contributes to sustainable crop production and food and nutrition security; therefore, access to and, consequently, use of PGRFA needs to be improved. Thus, the authors recommend, among others, expanding the scope of the ITPGRFA to include all PGRFA and making them and all related information accessible under a Standard Material Transfer Agreement (SMTA) combined, if necessary, with a subscription system or a seed sales tax. Such a transparent, functional and efficient system would erase legal uncertainties and minimise transaction costs for conservers, curators and users of genetic resources, thus aiding plant breeders to fulfil their mission.

The Impact of Vavilov's Concept of the Centres of Crop Origin and Diversity on Research, Conservation, and Utilisation of Plant Genetic Resources Today: A Review on the Occasion of Vavilov's 135th Anniversary.

This Special Issue of Plants is dedicated to the eminent scientist Nikolai Ivanovich Vavilov (1887-1943) in remembrance of his 135th birthday on 25 November 1887 [...].

Gestational and Non-gestational Trophoblastic Neoplasia. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 032/049, April 2022).

Purpose The aim was to develop and update a guideline which would improve the quality of care offered to women with gestational and non-gestational trophoblastic disease, a group of diseases characterized by their rarity and biological heterogeneity. Methods In accordance with the method used to compile S2k-guidelines, the guideline authors carried out a search of the literature (MEDLINE) for the period 1/2020 to 12/2021 and evaluated the recent literature. No key questions were formulated. No structured literature search with methodical evaluation and assessment of the level of evidence was carried out. The text of the precursor version of the guideline from 2019 was updated based on the most recent literature, and new statements and recommendations were drafted. Recommendations The updated guideline contains recommendations for the diagnosis and therapy of women with hydatidiform mole (partial and complete moles), gestational trophoblastic neoplasia after pregnancy or without prior pregnancy, persistent trophoblastic disease after molar pregnancy, invasive moles, choriocarcinoma, placental site nodules, placental site trophoblastic tumor, hyperplasia at the implantation site und epithelioid trophoblastic tumor. Separate chapters cover the determination and assessment of human chorionic gonadotropin (hCG), histopathological evaluation of specimens, and the appropriate molecular pathological and immunohistochemical diagnostic procedures. Separate chapters on immunotherapy, surgical therapy, multiple pregnancies with simultaneous trophoblastic disease, and pregnancy after trophoblastic disease were formulated, and the corresponding recommendations agreed upon.

Cross-sectional study for derivation of a cut-off value for identification of an early versus delayed diagnosis of endometriosis based on analytical and descriptive research methods.

BACKGROUND: Endometriosis is a benign, hormone-dependent, chronic inflammatory gynecological disease accompanied by cyclic and acyclic pelvic pain and other complaints. The long lists of research recommendations in the AWMF guideline (Burghaus et al., Geburtshilfe Frauenheilkd 81:422-46, 2021) and ESHRE Endometriosis Guideline (ESHRE Endometriosis Guideline Development Group, Endometriosis: Guideline of European Society of Human Reproduction and Embryology, 2022) show that there is still a great need for research in all aspects of the disease. Diagnostic delay, defined as the mean time between symptom onset and confirmed diagnosis, is a particular problem associated with endometriosis. Some quantitative and qualitative studies have investigated possible reasons for this. A range of physician-related (Dixon et al., Br J Gen Pract 71:e668-e676, 2021; van der Zanden and Nap, Reprod Biomed Online 32:527-31, 2016) and patient-related factors (Sayer-Jones and Sherman, Health Psychol Behav Med 9:456-79, 2021) as well as stigmatization of the topic of menstruation by society have been identified (Kruckenberg, Frauenarzt 59:2-5, 2018; Seear, Soc Sci Med 69:1220-7, 2009). The consequences of the disease being diagnosed late (or too late) on the course of disease, the quality of life and the costs of the disease have already been documented in studies (Sims Int J Environ Res Public Health 18(15):8210, 2021; Surrey Adv Ther 37:1087-99, 2020). However, a systematically derived cut-off value that clearly distinguishes between short and long delay is still lacking. Therefore, the aim of our study was to derive a threshold value for the definition of a target corridor for endometriosis diagnosis based on descriptive and analytical methods. METHODS: Since our review of the rather sparse publications on diagnostic delay did not yield satisfactory results, we used descriptive statistics and location parameters to calculate a cut-off value for German population data from the EndoCost study. Statistical methods were used for correlation analysis of shortDD versus longDD (correlation analysis and logistic regression) and group membership (discriminant analysis). RESULTS: Five years was identified as the cut-off value that significantly differentiated between shortDD and longDD based on various disease-related variables. This suggests that endometriosis should be definitively diagnosed within less than five years to minimize the risk of an unfavorable course of the disease. CONCLUSION: Our findings confirmed that an early onset of endometriosis-related symptoms is the most important risk factor for a long diagnostic delay. Consequently, adolescent females should receive increased attention as an especially vulnerable group. Evidently, there is an urgent need to develop adequate concepts to improve the endometriosis education and care among this target group.

Prognostic markers of post-stroke depression (PROMoSD): study protocol of a prospective single-center observational study on raphe hypoechogenicity as a predictor of post-stroke depression.

INTRODUCTION: Post-stroke depression (PSD) is an important and frequent non-motor complication after a stroke. As valid prediction of PSD occurrence is still not possible, the unselective use of preventive therapy in stroke patients has risen a questionable risk-to-benefit consideration. Therefore, there is a need to increase the prediction probability of PSD to identify patients at very high risk of a depressive complication who might benefit from preventive therapy. In this context, a brainstem raphe hypoechogenicity (BRH) in transcranial sonography (TCS) has previously been associated with depressive symptoms in a broad spectrum of diseases. BRH might therefore represent a valid maker of vulnerability for depressive symptoms that could be of interest in the risk assessment of PSD occurrence. METHODS: In the prognostic markers of post-stroke depression (PROMoSD) study, a prospective, observational, single-center, investigator-initiated study, we aim to include 100 patients with acute ischemic stroke (AIS). Besides data on clinical characteristics and baseline psychiatric assessment, we conduct a TCS examination to identify patients with BRH. The primary outcome is the incidence of PSD three months after inclusion, determined by a blinded investigator according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria. PERSPECTIVE: The results of PROMoSD will answer the question of whether screening of BRH after AIS improves the prediction of PSD occurrence. A positive result of this study could have direct consequences on psychiatric support after AIS by streamlining diagnostic and therapeutic algorithms. Trial registration ClinicalTrials.gov identifier no. NCT05580198.

Sprouts and Microgreens-Novel Food Sources for Healthy Diets.

With the growing interest of society in healthy eating, the interest in fresh, ready-to-eat, functional food, such as microscale vegetables (sprouted seeds and microgreens), has been on the rise in recent years globally. This review briefly describes the crops commonly used for microscale vegetable production, highlights Brassica vegetables because of their health-promoting secondary metabolites (polyphenols, glucosinolates), and looks at consumer acceptance of sprouts and microgreens. Apart from the main crops used for microscale vegetable production, landraces, wild food plants, and crops' wild relatives often have high phytonutrient density and exciting flavors and tastes, thus providing the scope to widen the range of crops and species used for this purpose. Moreover, the nutritional value and content of phytochemicals often vary with plant growth and development within the same crop. Sprouted seeds and microgreens are often more nutrient-dense than ungerminated seeds or mature vegetables. This review also describes the environmental and priming factors that may impact the nutritional value and content of phytochemicals of microscale vegetables. These factors include the growth environment, growing substrates, imposed environmental stresses, seed priming and biostimulants, biofortification, and the effect of light in controlled environments. This review also touches on microgreen market trends. Due to their short growth cycle, nutrient-dense sprouts and microgreens can be produced with minimal input; without pesticides, they can even be home-grown and harvested as needed, hence having low environmental impacts and a broad acceptance among health-conscious consumers.

Selective Serotonin Reuptake Inhibitors for the Prevention of Post-Stroke Depression: A Systematic Review and Meta-Analysis.

There are controversial data on the efficacy and safety profile of selective serotonin reuptake inhibitors (SSRIs) to prevent post-stroke depression (PSD). We performed a systematic search in MEDLINE and SCOPUS databases to identify randomized-controlled trials questioning the use of early SSRI therapy in the post-stroke population and its effect on PSD incidence. We included 6 studies with 6560 participants. We extracted the data on PSD occurrence in association with the treatment arm (SSRI versus placebo), as reported by each study. For safety analysis, we extracted the information on adverse events. A random-effects model was used to calculate the pooled relative risk estimates. Early SSRI therapy was associated with a significant reduction of PSD occurrence compared to placebo (10.4% versus 13.8%; relative risk: 0.75 [95% CI, 0.66-0.86]; absolute risk reduction: 3.4%). SSRI therapy increases the risk of bone fracture (RR 2.28 [95% CI, 1.58-3.30]) and nausea (RR 2.05 [95% CI, 1.10-3.82]) in the post-stroke population. Considering the risk-benefit ratio of early SSRI therapy in the post-stroke population, future research should identify high-risk patients for PSD to improve the risk-benefit consideration of this therapy for use in clinical practice.

A Critical Review of the Current Global Ex Situ Conservation System for Plant Agrobiodiversity. II. Strengths and Weaknesses of the Current System and Recommendations for Its Improvement.

In this paper, we review gene bank operations that have an influence on the global conservation system, with the intention to identify critical aspects that should be improved for optimum performance. We describe the role of active and base collections and the importance of linking germplasm conservation and use, also in view of new developments in genomics and phenomics that facilitate more effective and efficient conservation and use of plant agrobiodiversity. Strengths, limitations, and opportunities of the existing global ex situ conservation system are discussed, and measures are proposed to achieve a rational, more effective, and efficient global system for germplasm conservation and sustainable use. The proposed measures include filling genetic and geographic gaps in current ex situ collections; determining unique accessions at the global level for long-term conservation in virtual base collections; intensifying existing international collaborations among gene banks and forging collaborations with the botanic gardens community; increasing investment in conservation research and user-oriented supportive research; improved accession-level description of the genetic diversity of crop collections; improvements of the legal and policy framework; and oversight of the proposed network of global base collections.

A Critical Review of the Current Global Ex Situ Conservation System for Plant Agrobiodiversity. I. History of the Development of the Global System in the Context of the Political/Legal Framework and Its Major Conservation Components.

The history of ex situ conservation is relatively short, not more than a century old. During the middle of last century, triggered by the realization that genetic erosion was threatening the existing landraces and wild relatives of the major food crops, global efforts to collect and conserve the genetic diversity of these threatened resources were initiated, predominantly orchestrated by FAO. National and international genebanks were established to store and maintain germplasm materials, conservation methodologies were created, standards developed, and coordinating efforts were put in place to ensure effective and efficient approaches and collaboration. In the spontaneously developing global conservation system, plant breeders played an important role, aiming at the availability of genetic diversity in their breeding work. Furthermore, long-term conservation and the safety of the collected materials were the other two overriding criteria that led to the emerging international network of ex situ base collections. The political framework for the conservation of plant genetic resources finds its roots in the International Undertaking of the FAO and became 'turbulent rapid' with the conclusion of the Convention on Biological Diversity. This paper reviews the history of the global ex situ conservation system with a focus on the international network of base collections. It assesses the major ex situ conservation approaches and methods with their strengths and weaknesses with respect to the global conservation system and highlights the importance of combining in situ and ex situ conservation.

Evaluation of Integrated HPV DNA as Individualized Biomarkers for the Detection of Recurrent CIN2/3 during Post-Treatment Surveillance.

PURPOSE: Post-treatment follow-up in women with cervical pre-cancers (CIN3) is mandatory due to relapse in up to 10% of patients. Standard follow-up based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. The aim of our prospective, multicenter, observational study was to test the hypothesis that an individualized viral-cellular-junction test (vcj-PCR) combined with cytology has a lower false positive rate for the prediction of recurrence compared to standard co-testing. METHODS: Pre-surgical cervical swabs served for the identification of HPV16/18 DNA integration sites by next-generation-sequencing (NGS). Samples taken at 6, 12 and 24 months post-surgery were evaluated by cytology, hrHPV-DNA and the patients' individual HPV-integration sites (vcj-PCR on the basis of NGS). RESULTS: Integration sites were detected in 48 of 445 patients (10.8%), 39 of them had valid follow-up data. The false positive rate was 18.2% (95% CI 8.6-34.4%) for standard hrHPV/cytology at six months compared to 12.1% (95% CI 4.8-27.3%) for vcj-PCR/cytology, respectively (McNemar p = 0.50). Six patients developed recurrences (1 CIN2, 5 CIN3) during follow-up. Standard co-testing detected all, whereas vcj-PCR/cytology detected only five patients with recurrences. Data of 269 patients without evidence of HPV16/18 integration were subject to post-hoc analyses. Standard co-testing revealed a false positive rate of 15.7% (95% CI 11.7-20.7%) and predicted ten of fourteen recurrences at six months. CONCLUSIONS: Although highly specific on its own vcj-PCR could not detect all recurrent CIN2/3. Possible reasons for this unexpected result may be multifocal lesions, intratumoral heterogeneity with respect to HPV integration and/or incident CIN.

Plasma calcitonin gene-related peptide (CGRP) in migraine and endometriosis during the menstrual cycle.

OBJECTIVE: Migraine, endometriosis, and the comorbidity of both are frequent pain disorders of special relevance for women. The neuropeptide calcitonin gene-related peptide (CGRP) is critically involved in migraine, and circumstantial evidence suggests a role in endometriosis. We assessed CGRP levels at different times of menstrual cycle in four groups: healthy women, women with migraine or endometriosis and with the comorbidity of both. METHODS: Women with episodic migraine and women with a histologically confirmed endometriosis were recruited from specialized centers. For CGRP determination with a commercial enzyme immunoassay kit, cubital vein blood samples were collected on menstrual cycle day 2 ± 2 (during menstruation) and on day 15 ± 2 (periovulatory period). The primary endpoint of the study was the absolute difference of CGRP plasma levels between the menstrual and the periovulatory phase of all study groups. Groups were compared using nonparametric test procedures. RESULTS: A total of 124 women were included in the study. The change of CGRP plasma levels between menstruation and the periovulatory period was different between groups (p = 0.007). Women with comorbid migraine and endometriosis showed an increase of CGRP in the menstrual phase of +6.32 (interquartile range, IQR -3.64-13.60) compared to the periovulatory time, while healthy controls had a decrease of -10.14 (-22.54-0.91, p = 0.004). CGRP levels were different in the periovulatory phase among groups (p = 0.008), with highest values in healthy controls. INTERPRETATION: CGRP levels change significantly during the menstrual cycle. Different patterns in women with the comorbidity point to a deviant regulation of CGRP release.

Diagnosis and Treatment of Endometriosis. Guideline of the DGGG, SGGG and OEGGG (S2k Level, AWMF Registry Number 015/045, August 2020).

Aims The aim of this official guideline published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG) in cooperation with the Austrian Society for Gynaecology and Obstetrics (OEGGG) and the Swiss Society for Gynaecology and Obstetrics (SGGG) was to provide consensus-based recommendations for the diagnosis and treatment of endometriosis based on an evaluation of the relevant literature. Methods This S2k guideline represents the structured consensus of a representative panel of experts with different professional backgrounds commissioned by the Guideline Committee of the DGGG, OEGGG and SGGG. Recommendations Recommendations on the epidemiology, aetiology, classification, symptomatology, diagnosis and treatment of endometriosis are given and special situations are discussed.